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Sample records for hypogonadism

  1. Hypogonadotropic hypogonadism revisited.

    PubMed

    Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

    2013-01-01

    Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific

  2. Adult-Onset Hypogonadism.

    PubMed

    Khera, Mohit; Broderick, Gregory A; Carson, Culley C; Dobs, Adrian S; Faraday, Martha M; Goldstein, Irwin; Hakim, Lawrence S; Hellstrom, Wayne J G; Kacker, Ravi; Köhler, Tobias S; Mills, Jesse N; Miner, Martin; Sadeghi-Nejad, Hossein; Seftel, Allen D; Sharlip, Ira D; Winters, Stephen J; Burnett, Arthur L

    2016-07-01

    In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up. PMID:27343020

  3. Hypogonadism: Its Prevalence and Diagnosis.

    PubMed

    Ross, Anna; Bhasin, Shalender

    2016-05-01

    Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. PMID:27132573

  4. Hypogonadism in male cancer patients.

    PubMed

    Burney, Basil O; Garcia, Jose M

    2012-09-01

    Prevalence of hypogonadism in men with cancer has been reported between 40% and 90%, which is significantly higher than in the general population. Hypogonadism is likely to affect the quality of life in these patients by contributing to non-specific symptoms, including decreased energy, anorexia, sarcopenia, weight loss, depression, insomnia, fatigue, weakness, and sexual dysfunction. Pathogenesis of hypogonadism in cancer patients is thought to be multi-factorial. Inflammation may play an important role, but leptin, opioids, ghrelin, and high-dose chemotherapy through different mechanisms have all been implicated as the cause. Hypogonadism is also associated with poor survival in cancer patients. Data looking into the treatment of hypogonadal male cancer patients with testosterone are limited. However, improvements in body weight, muscle strength, lean body mass, and quality of life have been shown in hypogonadal men with other chronic diseases on testosterone replacement therapy. Prospective and interventional trials are needed to test the efficacy and safety of testosterone treatment in improving quality of life of these patients. PMID:22528986

  5. Genetics of Hypogonadotropic Hypogonadism.

    PubMed

    Topaloglu, A Kemal; Kotan, L Damla

    2016-01-01

    Hypogonadotropic hypogonadism (HH) often manifests as pubertal delay. A considerable proportion of cases of HH is due to genetic mutations. Recognizing those mutated genes and associated phenotypes may improve our diagnostic capabilities. GNRHR and TACR3 should be the first two genes to be screened in a clinical setting for equivocal cases such as constitutional delay in puberty versus idiopathic HH. In Kallmann syndrome (KS), according to the presence of certain accompanying clinical features, genetic screening for particular gene(s) may be prioritized: synkinesia (KAL1), dental agenesis (FGF8/FGFR1), bony anomalies (FGF8/FGFR1), and hearing loss (CHD7, SOX10). FEZF1 has recently been added to the growing list of KS genes. Also, discovery of mutations in KISS1/KISS1R and TAC3/TACR3 in kisspeptin and neurokinin B signaling, respectively, has provided major advancements in our understanding of the biology of the gonadotropin-releasing hormone pulse generator. Identification of further causative mutations accounting for the HH phenotype, which is now more feasible with the increasing popularity of whole exome sequencing, may provide deeper insight into the biology of the hypothalamic-pituitary-gonadal axis. PMID:26680571

  6. Male hypogonadism and metabolic syndrome.

    PubMed

    Naifar, M; Rekik, N; Messedi, M; Chaabouni, K; Lahiani, A; Turki, M; Abid, M; Ayedi, F; Jamoussi, K

    2015-06-01

    The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link. PMID:25040289

  7. Leydig cell aging and hypogonadism.

    PubMed

    Beattie, M C; Adekola, L; Papadopoulos, V; Chen, H; Zirkin, B R

    2015-08-01

    Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences. PMID:25700847

  8. Biochemical endocrinology of the hypogonadal male.

    PubMed

    Belchetz, Paul E; Barth, Julian H; Kaufman, Jean-Marc

    2010-11-01

    Hypogonadism in the male results from inadequate testicular function, especially defects in androgen synthesis and secretion, or action. Androgen action is important throughout normal male development: in the fetus, puberty, adult life and old age. Regulation is by variable activity of the hypothalamo-pituitary axis at different phases of the life span. Clinical aspects include: genetic aspects presenting at birth and pubertal failure/arrest. Aspects in adult life embrace sexuality, somatic symptoms and osteoporosis. Acquired causes of hypogonadism may arise from various forms of testicular damage (primary hypogonadism), pituitary and hypothalamic disorders, as well as aetiologies acting at several sites. Measurement of testosterone (T) is crucial to the diagnosis of hypogonadism and the technologies continue to develop, with recent major advances. A growing problem relates to the diagnosis and treatment of hypogonadism in the ageing male. T therapy is available in several forms, with major improvements in more newly available modalities. PMID:20956400

  9. Evaluation and treatment of male hypogonadism in primary care.

    PubMed

    Pickett, Kim Anne

    2016-08-18

    Male hypogonadism is increasing in prevalence, particularly in the older male population. Signs and symptoms associated with hypogonadism are often nonspecific and may be difficult to categorize. This article discusses parameters for screening patients at risk, reviews how to establish the diagnosis of primary or secondary male hypogonadism, and offers important considerations for treatment of patients with hypogonadism. PMID:27434384

  10. [Androgenic treatment of male hypogonadism].

    PubMed

    Kuhn, Jean-Marc; Prévost, Gaëtan

    2014-02-01

    The diagnosis of male hypogonadism should be clearly established on a clinical and biological basis before considering the initiation of a substitutive treatment with androgens. A careful evaluation of advantages, constraints and limitations of the treatment should be done previously. The potential advantages of an androgenic substitution include an improvement of the symptoms of hypogonadism and the prevention of its bone and metabolic consequences. Absolute (namely prostatic) or relative contraindications should be detected before starting any substitution. The modalities of treatment will be adapted to both the patient's age and the goals to reach. The different available formulations do not induce a similar pattern of plasma testosterone levels. Patches, gel applications and long-acting intramuscular formulations [injected every 3 months] result in stable plasma levels in the physiologic range. The main limitation to their use is linked to a financial aspect as they are not the object of any refund. A careful survey (on clinical, biological and radiological basis) should be established after starting the substitutive treatment with androgens. PMID:24268959

  11. Hypogonadism

    MedlinePlus

    ... Estrogen level (women) FSH level and LH level Testosterone level (men) Other tests may include: Blood tests ... the form of a pill or skin patch. Testosterone is used for boys and men. The medicine ...

  12. Hypogonadism

    MedlinePlus

    ... growth problems. In men the symptoms are: Breast enlargement Muscle loss Decreased interest in sex (low libido) ... care provider if you notice: Breast discharge Breast enlargement (men) Hot flashes (women) Impotence Loss of body ...

  13. Treatment of hypogonadism in males.

    PubMed

    Watson, Sara; Fuqua, John S; Lee, Peter A

    2014-02-01

    The treatment of adolescent males with hypogonadism using testosterone is dependent on the underlying diagnosis as well as the patient's and family's preferences. Those with testicular failure, always a pathologic condition, begin lifelong therapy, while short-term therapy is often begun for those who have a delayed puberty. There is a wide variety of testosterone formulations available, with differences in adverse events sometimes associated with the method of administration. The goals of treatment involve stimulating physical puberty, including achievement of virilization, a normal muscle mass and bone mineral density for age, and improvement in psychosocial wellbeing. While androgen therapy results in physical changes of puberty, the potential for fertility must be considered for those with permanent gonadotropin deficiency. in this population, therapy with gonadotropins or gonadotropin releasing hormone may be effective. For those with testicular failure, fertility may be possible but requires assisted reproductive procedures. PMID:24683947

  14. Neuroradiological findings in hypogonadotropic hypogonadism.

    PubMed

    Salvalaggio, Alessandro; Elefante, Andrea; Manara, Renzo

    2016-06-01

    Hypogonadotropic hypogonadism (HH) is a clinical hallmark of a heterogeneous group of acquired and inherited diseases. Patients with HH undergo brain imaging in order to investigate morphological or signal abnormalities at the level of the hypothalamic-pituitary structures. The presence of tumors, lesions or atrophy might be the explanation of the hormone dysfunction. Nonetheless, in most patients both the hypothalamus and the pituitary gland appear normal. In some cases, the presence of ancillary, not necessarily HH-related brain abnormalities might provide significant clues on the underlying condition. We addressed those conditions associated with HH subdividing them into acquired or inherited diseases, highlighting the neuroradiologic features that might help in the diagnosis. PMID:27050382

  15. Hypogonadism in the HIV-infected man.

    PubMed

    Rochira, Vincenzo; Guaraldi, Giovanni

    2014-09-01

    Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass. PMID:25169563

  16. Hypogonadotropic Hypogonadism in a Boy with Myopathy.

    PubMed

    Haq, T; Pathan, M F; Ikhtaire, S

    2016-01-01

    Hypogonadism is seldom seen together with myopathy, although testosterone contributes to muscle strength. We present here a rare case of hypogonadotropic hypogonadism with myopathy in a 20 year old male. He had flaccid quadriparesis with raised creatinine phosphokinase. Hormone assays revealed low testosterone as well as low luteinising hormone and follicle stimulating hormone levels. Tests to exclude androgen deficiency should be carried out in male patients with myopathy. PMID:26931274

  17. An update on male hypogonadism therapy

    PubMed Central

    Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

    2014-01-01

    Introduction Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Areas covered Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Expert opinion Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men. PMID:24758365

  18. Testosterone nasal gel (Natesto) for hypogonadism.

    PubMed

    2015-05-11

    In one study, Natesto nasal gel administered intranasally 3 times daily was effective in raising low serum testosterone levels into the normal range in patients with hypogonadism. Whether patients will find this method of administration more acceptable than an intramuscular injection every 2-4 weeks or once-daily application to the skin remains to be determined. Based on the lack of convincing evidence of benefit in older men and concerns about its safety, the FDA has warned against using testosterone to treat hypogonadism due solely to aging. PMID:25941957

  19. [Estrogens and male sexuality: efficiency of antiestrogens in case of hypothalamic hypogonadism and late onset hypogonadism].

    PubMed

    Martin-Du Pan, R C

    2011-03-23

    Estrogen treatment in eugonadal men diminishes libido, whereas libido is preserved by estrogens in orchidectomized transsexuals as well as in cases of aromatase deficiency. Hypothalamic hypogonadism can be caused by stress, depression, anorexia or excessive exercise. It may result in erectile dysfunction and decreased libido. A 7 day trial of clomiphen (25 mg/day) can be used to test the responsiveness of the axis and may be continued for up to 6 months as a means to stimulation endogenous LH and testosterone secretion. Other antiestrogens such as raloxifen or anastrazol may have similar effects in obese men and in aging men with late onset hypogonadism (LOH). PMID:21542378

  20. A Rare Presentation of Transfusional Hemochromatosis: Hypogonadotropic Hypogonadism

    PubMed Central

    Ucler, Rifki; Kara, Erdal; Atmaca, Murat; Olmez, Sehmus; Alay, Murat; Dirik, Yaren; Bora, Aydin

    2015-01-01

    Hemochromatosis is a disease caused by extraordinary iron deposition in parenchymal cells leading to cellular damage and organ dysfunction. β-thalassemia major is one of the causes of secondary hemochromatosis due to regular transfusional treatment for maintaining adequate levels of hemoglobin. Hypogonadism is one of the potential complications of hemochromatosis, usually seen in patients with a severe iron overload, and it shows an association with diabetes and cirrhosis in adult patients. We describe a patient with mild transfusional hemochromatosis due to β-thalassemia major, presenting with central hypogonadism in the absence of cirrhosis or diabetes. Our case showed an atypical presentation with hypogonadotropic hypogonadism without severe hyperferritinemia, cirrhosis, or diabetes. With this case, we aim to raise awareness of hypogonadotropic hypogonadism in patients with intensive transfused thalassemia major even if not severe hemochromatosis so that hypogonadism related complications, such as osteoporosis, anergia, weakness, sexual dysfunction, and infertility, could be more effectively managed in these patients. PMID:26266058

  1. A Rare Presentation of Transfusional Hemochromatosis: Hypogonadotropic Hypogonadism.

    PubMed

    Ucler, Rifki; Kara, Erdal; Atmaca, Murat; Olmez, Sehmus; Alay, Murat; Dirik, Yaren; Bora, Aydin

    2015-01-01

    Hemochromatosis is a disease caused by extraordinary iron deposition in parenchymal cells leading to cellular damage and organ dysfunction. β-thalassemia major is one of the causes of secondary hemochromatosis due to regular transfusional treatment for maintaining adequate levels of hemoglobin. Hypogonadism is one of the potential complications of hemochromatosis, usually seen in patients with a severe iron overload, and it shows an association with diabetes and cirrhosis in adult patients. We describe a patient with mild transfusional hemochromatosis due to β-thalassemia major, presenting with central hypogonadism in the absence of cirrhosis or diabetes. Our case showed an atypical presentation with hypogonadotropic hypogonadism without severe hyperferritinemia, cirrhosis, or diabetes. With this case, we aim to raise awareness of hypogonadotropic hypogonadism in patients with intensive transfused thalassemia major even if not severe hemochromatosis so that hypogonadism related complications, such as osteoporosis, anergia, weakness, sexual dysfunction, and infertility, could be more effectively managed in these patients. PMID:26266058

  2. Obesity and late-onset hypogonadism.

    PubMed

    Corona, G; Vignozzi, L; Sforza, A; Mannucci, E; Maggi, M

    2015-12-15

    Obesity and male hypogonadism (HG) are often associated, as demonstrated in all cross-sectional studies. Prospective studies have indicated that i) having HG at baseline increases the risk of visceral obesity (and metabolic syndrome) and that ii) obesity induces incident HG. Hence, there is a bidirectional relationship between the two conditions. This is the main topic of this review, along with some pathogenic considerations. Meta-analysis of intervention studies indicates that treating obesity is a very efficient treatment for obesity-induced HG. The mechanism by which obesity induces HG has not yet been completely understood, but dietary-induced hypothalamic inflammation, along with a decreased GnRH release, is plausible. Among patients seeking medical care for obesity, the proportion of HG is relatively high. The prevalence of obesity among patients referring for sexual dysfunction is also elevated. Hence, in symptomatic, obese, hypogonadal subjects, testosterone supplementation (TS) can be considered. Whereas long-term uncontrolled register studies suggest that TS could decrease weight, analysis of controlled studies only support a parallel increase in lean mass and decrease in fat mass, with a resulting null effect on weight. Considering that T induces an increase in muscle mass, it is conceivable that the amount of activity obese people can undertake after TS will increase, allowing a closer adherence to physical exercise programs. Some studies, here meta-analyzed, support this concept. PMID:26143633

  3. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

    SciTech Connect

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Greenspan, S.L.; Rosenthal, D.I.; Crowley, W.F. Jr.

    1987-03-01

    To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarly decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.

  4. Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

    PubMed

    Bhattacharya, Rajib K; Bhattacharya, Shelley B

    2015-11-01

    Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy. PMID:26476121

  5. Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

    PubMed

    Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

    2012-04-01

    Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with

  6. MANAGEMENT OF ENDOCRINE DISEASE: Reversible hypogonadotropic hypogonadism.

    PubMed

    Dwyer, Andrew A; Raivio, Taneli; Pitteloud, Nelly

    2016-06-01

    Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of puberty and infertility. Traditionally, it has been considered a life-long condition yet cases of reversibility have been described wherein patients spontaneously recover function of the reproductive axis following treatment. Reversibility occurs in both male and female CHH cases and appears to be more common (~10-15%) than previously thought. These reversal patients span a range of GnRH deficiency from mild to severe and many reversal patients harbor mutations in genes underlying CHH. However, to date there are no clear factors for predicting reversible CHH. Importantly, recovery of reproductive axis function may not be permanent. Thus, CHH is not always life-long and the incidence of reversal warrants periodic treatment withdrawal with close monitoring and follow-up. Reversible CHH highlights the importance of environmental (epigenetic) factors such as sex steroid treatment on the reproductive axis in modifying the phenotype. This review provides an overview and an update on what is known about this phenomenon. PMID:26792935

  7. Hypogonadotropic hypogonadism associated with hereditary hemorrhagic telangiectasia [corrected].

    PubMed

    Scarano, Valentina; Valentina, Scarano; De Santis, Daniele; Daniele, De Santis; Suppressa, Patrizia; Patrizia, Suppressa; Lastella, Patrizia; Patrizia, Lastella; Lenato, Gennaro Mariano; Mariano, Lenato Gennaro; Triggiani, Vincenzo; Vincenzo, Triggiani; Sabbà, Carlo; Carlo, Sabbà

    2013-01-01

    A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis. PMID:23710379

  8. Preserving fertility in the hypogonadal patient: an update

    PubMed Central

    Ramasamy, Ranjith; Armstrong, Joseph M; Lipshultz, Larry I

    2015-01-01

    An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism) including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG) has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men. PMID:25337850

  9. Clomiphene Citrate Effectively Increases Testosterone in Obese, Young, Hypogonadal Men

    PubMed Central

    Bendre, Sachin V.; Murray, Pamela J.; Basaria, Shehzad

    2016-01-01

    Background Obesity has been associated with low testosterone (T) in adult males and in pubertal boys. Therapy for hypogonadism with exogenous T may lead to testicular atrophy and later infertility. Only a few studies have demonstrated that the Selective Estrogen Receptor Modulator (SERM) clomiphene citrate (CC), an estrogen receptor antagonist, increases T in obese hypogonadal men while preventing testicular atrophy. No studies to date using CC have been done in younger obese post-pubertal hypogonadal males. Objective To determine whether CC therapy is effective in increasing serum T levels in hypogonadal post-pubertal obese males 18-21 years. Materials and Methods A retrospective chart analysis of records in obese men aged 18-21 years was done. Patients with early morning T level <350 ng/dl were given 25 mg CC on alternate days. Out of 18 patients found to have low T, 11 were analyzed. Baseline serum T, LH, FSH, weight and BMI were compared at baseline and after 3 months of CC treatment. Results Baseline T level was 233 ± 66 ng/dl and increased to 581 ± 161 ng/dl (p<0.0001) after 3 months of CC treatment. Baseline LH levels increased from 3.3 ± 1.6 mIU/mL to 5.7 ± 1.7 mIU/mL (p=0.027). Similarly, baseline FSH levels increased from 2.8 ± 1.5 mIU/mL to 6.2 ± 3 mIU/mL after CC treatment (p=0.026). There was no correlation between baseline or post treatment weight or BMI and the T level, LH, or FSH level. Conclusion This is the first study reporting on CC therapy in obese, hypogonadal post-pubertal men 18-21 years. The SERM CC increased T in obese post-pubertal hypogonadal men, similar to efficacy of CC in adult hypogonadal men over the age 21 years. Larger randomized controlled studies to study the safety and potential use of CC to improve T in young obese HG men are needed. PMID:26844009

  10. [Optimization of modern conservative therapy of micropenis in hypogonadal men].

    PubMed

    Petrovich, R Iu; Sokoll'shchik, M M; Tiuzikov, I A; Konstantinova, I V; Astakhova, M A

    2014-01-01

    The study was aimed to the optimization of conservative therapy of micropenis in hypogonadal men using combination of traction therapy and androgen replacment therapy (ART) with injections of prolonged testosterone undecanoate (Nebido) and to evaluatiom of the safety of ART in terms of the risk of prostate cancer against the background of combined treatment of micropenis by both methods within 12 months. The study included 16 men aged 22-62 years with micropenis and hypogonadism. 10 men were diagnosed with primary hypogonadism, 6 men were diagnosed with secondary hypogonadism without reserve gonadal function; therefore, all 16 patients were treated with testosterone undecanoate 1000 mg intramuscularly according to the scheme: the second injection 6 weeks after the first injection, then each injection once a 12 weeks, the course of 12 months. During the first 3 months of ART, hypogonadism in all men was eliminated, but only at 6 month of ART, the length of the penis in the flaccid state at maximum extension increased from 5.8±1.2 to 8.3±1.2 cm (p<0.05), and the length of the erect penis - from 6.8±1.1 to 11.8±0.9 (p<0,05). At the next stage, from the 6th to the 12th month of ART, traction therapy was simultaneously carried out. At the end of the treatment, the length of the penis in the flaccid state at maximum extension increased by 58% of the original length, and in a state of erection - by 114% (p<0.05). During the 12 months of treatment, prostate volume in all men increased from 3.4±1.2 to 16.3±1.2 (p<0.05), which corresponds to the size of the prostate in healthy men. Total blood PSA level increased from 0.72±0.03 to 1.4±0.05 ng/ml (p<0.05), but it was in the acceptable range of reference values for healthy men during whole period of ART in all patients. Start therapy with prolonged testosterone undecanoate for 6 months significantly increases the efficiency of traction therapy in men with hypogonadism and micropenis, but for maintenance of the effect

  11. The Role of Estrogen Modulators in Male Hypogonadism and Infertility

    PubMed Central

    Rambhatla, Amarnath; Mills, Jesse N.; Rajfer, Jacob

    2016-01-01

    Estradiol, normally considered a female hormone, appears to play a significant role in men in a variety of physiologic functions, such as bone metabolism, cardiovascular health, and testicular function. As such, estradiol has been targeted by male reproductive and sexual medicine specialists to help treat conditions such as infertility and hypogonadism. The compounds that modulate estradiol levels in these clinical conditions are referred to as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). In a certain subset of infertile men, particularly those with hypogonadism, or those who have a low serum testosterone to estradiol ratio, there is some evidence suggesting that SERMs and AIs can reverse the low serum testosterone levels or the testosterone to estradiol imbalance and occasionally improve any associated infertile or subfertile state. This review focuses on the role these SERMs and AIs play in the aforementioned reproductive conditions. PMID:27601965

  12. The Role of Estrogen Modulators in Male Hypogonadism and Infertility.

    PubMed

    Rambhatla, Amarnath; Mills, Jesse N; Rajfer, Jacob

    2016-01-01

    Estradiol, normally considered a female hormone, appears to play a significant role in men in a variety of physiologic functions, such as bone metabolism, cardiovascular health, and testicular function. As such, estradiol has been targeted by male reproductive and sexual medicine specialists to help treat conditions such as infertility and hypogonadism. The compounds that modulate estradiol levels in these clinical conditions are referred to as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). In a certain subset of infertile men, particularly those with hypogonadism, or those who have a low serum testosterone to estradiol ratio, there is some evidence suggesting that SERMs and AIs can reverse the low serum testosterone levels or the testosterone to estradiol imbalance and occasionally improve any associated infertile or subfertile state. This review focuses on the role these SERMs and AIs play in the aforementioned reproductive conditions. PMID:27601965

  13. MMACHC gene mutation in familial hypogonadism with neurological symptoms.

    PubMed

    Shi, Changhe; Shang, Dandan; Sun, Shilei; Mao, Chengyuan; Qin, Jie; Luo, Haiyang; Shao, Mingwei; Chen, Zhengguang; Liu, Yutao; Liu, Xinjing; Song, Bo; Xu, Yuming

    2015-12-15

    Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. PMID:26283149

  14. [The treatment of hypogonadism and maintenance of fertility in men].

    PubMed

    Rabijewski, Michał

    2016-03-01

    In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis. PMID:27088205

  15. [A woman with cerebellar ataxia and hypergonadotropic hypogonadism].

    PubMed

    Wada, Sayoko; Takaoka, Toshio; Kasama, Shuhei; Kimura, Takashi; Kajiyama, Koji; Takeda, Masanaka; Yoshikawa, Hiroo

    2010-01-01

    A 26-year-old woman with primary amenorrhea in association with hypergonadotropinism, and lacking a vagina and uterus, suffered from a gradually progressive gait disturbance in her adolescence. The patient has no family history of ataxia and a chromosome study showed a normal karyotype (46,XX). Using the revised Hasegawa Dementia Scale, her cognitive function was measured as that of a normal adult, however, neurological examination revealed symptoms of scanning speech, horizontal gaze-evoked nystagmus, and ataxia. Bulging eyes, high-arched palate, scoliosis and ventricular septal defect were also observed. A brain MRI showed atrophy of the cerebellum. A 123I-IMP brain SPECT study showed hypoperfusion in the cerebellum. Previous studies show that among patients with cerebellar ataxia and hypergonadotropic hypogonadism, some show an autosomal recessive inheritance, while others have no family history. As a cause, a chromosomal abnormality is unlikely because all reported karyotypes were normal. This case is different from other reported cases in that she is not mentally impaired or deaf. The present case indicates that there is a close relationship between cerebellar ataxia and hypogonadism, and that other symptoms such as deafness and mental impairment could be an additional variable in patients with cerebellar ataxia arid hypergonadotropic hypogonadism. PMID:20120350

  16. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men.

    PubMed

    O'Connor, Daryl B; Archer, John; Hair, W Morton; Wu, Frederick C W

    2002-04-01

    To investigate (1) the effects of exogenous testosterone (T) on self- and partner-reported aggression and mood and (2) the role of trait impulsivity in the T-aggression relationship. Thirty eugonadal men with partners were randomized into two treatment groups to receive: (1) 200 mg im T enanthate weekly for 8 weeks or (2) 200 mg im sodium chloride weekly for 8 weeks. Eight hypogonadal men received 200 mg im T enanthate biweekly for 8 weeks. All groups completed a battery of behavior measures at baseline (Week 0) and at Weeks 4 and 8. Cognitive and motor impulsivity were the only predictors of self-reported total aggression (over and above age and T levels) at Weeks 0, 4, and 8. No significant changes in aggression or mood levels were found in the eugonadal-treated group. Significant reductions in negative mood (tension, anger, and fatigue) followed by an increase in vigor were found in response to T treatment in the hypogonadal group. These results demonstrate that inability to control one's behavior when such control is required by a particular situation (impulsivity) was found to significantly predict levels of aggression over and above age and T level. These data do not support the hypothesis that supraphysiological levels of T (within this range) lead to an increase in self- and partner-reported aggression or mood disturbances. Instead, for the first time, this study has identified the high level of negative affect experienced by hypogonadal patients. These findings have implications for T replacement therapy and male contraception. PMID:12062320

  17. Basic consensus document on late-onset hypogonadism.

    PubMed

    Becerra Fernández, Antonio; Enríquez Acosta, Luis

    2008-01-01

    One of the most important elements in men's live is the ability to engage in normal sexual activity; loss of this activity has always been considered especially important. The relationship between sexual activity, as well as other masculine characteristics, and the testicles has been well known since ancient times and has been related to the slow decrease in testosterone secretion with advanced age. Male hypogonadism is one of the most frequent and under-diagnosed endocrine diseases. Several terms have been proposed to refer to clinical situations caused by the age-related decline in male gonadal function; currently, the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a clinical and biochemical syndrome associated with advanced age (in men), characterized by typical symptoms and reduced serum testosterone concentrations, which can affect multiple organs and systems and reduce quality of life. This syndrome can be treated and the alterations produced can be reversed. To achieve this, a diagnostic protocol that approaches the multiple factors related to the risks and benefits of treatment is required. PMID:22967848

  18. Kallman syndrome versus idiopathic hypogonadotropic hypogonadism at MR imaging

    SciTech Connect

    Vogl, T.J.; Stemmler, J.; Bergman, C.; Balzer, J.O.; Felix, R.; Heye, B.; Schopohl, J.; Danek, A.

    1994-04-01

    To identify morphologic differences between Kallman syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) and establish a role for magnetic resonance (MR) imaging in these disorders. Twenty-eight patients were compared with 10 eugonal male volunteers. Eighteen patients had KS (hypogonadotropic hypogonadism with anosmia) and 10 had IHH. All participants underwent hormone analysis, a sniff-bottle smell test, and gadolinium-enhanced MR imaging. Changes in the hypothalamic-hypophyseal region and the rhinencephalon were evaluated. MR imaging revealed intracranial morphologic changes in all patients on plain T1-weighted sections. Seventeen patients with KS demonstrated aplasia of an olfactory bulb; one olfactory sulcus was absent in six, rudimentary in four, and normal in eight. Olfactory bulbs were present in all 10 IHH patients and three showed one slightly hypoplastic bulb. Ten patients with KS and three with IHH showed an enlarged paranasal sinus system. Further MR findings were similar. MR imaging demonstrates abnormalities of the rhinencephalon present in KS patients and occasionally absent in IHH patients. 18 refs., 10 figs., 1 tab.

  19. Visceral fat dysfunction is positively associated with hypogonadism in Chinese men

    PubMed Central

    Wang, Ningjian; Zhai, Hualing; Han, Bing; Li, Qin; Chen, Yi; Chen, Yingchao; Xia, Fangzhen; Lin, Dongping; Lu, Yingli

    2016-01-01

    Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone < 11.3 nmol/L. VAI was calculated in male: (waist circumference/(39.68 + (1.88 × BMI))) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P < 0.01). Higher quartiles of VAI were associated with significantly increasing odds of hypogonadism (P for trend < 0.01). The fully adjusted odds ratio was 5.88 (95 CI% 4.09, 8.46) for the highest quartile compared with the lowest quartile of VAI. Among all the indices investigated, VAI showed the largest area under the curve (P < 0.001). In conclusion, the VAI was significantly associated with a higher prevalence of hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index). PMID:26796865

  20. Influence of testosterone gel treatment on spermatogenesis in men with hypogonadism.

    PubMed

    George, Mskhalaya; Yulia, Tishova; Svetlana, Kalinchenko

    2014-10-01

    The prevalence of androgen deficiency in reproductive-aged men is increasing and needs new approach to long-term hypogonadism treatment that can preserve fertility. An open non-controlled pilot study included 18 men with eugonadotropic hypogonadism, who received transdermal testosterone gel treatment for 3 months. Sperm analysis was made before treatment and after 3 month of testosterone therapy. Testosterone level was normalized in all patients, but no negative effect was observed on spermatogenesis. Testosterone gel therapy may be a therapy of choice in hypogonadal men of reproductive age but further studies are needed. PMID:25200823

  1. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men

    PubMed Central

    Lunenfeld, Bruno; Zitzmann, Michael; Arver, Stefan; Kalinchenko, Svetlana; Tishova, Yuliya; Morgentaler, Abraham

    2015-01-01

    Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men. PMID:25657080

  2. [Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

    PubMed

    Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

    2016-07-01

    Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described. PMID:27346312

  3. Hypogonadism and erectile dysfunction as harbingers of systemic disease.

    PubMed

    Chiles, Kelly A

    2016-04-01

    Prescription sales of Testosterone and erectile aids such as phosphodiesterase-5 inhibitors are at an all-time high, underscoring the importance of hypogonadism (HG) and erectile dysfunction (ED) to men's health. The effect of these debilitating conditions has a major impact on the quality of men's lives. Some risk factors for HG or ED including aging, obesity, smoking, and a sedentary lifestyle. Notably, these are the same risk factors for several other medical co-morbidities that contribute to significant morbidity and mortality in men. HG and ED often co-exist with cardiovascular disease, diabetes, and osteoporosis. This review will explore these three co-morbidities that overlap with HG and ED, and will provide a review of their relationship with each other. PMID:27141446

  4. Hypogonadism and erectile dysfunction as harbingers of systemic disease

    PubMed Central

    2016-01-01

    Prescription sales of Testosterone and erectile aids such as phosphodiesterase-5 inhibitors are at an all-time high, underscoring the importance of hypogonadism (HG) and erectile dysfunction (ED) to men’s health. The effect of these debilitating conditions has a major impact on the quality of men’s lives. Some risk factors for HG or ED including aging, obesity, smoking, and a sedentary lifestyle. Notably, these are the same risk factors for several other medical co-morbidities that contribute to significant morbidity and mortality in men. HG and ED often co-exist with cardiovascular disease, diabetes, and osteoporosis. This review will explore these three co-morbidities that overlap with HG and ED, and will provide a review of their relationship with each other. PMID:27141446

  5. Current topics in testosterone replacement of hypogonadal men.

    PubMed

    Nieschlag, Eberhard

    2015-01-01

    All forms of hypogonadism - primary, secondary and late-onset - require testosterone substitution. The indication is given when the patient presents with symptoms of androgen deficiency and the serum testosterone levels are below normal. Several testosterone preparations and modes of application are available of which those producing physiologic serum levels should be preferred e.g. preferentially transdermal gels and long-acting intramuscular testosterone undecanoate. Testosterone substitution must be monitored at regular intervals, best at 3, 6 and 12 months after initiation and then annually. Parameters for surveillance include well-being, libido and sexual activity, measurement of serum testosterone levels, haemoglobin and haematocrit, PSA and digital rectal examination, and, biannually, bone mineral density. Testosterone has positive effects on comorbidities such as obesity, metabolic syndrome, diabetes type II, cardiovascular diseases and osteoporosis. PMID:25617174

  6. Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease

    PubMed Central

    2014-01-01

    Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians. PMID:25254043

  7. The complex genetic basis of congenital hypogonadotropic hypogonadism.

    PubMed

    Vezzoli, Valeria; Duminuco, Paolo; Bassi, Ivan; Guizzardi, Fabiana; Persani, Luca; Bonomi, Marco

    2016-06-01

    Congenital hypogonadotropic hypogonadism (CHH) is a rare disease characterized by delayed/absent puberty and infertility due to an inadequate secretion or action of gonadotrophin-releasing hormone (GnRH), with an otherwise structurally and functionally normal hypothalamic-pituitary-gonadal (HPG) axis. CHH is genetically heterogeneous but, due to the infertility of affected individuals, most frequently emerges in a sporadic form, though numerous familial cases have also been registered. In around 50-60% of cases, CHH is associated with a variety of non-reproductive abnormalities, most commonly anosmia/hyposmia, which defines Kallmann Syndrome (KS) by its presence. Broadly-speaking, genetic defects that directly impact on hypothalamic secretion, regulation, or action of GnRH result in a pure neuroendocrine phenotype, normosmic CHH (nCHH), whereas genetic defects that impact of embryonic migration of GnRH neurons to the hypothalamus most commonly result in KS, though nCHH can also arise. Hence, the description of several pedigrees, comprising subjects exhibiting KS and others with nCHH. Although more than 24 genes have been described to be involved in CHH, molecular variants of these do not presently explain more than 35-45% of reported cases. Therefore, numerous other unidentified genes (or conceivably, epigenetic mechanisms) remain to be described to fully understand the pathogenesis of CHH, explaining the emergent idea that CHH is a complex genetic disease characterized by variable expressivity and penetrance. This review summarizes the current state of knowledge on the complex genetic basis of congenital hypogonadotropic hypogonadism and aims to be accessible to both researchers and clinicians. PMID:26934720

  8. Spino-Cerebellar Degeneration, Hormonal Disorder, Hypogonadism, Deaf Mutism and Mental Deficiency

    ERIC Educational Resources Information Center

    Sylvester, P. E.

    1972-01-01

    Post mortem examinations were done on two adult siblings (one female and one male) who had been clinically described as suffering from mental handicap, deaf mutism, ataxia, hypogonadism, and hormonal disorders. (DB)

  9. Familial cerebellar ataxia and hypogonadotropic hypogonadism: evidence for hypothalamic LHRH deficiency.

    PubMed Central

    Berciano, J; Amado, J A; Freijanes, J; Rebollo, M; Vaquero, A

    1982-01-01

    A family with familial cerebellar ataxia and hypogonadotropic hypogonadism is described. The condition was inherited as an autosomal recessive defect. CT scan in one case revealed cerebellar and brain stem atrophy. Endocrinological tests showed abnormalities only in two patients who were clinically affected. In both cases raised gonadotropic levels were found after repetitive stimulation with luteining hormone-releasing hormone which suggests that the hypogonadism was due to a primary hypothalamic disturbance. Images PMID:6813427

  10. Association of Free Testosterone with Hypogonadal Symptoms in Men with Near-Normal Total Testosterone Levels

    PubMed Central

    Ramasamy, Ranjith; Golan, Ron; Wilken, Nathan; Scovell, Jason M.; Lipshultz, Larry I.

    2015-01-01

    Objective To investigate the association between hypogonadal symptoms and free testosterone levels in men with near-normal total testosterone levels (250–350ng/dL) and to determine whether a discriminatory threshold for free testosterone exists below which hypogonadal symptoms become more prevalent. Methods We reviewed the charts of 3,167 men who presented to an outpatient men's health clinic. 231 men had symptoms of “low testosterone” and serum testosterone levels between 250 and 350ng/dL. We evaluated hypogonadal symptoms using the ADAM and qADAM questionnaires. Serum levels of total testosterone and SHBG were collected on the same day that men completed their questionnaires. We used linear regression to determine whether or not a threshold of free testosterone exists for hypogonadal symptoms. We performed univariate and multivariable analyses to evaluate factors that predicted a low free testosterone level. Results The median age was 43.5 y, and the median testosterone and free testosterone levels were 303ng/dL, and 6.3ng/dL respectively. Prevalence and severity of hypogonadal symptoms (ADAM and qADAM) were similar between men with low (<6.4ng/mL) and normal free testosterone levels. There was an association between age and three of the 10 hypogonadal symptoms (decreased enjoyment in life, sadness, and deterioration of work performance) with a low free testosterone on a univariate analysis. Only younger age was positively associated with free testosterone on multivariable analysis. Conclusions We did not observe a relationship between hypogonadal symptoms and free testosterone in men with near-normal testosterone levels. Symptom-specific free testosterone thresholds could not be defined, as age remains an important confounder. PMID:26199166

  11. R31C GNRH1 Mutation and Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Maione, Luigi; Albarel, Frederique; Bouchard, Philippe; Gallant, Megan; Flanagan, Colleen A.; Bobe, Regis; Cohen-Tannoudji, Joelle; Pivonello, Rosario; Colao, Annamaria; Brue, Thierry; Millar, Robert P.; Lombes, Marc; Young, Jacques; Guiochon-Mantel, Anne; Bouligand, Jerome

    2013-01-01

    Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative “hot spot”. Interestingly, all the nCHH patients carry this mutation in heterozygosis that strikingly contrasts with the recessive inheritance associated with frame shift and non-sense mutations. Therefore, after exclusion of a second genetic event, a comprehensive functional characterization of the mutant R31C GnRH was undertaken. Using different cellular models, we clearly demonstrate a dramatic reduction of the mutant decapeptide capacity to bind GnRH-receptor, to activate MAPK pathway and to trigger inositol phosphate accumulation and intracellular calcium mobilization. In addition it is less able than wild type to induce lh-beta transcription and LH secretion in gonadotrope cells. Finally, the absence of a negative dominance in vitro offers a unique opportunity to discuss the complex in vivo patho-physiology of this form of nCHH. PMID:23936060

  12. Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

    PubMed Central

    Crosnoe-Shipley, Lindsey E; Elkelany, Osama O; Rahnema, Cyrus D; Kim, Edward D

    2015-01-01

    The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment. PMID:25949938

  13. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

    PubMed Central

    2015-01-01

    The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime. PMID:26790381

  14. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.

    PubMed

    Kim, Soo Hyun

    2015-12-01

    The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime. PMID:26790381

  15. Hypogonadism and erectile dysfunction associated with soy product consumption.

    PubMed

    Siepmann, Timo; Roofeh, Joseph; Kiefer, Florian W; Edelson, David G

    2011-01-01

    Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations. PMID:21353476

  16. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty.

    PubMed

    Dwyer, Andrew A; Jayasena, Channa N; Quinton, Richard

    2016-06-01

    The phenomenon known as "mini-puberty" refers to activation of the neonatal hypothalamo-pituitary axis causing serum concentrations of gonadotrophins and testosterone (T) to approach adult male levels. This early neonatal period is a key proliferative window for testicular germ cells and immature Sertoli cells. Although failure to spontaneously initiate (adolescent) puberty is the most evident consequence of a defective gonadotropin-releasing hormone (GnRH) neurosecretory network, absent mini-puberty is also likely to have a major impact on the reproductive phenotype of men with congenital hypogonadotrophic hypogonadism (CHH). Furthermore, the phase of male mini-puberty represents a key window-of-opportunity to identify congenital GnRH deficiency (either isolated CHH, or as part of combined pituitary hormone deficiency) in childhood. Among male neonates exhibiting "red flag" indicators for CHH (i.e. maldescended testes with or without cryptorchidism) a single serum sample (between 4-8 weeks of life) can pinpoint congenital GnRH deficiency far more rapidly and with much greater accuracy than dynamic tests performed in later childhood or adolescence. Potential consequences for missing absent mini-puberty in a male neonate include the lack of monitoring of pubertal progression/lack of progression, and the missed opportunity for early therapeutic intervention. This article will review our current understanding of the mechanisms and clinical consequences of mini-puberty. Furthermore, evidence for the optimal clinical management of patients with absent mini-puberty will be discussed. PMID:27213784

  17. Loss of function mutations of the GnRH receptor: a new cause of hypogonadotropic hypogonadism.

    PubMed

    de Roux, N; Young, J; Misrahi, M; Schaison, G; Milgrom, E

    1999-04-01

    The association of hypogonadotropic hypogonadism with anosmia defines Kallmann's syndrome. The gene of the X-linked form of this syndrome has been cloned and several mutations described. However, the relatively small number of hypogonadotropic hypogonadic patients with Kallmann's gene defects supports the hypothesis that other genes may be involved. Idiopathic hypogonadotropic hypogonadism (IHH) is not associated with anosmia. The GnRH gene was excluded as a candidate gene in IHH since no abnormality was found in several patients. The action of the GnRH is mediated through a G-protein coupled receptor present in the cell membrane of gonadotropes. The GnRH receptor was thus another candidate gene. Recently, we described the first patient with partial hypogonadotropic hypogonadism without anosmia caused by loss of function mutations of the GnRH receptor. We compare this first family with a new family presenting complete hypogonadotropic hypogonadism and a variable degree of gonadotrope deficiency in the affected kindred, and discuss genotype-phenotype correlation. PMID:10698591

  18. Homozygous Loss-of-function Mutations in SOHLH1 in Patients With Nonsyndromic Hypergonadotropic Hypogonadism

    PubMed Central

    Bayram, Yavuz; Gulsuner, Suleyman; Guran, Tulay; Abaci, Ayhan; Yesil, Gozde; Gulsuner, Hilal Unal; Atay, Zeynep; Pierce, Sarah B.; Gambin, Tomasz; Lee, Ming; Turan, Serap; Bober, Ece; Atik, Mehmed M.; Walsh, Tom; Karaca, Ender; Pehlivan, Davut; Jhangiani, Shalini N.; Muzny, Donna; Bereket, Abdullah; Buyukgebiz, Atilla; Boerwinkle, Eric; Gibbs, Richard A.

    2015-01-01

    Context: Hypergonadotropic hypogonadism presents in females with delayed or arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and is further characterized by elevated gonadotropins and low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadal development or maintenance, sex steroid synthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function. Objectives: The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadism in two unrelated families. Design and Participants: Clinical evaluation and whole-exome sequencing were performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadism from two unrelated families. Results: Exome sequencing analysis revealed two different truncating mutations in the same gene: SOHLH1 c.705delT (p.Pro235fs*4) and SOHLH1 c.27C>G (p.Tyr9stop). Both mutations were unique to the families and segregation was consistent with Mendelian expectations for an autosomal-recessive mode of inheritance. Conclusions: Sohlh1 was known from previous mouse studies to be a transcriptional regulator that functions in the maintenance and survival of primordial ovarian follicles, but loss-of-function mutations in human females have not been reported. Our results provide evidence that homozygous-truncating mutations in SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism. PMID:25774885

  19. When is a varicocele repair indicated: the dilemma of hypogonadism and erectile dysfunction?

    PubMed Central

    Dabaja, Ali A; Goldstein, Marc

    2016-01-01

    In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were “varicocele and hypogonadism” and “varicocele surgery and testosterone.” We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair. PMID:26696437

  20. A practical guide to male hypogonadism in the primary care setting

    PubMed Central

    Dandona, P; Rosenberg, M T

    2010-01-01

    There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment. PMID:20518947

  1. Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

    PubMed

    Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

    2016-07-01

    This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. PMID:27235615

  2. Congenital hypogonadotropic hypogonadism in females: clinical spectrum, evaluation and genetics.

    PubMed

    Bry-Gauillard, H; Trabado, S; Bouligand, J; Sarfati, J; Francou, B; Salenave, S; Chanson, P; Brailly-Tabard, S; Guiochon-Mantel, A; Young, J

    2010-05-01

    Congenital hypogonadotropic hypogonadisms (CHH) are a well-known cause of pubertal development failure in women. In a majority of patients, the clinical spectrum results from an insufficient and concomitant secretion of both pituitary gonadotropins LH and FSH that impedes a normal endocrine and exocrine cyclical ovary functioning after the age of pubertal activation of gonadotropic axis. In exceptional but interesting cases, they can result from an elective deficit of one of the gonadotropins follicle-stimulating hormone (FSH) or luteinizing hormone (LH) by genetic anomaly of their specific ss sub-unit. CHH prevalence, estimated from teaching hospital series, is considered to be two to five fold less important in women compared to men bearing the disease. This frequency is probably under-estimated in reason of under-diagnosis of forms with partial pubertal development. Isolated or apparently isolated forms (i.e., Kallmann syndrome with anosmia or hyposmia not spontaneously expressed by the patients) of these diseases are most of the time discovered during adolescence or in adulthood in reason of lacking, incomplete or even apparently complete pubertal development, but with almost constant primary amenorrhea. In a minority of cases and mainly in familial forms, genetic autosomal causes have been found. These cases are related to mutations of genes impinging the functioning of the pituitary-hypothalamic pathways involved in the normal secretion of LH and FSH (mutations of GnRHR, GnRH1, KISS1R/GPR54, TAC3, TACR3), which are always associated to isolated non syndromic CHH without anosmia. Some cases of mutations of FGFR1, and more rarely of its ligand FGF8, or of PROKR2 or its ligand PROK2 have been shown in women suffering from Kallmann syndrome or its hyposmic or normosmic variant. In complex syndromic causes (mutations of CHD7, leptin and leptin receptor anomalies, Prader-Willi syndrome, etc.), diagnosis of the CHH cause is most often suspected or set down before

  3. A Florid Case of Iatrogenic Cushing's Syndrome Induced by Topical Steroid with Osteoporosis and Hypogonadism

    PubMed Central

    Sahana, Pranab Kumar; Sarma, Nilendu; Sengupta, Nilanjan; Somani, Prashant Subhash

    2015-01-01

    Here we report a case of a young male who developed full blown iatrogenic Cushing's syndrome after use of superpotent clobetasol propionate cream 0.05% for long duration to suppress psoriatic skin lesions. He also developed osteoporosis and hypogonadism. This case demonstrates that injudicious use of topical steroids can have disastrous consequences. PMID:26288430

  4. A Florid Case of Iatrogenic Cushing's Syndrome Induced by Topical Steroid with Osteoporosis and Hypogonadism.

    PubMed

    Sahana, Pranab Kumar; Sarma, Nilendu; Sengupta, Nilanjan; Somani, Prashant Subhash

    2015-01-01

    Here we report a case of a young male who developed full blown iatrogenic Cushing's syndrome after use of superpotent clobetasol propionate cream 0.05% for long duration to suppress psoriatic skin lesions. He also developed osteoporosis and hypogonadism. This case demonstrates that injudicious use of topical steroids can have disastrous consequences. PMID:26288430

  5. Hypogonadism in male Leprosy patients--a study from rural Uttar pradesh.

    PubMed

    Aggrawal, Kamal; Madhu, S V; Aggrawal, Kireet; Kannan, A T

    2005-09-01

    Hypogonadism in male patients with Leprosy is common and may identify patients with future risk for bone loss and osteoporosis. In the present study, we evaluated gonadal function in 71 male patients with Leprosy both clinically and by estimation of serum testosterone levels. The patients belonged to selected rural areas of Uttar pradesh, with majority aged less than 50 yrs (74.6%), Hindus (66.7%), illiterate (60.9%), and of low socioeconomic status (58% with per capita income < Rs.500 per month). Most patients had multibacillary Leprosy (83.1%), duration less than 2 years (75.4%) and had received antileprosy drugs for less than a year (95.6 %). Seven patients (9.9%) had clinical features of hypogonadism such as gynaecomastia, decreased sexual hair and infertility. Serum testosterone levels, estimated in 31 of the patients, revealed low values in 25.8% (8/31) patients (Mean 4.65+/-3.37 ng/ml). Age, duration of Leprosy and socioeconomic status but not type of Leprosy or treatment duration affected hypogonadism significantly. The results of the present study indicate a high frequency of hypogonadism among rural male Leprosy patients that warrants routine screening to identify patients at risk for osteoporosis and possible prevention with testosterone replacement therapy. PMID:17080706

  6. Waardenburg-like features with cataracts, small head size, joint abnormalities, hypogonadism, and osteosarcoma.

    PubMed Central

    Parry, D M; Safyer, A W; Mulvihill, J J

    1978-01-01

    A 32-year-old black man was observed with osteosarcoma and multiple anomalies including deafness, hypopigmentation, cataracts, small head size, hypogonadism, and restricted joint mobility. The birth defects may comprise a new syndrome or combination of syndromes, of which the malignancy may be a part. Images PMID:273099

  7. Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

    PubMed Central

    Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

    2016-01-01

    Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

  8. A Case of Primary Hypogonadism with Features of Albright’s Syndrome

    PubMed Central

    Lodh, Moushumi; Mukhopadhyay, Rajarshi

    2016-01-01

    Background: McCune Albright syndrome is rare with an estimated prevalence of 1 in 100,000 to 1 in 1,000,000 persons. The classical clinical triad consists of fibrous dysplasia of the bone, café-au-lait skin spots and precocious puberty. However, in rare cases, there may be primary hypogonadism and amenorrhea. Case Presentation: An eighteen-year-old female presented with amenorrhea. She had a short stature, round face, thick neck, and short fourth metacarpals and metatarsals. The secondary sexual characters were absent. Serum calcium, phosphorus and parathyroid concentrations were normal, but gonadotropin hormones were very low. X-ray examination revealed short fourth and fifth metacarpals, short left metatarsal, and short fibula. Conclusion: These local bony abnormalities along with the biochemical findings helped us to diagnose this case as an unusual presentation of primary hypogonadism with features of McCune Albright’s syndrome where there was amenorrhea rather than preocious puberty. PMID:27478774

  9. Osteopenia and bone fractures in a man with anorexia nervosa and hypogonadism

    SciTech Connect

    Rigotti, N.A.; Neer, R.M.; Jameson, L.

    1986-07-18

    Women with anorexia nervosa have reduced skeletal mass. Both anorexia and osteopenia are less common in men. We describe a 22-year-old man with anorexia nervosa and severe osteopenia involving both cortical and trabecular bone who developed a pelvic fracture and multiple vertebral compression fractures. He was found to have secondary hypogonadotropic hypogonadism that was reversible with weight gain. This case illustrates the need to consider osteopenia as a potential complication of anorexia nervosa in males as well as females.

  10. Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhäuser syndrome.

    PubMed Central

    Rump, R; Hamel, B C; Pinckers, A J; van Dop, P A

    1997-01-01

    We describe two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia, Boucher-Neuhäuser syndrome, a rare but distinct pleiotropic single gene disorder with an autosomal recessive pattern of inheritance. The cases presented illustrate that this syndrome is still poorly recognised. We provide a review and analysis of previously reported cases and the differential diagnosis, which might aid in the identification of additional cases. Images PMID:9321767

  11. [The "obese" and "old" male patient in dermatological practice. When should hypogonadism be considered?].

    PubMed

    Varwig-Janßen, D; Ochsendorf, F

    2015-12-01

    Hypogonadism refers to reduced endocrine function of the testicles and leads to testosterone deficiency. It is often observed in older and obese men. Symptoms with the highest predictive value are reduced sexual thoughts, decreased spontaneous erections, and erectile dysfunction. After excluding contraindications (e.g., desire for children), various forms of replacement therapy are available. Studies have shown that testosterone therapy is safe if regularly checked. PMID:26541589

  12. Discussion: 'Congenital hypogonadisms impair quality of life and sexual function,' by Ros et al.

    PubMed

    Robbins, Camaryn Chrisman; Wolfe, Morgan; Squires, Kathryn; Jungheim, Emily; Weiner, Linda

    2013-06-01

    In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Ros C, Alobid I, Balasch J, et al. Turner's syndrome and other forms of congenital hypogonadism impair quality of life and sexual function. Am J Obstet Gynecol 2013;208:484.e1-6. PMID:23571134

  13. Plasma miRNA expression profile in the diagnosis of late-onset hypogonadism

    PubMed Central

    Russell, Nicholas; Grossmann, Mathis

    2016-01-01

    Researchers reporting in the Nature journal Scientific Reports1 have used next generation sequencing and quantitative reverse transcriptase PCR (RT-PCR) technology to profile plasma microRNA (miRNA) expression in cohorts of men with and without late-onset hypogonadism (LOH). The study proposes a panel of three miRNAs as novel biomarkers to aid in the diagnosis of LOH. PMID:27364544

  14. Factors associated with bone metabolism in acromegalic patients: hypogonadism and female gender.

    PubMed

    Tütüncü, N B; Erbaş, T

    2004-06-01

    The purpose of the study was to determine the factors associated with bone metabolism in acromegalic patients. Thirty three patients with acromegaly who had been followed on a regular basis in the endocrinology clinic were enrolled for the study. Among the factors acting upon bone metabolism, age, gender, body mass index (BMI), duration and activity of the disease, length of remission, treatment modalities and functional status of the pituitary were evaluated. Their influences on the determinants of bone remodelling and bone mineral density (BMD) were tried to be elucidated. The median age of the 33 acromegalics (19 females, 14 males) was 39.73 +/- 10.1 years. Twenty-three patients (9 males and 14 females) were eugonadal. Ten patients had been diagnosed with history of at least one year of untreated hypogonadism (5 males and 5 females; for 1 - 10 years). The BMD values of the lumbar vertebrae, the femur and the radius were correlated with each other. Patients were grouped according to their T-scores as decreased, normal, and increased BMD. Groups were similar with regard to age, BMI, gender, duration of disease, and remission, GH, IGF-1, IGFBP-3 levels, markers of bone turnover. Presence of hypogonadism and duration of hypogonadism revealed statistically significant difference among the 3 groups (p = 0.005 and p = 0.035, respectively). Hypogonadal acromegalic patients had decreased BMD compared to eugonadal acromegalics and healthy population while the eugonadal female acromegalic patients revealed increased BMD of lumbar vertebrae, femur, and distal radius compared to the sex-matched healthy population. PMID:15216451

  15. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes.

    PubMed

    George, Jyothis T; Millar, Robert P; Anderson, Richard A

    2010-01-01

    Hypogonadism occurs commonly in men with type 2 diabetes (T2DM) and severe obesity. Current evidence points to a decreased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus and thereby decreased secretion of gonadotropins from the pituitary gland as a central feature of the pathophysiology in these men. Hyperglycaemia, inflammation, leptin and oestrogen-related feedback have been proposed to make aetiological contributions to the hypogonadotropic hypogonadism of T2DM. However, the neuroendocrine signals that link these factors with modulation of GnRH neurons have yet to be identified. Kisspeptins play a central role in the modulation of GnRH secretion and, thus, downstream regulation of gonadotropins and testosterone secretion in men. Inactivating mutations of the kisspeptin receptor have been shown to cause hypogonadotropic hypogonadism in man, whilst an activating mutation is associated with precocious puberty. Data from studies in experimental animals link kisspeptin expression with individual factors known to regulate GnRH secretion, including hyperglycaemia, inflammation, leptin and oestrogen. We therefore hypothesise that decreased endogenous kisspeptin secretion is the common central pathway that links metabolic and endocrine factors in the pathology of testosterone deficiency seen in men with obesity and T2DM. We propose that the kisspeptin system plays a central role in integrating a range of metabolic inputs, thus constituting the link between energy status with the hypothalamic-pituitary-gonadal axis, and put forward potential clinical studies to test the hypothesis. PMID:20628262

  16. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients

    PubMed Central

    2011-01-01

    Background In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. Methods To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route), we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol), pain (VAS and other pain questionnaires), andrological (Ageing Males' Symptoms Scale - AMS) and psychological (POMS, CES-D and SF-36) parameters were evaluated at baseline (T0) and after 3, 6 and 12 months (T3, T6, T12 respectively). Results The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID) progressively improved from T3 to T12 while the other pain parameters (VAS, Area%) remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. Conclusions In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management. PMID:21332999

  17. High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction

    PubMed Central

    Jimenez-Balderas, F Javier; Tapia-Serrano, Rosario; Fonseca, M Eugenia; Arellano, Jorge; Beltran, Arturo; Yañez, Patricia; Camargo-Coronel, Adolfo; Fraga, Antonio

    2001-01-01

    Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels. PMID:11714390

  18. Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model

    PubMed Central

    Abdelhamed, Amr; Hisasue, Shin-ichi; Shirai, Masato; Matsushita, Kazuhito; Wakumoto, Yoshiaki; Tsujimura, Akira; Tsukamoto, Taiji; Horie, Shigeo

    2015-01-01

    Background Patients with late-onset hypogonadism (LOH) benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5) and aged males treated with testosterone replacement therapy (TRT group, n=5). Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP) and mean arterial blood pressure (MAP) ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant). The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant). The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103) μm2 in the control group and 4.93×103 (range 6.42–19.7×103) μm2 in the TRT group (not statistically significant). In contrast, median visceral fat cell size was significantly smaller in the TRT group (4.93×103 μm2 [range 0.51–14.88×103]) than in the control group (6.08×103 μm2 [0.77–19.97×103]; P<0.001, Mann-Whitney U test). Conclusion This is the first study clearly indicating that TRT can decrease visceral fat cell size, which is a key modulator in the metabolic syndrome. However, a short course of TRT could not improve the ICP response in hypogonadal aged male rats. Further investigation is necessary to clarify the exact rationale of TRT on the visceral fat cell. PMID:25767790

  19. Management of Hypogonadism in Cardiovascular Patients: What Are the Implications of Testosterone Therapy on Cardiovascular Morbidity?

    PubMed

    Tanna, Monique S; Schwartzbard, Arthur; Berger, Jeffery S; Underberg, James; Gianos, Eugenia; Weintraub, Howard S

    2016-05-01

    Testosterone replacement therapy is recommended for men with clinical androgen deficiency with decades of evidence supporting its use for treatment of sexual, physical, and psychological consequences of male hypogonadism. In this updated review, the authors discuss the implications of testosterone deficiency and conflicting evidence regarding testosterone replacement therapy and its effects on the cardiovascular system. Based on mounting evidence, the authors conclude that testosterone therapy can be safely considered in men with appropriately diagnosed clinical androgen deficiency and concurrent cardiovascular risk factors and even manifest cardiovascular disease after a thorough discussion of potential risks and with guideline-recommended safety monitoring. PMID:27132583

  20. Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection.

    PubMed

    Cohen, P G

    2001-06-01

    In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time. PMID:11399122

  1. A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

    PubMed

    Valenta, L J

    1977-08-01

    A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular. PMID:69556

  2. Orchiectomized Fischer 344 male rat models body composition in hypogonadal state.

    PubMed

    Borst, Stephen E; Conover, Christine F

    2006-06-20

    The hypogonadal state in men is accompanied by substantial decreases in muscle and bone mass and by an increase in adiposity. Most of the strains of orchiectomized (ORX) rat that have been used to model this state display substantial losses in bone, but only subtle changes in adiposity and muscle mass. In order to identify a rat model displaying a robust catabolic response to ORX, we studied three strains: Fischer 344 (F344), Brown Norway and Wistar. ORX caused a significant and sustained decrease in weight gained by F344, but only a trend toward reduced weight gain in Brown Norway rats and a modest reduction weight gain in Wistar rats that was significant only after 56days. ORX suppressed food intake in F344 rats, and to a lesser degree in Brown Norway and Wistar rats. ORX reduced muscle mass significantly in F344 rats, but not in Brown Norway or Wistar rats. ORX increased adiposity moderately in F344 rats and substantially in Wistar rats. ORX caused a marked reduction in prostate mass and increase in bone resorption in all three strains. Thus, F344 was the only strain in which ORX produced substantial decreases in food intake, body weight and muscle mass with increased adiposity and increased bone resorption. We conclude that the F344 rat displays a broad range of catabolic effects following ORX and is the best rat model for studying the androgenic pathway and strategies for reversing catabolic changes induced by hypogonadism. PMID:16507309

  3. AB021. What and how should we monitor to diagnose and treat hypogonadism?

    PubMed Central

    Park, Jong Kwan

    2016-01-01

    Male hypogonadism is a clinically and biochemically defined the disease of men with serum testosterone (T) levels below the reference ranges of young man and with symptoms of T deficiency (TD). Morbidity and mortality of TD and the method to treat TD are different by the onset age or reserving fertility. Therefore, diagnostic skills and treatment methods should be set the age, desire (fertility or not) and situation of the patient. The main symptom is sexual dysfunction, anemia, reduced muscle mass and strength, metabolic syndrome, reduction of bone density and lessening of general performance, depressed mood, cardiovascular disease and infertility in young man got married. The diagnosis of hypogonadism is based on the presence of symptoms or signs, TD, and serum T levels. Young adult who need fertility should be treated in to both directions to recover fertility and overcome the low T relating diseases. In the patient who has late onset hypogonadism, we have to target the symptoms and signs, change of body composition and morbidity and mortality. We also have to consider the testosterone replacement therapy (TRT) inducing pathophysiological changes such as polycythemia, blood viscosity, and aggravated benign prostatic hyperplasia (BPH) inducing lower urinary tract symptoms (LUTS) and malignant prostate diseases before and after TRT. I would like to introduce the diagnostic algorithm for the hypogonadal patient before and after TRT. Before TRT for baseline, we have to check anthropometry, CBC, blood chemistry for metabolic syndrome, total T, free T, prostate specific antigen (PSA), transrectal prostate ultrasonography (TRUS), and questionnaires. For the follow-up after TRT, the anthropometry, blood viscosity, in addition CBC, total testosterone, free testosterone, PSA, TRUS, and questionnaires including voiding and erectile status. A semen analysis in the secondary hypogonadal patient who wants fertility has to be considered. I recommend that sample collection for

  4. Hypogonadotropic hypogonadism

    MedlinePlus

    ... or infections Certain medical conditions, such as iron overload Kallmann syndrome is an inherited form of HH. ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  5. Hypogonadotropic hypogonadism

    MedlinePlus

    ... levels such as FSH, LH, and TSH, prolactin, testosterone and estradiol LH response to GnRH MRI of ... of the problem, but may involve: Injections of testosterone (in males) Slow-release testosterone skin patch (in ...

  6. Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation

    PubMed Central

    Alqwaifly, Mohammed; Bohlega, Saeed

    2016-01-01

    Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A). We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases. PMID:27441066

  7. GnRH, anosmia and hypogonadotropic hypogonadism--where are we?

    PubMed

    Forni, Paolo E; Wray, Susan

    2015-01-01

    Gonadotropin releasing hormone (GnRH) neurons originate the nasal placode and migrate into the brain during prenatal development. Once within the brain, these cells become integral components of the hypothalamic-pituitary-gonadal axis, essential for reproductive function. Disruption of this system causes hypogonadotropic hypogonadism (HH). HH associated with anosmia is clinically defined as Kallman syndrome (KS). Recent work examining the developing nasal region has shed new light on cellular composition, cell interactions and molecular cues responsible for the development of this system in different species. This review discusses some developmental aspects, animal models and current advancements in our understanding of pathologies affecting GnRH. In addition we discuss how development of neural crest derivatives such as the glia of the olfactory system and craniofacial structures control GnRH development and reproductive function. PMID:25306902

  8. Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

    PubMed

    Sanyal, D; Chatterjee, S

    2016-06-01

    This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. PMID:26341841

  9. Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation.

    PubMed

    Alqwaifly, Mohammed; Bohlega, Saeed

    2016-06-15

    Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A). We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases. PMID:27441066

  10. Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis.

    PubMed

    Seftel, Allen D; Kathrins, Martin; Niederberger, Craig

    2015-08-01

    "Testosterone Therapy in Men With Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline" (Guidelines), published in 2010, serves as an important guide for the treatment of hypogonadal men. Using the Guidelines as a basis, we searched for the most recent level 1 evidence that continues to support the recommendations or provide an impetus to modify all or some of them. We performed a systematic analysis with a PubMed query from January 1, 2010, through March 2, 2015, using the following key words: testosterone/deficiency, testosterone/therapeutic use, cardiovascular, morbidity, mortality, screening, sexual function, lower urinary tract symptoms, obstructive sleep apnea, prostate cancer, fertility, bone mineral density, osteoporosis, quality of life, cognitive, erectile dysfunction, and adverse effects. We identified 17 trials representing level 1 evidence that specifically addressed recommendations made in the Guidelines. Trials examining outcomes of testosterone replacement therapy in men with severe lower urinary tract symptoms and untreated obstructive sleep apnea were identified, potentially refuting the current dogma against treatment in the setting of these conditions. Hypogonadal men with type 2 diabetes mellitus and metabolic syndrome were examined in several trials, demonstrating the beneficial effects of therapy on sexual function and insulin sensitivity. Several trials served as reinforcing evidence for the beneficial effects of testosterone therapy on osteoporosis, muscle strength, and symptoms of frailty. As in the Guidelines, inconsistent effects on quality of life, well-being, and erectile function were also noted in publications. Despite controversies surrounding cardiovascular morbidity and treatment in the setting of prostate cancer, no studies examining these issues as primary end points were identified. The low number of eligible studies since 2010 is a limitation of this analysis. PMID:26205546

  11. [Hypogonadotropic hypogonadism and delayed puberty: differential diagnosis using the LH-RH-infusion test].

    PubMed

    Vierhapper, H

    1983-08-26

    Serum concentrations of LH and FSH were determined during an intravenous infusion of LH-RH (200 micrograms, t = 4 hours) in 8 patients (age: 15 to 20 years) with delayed sexual maturation and retarded bone age. Four patients who by clinical criteria were later recognized as suffering from hypogonadotropic hypogonadism (HH) presented during the infusion of LH-RH with only a small response of LH (and, in three cases, of FSH). In 3 patients with HH a deficiency of endogenous LH-RH due to a hypothalamic defect was suggested by an enhanced secretion of LH and FSH during a second LH-RH infusion test performed after priming of the pituitary by pulsatile, subcutaneous infusions of LH-RH (50 micrograms/night for 9 consecutive nights). The fourth patient with HH, who suffered from a pituitary adenoma, failed to display this enhanced secretion of gonadotropins following pituitary priming by intermittent administration of LH-RH. As compared with the patients with HH, 4 patients in whom puberty, although delayed, later occurred spontaneously (pubertas tarda, PT), presented with a considerably more pronounced secretion of LH and FSH during the infusion of LH-RH, and priming by intermittent subcutaneous LH-RH failed to achieve further enhancement of the secretion of LH and FSH during a second infusion test in these patients. The intravenous infusion of LH-RH in combination with a protocol of pituitary priming offers a possibility of distinguishing patients with delayed puberty from those with various forms of hypogonadotropic hypogonadism. PMID:6417915

  12. Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

    PubMed Central

    Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

    2015-01-01

    Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

  13. Hypoplasia of the nose and eyes, hyposmia, hypogeusia, and hypogonadotrophic hypogonadism in two males.

    PubMed

    Bosma, J F; Henkin, R I; Christiansen, R L; Herdt, J R

    1981-01-01

    Two males, 9-11 and 29-31 years of age, with severe hypoplasia of the nose, hypoplasia of the eyes, sensory abnormalities of taste and smell, and hypogonadism were studied. The nasal septum, cribriform plates and foramina of the vomeronasal (vn) nerves were demonstrated in both; the capsule of the vn organ was shown in one. Their nasal skeleton, demonstrated by tomoradiography, had grown in early embryological form. The nose was not patent in either patient. In both, the cranial vaults, orbits, epipharynges, and oral cavities were indented toward the hypoplastic nasal composite and the peripheral dimensions of their faces were normal for their respective ages. Each patient had impaired visual function with cataracts and colobomata. Each was unable to recognize the smell of any vapor (Type I hyposmia), and had severe impairment of recognition of any tastant (recognition hypogeusia); detection of vapors and of tastants were in appropriate anatomical areas. Each was unable orally to recognize standard plastic forms (astereognosis) though each could recognize the forms manually. Each patient had bilateral inguinal hernias, one or two undescended testes, and hypogonadotrophic hypogonadism. These patients do not fall within the spectrum of arrhinencephaly because of the presence of medial structure of attachment of the falx cerebri and because of their normal intelligence. Distinction of patients with this pattern of abnormalities from arrhinencephaly is important by reason of their potentiality of normal mental development. We hypothesize that their abnormalities resulted from an embryological disruption that occurred in the first trimester of pregnancy. The embryogenesis of the nasal composite is presumed to have been adequate for reciprocal induction of the anlagen of the forebrain. Development of their faces to normal peripheral dimensions indicates that the nasal composite is not essential for gross facial enlargement. PMID:6802865

  14. Hypogonadism predisposes males to the development of behavioural and neuroplastic depressive phenotypes.

    PubMed

    Wainwright, Steven R; Lieblich, Stephanie E; Galea, Liisa A M

    2011-10-01

    The incidence of depression is 2-3× higher in women particularly during the reproductive years, an occurrence that has been associated with levels of sex hormones. The age-related decline of testosterone levels in men corresponds with the increased acquisition of depressive symptoms, and hormone replacement therapy can be efficacious in treating depression in hypogonadal men. Although it is not possible to model depression in rodents, it is possible to model some of the symptoms of depression including a dysregulated stress response and altered neuroplasticity. Among animal models of depression, chronic mild unpredictable stress (CMS) is a common paradigm used to induce depressive-like behaviours in rodents, disrupt the hypothalamic-pituitary adrenal axis and decrease hippocampal neuroplasticity. The purpose of this study was to assess the effect of hypogonadism, produced by gonadectomy, on the acquisition of depressive-like behaviours and changes in hippocampal neuroplasticity in adult male Sprague-Dawley rats. A 21-day unpredictable CMS protocol was used on gonadectomised (GDX) and sham-operated males which produced an attenuation of weight gain in the GDX males receiving CMS treatment (GDX-CMS). Behavioural analysis was carried out to assess anxiety- and depressive-like behaviours. The combination of GDX and CMS produced greater passive behaviours within the forced swim test than CMS exposure alone. Similarly, hippocampal cell proliferation, neurogenesis and the expression of the neuroplastic protein polysialated neural cell adhesion molecule (PSA-NCAM) were all significantly reduced in the GDX-CMS group compared to all other treatment groups. These findings indicate that testicular hormones confer resiliency to chronic stress in males therefore reducing the likelihood of developing putative physiological, behavioural or neurological depressive-like phenotypes. PMID:21481538

  15. Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43

    PubMed Central

    Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

    2016-01-01

    Aim: Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Methods: Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg−1·d−1, po) or testosterone replacement (0.5 mg·kg−1·d−1, sc) for 5 days, and STZ-injected rats were treated with argirein (40–120 mg·kg−1·d−1, po) or aminoguanidine (100 mg·kg−1·d−1, po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). Results: ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3–3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in

  16. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.

    PubMed

    Shi, Chang-He; Schisler, Jonathan C; Rubel, Carrie E; Tan, Song; Song, Bo; McDonough, Holly; Xu, Lei; Portbury, Andrea L; Mao, Cheng-Yuan; True, Cadence; Wang, Rui-Hao; Wang, Qing-Zhi; Sun, Shi-Lei; Seminara, Stephanie B; Patterson, Cam; Xu, Yu-Ming

    2014-02-15

    Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms. PMID:24113144

  17. The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations

    PubMed Central

    Constantinou, Caterina; Mpatsoulis, Diogenis; Natsos, Anastasios; Petropoulou, Peristera-Ioanna; Zvintzou, Evangelia; Traish, Abdulmaged M.; Voshol, Peter J.; Karagiannides, Iordanes; Kypreos, Kyriakos E.

    2014-01-01

    Here, we investigated how LDL receptor deficiency (Ldlr−/−) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr−/− mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr−/− mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr−/− mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr−/− mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr−/− mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr−/− mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism. PMID:24837748

  18. New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism

    SciTech Connect

    Yanase, Toshihiko; Takayanagi, Ryoichi; Oba, Koichi

    1996-02-01

    Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for the mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients` genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. 31 refs., 4 figs., 2 tabs.

  19. Effects of gonadotropin and testosterone treatments on plasma leptin levels in male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's syndrome.

    PubMed

    Ozata, M; Ozisik, G; Caglayan, S; Yesilova, Z; Bingöl, N; Saglam, M; Turan, M; Beyhan, Z

    1998-05-01

    Since little is known about the effects of gonadotropin and testosterone treatment on leptin levels in male hypogonadism, we determined fasting plasma leptin levels before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 16 patients with Klinefelter's syndrome and 20 male controls. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Plasma leptin levels were measured by an RIA with a sensitivity of 0.5 microg/L. Mean leptin levels in patients with IHH before treatment (9.23+/-4.09 microg/L) were not significantly different from those in patients with Klinefelter's syndrome (7.29+/-5.05 microg/L; z=-1.41; P=0.15). Leptin levels in both IHH and Klinefelter's syndrome groups were, however, significantly higher than in the normal men (3.91+/-1.67 microg/L) (P<0.001 and P<0.01, respectively). Mean leptin levels did not change significantly 3 months after the initiation of gonadotropin (11.6+/-6.44 microg/L) or T (8.32+/-5.17 microg/L) treatment in either IHH or Klinefelter's syndrome. Our study demonstrated that mean plasma leptin levels are not influenced by short-term gonadotropin or T treatment in male hypogonadism. PMID:9660087

  20. Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat diet experimental rabbit animal model.

    PubMed

    Morelli, Annamaria; Vignozzi, Linda; Maggi, Mario

    2016-06-01

    The etiology of metabolic syndrome (MetS) is complex and involves the interplay between environmental, lifestyle and genetic determinants. MetS in men can be associated with a biochemical pattern of partial hypogonadotropic hypogonadism (HH). A similar pattern has been noted in both men and women with a variety of acute illnesses and chronic diseases, and there is ongoing debate regarding whether this phenomenon might adaptive (e.g. diverting resources from reproduction into survival), or maladaptive (e.g. anemia, sarcopenia, osteopenia and fatigue of androgen-deficiency amplify and widen the adverse consequences of the original disease-trigger). In women with hypothalamic amenorrhea (HA-HH secondary to chronic bioenergetic deficit from dietary restriction and/or intensive exercise), a genetic link to congenital HH (CHH) was recently established; women carrying monoallelic CHH gene mutations will typically not develop CHH, but are significantly more susceptible to HA. However, the male reproductive axis seems to be more resistant to similar environmental insults. In contrast, MetS-associated HH (mHH) is specifically a male phenomenon; the reproductive phenotype of females with MetS tending instead towards hyperandrogenism, rather than hypogonadism. The underlying pathogenic mechanisms responsible for mHH have not been clearly identified and, as yet, there has been no investigation of a potential role for CHH mutation carriage in its etiology. Over the decades, the use of either genetic- or diet-induced obesity and/or MetS animal models has greatly helped to illuminate the complex etiology of metabolic dysregulation, but the strong relationship between obesity/MetS and mHH in males has been largely neglected, with little or no information about the regulation of reproductive function by metabolic factors under conditions of bioenergetic excess. However, the pathogenic link between MetS and HH in males has been recently investigated in an animal model of high fat

  1. An update on the role of testosterone replacement therapy in the management of hypogonadism

    PubMed Central

    Hackett, Geoffrey

    2015-01-01

    While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Some authors blame advertising and the availability of more convenient formulations whilst other have pointed out that the routine testing of men with erectile dysfunction (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous underdiagnosis and undertreatment by adherence to evidence-based guidelines. Urologists and primary care physicians are the most frequent initiators of TRT, usually for erectile dysfunction. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing clearly that therapy associated with clear rise in testosterone levels are associated with reduced mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively they have compared nontreated patients with undertreated or on-compliant subjects involving a range of different therapy regimens. Recent evidence suggests long acting injections may be associated with decreased cardiovascular risk but the transdermal route may be associated with potentially relatively greater risk because of conversion to dihydrotestosterone by the effect of 5α reductase in skin. The multiple effects of TRT

  2. Natesto™ , a novel testosterone nasal gel, normalizes androgen levels in hypogonadal men.

    PubMed

    Rogol, A D; Tkachenko, N; Bryson, N

    2016-01-01

    Advantages of testosterone nasal gel include ease of administration, low dose, and no risk of secondary transference. The efficacy and safety of testosterone nasal gel was evaluated in hypogonadal males. The ninety-day, randomized, open-label, dose-ranging study, included potential dose titration and sequential safety extensions to 1 year. At 39 US outpatient sites, 306 men (mean age 54.4 years) with two fasting morning total serum testosterone levels <300 ng/dL were randomized (n = 228, b.i.d. dosing; n = 78, t.i.d. dosing). Natesto(™) Testosterone Nasal Gel was self-administered, using a multiple-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose). Total daily doses were 22 mg or 33 mg. The primary endpoint was the Percentage of patients with Day-90 serum total testosterone average concentration (C(avg)) value within the eugonadal range (≥300 ng/dL, ≤1050 ng/dL). At Day 90, 200/273 subjects (73%; 95% CI 68, 79) in the intent-to-treat (ITT) population and 180/237 subjects (76%; 71, 81) in the per-protocol (PP) population were in the normal range. Also, in the normal range were 68% (61, 74) of ITT subjects and 70% (63, 77) of PP subjects in the titration arm, as well as, 90% (83, 97) of ITT subjects and 91% (84, 98) of PP subjects in the fixed-dose arm. Natesto(™) 11 mg b.i.d. or 11 mg t.i.d. restores normal serum total testosterone levels in most hypogonadal men. Erectile function, mood, body composition, and bone mineral density improved from baseline. Treatment was well tolerated; adverse event rates were low. Adverse event discontinuation rates were 2.1% (b.i.d.) and 3.7% (t.i.d.). This study lacked a placebo or an active comparator control which limited the ability to adequately assess some measures. PMID:26695758

  3. An update on the role of testosterone replacement therapy in the management of hypogonadism.

    PubMed

    Hackett, Geoffrey

    2016-04-01

    While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Some authors blame advertising and the availability of more convenient formulations whilst other have pointed out that the routine testing of men with erectile dysfunction (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous underdiagnosis and undertreatment by adherence to evidence-based guidelines. Urologists and primary care physicians are the most frequent initiators of TRT, usually for erectile dysfunction. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing clearly that therapy associated with clear rise in testosterone levels are associated with reduced mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively they have compared nontreated patients with undertreated or on-compliant subjects involving a range of different therapy regimens. Recent evidence suggests long acting injections may be associated with decreased cardiovascular risk but the transdermal route may be associated with potentially relatively greater risk because of conversion to dihydrotestosterone by the effect of 5α reductase in skin. The multiple effects of TRT

  4. Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism.

    PubMed

    Giagulli, V A; Carbone, M D; Ramunni, M I; Licchelli, B; De Pergola, G; Sabbà, C; Guastamacchia, E; Triggiani, V

    2015-11-01

    The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol

  5. Hypogonadism Associated with Cyp19a1 (Aromatase) Posttranscriptional Upregulation in Celf1 Knockout Mice

    PubMed Central

    Boulanger, Gaella; Cibois, Marie; Viet, Justine; Fostier, Alexis; Deschamps, Stéphane; Pastezeur, Sylvain; Massart, Catherine; Gschloessl, Bernhard

    2015-01-01

    CELF1 is a multifunctional RNA-binding protein that controls several aspects of RNA fate. The targeted disruption of the Celf1 gene in mice causes male infertility due to impaired spermiogenesis, the postmeiotic differentiation of male gametes. Here, we investigated the molecular reasons that underlie this testicular phenotype. By measuring sex hormone levels, we detected low concentrations of testosterone in Celf1-null mice. We investigated the effect of Celf1 disruption on the expression levels of steroidogenic enzyme genes, and we observed that Cyp19a1 was upregulated. Cyp19a1 encodes aromatase, which transforms testosterone into estradiol. Administration of testosterone or the aromatase inhibitor letrozole partly rescued the spermiogenesis defects, indicating that a lack of testosterone associated with excessive aromatase contributes to the testicular phenotype. In vivo and in vitro interaction assays demonstrated that CELF1 binds to Cyp19a1 mRNA, and reporter assays supported the conclusion that CELF1 directly represses Cyp19a1 translation. We conclude that CELF1 downregulates Cyp19a1 (Aromatase) posttranscriptionally to achieve high concentrations of testosterone compatible with spermiogenesis completion. We discuss the implications of these findings with respect to reproductive defects in men, including patients suffering from isolated hypogonadotropic hypogonadism and myotonic dystrophy type I. PMID:26169831

  6. Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism.

    PubMed

    Yi, Hyon-Seung; Kim, Ji Min; Ju, Sang Hyeon; Lee, Younghak; Kim, Hyun Jin; Kim, Koon Soon

    2016-02-01

    Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea. PMID:26981520

  7. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment.

    PubMed

    Boehm, Ulrich; Bouloux, Pierre-Marc; Dattani, Mehul T; de Roux, Nicolas; Dodé, Catherine; Dunkel, Leo; Dwyer, Andrew A; Giacobini, Paolo; Hardelin, Jean-Pierre; Juul, Anders; Maghnie, Mohamad; Pitteloud, Nelly; Prevot, Vincent; Raivio, Taneli; Tena-Sempere, Manuel; Quinton, Richard; Young, Jacques

    2015-09-01

    Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ∼50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field. PMID:26194704

  8. Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism

    PubMed Central

    Yi, Hyon-Seung; Kim, Ji Min; Ju, Sang Hyeon; Lee, Younghak; Kim, Hyun Jin

    2016-01-01

    Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea. PMID:26981520

  9. Distribution of Gene Mutations Associated with Familial Normosmic Idiopathic Hypogonadotropic Hypogonadism

    PubMed Central

    Gürbüz, Fatih; Kotan, L. Damla; Mengen, Eda; Şıklar, Zeynep; Berberoğlu, Merih; Dökmetaş, Sebila; Kılıçlı, Mehmet Fatih; Güven, Ayla; Kirel, Birgül; Saka, Nurçin; Poyrazoğlu, Şükran; Cesur, Yaşar; Doğan, Murat; Özen, Samim; Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Kekil, M. Burcu; Temiz, Fatih; Önenli Mungan, Neslihan; Yüksel, Bilgin; Topaloğlu, Ali Kemal

    2012-01-01

    Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty. Conflict of interest:None declared. PMID:22766261

  10. The role of semaphorin signaling in the etiology of hypogonadotropic hypogonadism.

    PubMed

    Lettieri, Antonella; Oleari, Roberto; Gimmelli, Jessica; ANDRé, Valentina; Cariboni, Anna

    2016-06-01

    In mammals fertility depends on timely onset and cyclic secretion of gonadotropin-releasing hormone (GnRH), secreted by scattered hypothalamic neurons (GnRH neurons). These cells originate in the nasal placode and migrate first in the nasal compartment, then through the cribriform plate and finally across the basal forebrain, before they set in their final position in the hypothalamus. This long journey is regulated by many different factors that could be mutated in neuroendocrine syndromes such as congenital hypogonadotropic hypogonadism (CHH), Kallmann Syndrome (KS) and CHARGE syndrome. Recently, semaphorins, a large family of molecules, previously discovered as axon guidance cues, are emerging as key regulators of the neuroendocrine control of GnRH neurons and are acquiring an increasing role in the etiopathogenesis of CHH and KS. Specifically, semaphorins play a multifaceted action in GnRH neuron biology: on one hand regulating their migration and survival during embryonic development and, on the other, controlling the plasticity of the median eminence (ME) in terms of its response to varying sex steroid hormone levels. In this review we will focus our attention on recent studies describing the roles of different semaphorins in the normal and pathological biology of the GnRH neuronal system. PMID:26940457

  11. A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

    PubMed Central

    Zhu, Jia; Choa, Ruth E.-Y.; Guo, Michael H.; Plummer, Lacey; Buck, Cassandra; Palmert, Mark R.; Hirschhorn, Joel N.; Seminara, Stephanie B.

    2015-01-01

    Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. PMID:25636053

  12. Risk of Hypogonadism From Scatter Radiation During Pelvic Radiation in Male Patients With Rectal Cancer

    SciTech Connect

    Yau, Ivan; Vuong, Te Garant, Aurelie; Ducruet, Thierry; Doran, Patrick; Faria, Sergio; Liberman, Sender; Richard, Carole; Letellier, Francois; Charlebois, Patrick; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2009-08-01

    Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. Methods and Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0-50.4 Gy in 25-28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. Results: Thirty patients with initially abnormal profiles were excluded. Profiles included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort-14 and 20 months, respectively-for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. Conclusion: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer.

  13. Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients.

    PubMed

    Mao, Jiang-Feng; Xu, Hong-Li; Duan, Jin; Chen, Rong-Rong; Li, Li; Li, Bin; Nie, Min; Min, Le; Zhang, Hong-Bing; Wu, Xue-Yan

    2015-01-01

    Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21-34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l -[1] vs 0.4 ± 0.4 IU l-1 , P< 0.05) and stimulated LH (28.3 ± 22.6 IU l-1 vs 1.9 ± 1.1 IU l-1 , P< 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P< 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. PMID:25578938

  14. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

    SciTech Connect

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr. )

    1989-10-01

    To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.

  15. [Hypogonadotropic hypogonadism: new aspects in the regulation of hypothalamic-pituitary-gonadal axis].

    PubMed

    Brioude, F; Bouvattier, C-E; Lombès, M

    2010-09-01

    Hypogonadotropic hypogonadism (HH) is defined by the absence of sex steroid synthesis associated with the lack of appropriate gonadotrophin secretion. This leads to a variable degree of impuberism, often diagnosed during childhood or adolescence. Genetics of HH involve many genes. However, molecular defects have been identified in only 30 % of patients. Kallmann syndrome (KS) is defined by the association of HH and anosmia. Six genes are involved in KS (KAL1, FGFR1, FGF8, PROK2, PROKR2 and CHD7). However, genetics of KS is complex, because of the variability of the phenotype for a similar molecular defect. Otherwise, heterozygous anomalies are frequently described. Identification in the same patient of several mutations in some of these genes (digenism) could account for this variability. Autosomal recessive transmission is frequently observed in familial cases of HH without anosmia. Molecular alterations have been identified for several neuropeptides or their corresponding receptors, which are involved in the physiology of the gonadotropic axis : GNRHR, KISS1R/GPR54, neurokinin B (TAC3), TACR3 and GNRH1 (and PROK2, PROKR2 and CHD7). Anomalies of leptin or its receptor are also involved in HH cases. A new negative regulating element has been recently identified in humans : RFRP3, which is ortholog of the avian GnIH (gonadotrophin inhibitory hormone). Recent progress about these neuropeptides leads to a new model of comprehension of the gonadotropic axis physiology, from a linear model to a network model, which regulates the central element of regulation of the gonadotropic axis, represented by the GnRH neurons. PMID:21237329

  16. Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

    PubMed Central

    Mao, Jiang-Feng; Xu, Hong-Li; Duan, Jin; Chen, Rong-Rong; Li, Li; Li, Bin; Nie, Min; Min, Le; Zhang, Hong-Bing; Wu, Xue-Yan

    2015-01-01

    Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l-1 vs 0.4 ± 0.4 IU l−1, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l−1 vs 1.9 ± 1.1 IU l−1, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. PMID:25578938

  17. Identifying nutritional, functional, and quality of life correlates with male hypogonadism in advanced cancer patients

    PubMed Central

    Fuoco, Domenico; di Tomasso, Jonathan; Boulos, Caroline; Kilgour, Robert D; Morais, Jose A; Borod, Manuel; Vigano, Antonio

    2015-01-01

    With the availability of a potential treatment to reverse male hypogonadism (MH), the primary aim of this case series study was to determine independent relationships between this condition and the nutritional, functional, and quality of life characteristics of advanced cancer patients (ACP). Free testosterone levels were measured in 100 male patients with advanced lung and gastrointestinal (GI) cancer. Routine blood markers of nutrition and inflammation, self-reporting questionnaires for symptom, nutrition, and functional status along with handgrip dynamometry were assessed for all patients at bedside. Almost half of this cohort underwent further assessments (body composition, lower body strength, in depth quality of life and fatigue questionnaires) at the McGill Nutrition and Performance Laboratory (mnupal.mcgill.ca). Multiple regression analyses were performed to identify independent correlations between free testosterone and the above measures. Seventy-six percent of patients were diagnosed with MH. Using multiple linear regression, low free testosterone (31.2 pmol/L) was independently associated with lower albumin (B = –3.8 g/L; 95% confidence interval CI –6.8:–0.8), muscle strength (–11.7 lbs; –20.4: –3.0) and mass in upper limbs (–0.8 kg; –1.4: –0.1), overall performance status (Eastern Cooperative Oncology Group Performance Scale, ECOG PS 0.6; 0.1:1.1), cancer-related fatigue (Brief Fatigue Inventory, BFI 16.7; 2.0: 31.3), and overall quality of life (MQoL total score –1.42; –2.5: –0.3). Thus MH seems to be highly prevalent in ACP, and it is independently associated with important nutritional, functional, and quality of life characteristics in this patient population. PMID:26316882

  18. Risks and Benefits of Late Onset Hypogonadism Treatment: An Expert Opinion

    PubMed Central

    Corona, Giovanni; Vignozzi, Linda; Sforza, Alessandra

    2013-01-01

    Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized association with sexual and reproductive failure. LOH is frequently associated with chronic conditions including cardiovascular diseases (CVD), obesity, osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases. Despite this evidence, in patients with these conditions, LOH is still only rarely investigated and testosterone replacement therapy (TRT) rarely considered. In this paper, we critically reviewed the available evidence on LOH treatment focusing on possible risks and benefits. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. The fear of prostate cancer and the risk of erythrocytosis probably represent the main limitations of TRT in aging men. However, TRT in healthy older men in near physiological doses does not appear to incur serious adverse events, although regular monitoring of prostate-specific antigen and hematocrit levels is required. Available evidence also suggests that TRT might ameliorate central obesity and glycometabolic control in patients with metabolic syndrome and type 2 diabetes. In addition, TRT has been associated with an increase in bone mineral density in men with osteoporosis, with an improvement in lean body mass in subjects with human immunodeficiency virus infection or chronic obstructive pulmonary disease, as well as with peripheral oxygenation in patients with chronic kidney diseases. Despite this evidence, however, it should be recognized that the results of these trials were heterogeneous and limited by small sample sizes. Hence, further research is required regarding the long-term benefits and adverse effects of TRT in LOH. PMID:24044106

  19. Pregnancy outcome of assisted reproductive technology cycle in patients with hypogonadotropic hypogonadism

    PubMed Central

    Pandurangi, Monna; Tamizharasi, M.; Reddy, N. Sanjeeva

    2015-01-01

    CONTEXT: Ovulation induction in patients with hypogonadotropic hypogonadism (HH) is a challenge to the treating physician. The threshold for ovarian response in HH may differ substantially from that of normal patients. To reach that threshold levels of follicle stimulating hormone, in a step-up protocol longer duration of stimulation is required in some cases so as to prevent multiple pregnancy and to eliminate the risk of ovarian hyperstimulation syndrome. AIM: To evaluate the duration of stimulation, quality of oocytes, and embryo, and the pregnancy outcome in the assisted reproductive technology (ART) cycles in patients with HH. MATERIALS AND METHODS: Over the period of 4 years, we had 14 patients with HH in whom 21 cycles of ovulation induction were done. Of these 7 patients underwent oocyte retrieval and intracytoplasmic sperm injection (ICSI). We present a retrospective study of these 7 patients who underwent ART to evaluate the duration of stimulation, quality of oocytes and embryo, and the pregnancy outcome. RESULTS: In the study group on ovulation induction with gonadotropins, only one patient had the duration of stimulation of the standard 12 days, the remaining 6 patients took ≥12 days to respond to stimulation (maxium being 54 days). Mean ET in these patients was 8.9 mm. Six patients had >70% good quality MII oocytes. One patient responded poorly and had only 2 good quality MII oocytes (50%). After ICSI procedure, resultant embryos were of grade 1 and 2 in all the patients irrespective of the duration of stimulation. Fertilization rate in these patients was 85% (except in one 50% fertilization rate), and the cumulative pregnancy rate was 68.6%. CONCLUSION: In the patients with HH the quality of oocytes and embryos, and the pregnancy rate is not affected even if the duration of stimulation is prolonged. PMID:26538857

  20. Reversal and Relapse of Hypogonadotropic Hypogonadism: Resilience and Fragility of the Reproductive Neuroendocrine System

    PubMed Central

    Sidhoum, Valerie F.; Chan, Yee-Ming; Lippincott, Margaret F.; Balasubramanian, Ravikumar; Quinton, Richard; Plummer, Lacey; Dwyer, Andrew; Pitteloud, Nelly; Hayes, Frances J.; Hall, Janet E.; Martin, Kathryn A.; Boepple, Paul A.

    2014-01-01

    Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. Design, Setting, and Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. Main Outcome Measures: History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Results: Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial pubertal development in patients with reversal vs IHH patients without reversal. Fifteen patients with reversal (30%) had Kallmann syndrome (IHH and anosmia); one had undetectable olfactory bulbs on a brain magnetic resonance imaging scan. Subjects with reversal were enriched for mutations affecting neurokinin B signaling compared with a cohort of IHH patients without reversal (10% vs 3%, P = .044), had comparable frequencies of mutations in FGFR1, PROKR2, and GNRHR, and had no mutations in KAL1. Five men did not sustain their reversal and again developed hypogonadotropism. Conclusions: Reversal of IHH may be more widespread than previously appreciated and occurs across a broad range of genotypes and phenotypes. Enrichment for mutations that disrupt neurokinin B signaling in patients who reversed indicates that, despite the importance of this signaling pathway for normal pubertal timing, its function is dispensable later in life. The occurrence of reversal in a

  1. Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

    2016-01-01

    Abstract Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5–16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis. PMID:26945370

  2. The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization.

    PubMed

    Yilmaz, Saynur; Ozgu-Erdinc, A Seval; Yumusak, Omer; Kahyaoglu, Serkan; Seckin, Berna; Yilmaz, Nafiye

    2015-01-01

    The aim of this study was to evaluate the reproductive outcome and assisted reproductive technology (ART) outcomes of patients with hypogonadotropic hypogonadism (HH) and to compare the results with male factor (MF) infertility patients. The reproductive outcome of 33 HH patients was evaluated retrospectively and compared with results of 47 patients with mild male factor infertility. For ovulation induction, human menopausal gonadotropin (hMG) was used in HH patients and recFSH was used in MF infertility patients. HH patients were divided into subgroups according to retrieved oocyte numbers and the groups were compared with each other. The main outcome measures were total gonadotropin dose used, duration of stimulation, human chorionic gonadotropin (hCG) day estradiol level and endometrial thickness, oocyte number retrieved, and rate of clinical pregnancy. ART outcomes and cycle characteristics of 33 HH patients were compared with 47 MF infertility patients. There was no difference in age and body mass index (BMI) between the groups, but mean follicle stimulating hormone FSH and luteinizing hormone LH levels were significantly lower in the HH group (p < 0.001). Duration of stimulation was 12.5 ± 2.06 days in the HH patients and 10.08 ± 1.62 days in the MF infertility patients and the difference was significant (p < 0.001). Total gonadotropin dose used was higher in the HH group than the MF infertility group (p < 0.001). However, there were no differences in hCG day estradiol levels, endometrial thickness on hCG day, total oocyte number retrieved, MII oocyte number, and pregnancy rate. In the HH subgroups, patient ages were significantly lower in the >15 oocyte retrieved group. Although patients with HH have a long-term estrogen deficiency, their response to controlled ovarian hyperstimulation treatment is similar to normal women. However, the HH group is heterogeneous and estimating the ovarian reserve before treatment is not always possible in

  3. Prevalence of Olfactory and Other Developmental Anomalies in Patients with Central Hypogonadotropic Hypogonadism

    PubMed Central

    Della Valle, Elisa; Vezzani, Silvia; Rochira, Vincenzo; Granata, Antonio Raffaele Michele; Madeo, Bruno; Genovese, Elisabetta; Pignatti, Elisa; Marino, Marco; Carani, Cesare; Simoni, Manuela

    2013-01-01

    Introduction: Hypogonadotropic hypogonadism (HH) is a heterogeneous disease caused by mutations in several genes. Based on the presence of hyposmia/anosmia it is distinguished into Kallmann syndrome (KS) and isolated HH. The prevalence of other developmental anomalies is not well established. Methods: We studied 36 patients with HH (31 males, 5 females, mean age 41.5), 9 with familial and 27 with sporadic HH (33 congenital, 3 adult-onset), by physical examination, smell test (BSIT Sensonics), audiometry, renal ultrasound, and magnetic resonance imaging of the olfactory structures. Results: Based on the smell test, patients were classified as normosmic (n = 21, 58.3%) and hypo/anosmic (n = 15, 41.6%). Hypoplasia/agenesis of olfactory bulbs was found in 40% of patients (10/25; 75% hypo/anosmic, 7.6% normosmic, p < 0.01, Fisher’s test). Remarkably, olfactory structures were normal in two anosmic patients, while one normosmic patient presented a unilateral hypoplastic bulb. Fourteen of 33 patients (42.4%) presented neurosensorial hearing loss of various degrees (28.5% hypo/anosmic, 52.6% normosmic, p = NS). Renal ultrasound revealed 27.7% of cases with renal anomalies (26.6% hypo/anosmic, 28.5% normosmic, p = NS). At least one midline defect was found in 50% of the patients (53.3% hypo/anosmic, 47.6% normosmic, p = NS), including abnormal palate, dental anomalies, pectus excavatum, bimanual synkinesis, iris coloboma, and absent nasal cartilage. Anamnestically 4/31 patients reported cryptorchidism (25% hypo/anosmic, 5.2% normosmic, p = NS). Conclusion: Hypo/anosmia is significantly related to anatomical anomalies of the olfactory bulbs/tracts but the prevalence of other developmental anomalies, especially midline defects and neurosensorial hearing loss, is high both in HH and KS and independent of the presence of anosmia/hyposmia. From the clinical standpoint KS and normosmic HH should be considered as the same complex, developmental

  4. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters.

    PubMed

    Yassin, Aksam; Nettleship, Joanne E; Talib, Raidh A; Almehmadi, Yousef; Doros, Gheorge

    2016-01-01

    Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function - erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT. PMID:26742589

  5. Genetic analysis of NR0B1 in congenital adrenal hypoplasia patients: identification of a rare regulatory variant resulting in congenital adrenal hypoplasia and hypogonadal hypogonadism without testicular carcinoma in situ.

    PubMed

    Walker, A P; Fowkes, R C; Saleh, F; Kim, S-H; Wilkinson, P; Cabrera-Sharp, V; Talmud, P J; Humphries, S E; Looijenga, L H J; Bouloux, P M G

    2012-01-01

    There have been few testicular histology reports of adult patients with congenital adrenal hypoplasia/hypogonadal hypogonadism (AHC/HH), but Leydig cell hyperplasia has been observed, an indicator of the possibility of malignant transformation. We aimed to define the basis of AHC/HH in 4 pedigrees of different ethnic backgrounds. One patient was elected to have testicular biopsy which was examined for evidence of carcinoma in situ (CIS). NR0B1 mutation analysis was performed by sequence analysis. NR0B1 expression was investigated by RT-PCR. Testicular biopsy sections were stained with HE or immunostained for OCT3/4, an established marker of CIS. We identified NR0B1 variants in the 4 AHC pedigrees: pedigree 1 (United Arab Emirates), c.1130A>G predicting p.(Glu377Gly); pedigree 2 (English Caucasian), c.327C>A predicting p.(Cys109*); pedigree 3 (Oman), a 6-bp deletion of a direct repeat, c.857_862delTGGTGC predicting p.(Leu286_Val287del); pedigree 4 (English Caucasian), c.1168+1G>A, a regulatory variant within the NR0B1 splice donor site. This last male patient, aged 30 years, presented with evidence of HH but incomplete gonadotrophin deficiency, following an earlier diagnosis of Addison's disease at 3 years. Hormonal therapy induced virilisation. Testicular biopsy was performed. The c.1168+1G>A variant abrogated normal splicing of testicular mRNA. Histological examination showed poorly organised testicular architecture and absence of spermatozoa. Morphological analyses and the absence of immunohistochemical staining for OCT3/4 excluded the presence of malignant germ cell cancer and its precursor lesion, CIS. These studies add to the knowledge of the types and ethnic diversity of NR0B1 mutations and their associated phenotypes, and provide insight into the assessment and interpretation of testicular histology in AHC and HH. PMID:23018754

  6. Acquired Hypogonadotropic Hypogonadism (AHH) in Thalassaemia Major Patients: An Underdiagnosed Condition?

    PubMed Central

    De Sanctis, Vincenzo; Elsedfy, Heba; Soliman, Ashraf T; Elhakim, Ihab Zaki; Pepe, Alessia; Kattamis, Christos; Soliman, Nada A.; Elalaily, Rania; El Kholy, Mohamed; Yassin, Mohamed

    2016-01-01

    Introduction In males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function, and strength, a worsened sense of well-being and degraded quality of life (QOL). Patients and methods We studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy. Fasting venous blood samples were collected two weeks after transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*. Bone mineral density was measured at the lumbar spine (L1–L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine. Results The mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH showed azoospermia in 3 and oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml (severe iron load) was significantly higher in AHH patients compared to controls, 5/11 (45

  7. Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults.

    PubMed

    Rohayem, J; Sinthofen, N; Nieschlag, E; Kliesch, S; Zitzmann, M

    2016-01-01

    Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic-pituitary-gonadal (HPG) axis. In hypogonadotropic hypogonadism (HH), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in HH men is predictable by the origin of HH, indicating time of onset and severity of GnRH/gonadotropin deficiency. The data of 51 adult HH patients who had undergone one cycle of hCG/FSH treatment were reviewed. Five groups were established, according to the underlying HH origin. Therapeutic success by final bi-testicular volumes (BTVs) final sperm concentrations (SC) and conception rates were compared and related to baseline parameters, indicative of the degree of HPG-axis disruption. Overall, BTVs rose from 13 ± 15 to 27 ± 15 mL, spermatogenesis was induced in 98%, with mean SCs of 15 ± 30 mill/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses (BTV: 16.9 ± 10 mL; SC: 3.5 ± 5.6 mill/mL), followed by patients with congenital/infancy-acquired multiple pituitary hormone deficiencies (MPHD) and patients with HH+absent puberty (BTV: 21 ± 14/24 ± 9 mL; SC: 5.5 ± 6.5/ 14.5 ± 23.8 mill/mL). HH men with pubertal arrest and with post-pubertally acquired MPHD had the best results (BTV: 36 ± 14/38 ± 16 mL; SC: 25.4 ± 34.2/29.9 ± 50.5 mill/mL). Earlier conception after 20.3 ± 11.5 months (vs. 43.1 ± 43.8; p = 0.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post-pubertally acquired HH subgroups, compared to the three pre-pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline BTVs

  8. A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.

    PubMed Central

    Telvi, L; Ion, A; Carel, J C; Desguerre, I; Piraud, M; Boutin, A M; Feingold, J; Ponsot, G; Fellous, M; McElreavey, K

    1996-01-01

    An unusual familial case of three sibs with a partial duplication of distal Xp sequences is described. The proband, an 18 year old boy, showed mental retardation, severe dysmorphic features, hypogonadotrophic hypogonadism (HHG), and hypoplastic external genitalia. His karyotype was 46,Y,inv dup(X) (p22.11-->p 22.32). The proband has two sisters each with the same inv dup(Xp) chromosome. Both sisters presented with short stature but were otherwise phenotypically normal. The abnormal X chromosome was inactive in the majority of cells examined. Southern blot dosage analysis indicated a duplication of distal Xp sequences. The proximal breakpoint is located between DXS28 and DXS41, and is therefore at least 2 Mb distal to the DSS locus. The relationship between the phenotype and the Xp duplication is discussed. Images PMID:8880579

  9. Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting.

    PubMed

    Grinspoon, S; Corcoran, C; Lee, K; Burrows, B; Hubbard, J; Katznelson, L; Walsh, M; Guccione, A; Cannan, J; Heller, H; Basgoz, N; Klibanski, A

    1996-11-01

    The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was

  10. Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects.

    PubMed

    Hayes, V Y; Urban, R J; Jiang, J; Marcell, T J; Helgeson, K; Mauras, N

    2001-05-01

    Severe gonadal androgen deficiency can have profound catabolic effects in man. Hypogonadal men develop a loss of lean body mass, increased adiposity, and decreased muscle strength despite normal GH and insulin-like growth factor I (IGF-I) concentrations. We designed these studies to investigate whether GH or IGF-I administration to male subjects with profound hypogonadism can diminish or abolish the catabolic effects of testosterone deficiency. Moreover, we also examined the nature of the interactions among GH, IGF-I, and androgens in specific genes of the im system. A group of 13 healthy subjects (mean age, 22 +/- 1 yr) was studied at baseline (D1) and 10 weeks after being made hypogonadal using a GnRH analog (GnRHa; D2). At 6 weeks from baseline they were started on either recombinant human (rh) IGF-I (60 microg/kg, sc, twice daily) or rhGH (12.5 microg/kg, sc, daily) for 4 weeks. On each study day subjects had infusions of L-[(13)C]leucine; indirect calorimetry; isokinetic dynamometry of the knee extensors; determination of body composition (dual energy x-ray absortiometry) and hormone and growth factor concentrations, as well as percutaneous muscle biopsies. Their data were compared with those of previously studied male subjects who received only GNRHA: Administration of rhIGF-I and rhGH to the hypogonadal men had similar effects on whole body metabolism, with maintenance of protein synthesis rates, fat oxidation rates, and fat-free mass compared with the eugonadal state, preventing the decline observed with hypogonadism alone. This was further amplified by the molecular assessment of important genes in muscle function. During rhIGF-I treatment, im expression of IGF-I declined, and IGF-binding protein-4 increased, similar to the changes during GnRHa alone. However, rhGH administration was associated with a marked increase in IGF-I and androgen receptor messenger ribonucleic acid concentrations in skeletal muscle with a reciprocal decline in IGF-binding protein

  11. Validation of the German version of the 'Hypogonadism Related Symptom Scale' (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome.

    PubMed

    Alidjanov, J; Wolf, J; Schuppe, H-C; Weidner, W; Diemer, T; Linn, T; Halefeldt, I; Wagenlehner, F; Wiltink, J; Pilatz, A

    2014-12-01

    As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19-71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman-Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P < 0.001), and HADS (ρ = -0.6, P < 0.001). In addition, HRS was significantly correlated with total testosterone (ρ = 0.135, P < 0.05), free testosterone (ρ = 0.148, P < 0.05) and oestradiol (ρ = -0.134, P < 0.05). Our validation study confirms the data from the initial development of the HRS questionnaire. Clinicians might have an additional advantage from the HRS when investigating males with suspected hypogonadism. PMID:24387031

  12. Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) - a novel theory for the development of late onset hypogonadism in obese men.

    PubMed

    Tremellen, Kelton

    2016-01-01

    Obesity is an increasing public health problem, with two-thirds of the adult population in many Western countries now being either overweight or obese. Male obesity is associated with late onset hypogonadism, a condition characterised by decreased serum testosterone, sperm quality plus diminished fertility and quality of life. In this paper we propose a novel theory underlying the development of obesity related hypogonadism- the GELDING theory (Gut Endotoxin Leading to a Decline IN Gonadal function). Several observational studies have previously reported an association between obesity related hypogonadism (low testosterone) and systemic inflammation. However, for the first time we postulate that the trans-mucosal passage of bacterial lipopolysaccharide (LPS) from the gut lumen into the circulation is a key inflammatory trigger underlying male hypogonadism. Obesity and a high fat/high calorie diet are both reported to result in changes to gut bacteria and intestinal wall permeability, leading to the passage of bacterial endotoxin (lipopolysaccharide- LPS) from within the gut lumen into the circulation (metabolic endotoxaemia), where it initiates systemic inflammation. Endotoxin is known to reduce testosterone production by the testis, both by direct inhibition of Leydig cell steroidogenic pathways and indirectly by reducing pituitary LH drive, thereby also leading to a decline in sperm production. In this paper we also highlight the novel evolutionary benefits of the GELDING theory. Testosterone is known to be a powerful immune-suppressive, decreasing a man's ability to fight infection. Therefore we postulate that the male reproductive axis has evolved the capacity to lower testosterone production during times of infection and resulting endotoxin exposure, decreasing the immunosuppressive influence of testosterone, in turn enhancing the ability to fight infection. While this response is adaptive in times of sepsis, it becomes maladaptive in the setting of "non

  13. Lean tissue mass and energy expenditure are retained in hypogonadal men with spinal cord injury after discontinuation of testosterone replacement therapy

    PubMed Central

    Bauman, William A.; La Fountaine, Michael F.; Cirnigliaro, Christopher M.; Kirshblum, Steven C.; Spungen, Ann M.

    2015-01-01

    Objective To determine whether favorable changes to lean tissue mass (LTM), resting energy expenditure (REE), and testosterone (T) that occurred with 12 months of physiological testosterone replacement therapy (TRT) were retained 6 months after discontinuing treatment. Design Prospective, open-label, controlled drug intervention trial. Setting Metropolitan area hospitals. Subjects Eugonadal (n = 11) and hypogonadal (n = 13) men with chronic spinal cord injury (SCI). Interventions Hypogonadal subjects received a 5 or 10 mg transdermal T patch daily for 12 months, with adjustment of the dose to normalize the serum T concentration; TRT was discontinued after 12 months (TRT-12M) and subjects were followed for an additional 6 months and re-evaluated (Post-TRT). Total body dual energy X-ray absorptiometry and blood draws were performed at baseline (BL) prior to TRT, TRT-12M, and Post-TRT. Eugonadal subjects did not receive treatment and were evaluated at comparable time points. Results There were no significant differences between groups prior to TRT at BL for any of the study endpoints. In the hypogonadal group, a significant increase in LTM was observed from BL to TRT-12M (50.2 ± 7.4 vs. 52.9 ± 6.8 kg, P < 0.01), which persisted Post-TRT compared to BL (52.2 ± 7.8 kg, P < 0.05). The increase in REE from BL to TRT-12M (1283 ± 246 vs. 1410 ± 250 kcal/day) was also retained at Post-TRT (1393 ± 220 kcal/day). These sustained improvements in LTM and REE after termination of anabolic hormonal therapy may be associated with persistent beneficial effects on health and physical function of hypogonadal men with chronic SCI. PMID:24968251

  14. Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

    PubMed

    Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

    2016-02-01

    The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk. PMID:26909487

  15. [Effect of testosterone on the in vitro proliferation of bone marrow granulocyte-macrophage cells (CFU-GM). II. Observations in hypogonadal subjects].

    PubMed

    De Caro, L; Ghizzi, A

    1989-03-01

    CFU-GM cultures in agar double layers were performed from bone marrow unfractionated cells of four subjects with hypogonadism, before and 24 hours after acute administration of 100 mg of testosterone propionate (Tp). Cell aggregates (CA) of CFU-GM were classified according to their sizes (P1 = 3-10 cells; P2 = 11-30; P3 = 31-50; P4 = over 50 cells) and according to their appearance time in culture (CA-A: appearing at the 7th day; CA-C: appearing only at the 12th day). The total of proliferating progenitors (tPP) also embraces CA present, in the same microscopic field, on both scoring times (CA-B). In all hypogonadal men studied, the treatment with Tp yielded increase of tPP (on the average of 65%) and increase of the total number of cells appeared in culture (TCP, increase on the average of 82%) calculated as product [CA number] x [average size of CA]. These results are in agreement with those already observed by us in CFU-GM cultures of normal subjects. Yet it is interesting to note that, while in normal subjects the exogenous testosterone effect expresses itself with a higher increase of CFU-GM number in the second interval of culture (CA-C), in hypogonadal men the CFU-GM number increase occurs mostly in the first period of the culture (CA-A).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2765242

  16. Psychosexual Development in Men with Congenital Hypogonadotropic Hypogonadism on Long-Term Treatment: A Mixed Methods Study

    PubMed Central

    Dwyer, Andrew A; Quinton, Richard; Pitteloud, Nelly; Morin, Diane

    2015-01-01

    Introduction Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetic, reproductive endocrine disorder characterized by absent puberty and infertility. Limited information is available on the psychosocial impact of CHH and psychosexual development in these patients. Aim The aim of this study was to determine the impact of CHH on psychosexual development in men on long-term treatment. Methods A sequential mixed methods explanatory design was used. First, an online survey (quantitative) was used to quantify the frequency of psychosexual problems among CHH men. Second, patient focus groups (qualitative) were conducted to explore survey findings in detail and develop a working model to guide potential nursing and interdisciplinary interventions. Main Outcome Measures Patient characteristics, frequency of body shame, difficulty with intimate relationships, and never having been sexually active were assessed. Additionally, we collected subjective patient-reported outcomes regarding the impact of CHH on psychological/emotional well-being, intimate relationships, and sexual activity. Results A total of 101 CHH men on long-term treatment (>1 year) were included for the analysis of the online survey (mean age 37 ± 11 years, range 19–66, median 36). Half (52/101, 51%) of the men had been seen at a specialized academic center and 37/101 (37%) reported having had fertility-inducing treatment. A high percentage of CHH men experience psychosexual problems including difficulty with intimate relationships (70%) and body image concerns/body shame (94/101, 93%), and the percentage of men never having been sexually active is five times the rate in a reference group (26% vs. 5.4%, P < 0.001). Focus groups revealed persisting body shame and low self-esteem despite long-term treatment that has lasting impact on psychosexual functioning. Conclusions CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual

  17. The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

    PubMed Central

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Abstract Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels. Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer. After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117–0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48–2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls. Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration

  18. A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism.

    PubMed

    Wang, Chun Lin; Fen, Zhu Wei; Liang, Li

    2014-03-01

    We report the case of a 12-year-old boy with a de novo mutation in the DAX1 gene (for dosage-sensitive sex reversal, congenital adrenal hypoplasia critical region on the X chromosome, gene 1; also called NROB1). He was born at term, Addison's disease was diagnosed at 8 years with a salt-wasting syndrome, and then hydrocortisone substitution was taken; the child continued to develop normally. A reoccurrence of salt-wasting syndrome usually happened after an episode of an abrupt withdrawal of hydrocortisone substitution. Because of adrenal insufficiency without hypogonadotropic hypogonadism, he came to the clinic at 12 years of age and hypoplasia of adrenal glands was found by MRI scans. We proposed the diagnosis of congenital adrenal hypoplasia in this patient and identified a hemizygous mutation (c.999_1000insCTCA, p.Leu335ThrfsX389) in exon 1 of the DAX1 gene. To our knowledge, it is a de novo mutation that leads to a frame-shift, a premature stop codon. In conclusion, it is very important to identify mutation in the DAX1 gene for a boy with adrenal insufficiency of unknown etiology. PMID:24197767

  19. The Relationship between Periodontal Status and Alkaline Phosphatase Levels in Gingival Crevicular Fluid in Men with Hypergonadotropic Hypogonadism

    PubMed Central

    Saygun, Işıl; Daltaban, Özlem; Bal, Belgin; Bolu, Erol

    2008-01-01

    Purpose The aim of this preliminary study was to determine the possible relationship between alkaline phosphatase (ALP) levels in the gingival crevicular fluid (GCF) and periodontal disease in men with hypergonadotropic hypogonadism (HH). Materials and Methods A total of 41 patients were divided into four groups. 9 with HH and periodontitis (P/HH), 11 with HH and gingivitis (G/HH), 12 with systemically healthy and periodontally healthy (H/C) and 9 with systemically healthy and periodontitis (P/C). The clinical evaluation of patients was based on the following parameters; the plaque index (PI), gingival index (GI), probing depths (PD) and attachment level (AL). The levels of ALP in the GCF were measured by enzyme-linked immunosorbent assay (ELISA). Results No significant difference could be detected in the mean clinical parameter data between the P/HH and P/C groups (p > 0.05). The periodontitis patients in both groups (P/C and P/HH) had higher mean probing depths than the H/C and G/HH patients (p < 0.001). The concentrations and total amounts of ALP in the GCF were significantly higher in both periodontitis groups compared to healthy and gingivitis groups (p < 0.01). The serum ALP levels were significantly higher in the P/HH group when compared to the other groups (p < 0.001). Conclusion The findings of this study suggested that HH could be implicated as a contributing factor to the progress of periodontal disease. PMID:18306472

  20. Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism

    PubMed Central

    Li, Chen-Xi; Tang, Song-Tao; Zhang, Qiu

    2015-01-01

    To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH) and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45%) than the control subjects (10.00%) (P < 0.001). The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (P < 0.001, for all) and higher fasting insulin (P = 0.001), HOMA-IR (P = 0.002), and SHBG (P < 0.001) compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI (P = 0.021) and BMD in lumbar spine 2–4, femoral neck, and total hip (P = 0.002, P = 0.003, and P = 0.003, resp.) increased dramatically and total cholesterol (P = 0.034), fasting insulin (P = 0.025), HOMA-IR (P = 0.021), and SHBG (P = 0.001) decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients. PMID:26417369

  1. A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17 beta-oestradiol.

    PubMed

    Illig, R; DeCampo, C; Lang-Muritano, M R; Prader, A; Torresani, T; Werder, E A; Willi, U; Schenkel, L

    1990-12-01

    Transdermal 17 beta-oestradiol administration (17 beta-E2), used mainly in menopausal women, allows a continuous 17 beta-E2 delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17 beta-E2 could be used for the induction of puberty, 17 beta-E2 patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age greater than 10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 micrograms/day for 6-9 months, 10 micrograms/day for 6-9 months, 25 micrograms/day for long-term substitution; addition of cyclic gestagen p.o. after 18-24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E2) and urinary E2 conjugates increased proportionally with 17 beta-E2 doses, serum oestrone (E1) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17 beta-E2 is optimally suited for hormonal substitution in girls with hypogonadism. PMID:2126236

  2. Successful use of a gonadotropin-releasing hormone (GnRH) analog for the treatment of tertiary hypogonadism (GnRH deficiency) in a 5-year-old Belgian Blue bull.

    PubMed

    Contri, Alberto; Gloria, Alessia; Wegher, Laura; Carluccio, Augusto

    2012-01-01

    A bull was referred for a progressive oligoasthenotheratozoospermia that resulted in a unsuitable seminal quality for the cryopreservation. Breeding soundness evaluation results suggested gonadal dysfunction. Because of the lack of normal ranges for these hormones in the bull, in this study, the hypogonadism and the site of the dysfunction (hypothalamus) were diagnosed by the gonadotropin-releasing hormone (GnRH) stimulation test. The evaluation of pituitary and testicular responsiveness by a GnRH stimulating test revealed a responsiveness of the pituitary and testis, thus a secondary hypogonadism (hypothalamic hypogonadism) was postulated and a therapeutic approach based on the subcutaneous administration of GnRH analog was attempted. An increase in semen volume, concentration and sperm characteristics were detected 9 weeks after the start of the treatment, corroborating the hypothalamic origin of the disease and the useful of the GnRH therapy. PMID:22493993

  3. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations

    PubMed Central

    Villanueva, Carine; Jacobson-Dickman, Elka; Xu, Cheng; Manouvrier, Sylvie; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Beenken, Andrew; Liu, Yang; Tommiska, Johanna; Hu, Youli; Tiosano, Dov; Gerard, Marion; Leger, Juliane; Drouin-Garraud, Valérie; Lefebvre, Hervé; Polak, Michel; Carel, Jean-Claude; Phan-Hug, Franziska; Hauschild, Michael; Plummer, Lacey; Rey, Jean-Pierre; Raivio, Taneli; Bouloux, Pierre; Sidis, Yisrael; Mohammadi, Moosa; de Roux, Nicolas; Pitteloud, Nelly

    2014-01-01

    Purpose Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising CHH and SHFM. Methods We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions, and/or functional assays. Results We identified 8 probands with CHH with (n=3, Kallmann Syndrome) or without anosmia (n=5) and SHFM, 7 of whom (88%) harbor FGFR1 mutations: one individual is homozygous for p.V429E; six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, and p.L712P. All mutations were predicted to be loss-of-function by in silico analysis. Probands with FGFR1 mutations have severe GnRH deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was only observed in the patient with the homozygous p.V429E mutation; V429 maps to the FRS2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of FRS2α to FG FR 1 , thereby resulting in reduced MAPK signaling. Conclusion FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM, because the likelihood of a mutation increases from 10% in the general CHH population to 88%. PMID:25394172

  4. Trial of Recombinant Follicle-Stimulating Hormone Pretreatment for GnRH-Induced Fertility in Patients with Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Hayes, Frances J.; Boepple, Paul A.; Lee, Hang; Loughlin, Kevin R.; Dym, Martin; Sluss, Patrick M.; Crowley, William F.

    2013-01-01

    Context and Objective: The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method. Design and Setting: This was a randomized, open-label treatment protocol at an academic medical center. Patients and Interventions: GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses. Results: rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts. Conclusions: rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles. PMID:24037890

  5. Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China

    PubMed Central

    Liu, Zhi-Yong; Zhou, Ren-Yuan; Lu, Xin; Zeng, Qin-Song; Wang, Hui-Qing; Li, Zheng; Sun, Ying-Hao

    2016-01-01

    In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone–binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l−1 for a decreased ability/frequency to perform sex, 12.55 nmol l−1 for decreased frequency of morning erections, and 14.35 nmol l−1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l−1, respectively. TT <13.21 nmol l−1 (OR = 1.4, 95%CI: 1.0–1.9, P = 0.037) or CFT <268.89 pmol l−1 (OR = 1.5, 95%CI: 1.1–20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l−1 and CFT levels <268.89 pmol l−1. Our results may improve the diagnostic accuracy of LOH in older men. PMID:26354142

  6. Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China.

    PubMed

    Liu, Zhi-Yong; Zhou, Ren-Yuan; Lu, Xin; Zeng, Qin-Song; Wang, Hui-Qing; Li, Zheng; Sun, Ying-Hao

    2016-01-01

    In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l-1 for a decreased ability/frequency to perform sex, 12.55 nmol l-1 for decreased frequency of morning erections, and 14.35 nmol l-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l-1 , respectively. TT <13.21 nmol l-1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l-1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l-1 and CFT levels <268.89 pmol l-1 . Our results may improve the diagnostic accuracy of LOH in older men. PMID:26354142

  7. Hypogonadotropic Hypogonadism due to a Novel Missense Mutation in the First Extracellular Loop of the Neurokinin B Receptor

    PubMed Central

    Bereket, Abdullah; Rocha, Nuno; Porter, Keith; Turan, Serap; Gribble, Fiona M.; Kotan, L. Damla; Akcay, Teoman; Atay, Zeynep; Canan, Husniye; Serin, Ayse; O’Rahilly, Stephen; Reimann, Frank; Semple, Robert K.; Topaloglu, A. Kemal

    2015-01-01

    Context The neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed within the central nervous system, including hypothalamic nuclei involved in regulating GnRH release. We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). Patients and Methods We sequenced the TACR3 gene in a family in which three siblings had nIHH. The novel mutant receptor thus identified was studied in a heterologous expression system using calcium flux as the functional readout. Results All affected siblings were homozygous for the His148Leu mutation, in the first extracellular loop of the NKB receptor. The His148Leu mutant receptor exhibited profoundly impaired signaling in response to NKB (EC50 = 3 ± 0.1 nm and >5 μm for wild-type and His148Leu, respectively). The location of the mutation in an extracellular part of the receptor led us also to test whether senktide, a synthetic NKB analog, may retain ability to stimulate the mutant receptor. However, the signaling activity of the His148Leu receptor in response to senktide was also severely impaired (EC50 = 1 ± 1 nm for wild-type and no significant response of His148Leu to 10 μm). Conclusions Homozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. These observations further strengthen the link between NKB, the NKB receptor, and regulation of human reproductive function. PMID:19755480

  8. Testosterone replacement therapy improves the health-related quality of life of men diagnosed with late-onset hypogonadism

    PubMed Central

    Almehmadi, Yousef; Yassin, Aksam A.; Nettleship, Joanne E.; Saad, Farid

    2015-01-01

    Objectives To test the hypothesis that testosterone replacement therapy (TRT) improves the long-term health-related quality of life (HRQoL) of men with late-onset hypogonadism (LOH), as studies have shown that sub-physiological testosterone levels have a negative impact on psychological (e.g. mood, vitality, libido and sexual interest) and physical features (e.g. erectile function and physical strength), all of which contribute to a sense of well-being. Patients and methods In all, 261 patients (mean age 58 years) diagnosed with LOH were treated with long-acting intramuscular testosterone undecanoate (TU) for up to 5 years. Health quality indicators including the International Prostate Symptom Score (IPSS), the five-item version of the International Index of Erectile Function (IIEF-5), the Aging Males’ Symptoms (AMS) scale, and the percentage of patients reporting joint and muscle pain were measured at baseline and at each visit. The means were then plotted over time in parallel with mean total testosterone (TT) levels. Results Both the mean IPSS and AMS scores fell significantly within the first 3 months and the mean IIEF-5 score and TT levels increased within the first 3 months. All four parameters continued to improve over the course of the trial. The percentage of patients reporting both joint and muscle pain decreased during TRT. Conclusions This prospective, observational and longitudinal analysis shows a clear improvement in both psychological and physical characteristics as physiological testosterone levels are reached and maintained contributing to an improvement in the HRQoL in men with diagnosed LOH. PMID:26966591

  9. Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures.

    PubMed

    Calderón, Berniza; Galdón, Alba; Calañas, Alfonso; Peromingo, Roberto; Galindo, Julio; García-Moreno, Francisca; Rodriguez-Velasco, Gloria; Martín-Hidalgo, Antonia; Vazquez, Clotilde; Escobar-Morreale, Héctor F; Botella-Carretero, José I

    2014-10-01

    Bariatric surgery results in the complete resolution of male obesity-associated secondary hypogonadism (MOSH) in many patients. However, the effects of different bariatric surgical procedures on male sexual hormone profiles and sexual dysfunction have not been compared to date. We compared the pre- and post-operative (at least 6 months after initial surgery) sex hormone profiles of 20 severely obese men submitted to laparoscopic gastric bypass (LGB) with 15 similar patients submitted to restrictive techniques (sleeve gastrectomy in 10 and adjustable gastric banding in 5). We calculated free testosterone (FT) levels from total testosterone (TT) and sex hormone binding globulin (SHBG) concentrations. Fasting glucose and insulin levels served for homeostatic model assessment of insulin resistance (HOMAIR). MOSH was present in 25 and 16 of the 35 patients when considering TT and FT concentrations respectively, resolving after surgery in all but one of them. When considering all obese men as a whole, patients submitted to LGB or restrictive procedures did not differ in terms of excess weight loss, in the decrease of fasting glucose and insulin, HOMAIR and waist circumference, or in the increase of serum 25-hydroxyvitamin D, TT and FT levels. The improvement in TT correlated with the decrease in fasting glucose (r = -0.390, P = 0.021), insulin (r = -0.425, P = 0.015) and HOMAIR (r = -0.380, P = 0.029), and with the increase in SHBG (r = 0.692, P < 0.001). The increase in FT correlated with the decrease in fasting glucose (r = -0.360, P = 0.034). LGB and restrictive techniques are equally effective in producing a remission of MOSH. PMID:24664512

  10. Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats.

    PubMed

    Mittelman-Smith, Melinda A; Krajewski-Hall, Sally J; McMullen, Nathaniel T; Rance, Naomi E

    2016-05-01

    In the human infundibular (arcuate) nucleus, a subpopulation of neurons coexpress kisspeptin and neurokinin B (NKB), 2 peptides required for normal reproductive function. A homologous group of neurons exists in the arcuate nucleus of rodents, termed KNDy neurons based on the coexpression of kisspeptin, NKB, and dynorphin. To study their function, we recently developed a method to selectively ablate KNDy neurons using NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (SAP). Here, we ablated KNDy neurons in female rats to determine whether these neurons are required for estrous cyclicity and the steroid induced LH surge. NK3-SAP or Blank-SAP (control) was microinjected into the arcuate nucleus using stereotaxic surgery. After monitoring vaginal smears for 3-4 weeks, rats were ovariectomized and given 17β-estradiol and progesterone in a regimen that induced an afternoon LH surge. Rats were killed at the time of peak LH levels, and brains were harvested for NKB and dual labeled GnRH/Fos immunohistochemistry. In ovary-intact rats, ablation of KNDy neurons resulted in hypogonadotropic hypogonadism, characterized by low levels of serum LH, constant diestrus, ovarian atrophy with increased follicular atresia, and uterine atrophy. Surprisingly, the 17β-estradiol and progesterone-induced LH surge was 3 times higher in KNDy-ablated rats. Despite the marked increase in the magnitude of the LH surge, the number of GnRH or anterior ventral periventricular nucleus neurons expressing Fos was not significantly different between groups. Our studies show that KNDy neurons are essential for tonic levels of serum LH and estrous cyclicity and may play a role in limiting the magnitude of the LH surge. PMID:26937713

  11. The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance.

    PubMed

    Krysiak, R; Gilowski, W; Okopien, B

    2015-11-01

    No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone. PMID:26600057

  12. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men

    PubMed Central

    Yassin, Aksam; Haider, Ahmad; Doros, Gheorghe; Gooren, Louis

    2015-01-01

    Purpose To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. Materials and Methods A total of 561 hypogonadal men from two registry studies were divided into age groups of ≤65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. Results Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. Conclusions The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH. PMID:25874045

  13. Definitive localization of X-linked Kallman syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232.

    PubMed Central

    Meitinger, T; Heye, B; Petit, C; Levilliers, J; Golla, A; Moraine, C; Dalla Piccola, B; Sippell, W G; Murken, J; Ballabio, A

    1990-01-01

    Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism and anosmia. Six families in which the disorder followed an X-linked inheritance were investigated by linkage analysis. Diagnostic criteria were uniformly applied and included tests for hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of 30 fully informative meioses, one recombination between the disease locus and the loci recognized by probe CRI-S232 was observed. When an independent approach is used, these results confirm the X-linked Kallmann syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome to the Xp22.3 region. This opens the way to carrier detection and to the identification of a gene responsible for this disorder. Images Figure 2 PMID:1977309

  14. Pharmacokinetics and drying time of testosterone 2% gel in men with hypogonadism: a multicenter, open-label, single-arm trial.

    PubMed

    Morgentaler, A; McGettigan, J; Xiang, Q; Danoff, T M; Gould, E M

    2015-01-01

    The objective of this study was to assess drying time after application of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum total testosterone (TT) to reach the eugonadal range (⩾ 300 ng dl(-1)), and time to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism were enrolled in the study; 31 men were included in the pharmacokinetics (PKs) population. Testosterone 2% gel (40 mg) was applied once daily in the morning to the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95% confidence interval (CI), 1.7-3.4 min; n = 31). Serum TT concentrations reached the target eugonadal range with a median time of 2.9 h (95% CI, 1.9-4.3 h; n = 24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7-3.4 days; n = 31). Six patients (17.6%; n = 34) reported treatment-related adverse events; all were mild. The results from this 14-day PK study in men with hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after application and that testosterone 2% gel rapidly reaches the target eugonadal range and attains steady-state serum TT concentrations in about 1 day. PMID:25056809

  15. Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.

    PubMed

    Sato, Naoko; Hasegawa, Tomonobu; Hasegawa, Yukihiro; Arisaka, Osamu; Ozono, Keiichi; Amemiya, Shin; Kikuchi, Toru; Tanaka, Hiroyuki; Harada, Shohei; Miyata, Ichiro; Tanaka, Toshiaki

    2015-04-01

    Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing subjects into

  16. Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols

    PubMed Central

    Sato, Naoko; Hasegawa, Tomonobu; Hasegawa, Yukihiro; Arisaka, Osamu; Ozono, Keiichi; Amemiya, Shin; Kikuchi, Toru; Tanaka, Hiroyuki; Harada, Shohei; Miyata, Ichiro; Tanaka, Toshiaki

    2015-01-01

    Abstract Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing

  17. Normosmic Congenital Hypogonadotropic Hypogonadism Due to TAC3/TACR3 Mutations: Characterization of Neuroendocrine Phenotypes and Novel Mutations

    PubMed Central

    Voican, Adela; Amazit, Larbi; Trabado, Séverine; Fagart, Jérôme; Meduri, Geri; Brailly-Tabard, Sylvie; Chanson, Philippe; Lecomte, Pierre; Guiochon-Mantel, Anne; Young, Jacques

    2011-01-01

    Context TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. Objective To evaluate the prevalence of TAC3/TACR3 mutations, characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH caused by deleterious TAC3/TACR3 biallelic mutations. Results From a cohort of 352 CHH, we selected 173 nCHH patients and identified nine patients carrying TAC3 or TACR3 variants (5.2%). We describe here 7 of these TACR3 variants (1 frameshift and 2 nonsense deleterious mutations and 4 missense variants) found in 5 subjects. Modeling and functional studies of the latter demonstrated the deleterious consequence of one missense mutation (Tyr267Asn) probably caused by the misfolding of the mutated NK3R protein. We found a statistically significant (p<0.0001) higher mean FSH/LH ratio in 11 nCHH patients with TAC3/TACR3 biallelic mutations than in 47 nCHH patients with either biallelic mutations in KISS1R, GNRHR, or with no identified mutations and than in 50 Kallmann patients with mutations in KAL1, FGFR1 or PROK2/PROKR2. Three patients with TAC3/TACR3 biallelic mutations had an apulsatile LH profile but low-frequency alpha-subunit pulses. Pulsatile GnRH administration increased alpha-subunit pulsatile frequency and reduced the FSH/LH ratio. Conclusion The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. This ratio might be useful for pre-screening nCHH patients for TAC3/TACR3 mutations. PMID:22031817

  18. The prevalence of erectile dysfunction among subjects with late-onset hypogonadism: a population-based study in China

    PubMed Central

    Tang, Wen-Hao; Zhuang, Xin-Jie; Shu, Ru-Ming; Guan, Di; Ji, Yu-Dang; Zhang, Bao-Long; Wang, Can-Gang; Zhuang, Li-Hua; Yang, Zhuo; Hong, Kai; Ma, Lu-Lin; Jiang, Hui; Zhou, Shan-Jie; Gu, Yi-Qun

    2015-01-01

    Introduction: The concurrence of chronic diseases and some well-defined risk factors significantly impacts the prevalence of erectile dysfunction (ED). Aim: To determine whether late-onset hypogonadism (LOH) impacts the prevalence of ED using investigation reproductive health data of middle-aged and aging males in China. Methods: The reproductive health status of 1498 males, aged 40-69 years, was evaluated using questionnaires of LOH based on the Androgen Deficiency in Aging Males (ADAM) and Aging Male Symptoms scale (AMS), as well as the International Index of Erectile Function-5 (IIEF-5) assessment. The 10th percentile of serum total testosterone (TT) and calculated free testosterone (cFT) levels of controls were set as cut-off levels of AD. The main outcome measures were used to assess the prevalence of LOH and ED according to different subject characteristics. Results: Of the 1472 subjects who completed the questionnaires who supplied hormone measurements, the prevalence of self-reported ED and identified by the IIEF-5 assessment were 11.28% and 77.85%, respectively. The IIEF-5 assessment revealed a prevalence of ED of 55.34%, 88.20%, and 91.77%, respectively, among those aged 40-49, 50-59, and 60-69 years. AD rates of ED subjects were 13.73% and 40.69% according to the TT and cFT cut-off levels. The prevalence of ED among subjects positive for LOH (ADAM+ and AMS+) were 88.81% and 95.80%, respectively. The prevalence of ED among the AD subjects (TT and cFT cut-off levels) with LOH (ADAM+ and AMS+) were 86.67%/81.82%. And the prevalence of ED among clinical LOH subjects (ADAM+ and AMS+) were 89.51%/98.48%. Conclusions: We found that middle-aged and aging Chinese males were at a relatively high risk of ED. The prevalence of ED among subjects with LOH symptoms was greater than in all recruited subjects. The effect of LOH on the prevalence of ED far outweighed the risk of decreased testosterone levels. PMID:26550346

  19. Is there a relationship between the severity of erectile dysfunction and the comorbidity profile in men with late onset hypogonadism?

    PubMed Central

    Yassin, Aksam A.; Nettleship, Joanne E.; Almehmadi, Yousef; Yassin, Dany-Jan; El Douaihy, Youssef; Saad, Farid

    2015-01-01

    Objective To determine whether the severity of erectile dysfunction (ED) in a man diagnosed with late-onset hypogonadism (LOH) gives information about his metabolic syndrome state, as patients with LOH often have sexual symptoms and associated cardiovascular and metabolic comorbidities, but the role of ED in predicting the prevalence of comorbid disease in men with low levels of testosterone is currently unknown. Patients and methods Men (130) diagnosed with LOH and fulfilling the criteria of a total testosterone level of <3.5 ng/mL (<12 nmol/L), and with an erectile function domain score of <21 on the International Index of Erectile Function questionnaire (IIEF, questions 1–5), were enrolled for a subsequent trial of supplementation with testosterone undecanoate. Demographic data were recorded at baseline. The men completed three standardised questionnaires to assess sexual health, including the International Prostate Symptom Score, Ageing Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by the severity of ED, with SHIM scores of 1–7 considered severe, 8–11 moderate, and 12–16 mild to moderate. Levels of serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density and low-density lipoprotein) were assessed, along with plasma fasting glucose and glycated haemoglobin (HbA1c) levels. Body weight, body mass index and waist circumference were also recorded. Results There was a significant association between the severity of ED and mean weight (P < 0.001), waist circumference (P < 0.001), triglycerides (P = 0.009), total cholesterol (P = 0.027), HbA1c (P < 0.001), fasting glucose (P = 0.003) and AMS scores (P = 0.043). There were no significant differences in testosterone fractions and SHBG levels between the ED subgroups. There was a positive correlation between the prevalence of diabetes mellitus (type 1 and type 2) and the severity of ED in

  20. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study

    PubMed Central

    Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

    2016-01-01

    Aims Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. Methods This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18–50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Results Former AAS abusers exhibited significantly lower median (25th –75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9–17.7) nmol/l vs. 18.8 (16.6–22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Conclusions Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation

  1. WDR11, a WD Protein that Interacts with Transcription Factor EMX1, Is Mutated in Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome

    PubMed Central

    Kim, Hyung-Goo; Ahn, Jang-Won; Kurth, Ingo; Ullmann, Reinhard; Kim, Hyun-Taek; Kulharya, Anita; Ha, Kyung-Soo; Itokawa, Yasuhide; Meliciani, Irene; Wenzel, Wolfgang; Lee, Deresa; Rosenberger, Georg; Ozata, Metin; Bick, David P.; Sherins, Richard J.; Nagase, Takahiro; Tekin, Mustafa; Kim, Soo-Hyun; Kim, Cheol-Hee; Ropers, Hans-Hilger; Gusella, James F.; Kalscheuer, Vera; Choi, Cheol Yong; Layman, Lawrence C.

    2010-01-01

    By defining the chromosomal breakpoint of a balanced t(10;12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty. We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q, and H690Q) in WD domains important for β propeller formation and protein-protein interaction. In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction. PMID:20887964

  2. Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism

    PubMed Central

    Buxton, Jessica L.; Zekavati, Anna; Sosinsky, Alona; Yiorkas, Andrianos M.; Holder, Susan; Klaber, Robert E.; Bridges, Nicola; van Haelst, Mieke M.; le Roux, Carel W.; Walley, Andrew J.; Walters, Robin G.; Mueller, Michael; Blakemore, Alexandra I. F.

    2015-01-01

    Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous peptide precursors, including neuropeptides and hormones involved in appetite control and glucose metabolism. Exome sequencing of a morbidly obese female from a consanguineous family revealed homozygosity for a truncating mutation of the CPE gene (c.76_98del; p.E26RfsX68). Analysis detected no CPE expression in whole blood-derived RNA from the proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotrophic hypogonadism seen in this individual recapitulates phenotypes in the previously described fat/fat and Cpe knockout mouse models, evidencing the importance of this peptide/hormone-processing enzyme in regulating body weight, metabolism, and brain and reproductive function in humans. PMID:26120850

  3. The efficacy, bioavailability and safety of a novel hydroalcoholic testosterone gel 2% in hypogonadal men: results from phase II open-label studies.

    PubMed

    Efros, M; Carrara, D; Neijber, A

    2016-08-01

    Pharmacokinetics, pharmacodynamics and safety of a novel hydroalcoholic testosterone gel 2% (TG) were evaluated in phase II sequential dose escalation studies using 3 application sites (thigh, abdomen and shoulder/upper arm) and 2 application methods. Hypogonadal men (n = 40), 18-75 years, with serum testosterone <300 ng dl(-1) were included in both studies. Study 1 evaluated hand-applied multiple doses of TG 1.25, 2.50 and 3.75 ml (23, 46 and 70 mg of testosterone, respectively), once daily for 10 days to shoulder/upper arm. Study 2 evaluated applicator-applied (TG 1.25, 2.50 and 3.75 ml) versus hand-applied (TG 2.5 ml) doses, once daily for 7 days to shoulder/upper arm. Primary endpoint for both studies was responder rate (Cave testosterone levels between 298 and 1050 ng dl(-1) ). In Study 1 following multiple applications, >70% participants in each group were responders. Dose-dependent increase was observed in PK values for total testosterone, free testosterone and DHT. In Study 2, responder rate was dose proportional: 16.7%, 50.0% and 77.8% responders in TG 1.25, 2.50 and 3.75 ml groups respectively. The bioavailability was highest for the shoulder application. There was a significant improvement in almost all the domains of sexual functioning. Applicator-application was preferred over hand-application by majority of the participants. TG was found to be safe and well tolerated in hypogonadal men. PMID:26598279

  4. AB098. Can concomitant dutasteride reduce the effect of testosterone replacement therapy in men with late-onset hypogonadism? A 24-week, randomized, parallel study

    PubMed Central

    Park, Hyun Jun; Moon, Du Guen; Park, Nam Cheol

    2016-01-01

    Objectives 5ARIs have sexual side effects, including erectile dysfunction (ED), loss of libido and ejaculatory dysfunction due to their action mechanism which decreases serum DHT levels. We examined whether concomitant dutasteride reduced the efficacy of testosterone replacement therapy (TRT) in men with late-onset hypogonadism. Methods This was a 24-week, randomized, parallel study of the clinical outcomes in men age >40 years with symptomatic benign prostatic hypertrophy [BPH; International Prostate Symptom Score (IPSS) th], prostate volume Prostate Symptom Score (IPSS) 300 ng/dL with aging male symptoms, who were taking stable doses of alpha-blockers 4 weeks before participation. Eligible patients received a combination of dutasteride 0.5 mg once daily and a transdermal gel containing 10 g testosterone (T) (DT group, n=30) or the transdermal gel alone (T group, n=30). The primary outcomes were the change in the aging male symptom (AMS) score, sexual desire (question 17, AMS score), and erectile function (International Index of Erectile Function-5). Secondary outcomes were the post-treatment IPSS, peak urinary flow rate, post-void residual urine volume (PVR), and prostate volume. Results Both groups showed significant improvements from baseline in all primary outcome parameters. However, there were no significant differences in the changes in the AMS total score (DT −5.2 vs. T −5.0; P=0.55), sexual desire (DT −2.5 vs. T −2.3; P=0.23), and IIEF-5 score (DT −2.1 vs. T −1.9; P=0.13) between groups. The extent of IPSS improvement from baseline to 24 weeks was the same in both groups (DT −1.2 vs. T −1.0; P=0.64). In addition, the changes in Q(max) and PVR from baseline were very similar in both groups. However, prostate volume decreased significantly (P<0.01) in the DT group (DT −6.1 cc vs. T +0.6 cc). Conclusions Concomitant dutasteride did not reduce the effect of testosterone replacement therapy in men with late-2onset hypogonadism. Otherwise it

  5. UGT2B17 Genotype and the Pharmacokinetic Serum Profile of Testosterone during Substitution Therapy with Testosterone Undecanoate. A Retrospective Experience from 207 Men with Hypogonadism

    PubMed Central

    Bang, Anne Kirstine; Jørgensen, Niels; Rajpert-De Meyts, Ewa; Juul, Anders

    2013-01-01

    Background: Testosterone (T) is mainly excreted in the urine as testosterone glucuronide (TG). This glucuronidation is partly dependent on the UGT2B17 genotype, and TG excretion is therefore lower in men having the UGT2B17 deletion. However, the possible influence of UGT2B17 genotype on serum T during androgen therapy is unknown. We retrospectively investigated the possible association between the UGT2B17 gene polymorphism and serum T levels in hypogonadal men during Testosterone undecanoate (TU) substitution therapy. Subjects and Methods: Two hundred and seven patients treated with TU (Nebido®) were genotyped by quantitative polymerase chain reaction for the UGT2B17 deletion polymorphism. All were given 1000 mg TU per injection at 0, 6, and 18 weeks. Blood samples were taken 2 and 6 weeks after the first and second injection, prior to the third injection, and after 2–3 years of treatment. We analyzed for the levels of T, luteinizing hormone (LH), sex-hormone-binding globulin, estradiol, prostate specific antigen, hematocrit, hemoglobin, and total cholesterol. Results: The UGT2B17 genotype frequency was: ins/ins: 42%, ins/del: 44%, and del/del: 14%. During the initial 18 weeks of TU treatment, large intra- and inter-individual variations in serum T levels were observed. Large peaks in T levels, ranging from 6.7 to 69.5 nmol/l, were noted 2 weeks after injections, regardless of the genotype. T levels did not differ between the three genotypes prior to the third injection, but the del/del group had significantly lower levels of LH. At follow-up after 2–3 years, the injection interval or daily T dosage was not dependent on the UGT2B17 genotype. Conclusion: In conclusion, we found large intra- and inter-individual variations in serum T during standard TU treatment regimen in hypogonadal men. Only subtle differences in serum T and LH were noted according to UGT2B17 genotype, which however suggest that the UGT2B17 genotype exert modest influence on

  6. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials

    PubMed Central

    GUO, CHANGCHENG; GU, WENYU; LIU, MIN; PENG, BO; YAO, XUDONG; YANG, BIN; ZHENG, JUNHUA

    2016-01-01

    The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non-significantly manner (MD, −0.85; 95% CI, −1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, −0.16; 95% CI, −0.29 to −0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, −1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, −0.62 to 0.82; P=0.78) or bone mineral density (MD, −0.01; 95% CI, −0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, −0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, −0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml. PMID:26998003

  7. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis.

    PubMed

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer.After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117-0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48-2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls.Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration is minimal

  8. Two Families with Normosmic Congenital Hypogonadotropic Hypogonadism and Biallelic Mutations in KISS1R (KISS1 Receptor): Clinical Evaluation and Molecular Characterization of a Novel Mutation

    PubMed Central

    Francou, Bruno; Fagart, Jérôme; Roussel, Ronan; Viengchareun, Say; Combettes, Laurent; Brailly-Tabard, Sylvie; Lombès, Marc; Young, Jacques; Guiochon-Mantel, Anne

    2013-01-01

    Context KISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). Objective To describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation. Results An original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male) from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg). In this man, pulsatile GnRH (Gonadotropin Releasing Hormone) administration restored pulsatile LH (Luteinizing Hormone) secretion and testicular hormone secretion. Later, long-term combined gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy. Conclusion We show that a novel loss-of-function mutation (p.Tyr313His) in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropin deficiency in this genetic form of nCHH. PMID:23349759

  9. The plasma miR-125a, miR-361 and miR-133a are promising novel biomarkers for Late-Onset Hypogonadism

    PubMed Central

    Chen, Yao-ping; Wang, Ju; Zhao, Kai; Shang, Xue-jun; Wu, Hui-qin; Qing, Xing-rong; Fang, Fang; Zhang, Yan; Shang, Jin; Li, Hong-gang; Zhang, Hui-ping; Guan, Huang-tao; Zhou, Yuan-zhong; Gu, Yi-qun; Wu, Wei-xiong; Xiong, Cheng-liang

    2016-01-01

    Circulating miRNAs have been shown to serve as diagnostic/prognostic biomarkers in cancers and other diseases. However, the role of plasma miRNAs in Late-onset hypogonadism (LOH) diagnosis is still unknown. Using Illumina HiSeq2000 sequencing at discovery phase, and then two-step validated by reverse transcriptase polymerase chain reaction (RT-PCR) assays in verification phases. We verified that the expression levels of miR-125a-5p, miR-361-5p and miR-133a-3p were significantly altered in LOH group compared to the control group. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.682, 0.698 and 0.765, respectively. The combination of three miRNAs showed a larger AUC (0.835) that was more efficient for the diagnosis of LOH. Among three miRNAs, miR-133a-3p had the best diagnostic value for LOH with 68.2% sensitivity and 77.3% specificity. Regression analyses show that miR-133a-3p level was negatively associated with the ageing males’ symptoms (AMS) scale. However, miR-361-5p level was positively associated with serum testosterone concentrations. In summary, plasma miRNAs are differentially expressed between LOH and healthy controls. We validated three miRNAs that could act as novel biomarkers for diagnosis of LOH. These miRNAs may be involved in the development of LOH. However, further large and functional studies are warranted to confirm our findings. PMID:27000524

  10. X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism: Identification and in vitro study of a novel small indel in the NR0B1 gene.

    PubMed

    Yu, Tingting; Wang, Jian; Yu, Yongguo; Huang, Xiaodong; Fu, Qihua; Shen, Yiping; Chen, Fuxiang

    2016-05-01

    DAX1 is an orphan nuclear receptor that has a key role in the development and function of the adrenal and reproductive axes. Mutations in NR0B1, the gene encoding DAX1, result in X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). A Chinese pedigree with X-linked AHC and HHG was investigated in the present study. Sequence analysis identified a novel small indel variant, c.195_207delinsTG, in the NR0B1 gene. To determine the effect of this variant on DAX1 expression, reverse‑transcription quantitative PCR and western blot assays were performed. The mRNA expression levels in carriers of mutant NR0B1 were significantly reduced (62% decrease) compared to those in individuals with wild-type NR0B1 (WT). The c.195_207delinsTG mutation was demonstrated to lead to various truncated DAX1 proteins, including the C‑terminal truncated DAX1, which was only detected in the cytoplasm, and the N‑terminal truncated DAX1, which was present in the cytoplasm and nucleus. A luciferase assay was then performed to assess the repressor function of DAX1 in modulating steroidogenic factor 1 (SF‑1)‑mediated transactivation. WT DAX1 significantly suppressed the SF‑1‑mediated promoter activity of the steroidogenic acute regulatory protein by 35.5±1.9%. In contrast to other known pathogenic mutations which abolish the repressor function of DAX1, the c.195_207delinsTG mutant proxkduced a higher repressor activity, demonstrating a 49.9±2.6% reduction of promoter activity. These findings suggested that the mutation of NR0B1 in X‑linked AHC with HHG enhanced the function of DAX1 to repress SF-1 activation, while DAX1 is expected to have additional roles in the pathological mechanism. PMID:27035099

  11. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.

    PubMed

    Miraoui, Hichem; Dwyer, Andrew A; Sykiotis, Gerasimos P; Plummer, Lacey; Chung, Wilson; Feng, Bihua; Beenken, Andrew; Clarke, Jeff; Pers, Tune H; Dworzynski, Piotr; Keefe, Kimberley; Niedziela, Marek; Raivio, Taneli; Crowley, William F; Seminara, Stephanie B; Quinton, Richard; Hughes, Virginia A; Kumanov, Philip; Young, Jacques; Yialamas, Maria A; Hall, Janet E; Van Vliet, Guy; Chanoine, Jean-Pierre; Rubenstein, John; Mohammadi, Moosa; Tsai, Pei-San; Sidis, Yisrael; Lage, Kasper; Pitteloud, Nelly

    2013-05-01

    Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. PMID:23643382

  12. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Miraoui, Hichem; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Plummer, Lacey; Chung, Wilson; Feng, Bihua; Beenken, Andrew; Clarke, Jeff; Pers, Tune H.; Dworzynski, Piotr; Keefe, Kimberley; Niedziela, Marek; Raivio, Taneli; Crowley, William F.; Seminara, Stephanie B.; Quinton, Richard; Hughes, Virginia A.; Kumanov, Philip; Young, Jacques; Yialamas, Maria A.; Hall, Janet E.; Van Vliet, Guy; Chanoine, Jean-Pierre; Rubenstein, John; Mohammadi, Moosa; Tsai, Pei-San; Sidis, Yisrael; Lage, Kasper; Pitteloud, Nelly

    2013-01-01

    Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called “FGF8 synexpression” group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. PMID:23643382

  13. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies

    PubMed Central

    Saad, F; Yassin, A; Doros, G; Haider, A

    2016-01-01

    Background/Objectives: Long-term testosterone replacement therapy (TRT) up to 5 years has been shown to produce progressive and sustainable weight loss (WL) in hypogonadal men. This study investigated effects of long-term TRT up to 8 years in hypogonadal men with different obesity classes. Subjects/Methods: From two independent observational registries we identified a total of 411 obese, hypogonadal men receiving TRT in urological clinics. The effects of TRT on anthropometric as well as metabolic parameters were studied for a maximum duration of 8 years, mean follow-up: 6 years. All men received long-acting injections of testosterone undecanoate in 3-monthly intervals. Results: In all three classes of obesity, T therapy produced significant WL, decrease in waist circumference (WC) and body mass index (BMI). In patients with class I obesity, mean weight decreased from 102.6±6.4 to 84.1±4.9 kg, change from baseline: −17.4±0.5 kg and −16.8±0.4%. WC in this group of patients decreased from 106.8±7.4 to 95.1±5.3 cm, change from baseline: −10.6±0.3 cm. BMI decreased from 32.69±1.4 to 27.07±1.57, change from baseline: −5.52±0.15 kg m−2. In patients with class II obesity, weight decreased from 116.8±6.9 to 91.3±6.3 kg, change from baseline: −25.3±0.5 kg and −21.5±0.4%. WC decreased from 113.5±7.5 to 100.0±5.4 cm, change from baseline: −13.9±0.4 cm. BMI decreased from 37.32±1.45 to 29.49±1.71, change from baseline: −8.15±0.17 kg m−2. In patients with class III obesity, weight decreased from 129.0±5.6 to 98.9±4.8 kg, change from baseline: −30.5±0.7 kg and −23.6±0.5%. WC decreased from 118.5±5.6 to 103.8±4.9 cm, change from baseline: −14.3±0.4 cm. BMI decreased from 41.93±1.48 to 32.46±1.59, change from baseline −9.96±0.29 kg m−2. Conclusions: Testosterone therapy appears to be an effective approach to achieve sustained WL in obese hypogonadal men irrespective of severity of

  14. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

    PubMed Central

    Wang, Wen-Bo; She, Fei; Xie, Li-Fang; Yan, Wen-Hua; Ouyang, Jin-Zhi; Wang, Bao-An; Ma, Hang-Yun; Zang, Li; Mu, Yi-Ming

    2016-01-01

    Background: Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. Methods: This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17–30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests. Results: Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all P <0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P < 0.05). Basal serum ACTH (9.91 ± 4.98 pmol/L vs. 7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs. 1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289, P <0.05) and triglyceride levels (r = 0.268, P < 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy

  15. Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism.

    PubMed

    Rohayem, J; Nieschlag, E; Kliesch, S; Zitzmann, M

    2015-09-01

    In pre-pubertal boys ≥ 14 years, the differentiation between constitutional delay of growth and puberty (CDGP) and hypogonadotropic hypogonadism (HH) is challenging, as current diagnostic tools have limitations in sensitivity and specificity. The aim of this study was to assess the usefulness of markers of gonadal activity, growth axis activation and adrenarche in differentiation between pre-pubertal CDGP and HH. This retrospective study was carried out between 2006 and 2015 in an academic out-patient referral centre. The clinical data of 94 boys, aged 13.9-23.2 years and referred for "pubertal delay" were reviewed. Definite diagnoses were established on initial work-up and clinical follow-up: 24 boys were diagnosed with HH, 22 boys with CDGP, pre-pubertal (PP CDGP) at referral and 28 boys with CDGP, early pubertal at referral (EP CDGP), the latter serving as control group. Twenty patients were excluded from evaluation because of previous sex steroid treatment or associated chronic disease. Inhibin B and AMH were measured in all (n = 74); INSL3, IGF1, IGFBP3 and DHEAS in a subset of patients (n = 45) in serum of first presentation. Inhibin B and AMH were higher in boys with PP CDGP than in boys with HH: inhibin B: 87.6 ± 42.5 vs. 19.8 ± 13.9 pg/mL; p < 0.001; AMH: 44.9 ± 27.1 vs. 15.4 ± 8.3 ng/mL; p < 0.001. Receiver operating characteristics (ROC) for the diagnosis of PPCDGP vs. HH (inhibin B ≥ 28.5 pg/mL): sensitivity: 95%, specificity: 75%; AUC: 0.955. In combination with an AMH cut-off ≥20 ng/mL the specificity increased to 83%. INSL3, IGF1, IGFBP3 and DHEAS levels were not different. In boys with EP CDGP, inhibin B and IGF1 levels were highest (138.7 ± 59.9 pg/mL/289.7 ± 117 ng/mL), whereas AMH levels were lowest (11.7 ± 9.1 ng/mL). Sertoli cell markers are helpful for establishing a prognosis, whether a boy with pubertal delay will enter puberty spontaneously, whereas Leydig cell, growth and adrenal markers are not

  16. Mutations in CUL4B, Which Encodes a Ubiquitin E3 Ligase Subunit, Cause an X-linked Mental Retardation Syndrome Associated with Aggressive Outbursts, Seizures, Relative Macrocephaly, Central Obesity, Hypogonadism, Pes Cavus, and Tremor

    PubMed Central

    Tarpey, Patrick S. ; Raymond, F. Lucy ; O’Meara, Sarah ; Edkins, Sarah ; Teague, Jon ; Butler, Adam ; Dicks, Ed ; Stevens, Claire ; Tofts, Calli ; Avis, Tim ; Barthorpe, Syd ; Buck, Gemma ; Cole, Jennifer ; Gray, Kristian ; Halliday, Kelly ; Harrison, Rachel ; Hills, Katy ; Jenkinson, Andrew ; Jones, David ; Menzies, Andrew ; Mironenko, Tatiana ; Perry, Janet ; Raine, Keiran ; Richardson, David ; Shepherd, Rebecca ; Small, Alexandra ; Varian, Jennifer ; West, Sofie ; Widaa, Sara ; Mallya, Uma ; Moon, Jenny ; Luo, Ying ; Holder, Susan ; Smithson, Sarah F. ; Hurst, Jane A. ; Clayton-Smith, Jill ; Kerr, Bronwyn ; Boyle, Jackie ; Shaw, Marie ; Vandeleur, Lucianne ; Rodriguez, Jayson ; Slaugh, Rachel ; Easton, Douglas F. ; Wooster, Richard ; Bobrow, Martin ; Srivastava, Anand K. ; Stevenson, Roger E. ; Schwartz, Charles E. ; Turner, Gillian ; Gecz, Jozef ; Futreal, P. Andrew ; Stratton, Michael R. ; Partington, Michael 

    2007-01-01

    We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority. PMID:17236139

  17. Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: real-life experience from an observational registry study.

    PubMed

    Yassin, A A; Nettleship, J; Almehmadi, Y; Salman, M; Saad, F

    2016-09-01

    Subnormal levels of testosterone are associated with significant negative health consequences, with higher risks of all-cause and cardiovascular mortality. The numbers of studies reporting on the benefits of normalisation of testosterone is increasing but longer-term data on (elderly) men receiving testosterone treatment are almost nonexistent. In this single-centre, cumulative, prospective, registry study, 115 hypogonadal men (mean age 59.05 years) received injections with testosterone undecanoate in 12-week intervals for up to 10 years. Waist circumference, body weight and mean BMI dropped progressively with statistical significance versus previous year for 7 years and, respectively, 8 years for weight and body mass index. Similarly, fasting glucose displayed a significant decrease after the first year continuing to decrease thereafter. A decline in HbA1c , from 6.4% to 5.6% (mean <6%), was observed from year 2 on, together with a decrease in the ratio of triglycerides:high-density lipoprotein (HDL), a surrogate marker of insulin resistance, with an increase in HDL levels. The total cholesterol:HDL ratio and non-HDL cholesterol declined significantly. A decrease was also observed in systolic and diastolic blood pressure, with a decrease in levels of the inflammation marker C-reactive protein. No major adverse cardiovascular events were observed throughout the study. PMID:26762680

  18. Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter randomized controlled trial in Japan (EARTH Study).

    PubMed

    Konaka, Hiroyuki; Sugimoto, Kazuhiro; Orikasa, Hideki; Iwamoto, Teruaki; Takamura, Toshinari; Takeda, Yoshiyu; Shigehara, Kazuyoshi; Iijima, Masashi; Koh, Eitetsu; Namiki, Mikio

    2016-01-01

    Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second question on IIEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area. PMID:25761833

  19. Male central hypogonadism secondary to exogenous androgens: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects.

    PubMed

    Karavolos, Stamatios; Reynolds, Michael; Panagiotopoulou, Nikoletta; McEleny, Kevin; Scally, Michael; Quinton, Richard

    2015-05-01

    Androgen- or anabolic steroid-induced hypogonadism (ASIH) is no longer confined to professional athletes; its prevalence amongst young men and teenagers using androgens and/or anabolic steroids (AASs) is rising fast, and those affected can experience significant symptoms. Clinicians are increasingly encountering demanding, well-informed men affected by ASIH, yet lacking authoritative information on the subject may struggle to project a credible message. In this article, we overview the methods and drugs that men use in an attempt to counteract ASIH (with a view to either preventing its onset, or reversing it once it has developed) and summarize the scientific evidence underpinning these. The main channel for obtaining these drugs is the Internet, where they can be readily sourced without a valid prescription. An Internet search using relevant terms revealed a huge number of websites providing advice on how to buy and use products to counteract ASIH. Drugs arising repeatedly in our search included human chorionic gonadotrophin (hCG), selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The quality and accuracy of the online information was variable, but review of medical literature also highlighted a lack of scientific data to guide clinical practice. It is important for clinicians to be aware of the AAS user's self-treatment strategies with regard to ASIH side-effect mitigation. By ensuring that they are well-informed, clinicians are more likely to retain the credibility and trust of AAS users, who will in turn likely be more open to engage with appropriate management. PMID:25333666

  20. Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter, randomized controlled trial in Japan (EARTH Study)

    PubMed Central

    Konaka, Hiroyuki; Sugimoto, Kazuhiro; Orikasa, Hideki; Iwamoto, Teruaki; Takamura, Toshinari; Takeda, Yoshiyu; Shigehara, Kazuyoshi; Iijima, Masashi; Koh, Eitetsu; Namiki, Mikio

    2016-01-01

    Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second question on IIEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area. PMID:25761833

  1. Vitamin C reverses hypogonadal bone loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, ...

  2. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene

    PubMed Central

    d'Anglemont de Tassigny, Xavier; Fagg, Lisa A.; Dixon, John P. C.; Day, Kate; Leitch, Harry G.; Hendrick, Alan G.; Zahn, Dirk; Franceschini, Isabelle; Caraty, Alain; Carlton, Mark B. L.; Aparicio, Samuel A. J. R.; Colledge, William H.

    2007-01-01

    The G protein-coupled receptor GPR54 (AXOR12, OT7T175) is central to acquisition of reproductive competency in mammals. Peptide ligands (kisspeptins) for this receptor are encoded by the Kiss1 gene, and administration of exogenous kisspeptins stimulates hypothalamic gonadotropin-releasing hormone (GnRH) release in several species, including humans. To establish that kisspeptins are the authentic agonists of GPR54 in vivo and to determine whether these ligands have additional physiological functions we have generated mice with a targeted disruption of the Kiss1 gene. Kiss1-null mice are viable and healthy with no apparent abnormalities but fail to undergo sexual maturation. Mutant female mice do not progress through the estrous cycle, have thread-like uteri and small ovaries, and do not produce mature Graffian follicles. Mutant males have small testes, and spermatogenesis arrests mainly at the early haploid spermatid stage. Both sexes have low circulating gonadotropin (luteinizing hormone and follicle-stimulating hormone) and sex steroid (β-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appears normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic–pituitary axis is functional in these mice as shown by robust luteinizing hormone secretion after peripheral administration of kisspeptin. The virtually identical phenotype of Gpr54- and Kiss1-null mice provides direct proof that kisspeptins are the true physiological ligand for the GPR54 receptor in vivo. Kiss1 also does not seem to play a vital role in any other physiological processes other than activation of the hypothalamic–pituitary–gonadal axis, and loss of Kiss1 cannot be overcome by compensatory mechanisms. PMID:17563351

  3. A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism

    PubMed Central

    2014-01-01

    Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure. Study design 20 prepubertal adolescent females with ovarian failure, ages 12–18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test. Results Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone. Conclusions Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required. Trial registration Clinical Trials Identifier: NCT01023178. PMID:24982681

  4. From Mental Disorder to Iatrogenic Hypogonadism - Dilemmas in Conceptualizing Gender Identity Variants as Psychiatric Conditions

    PubMed Central

    Meyer-Bahlburg, Heino F. L.

    2009-01-01

    The categorization of gender identity variants (GIVs) as “mental disorders” in the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association (APA) is highly controversial among professionals as well as among persons with GIV. After providing a brief history of GIV categorizations in the DSM, this paper presents some of the major issues of the ongoing debate: GIV as psychopathology versus natural variation; definition of “impairment” and “distress” for GID; associated psychopathology and its relation to stigma; the stigma impact of the mental-disorder label itself; the unusual character of “sex reassignment surgery” as a psychiatric treatment; and the consequences for health and mental-health services if the disorder label is removed. Finally, several categorization options are examined: Retaining the GID category, but possibly modifying its grouping with other syndromes; narrowing the definition to dysphoria and taking “disorder” out of the label; categorizing GID as a neurological or medical rather than a psychiatric disorder; removing GID from both the DSM and the International Classification of Diseases (ICD); and creating a special category for GIV in the DSM. I conclude that--as also evident in other DSM categories--the decision on the categorization of GIVs cannot be achieved on a purely scientific basis, and that a consensus for a pragmatic compromise needs to be arrived at that accommodates both scientific considerations and the service needs of persons with GIVs. PMID:19851856

  5. Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.

    PubMed

    Norjavaara, Ensio; Ankarberg-Lindgren, Carina; Kriström, Berit

    2016-01-01

    The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 µg/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated. PMID:26680580

  6. Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation.

    PubMed

    Carod-Artal, F J; Herrero, M D; Lara, M C; López-Gallardo, E; Ruiz-Pesini, E; Martí, R; Montoya, J

    2007-05-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene (ECGF1). We present the first detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions and the T5814C change were found in mitochondrial DNA. Together with gastrointestinal symptoms, endocrine involvement and memory dysfunction, not reported in MNGIE to date, were the most preeminent features. PMID:17437622

  7. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    SciTech Connect

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-03-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses.

  8. TAC3 and TACR3 Mutations in Familial Hypogonadotropic Hypogonadism Reveal a Key Role for Neurokinin B in the Central Control of Reproduction

    PubMed Central

    Guclu, Metin; Yalin, Ayse Serap; Kotan, L. Damla; Porter, Keith M; Serin, Ayse; Mungan, Neslihan O; Cook, Joshua R; Imamoglu, Sazi; Akalin, N. Sema; Yuksel, Bilgin; O’Rahilly, Stephen; Semple, Robert K

    2015-01-01

    The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the post-pubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonatrophins, LH and FSH. We report four human pedigrees with severe congenital gonadotrophin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin1, a recently identified regulator of gonadotropin-releasing hormone secretion2. These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest novel approaches to the pharmacological control of human reproduction and sex hormone-related diseases. PMID:19079066

  9. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

    SciTech Connect

    Conte, F.A.; Grumbach, M.M.; Ito, Y.; Fisher, C.R.; Simpson, E.R.

    1994-06-01

    The authors report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (<37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris has enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. 32 refs., 6 figs., 2 tabs.

  10. What Are Normal Puberty, Precocious Puberty, and Delayed Puberty?

    MedlinePlus

    ... a long-lasting condition known as hypogonadism (pronounced HI-poe-GO-nad-iz-uhm ) in which the ... Turner syndrome or in individuals with hypogonadotropic (pronounced HI-po-GO-nah-doe-TROH-pik ) hypogonadism, which ...

  11. Pseudohypoparathyroidism

    MedlinePlus

    ... to have other endocrine system problems (such as hypothyroidism and hypogonadism ). Pseudohypoparathyroidism may be connected to other ... 565. Read More Central nervous system Hypogonadism Hypoparathyroidism Hypothyroidism Parathyroid hormone (PTH) blood test Renal Update Date ...

  12. An assessment of sex chromosome copy number in a phenotypic female patient with hypergonadtropic hypogonadism, primary amenorrhea and growth retardation by GTG-banding and FISH in peripheral blood and skin tissues

    SciTech Connect

    Jackson, I.M.D.; DeMoranville, B.; Grollino, M.G.

    1994-09-01

    The present report describes studies performed on an 18-year-old phenotypic female referred because of primary amenorrhea, hypergonadotropic hypoganadism and growth retardation. The clinical features raised the possibility of a gonadal dysgenesis. The ovaries were not identified on either side. Her testosterone was significantly elevated, with serum level at 48 ng/dl, and her free testosterone at 7 pg/ml. A GTG-banding analysis of 33 peripheral blood leukocytes revealed the modal number of chromosomes to be 46 per cell with a male sex constitution and normal appearing banding patterns (46,XY). In view of the clinical findings, additional cells were scored to rule out low percentage mosaicism. Out of 35 additional GTG-banded cells scored for the sex chromosomes, 4 cells (11.5%) were found to contain only one copy of the X chromosome. Fluorescent in situ hybridization (FISH) using dual color biotinylated X and Y probes (Imagenetics) was subsequently performed. Out of approximately 500 cells scored, 87% were found to be XY and 9% were found to be positive for the X signal only, versus 7% and 3% X signal only for 2 XY controls, aged 61 and 46, respectively. As loss of the Y chromosome has been reported in elderly males as well as certain males with leukemia, the age of the controls was important to note. To unequivocally establish the presence of mosaicism, a skin biopsy was obtained for fibroblast culture. Out of 388 total cells scored, 286 (74%) were found to be XY and 46 (12%) were found to be X, versus 99% XY and <1% X in controls. GTG-banding analysis of the same fibroblast culture is currently in progress. Preliminary data on this specimen thus far corroborate results of the FISH study. The presence of XY cells, along with an increased testosterone level, raises the distinct possibility of a gonadoblastoma. In view of this increased risk, arrangements are being made for the patient to have a laparoscopy and surgical removal of her presumptive streak gonads.

  13. An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101.

    PubMed

    Wittert, G A; Harrison, R W; Buckley, M J; Wlodarczyk, J

    2016-01-01

    We compared a novel 5% testosterone (T) cream (AndroForte 5, Lawley Pharmaceuticals, Australia) with a 1% T gel (Testogel, Besins Healthcare, Australia). Using an open-label crossover design, subjects were randomized to one of two treatment sequences using either the T gel or T cream first in a 1 : 1 ratio. Each treatment period was 30 days with a 7-14 days washout period between them. On Days 1 and 30 of each treatment period blood was sampled at -15, -5 min, 0, 2, 4, 5, 6, 7, 8, 9, 10, 12 and 16 h post study drug administration. Sixteen men with established androgen deficiency aged between 29 and 73 years, who had undertaken a washout from prior testosterone therapy participated in the study. One subject failed to complete both arms and another was excluded post-completion because of a major protocol violation. Bioequivalence was established based on key pharmacokinetic (PK) variables: AUC, C(avg), C(max), T(max), % fluctuation (with and without baseline correction) for the two formulations of testosterone on Day 1 and Day 30. The ratio and 90% CI of AUC 0.99 (0.86-1.14), C(max) 1.02 (0.84-1.24) and C(avg) 0.99 (0.86-1.14) for T cream/T gel were within the predetermined bio-equivalence criteria of 80% to 125% at Day 30. There were no statistically significant differences between secondary biochemical markers: serum dihydrotestosterone (DHT), oestradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and (FSH). The two testosterone formulations were shown to be bioequivalent. PMID:26754331

  14. Bardet-Biedl syndrome in two sisters: A rare incidence

    PubMed Central

    Varma, Chaitanya; Bhat, Ramesh Y.; Bhatt, Sonia

    2013-01-01

    Bardet-Biedl syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, obesity, polydactyly, mental retardation and hypogonadism. We present two sisters with this rare genetic condition.

  15. Genetics Home Reference: Kallmann syndrome

    MedlinePlus

    ... Encyclopedia: Hypogonadotropic Hypogonadism Encyclopedia: Smell - Impaired Health Topic: Endocrine Diseases Health Topic: Taste and Smell Disorders Genetic and Rare Diseases Information Center (7 links) ...

  16. Age-Related Testosterone Decline is due to Waning of Both Testicular and Hypothalamic-Pituitary Function

    PubMed Central

    Golan, Ron; Scovell, Jason M.; Ramasamy, Ranjith

    2016-01-01

    Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males. PMID:26075536

  17. Testicular failure following severe diabetic ketoacidosis complicated by hypotensive shock.

    PubMed

    Janem, Waleed; Mastrandrea, Lucy D

    2016-04-01

    The stalling or regression of pubertal development may be the first sign of hypergonadotropic hypogonadism in adolescent males. We report here a case of pediatric hypergonadotropic hypogonadism that likely developed secondary to ischemic injury during severe diabetic ketoacidosis (DKA). This case highlights the importance of performing genital exams during all evaluations of pediatric patients. PMID:27099736

  18. GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization-embryo transfer cycles.

    PubMed

    Bloch, Miki; Azem, Foad; Aharonov, Inbar; Ben Avi, Irit; Yagil, Yaron; Schreiber, Shaul; Amit, Ami; Weizman, Abraham

    2011-01-01

    To determine whether the use of a GnRH agonist inducing a hypogonadic state during IVF-ET cycles induces negative mood symptoms, we conducted a prospective randomized study in 108 women comparing two different controlled ovarian stimulation protocols. A significant phase effect was observed for depression and anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between the hypogonadal phase and the peak in gonadotropin stimulation; however, the hypogonadal phase induced by the GnRH agonist was not associated with a significant increase in any of the studied mood parameters. PMID:20801439

  19. Testosterone Nasal Gel

    MedlinePlus

    Testosterone nasal gel is used to treat symptoms of low testosterone in men who have hypogonadism (a condition in which the body does not produce enough natural testosterone). Testosterone nasal gel is used only for men ...

  20. Testosterone Buccal

    MedlinePlus

    Testosterone buccal systems are used to treat symptoms of low testosterone in men who have hypogonadism (a condition in which the ... sexual organs and typical male characteristics. Testosterone buccal systems work by replacing testosterone that is normally produced ...

  1. Could you have low testosterone?

    MedlinePlus

    ... menopause; Andropause; Testosterone deficiency; Androgen deficiency of the aging male; Late-onset hypogonadism ... Some symptoms may be a normal part of aging. For example, it is normal to feel less ...

  2. Pituitary apoplexy

    MedlinePlus

    ... body's sex glands produce little or no hormones) Hypothyroidism (thyroid gland does not make enough thyroid hormone) ... other missing hormones are not replaced, symptoms of hypothyroidism and hypogonadism may develop.

  3. Bromocriptine

    MedlinePlus

    ... lack of menstrual periods, discharge from the nipples, infertility (difficulty becoming pregnant) and hypogonadism (low levels of ... Parlodel) to treat lack of menstrual periods and infertility caused by hyperprolactinemia, use a method of birth ...

  4. Genetics Home Reference: CHARGE syndrome

    MedlinePlus

    ... developmental delay, and an opening in the lip ( cleft lip ) with or without an opening in the roof of the mouth ( cleft palate ). Individuals frequently have hypogonadotropic hypogonadism, which affects ...

  5. Could you have low testosterone?

    MedlinePlus

    Male menopause; Andropause; Testosterone deficiency; Androgen deficiency of the aging male; Late-onset hypogonadism ... Testosterone makes a man look and feel like a man. In a man, this hormone helps: Keep ...

  6. Testosterone Plus Finasteride Treatment After Spinal Cord Injury

    ClinicalTrials.gov

    2016-07-07

    Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

  7. Testosterone deficiency in the aging male

    PubMed Central

    McBride, J. Abram; Carson, Culley C.; Coward, Robert M.

    2016-01-01

    Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm. PMID:26834840

  8. Pathology or normal variant: what constitutes a delay in puberty?

    PubMed

    Villanueva, Carine; Argente, Jesús

    2014-01-01

    Puberty is a complex maturation process that begins during fetal life and persists until the acquisition of reproduction function. The fundamental event that activates puberty occurs in the hypothalamus. A complex neuron network stimulates GnRH secretion, which stimulates pituitary gonadotropin secretion and then gonadal steroid secretion. Pubertal delay is defined as the presentation of clinical signs of puberty 2-2.5 SD later than in the normal population. Three major groups of etiopathogeneses are described: (1) hypogonadotropic hypogonadism, (2) hypergonadotropic hypogonadism, and (3) constitutional delay of puberty (CDP) - the most common cause of delayed puberty in boys. The differential diagnosis between CDP and isolated hypogonadotropic hypogonadism remains difficult. Mechanisms of pubertal timing are now better understood and genetic or epigenetic causes can explain some pubertal delays. However, there are still unexplained mechanisms. Treatment of delayed puberty is necessary to ensure full pubertal development for the adolescent and in case of hypogonadism, to restore fertility. Finally, precocious diagnosis of hypogonadism is primordial but can be difficult during childhood and in cases of partial hypogonadism. The study of genetic pubertal diseases or of different animal models could help to discover new diagnostic or therapeutic tools. PMID:25011467

  9. Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health.

    PubMed

    Wu, Christopher; Kovac, Jason R

    2016-10-01

    There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states. We also provide a brief synopsis of selective androgen receptor modulators (SARMs) and postulate how these orally active, non-aromatizing, tissue-selective agents might be used in contemporary andrology. Currently, the applications of testosterone alternatives in hypogonadism are limited. However, it is tempting to speculate that these agents may one day become accepted as alternatives, or adjuncts, to the treatment of male hypogonadism. PMID:27535042

  10. 20 years of leptin: role of leptin in human reproductive disorders.

    PubMed

    Chou, Sharon H; Mantzoros, Christos

    2014-10-01

    Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin. PMID:25056118

  11. Hypotestosteronaemia in the aging male: should we treat it?

    PubMed

    Christe, Nora; Meier, Christoph A

    2015-01-01

    The term male hypogonadism is defined as the failure to maintain physiological concentrations of testosterone, a physiological quantity of sperm or the combination of both. Aetiologically, androgen deficiency can originate from the testes (primary hypogonadism) or from the hypothalamic-pituitary regulation of the testicular function (secondary hypogonadism). The causes of hypogonadism are very diverse and may be genetically determined (e.g. Klinefelter's syndrome) or acquired (tumours, infections, haemochromatosis). Classical hypogonadism linked to an underlying disease, such as a pituitary tumour, is a distinct indication for androgen substitution. But how about the aging male? It is known that there is a highly variable age-related decline in testosterone levels; whether this represents a variation of normality or has a true disease value requiring therapy has been disputed over more than a decade. The key questions surrounding this debate concern not only the age-dependent threshold for serum testosterone but, more importantly, the risks and benefits of testosterone replacement therapy in the aging male. We searched the literature for randomised controlled trials of testosterone administration in aging males with a size of at least 100 patients and a follow-up of at least 6 months, and identified eight studies. These studies mostly tried to evaluate the effect of testosterone on bone density, muscle strength and body composition, rather than clinically meaningful endpoints. Moreover, these trials have provided evidence for relevant cardiovascular adverse events in elderly men. This supports the need for further studies to define the treatment threshold for testosterone levels in the aging male, as well as with regard to the long-term risks and relevant benefits of testosterone therapy in this population. Until we have more solid data in aging males, testing for testosterone deficiency and testosterone replacement should remain reserved for patients with

  12. Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study

    PubMed Central

    Haider, Ahmad; Yassin, Aksam; Haider, Karim Sultan; Doros, Gheorghe; Saad, Farid; Rosano, Giuseppe MC

    2016-01-01

    Background/objectives Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD). Patients and methods In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD. The effects of TTh on anthropometric and metabolic parameters were investigated for a maximum duration of 8 years. Any occurrence of major adverse cardiovascular events was reported. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. Results In 77 hypogonadal men with a history of CVD who received TTh, we observed a significant weight loss and a decrease in waist circumference and body mass index. Mean weight decreased from 114±13 kg to 91±9 kg, change from baseline: −24±1 kg and −20.2%±0.5%. Waist circumference decreased from 112±8 cm to 99±6 cm, change from baseline: −13±0.3 cm. Body mass index decreased from 37±4 to 29±3, change from baseline: −8±0.2 kg/m2. Cardio-metabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure all improved significantly and sustainably. No patient suffered a major adverse cardiovascular event during the full observation time. Conclusion In men with hypogonadism, TTh appears to be effective in achieving sustained improvements in all cardiometabolic risk factors and may be effective as an add-on measure in the secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. PMID:27366080

  13. [Pathologic manifestations of hormonal receptor mutations].

    PubMed

    Milgrom, E

    2000-01-01

    Mutations of receptor genes are involved in various aspects of thyroid and gonadal pathology. Activating mutations of TSH and LH receptors are associated with hyperthyroidism and premature puberty. These mutations are dominant and lead to the synthesis of a constitutive receptor, i.e. a receptor active even in the absence of hormone. Inactivating mutations of TSH, gonadotropin and GnRH receptors are recessive. They determine either a hypothyroidism or a hypogonadism. In the case of alterations of gonadotropin receptors the hypogonadism is hypergonadotrophic. It is hypogonadotrophic in the case of mutations of the GnRH receptor. PMID:10989556

  14. Kallmann's syndrome: clues to clinical diagnosis.

    PubMed

    John, H; Schmid, C

    2000-04-01

    Hypogonadotropic patients may visit pediatricians, general practitioners, endocrinologists or urologists, presenting with microphallus, cryptochidism or pubertas tarda and delayed bone maturation. Congenital hypogonadotropic hypogonadism is characterized, apart from small testes, by the constellation of low serum levels of testosterone, LH and FSH. Kallman's syndrome is characterized by congenital hypogonadotropic hypogonadism with midline defects such as anosmia (a deficiency of the sense of smell). The first case report dates back to 1856, and genetic defects causing the syndrome have been recently described. The diagnosis can be clinically suspected and is established by confirming hormonal studies. PMID:11052640

  15. Testosterone and Male Infertility.

    PubMed

    Ohlander, Samuel J; Lindgren, Mark C; Lipshultz, Larry I

    2016-05-01

    Hypogonadism and its therapies have a significant impact on male fertility potential. It is necessary to determine the etiology to treat and counsel the patient appropriately on therapeutic options. For the hypogonadal male on exogenous testosterone, management should begin with cessation of the exogenous testosterone and supplemental subcutaneous human chorionic gonadotropin and an oral follicle-stimulating hormone (FSH)-inducing agent to allow reestablishment of the hypothalamic-pituitary-gonadal axis and spermatogenesis. Further supplemental therapy with recombinant FSH in some patients may be necessary to achieve optimal semen parameters. PMID:27132576

  16. Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study.

    PubMed

    O'Carrigan, B; Fournier, M; Olver, I N; Stockler, M R; Whitford, H; Toner, G C; Thomson, D B; Davis, I D; Hanning, F; Singhal, N; Underhill, C; Clingan, P; McDonald, A; Boland, A; Grimison, P

    2014-08-01

    This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity. PMID:25081047

  17. Alternatives to testosterone replacement: testosterone restoration

    PubMed Central

    McCullough, Andrew

    2015-01-01

    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH. PMID:25578932

  18. Visual-Motor Integration in Children with Prader-Willi Syndrome

    ERIC Educational Resources Information Center

    Lo, S. T.; Collin, P. J. L.; Hokken-Koelega, A. C. S.

    2015-01-01

    Background: Prader-Willi syndrome (PWS) is characterised by hypotonia, hypogonadism, short stature, obesity, behavioural problems, intellectual disability, and delay in language, social and motor development. There is very limited knowledge about visual-motor integration in children with PWS. Method: Seventy-three children with PWS aged 7-17 years…

  19. Cognitive, Emotional, Physical and Social Effects of Growth Hormone Treatment in Adults with Prader-Willi Syndrome

    ERIC Educational Resources Information Center

    Hoybye, C; Thoren, M.; Bohm, B.

    2005-01-01

    Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of…

  20. Testosterone deficiency myopathy.

    PubMed Central

    Orrell, R W; Woodrow, D F; Barrett, M C; Press, M; Dick, D J; Rowe, R C; Lane, R J

    1995-01-01

    Testosterone is recognized to have a positive effect on nitrogen balance and muscle development in hypogonadal men, but significantly myopathy secondary to testosterone deficiency has been reported only rarely. We describe a patient who presented with a myopathy associated with testosterone deficiency, and who demonstrated a significant functional and myometric response to treatment. PMID:7562829

  1. Quality of Life and Psychological Well-Being in GH-Treated, Adult PWS Patients: A Longitudinal Study

    ERIC Educational Resources Information Center

    Bertella, L.; Mori, I.; Grugni, G.; Pignatti, R.; Ceriani, F.; Molinari, E.; Ceccarelli, A.; Sartorio, A.; Vettor, R.; Semenza, C.

    2007-01-01

    Background: Prader-Willi syndrome (PWS) is a congenital alteration of chromosome pair 15. It is characterized by short stature, muscular hypotonia, hyperphagia, obesity, behavioural and emotional disturbances, hypogonadism and partial Growth Hormone (GH) deficiency. The aim of this study was to assess the long-term effect of GH treatment on the…

  2. An unusual case of adolescent type 2 diabetes mellitus: Prader-Willi syndrome.

    PubMed

    Basheer, Riyas; Jalal, Muhammed Jasim Abdul; Gomez, Ramesh

    2016-01-01

    Prader-Willi syndrome (PWS) is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms - polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m(2). He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases. PMID:27453871

  3. [In Process Citation].

    PubMed

    Bucher, Julie; Christ, Emanuel R

    2014-04-01

    Diagnosis and therapy of male hypogonadism is still a challenge because of the unspecific clinical signs and symptoms. The clinical presentation of a androgen deficiency is age-related. In the adult men, one can often observe fatigue, decrease in physical capacity, loss of libido and erectile dysfunction. At the physical examination, genitalia have always to be assessed in search of a testes/penis atrophy. Two fasting measurements of total testosterone concentrations by a reliable assay are needed to confirm the diagnosis. By assessing gonadotropines the origin of hypogonadism can be determined (central/secondary or peripheral/primary). Exogenous administration of androgens should be considered in young, sportive, healthy and muscular males. Patients with metabolic syndrome should only be screened for hypogonadism in the presence of suggestive symptoms. Prostate disease, hematocrit higher than 50 %, uncontrolled heart failure and severe obstructive sleep apnea are contraindications of a testosterone replacement therapy. Patients with metabolic-syndrome-associated low testosterone levels should firstly benefit from a lifestyle intervention that can normalize clinical and biochemical hypogonadism. So far, there is no clear evidence for a possible benefit of testosterone therapy in patients with the metabolic syndrome. Similarly, in patients with PADAM (partial androgen deficiency of the aging male) testosterone therapy is not established or recommended. PMID:24670603

  4. Basal cell carcinomas in a young woman with Steinert's disease.

    PubMed

    Miraglia, E; Cantisani, C; Giustini, S; Ambrifi, M; Soda, G; Calvieri, S

    2014-08-01

    Steinert's disease or Myotonic dystrophy type I (DM1) is an autosomal dominant disease characterized by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and electrocardiographic alterations.Several tumors have been associated with DM1 such as pilomatricoma, thymomas and insulinomas. Herein, we describe the unusual onset of multiple basal cell carcinomas in a young woman with DM1. PMID:25148278

  5. A comprehensive approach to the spectrum of abnormal pubertal development.

    PubMed

    Appelbaum, Heather; Malhotra, Shilpa

    2012-04-01

    Puberty is the biological transition from childhood to adulthood. The process involves the coordination of hormonal, physical, psychosocial, and cognitive systems to result in physiologic change. Precocious puberty is defined as pubertal development beginning earlier than expected based on normal standards. Gonadotropin dependent precocious puberty is caused by premature activation of the hypothalamus resulting in pulsatile secretion of GnRH. Gonadotropin independent precocious puberty is caused by excess sex hormones from peripheral or external sources. Treatment with GnRH agonists should be offered to prevent early fusion of the epiphyseal plates to avoid unnecessary short stature and should not be based on perceived psychosocial consequences of early puberty. Delayed puberty is the absence of or incomplete development of secondary sexual characteristics. Hypergonadotropic hypogonadism or primary hypogonadism may result from genetic mutation syndromes or can be acquired from antiovarian antibodies, exposure to radiation or chemotherapy, inflammatory insult, or surgical removal of the gonads. Hypogonadotropic hypogonadism or secondary hypogonadism is due to hypothalamic dysfunction resulting in impaired secretion of GnRH. The long-term goal for patients with inadequate estrogen stimulation is to maintain the serum concentration of sex steroids within the normal adult range to promote the development of secondary sexual characteristics, prevent premature bone loss, and ultimately to induce fertility when indicated. PMID:22764552

  6. Pituitary Disorders and Osteoporosis

    PubMed Central

    Jawiarczyk-Przybyłowska, Aleksandra

    2015-01-01

    Various hormonal disorders can influence bone metabolism and cause secondary osteoporosis. The consequence of this is a significant increase of fracture risk. Among pituitary disorders such effects are observed in patients with Cushing's disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis is the result of the coexistence of some of these disorders and hypogonadism at the same time, which is quite often. PMID:25873948

  7. Prevalence of Pituitary Hormone Dysfunction, Metabolic Syndrome, and Impaired Quality of Life in Retired Professional Football Players: A Prospective Study

    PubMed Central

    Chaloner, Charlene; Evans, Diana; Mathews, Amy; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Sim, Myung-Shin; Lee, Jihey; Wright, Mathew J.; Kernan, Claudia; Barkhoudarian, Garni; Yuen, Kevin C.J.; Guskiewicz, Kevin

    2014-01-01

    Abstract Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30–65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and

  8. Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study.

    PubMed

    Kelly, Daniel F; Chaloner, Charlene; Evans, Diana; Mathews, Amy; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Sim, Myung-Shin; Lee, Jihey; Wright, Mathew J; Kernan, Claudia; Barkhoudarian, Garni; Yuen, Kevin C J; Guskiewicz, Kevin

    2014-07-01

    Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30-65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had Met

  9. Early onset of puberty in an obese boy with Klinefelter syndrome

    PubMed Central

    Cho, Byoung-Wook; Kwon, Seung-Eun; Kim, Soon-Ki; Lee, Taek; Han, Jee-Young

    2016-01-01

    Klinefelter syndrome (KS) is one of the most common disease entities characterized by X-chromosomal aberration causing the primary hypogonadism in adult men. Patients with KS seem to be typically characterized by tall, slender bodies with delayed puberty and hypergonadotropic hypogonadism. However, it has been known that they have a broad spectrum of phenotype ranging from almost normal external appearances to typical phenotype. Only 25% KS Patients are ever diagnosed because KS remains unrecognized. Also, boys with KS have an onset of pubertal development within the normal range, not delayed onset of puberty. Adolescents with KS are generally diagnosed as having the lack of pubertal progress. Early detection of KS can be difficult without awareness. We report an unusual case of early onset of puberty in obese boy with KS who presented with a unilateral non-hormone secreting testicular teratoma. PMID:27104178

  10. Familial cytomegalic adrenocortical hypoplasia: an X-linked syndrome of pubertal failure.

    PubMed Central

    Hay, I D; Smail, P J; Forsyth, C C

    1981-01-01

    Five boys with familial cytomegalic adrenocortical hypoplasia have been followed up for an average of 19 years. Despite treatment with replacement corticosteroids, all 5 failed to show a spontaneous onset of puberty and, when assessed at ages 13 to 19 years, all had both sexual infantilism and skeletal immaturity. Hypogonadism was confirmed by low levels of plasma testosterone, and pituitary reserve of gonadotrophin was shown to be inadequate by testing with gonadotrophin-releasing hormone. Two boys, both with adequate testosterone output on human chorionic gonadotrophin stimulation, were given gonadotrophin therapy, whereas the other 3 were treated with parenterally administered testosterone. With treatment, all 5 patients showed advances in pubertal staging. Although the mechanism of the hypogonadotropism remains unclear, the association of hypogonadotrophic hypogonadism with familial cytomegalic adrenocortical hypoplasia appears to be a constant one and may be considered as a treatable inherited syndrome of pubertal failure. PMID:7197507

  11. Androgen function in the pathophysiology and treatment of male Huntington's disease patients.

    PubMed

    Ransome, M I

    2012-10-01

    Low concentrations of circulating testosterone have been associated with dementia manifesting with advancing age and in neurodegenerative conditions. Huntington's disease (HD) is a dominantly inherited neurodegenerative disease with an invariably fatal outcome. Severe motor symptoms, psychosis and dementia are symptomatic hallmarks of the progression of HD that result from the dysfunction and death of neocortical and basal ganglia neurones. Treatments are directed toward manifest symptoms, although they are largely ineffectual in slowing or preventing disease progression. Emerging data have identified hypothamic pathologies in HD that result in endocrine disturbances. Clinically defined primary or secondary hypogonadism elicit low circulating testosterone concentrations and have been linked to the development of Alzheimer's disease in men. Examining similar neuroendocrine dysfunction in HD including the nature of manifest hypogonadism in male patients could allow an elucidation of the complex pathophysiology of HD and provide an impetus for hitherto untested testosterone replacement therapy. PMID:22672384

  12. Operative considerations for late-presenting persistent Müllerian duct syndrome.

    PubMed

    Ark, Jacob T; Moses, Kelvin A

    2016-01-01

    Persistent Müllerian duct syndrome (PMDS) is a condition in which a 46, XY male displays masculine external genitalia, but internally retains developed Müllerian duct structures (uterus, fallopian tubes, and upper two-thirds vagina). Thoughtful operative consideration is needed to maximize the therapeutic benefit while minimizing the risk of hypogonadism, infertility, and erectile dysfunction. We report a 53-year-old male with a pelvic mass incidentally discovered on routine ultrasound, intra-operatively discovered to be PMDS. PMDS is a rare condition that may present late in life. The primary operative consideration is performing orchiopexy for cancer surveillance or orchiectomy if orchiopexy is not possible. Additional considerations include surveillance and counseling of infertility, hypogonadism, and assessment of the potential need for involvement of psychiatry. Removal of Müllerian remnants is a subject to debate. If possible, discuss with the patient their risks and options in the preoperative setting to guide operative planning. PMID:27453663

  13. Subcutaneous pellet testosterone replacement therapy: the "first steps" in treating men with spinal cord injuries.

    PubMed

    Gray, Kendra M; Derosa, Angela

    2013-12-01

    The authors describe the case of a 36-year-old man who presented with hormone level concerns 6 months after a rock climbing accident that resulted in paraplegia. Hypogonadism was diagnosed, and the patient received subcutaneous pellet testosterone replacement therapy. Within 6 months, the patient had substantial improvement in muscle function and was able to take several steps with the assistance of crutches or a walker. This case highlights the potential improvement in quality of life and overall prognosis resulting from the subcutaneous pellet form of testosterone when used as part of the overall treatment plan in such patients. Considering the overwhelming preponderance of hypogonadism in men with spinal cord injuries, the standard of care for such patients should include screening, laboratory hormone evaluation, and prompt treatment for testosterone deficiency. PMID:24285035

  14. The unsolved case of "bone-impairing analgesics": the endocrine effects of opioids on bone metabolism.

    PubMed

    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  15. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    PubMed Central

    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  16. Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review.

    PubMed

    O'Rourke, Timothy K; Wosnitzer, Matthew S

    2016-10-01

    Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation. PMID:27586511

  17. 48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome

    PubMed Central

    Tartaglia, Nicole; Ayari, Natalie; Howell, Susan; D’Epagnier, Cheryl; Zeitler, Philip

    2012-01-01

    Sex chromosome tetrasomy and pentasomy conditions occur in 1:18 000–1:100 000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype–phenotype relationships and the development of evidence-based treatments. Conclusion The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments. PMID:21342258

  18. Metabolic Syndrome in Childhood: Rare Case of Alstrom Syndrome with Blindness.

    PubMed

    Ahmad, Afzal; D'Souza, Benedicta; Yadav, Charu; Agarwal, Ashish; Kumar, Anand; Nandini, M; D'Souza, Vivian; Poornima, A M; Kamath, Nutan

    2016-10-01

    Alstrom's syndrome (AS) is a rare autosomal recessive ciliopathic condition affecting 1:10,00,000 children. It's a single gene disorder of ALMS1 on chromosome 2 with multisystem involvement with cone-rod retinal dystrophy causing juvenile blindness, obesity, insulin resistance, type 2 Diabetes mellitus, hypogonadism and sensorineural hearing loss. Till now only 800 patients with this disorder has been identified so far. In this report, we describe the case of a 9-year old male boy from south India. He had been initially referred for polyphagia, polyuria, polydipsia, generalized weakness from 1 weeks. On examination he was demonstrated features suggestive of AS, including blindness, obesity, type 2 diabetes, altered lipid profile, hypogonadism, acanthosis nigricans, seborrheic dermatitis, right ear discharge and episodes of respiratory tract infections. So, diagnosis of AS is critical as it can easily be overlooked because of the many features associated with metabolic syndrome starting at age 7, a relatively early age. PMID:27605748

  19. Modifying Risk Factors in the Management of Erectile Dysfunction: A Review

    PubMed Central

    DeLay, Kenneth J; Haney, Nora

    2016-01-01

    Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patient's overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process. PMID:27574592

  20. Modifying Risk Factors in the Management of Erectile Dysfunction: A Review.

    PubMed

    DeLay, Kenneth J; Haney, Nora; Hellstrom, Wayne Jg

    2016-08-01

    Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patient's overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process. PMID:27574592

  1. Testosterone therapy in the new era of Food and Drug Administration oversight

    PubMed Central

    Desroches, Bethany; Kohn, Taylor P.; Welliver, Charles; Pastuszak, Alexander W.

    2016-01-01

    The Food and Drug Administration (FDA) introduced changes in labeling and indications for use to testosterone products in 2015 due to a possible increased risk of cardiovascular (CV) events. This decision was made based on six clinical studies—some that supported an increased CV risk, and some that did not. Since this decision, additional studies have been published examining the interplay between hypogonadism, CV risk, and testosterone, demonstrating that the risk may be lower than originally estimated. Clinicians are placed in a difficult position, as studies support an increased mortality risk in hypogonadal men, but also an increased risk of CV events in men on testosterone therapy. As a result, many clinicians will be more selective in their prescribing of testosterone. In this review, we examine how these new guidelines arose and how they may affect prescribing habits. PMID:27141448

  2. Early onset of puberty in an obese boy with Klinefelter syndrome.

    PubMed

    Cho, Byoung-Wook; Kwon, Seung-Eun; Kim, Soon-Ki; Lee, Taek; Han, Jee-Young; Lee, Ji-Eun

    2016-03-01

    Klinefelter syndrome (KS) is one of the most common disease entities characterized by X-chromosomal aberration causing the primary hypogonadism in adult men. Patients with KS seem to be typically characterized by tall, slender bodies with delayed puberty and hypergonadotropic hypogonadism. However, it has been known that they have a broad spectrum of phenotype ranging from almost normal external appearances to typical phenotype. Only 25% KS Patients are ever diagnosed because KS remains unrecognized. Also, boys with KS have an onset of pubertal development within the normal range, not delayed onset of puberty. Adolescents with KS are generally diagnosed as having the lack of pubertal progress. Early detection of KS can be difficult without awareness. We report an unusual case of early onset of puberty in obese boy with KS who presented with a unilateral non-hormone secreting testicular teratoma. PMID:27104178

  3. From the gut to the strut: where inflammation reigns, bone abstains.

    PubMed

    Iqbal, Jameel; Yuen, Tony; Sun, Li; Zaidi, Mone

    2016-06-01

    In this issue of the JCI, Li et al. show that germ-free mice, when chemically castrated, do not lose bone - a finding that unequivocally establishes a role of gut microbiota in mediating hypogonadal bone loss. Additionally and not unexpectedly, probiotics reversed hypogonadal osteopenia in sex steroid-deficient mice by preventing the disruption of gut barrier function and dampening cytokine-induced inflammation. The authors propose that TNFα is a key mediator; however, it is very likely that other molecules - including IL-1, IL-6, IL-17, RANKL, OPG, and CCL2 - modulate probiotic action. The results of this study highlight the potential for repurposing probiotics for the therapy of osteoporosis. Future placebo-controlled clinical trials will be required to establish safety and efficacy of probiotics in reducing fracture risk in people. PMID:27111233

  4. A summary of the controversy surrounding off-label medications in men's health.

    PubMed

    Parker, Adam; Bruha, Matthew; Akinola, Oluwaseun; Welliver, Charles

    2016-04-01

    While there are common and accepted practices in men's health, barriers exist to treatment of these disorders with Food and Drug Administration (FDA) approved medications. In male factor infertility, these barriers include studies that are often underpowered for desired outcomes. This has led to the use of medications previously examined in females in an off-label fashion for treatment of male infertility. Issues surrounding the treatment of hypogonadism in men are more complex, becoming increasingly so in the last few years. Drug companies have developed compounds for treatment of hypogonadism for particular subgroups of men. However, the indicated groups for these medications are narrow leading to these medications being regularly used for an indication the FDA considers to be part of "normal aging". This work will examine the controversy surrounding the use of off-label medications in men's health and how factors like pharma advertising, FDA regulation and difficulties in creating adequate studies has affected the current paradigm. PMID:27141447

  5. Progressive hearing loss associated with a unique cervical node due to a homozygous SLC29A3 mutation: a very mild phenotype.

    PubMed

    Jonard, Laurence; Couloigner, Vincent; Pierrot, Sébastien; Louha, Malek; Gherbi, Souad; Denoyelle, Françoise; Marlin, Sandrine

    2012-01-01

    In 2008, SLC29A3 has been implicated in a syndromic form of genodermatosis: H syndrome. The major features encountered in H syndrome are Hearing loss, Hyperglycaemia, Heart anomalies, Hypertrichosis, Hyperpigmentation, Hepatomegaly and Hypogonadism. More recently, SLC29A3 mutations have been described in families presenting syndromes associating generalized histiocytosis to systemic progressive features: severe camptodactyly, hearing loss, hypogonadism, hepatomegaly, heart defects and skin hyperpigmentation. We have identified a homozygous missense SLC29A3 mutation in a patient presenting with only a progressive sensorineural hearing impairment and a single cervical node (Rosai Dorfman). SLC29A3 mutations appear to be involved in a large phenotypic continuum which should prompt physicians to study this gene even in mild clinical presentations. PMID:21888995

  6. Operative considerations for late-presenting persistent Müllerian duct syndrome

    PubMed Central

    Ark, Jacob T.; Moses, Kelvin A.

    2016-01-01

    Persistent Müllerian duct syndrome (PMDS) is a condition in which a 46, XY male displays masculine external genitalia, but internally retains developed Müllerian duct structures (uterus, fallopian tubes, and upper two-thirds vagina). Thoughtful operative consideration is needed to maximize the therapeutic benefit while minimizing the risk of hypogonadism, infertility, and erectile dysfunction. We report a 53-year-old male with a pelvic mass incidentally discovered on routine ultrasound, intra-operatively discovered to be PMDS. PMDS is a rare condition that may present late in life. The primary operative consideration is performing orchiopexy for cancer surveillance or orchiectomy if orchiopexy is not possible. Additional considerations include surveillance and counseling of infertility, hypogonadism, and assessment of the potential need for involvement of psychiatry. Removal of Müllerian remnants is a subject to debate. If possible, discuss with the patient their risks and options in the preoperative setting to guide operative planning. PMID:27453663

  7. Osteoporotic fracture healing: potential use of medicinal plants from the tropics.

    PubMed

    Abdul Jalil, Mohd Azri; Shuid, Ahmad Nazrun; Muhammad, Norliza

    2013-12-01

    With improvements in living standards and healthcare, life expectancy has been increasing dramatically in most parts of the world. These situations lead to the increase in the reported cases of geriatrics-related diseases such as hypogonadal osteoporosis with skeletal fracture being the ultimate outcome, which eventually causes significant morbidity and mortality. The deficient gonadal hormones, which are the main cause of hypogonadal osteoporosis, could be substituted with hormone replacement therapy to hinder bone loss. However, the artificial hormonal therapy has been linked to grievous conditions such as breast and prostate cancers. In view of the various adverse effects associated with conventional treatment, many researchers are now focusing on finding alternative remedies from nature. This article explores the possibilities of certain medicinal plants native to Malaysia that possess androgenic and antioxidant properties to potentially be used in the treatment of fracture due to osteoporosis in ageing people. PMID:24354586

  8. Warburg micro syndrome in siblings from India

    PubMed Central

    Sekhon, Prabhjot Kaur; Premalatha, R.; Sabapathy, Sarala

    2016-01-01

    Warburg syndrome is a rare disorder characterized by microcephaly, microcornea, congenital cataract, developmental delay, and hypogonadism. Here, we report two siblings from India who presented with developmental delay, microcornea, microphthalmia, and bilateral congenital cataracts, born to the third-degree consanguineously married couple. Both children had hypoplasia of corpus callosum. In this report, we aim to highlight and compare clinical features of these two cases with previously reported cases. PMID:27195044

  9. Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency.

    PubMed Central

    Doriguzzi, C; Palmucci, L; Mongini, T; Bresolin, N; Bet, L; Comi, G; Lala, R

    1989-01-01

    A 19-year-old man born with thyroprivic hypothyroidism, due to congenital development defect, manifested hypogonadism, stunted growth, chronic progressive external ophthalmoplegia (CPEO), diffuse muscle weakness and wasting, right bundle branch block, cerebral atrophy. Muscle biopsy showed mitochondrial abnormalities. Biochemical investigations on muscle disclosed partial (50%) cytochrome c oxidase deficiency, 58% decrease of cytochrome aa3 and 41% decrease of cytochrome b. Enzyme-linked immunosorbent assay showed decrease of the immunologically active enzyme protein. Images PMID:2540284

  10. Estradiol: micrograms or milligrams

    PubMed Central

    Wickramasuriya, Nalin; Shaw, Nicholas J

    2016-01-01

    Summary Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. Learning points Girls with primary and secondary gonadal failure require assistance with pubertal induction. Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol. Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose. Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height. PMID

  11. Add on testosterone therapy in negative symptoms of schizophrenia with gonadal trauma: Hitting the bull's eye.

    PubMed

    Jha, Shailesh; Garg, Amit

    2016-06-30

    The coincidence or causal incidence of hormonal dysregulation leading to psychotic manifestation had been a point of debate. The interplay of these hormones in pathogenesis of psychotic symptom domains is still inconclusive along with some symptom domains which worsen with antipsychotics. Early detection and treatment with liaison approach is of great help to such patients. We report a case of schizophrenia with primary hypogonadism that responded dramatically to add on testosterone supplement. PMID:27138816

  12. Mutation analyses in pedigrees and sporadic cases of ethnic Han Chinese Kallmann syndrome patients.

    PubMed

    Gu, Wei-Jun; Zhang, Qian; Wang, Ying-Qian; Yang, Guo-Qing; Hong, Tian-Pei; Zhu, Da-Long; Yang, Jin-Kui; Ning, Guang; Jin, Nan; Chen, Kang; Zang, Li; Wang, An-Ping; Du, Jin; Wang, Xian-Ling; Yang, Li-Juan; Ba, Jian-Ming; Lv, Zhao-Hui; Dou, Jing-Tao; Mu, Yi-Ming

    2015-11-01

    Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron-exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients' sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype-phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights. PMID:26031747

  13. [48,XXYY men with azoospermia: how to manage infertility?].

    PubMed

    Roche, C; Sonigo, C; Benmiloud-Tandjaoui, N; Boujenah, J; Benzacken, B; Poncelet, C; Hugues, J-N

    2014-01-01

    48,XXYY syndrome is a rare form of sex chromosomal aneuploidy. Usually considered as a variant of Klinefelter syndrome because of shared features (azoospermia, tall stature, hypergonadotropic hypogonadism), it is a separate entity because diagnostic is currently made in prepubertal boy with neuro-psychological disorders. We here report the case of a 48,XXYY patient consulting for adult infertility and the indication to perform testicular sperm extraction is discussed. PMID:24934769

  14. [A report of 2 cases of Turner's syndrome with a ring X chromosome].

    PubMed

    Migliori, M V; Bartolotta, E; Maurizi, M; Bonazzi, P; Cardinale, G; Manunza, V

    1991-09-01

    The authors report two cases of Turner syndrome with clinical evidence of only primitive hypogonadism and short stature. Karyotype analysis showed X ring mosaicism which is present only in 5% of cases of Turner syndrome. The authors agree with the hypothesis suggesting no relationship between break points on the X chromosome and phenotypical aspect. An earlier diagnosis is auspicious so that, using correct therapy, final height should be improved. PMID:1758399

  15. Can Serum Testosterone Be Used as a Marker of Overall Health?

    PubMed Central

    Mederos, Michael A; Bernie, Aaron M; Scovell, Jason M; Ramasamy, Ranjith

    2015-01-01

    Low serum testosterone has been associated with obesity, type 2 diabetes, metabolic syndrome, and atherosclerosis. Individuals with these comorbidities are at increased risk of premature death and other adverse health effects. Clinical data portend low testosterone as a risk factor for developing these conditions which are supported by the hypogonadal-obesity-adipocytokine hypothesis. The authors support comprehensive evaluation for these comorbid conditions in men found to have low serum testosterone. PMID:26839520

  16. Physiology of the Hypothalamic Pituitary Gonadal Axis in the Male.

    PubMed

    Corradi, Patricia Freitas; Corradi, Renato B; Greene, Loren Wissner

    2016-05-01

    Testosterone synthesis and male fertility are the results of the perfect coordination of the hypothalamic-pituitary-gonadal axis. A negative feedback finely controls the secretion of hormones at the 3 levels. Congenital or acquired disturbance at any level leads to an impairment of reproductive function and the clinical syndrome of hypogonadism. In some cases, this condition is reversible. Once the diagnosis is made, testosterone replacement therapy is the standard therapy; however, novel therapies may improve spermatogenesis while elevating testosterone levels. PMID:27132572

  17. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

    PubMed Central

    Michaud, Jason E.; Billups, Kevin L.; Partin, Alan W.

    2015-01-01

    Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The ‘androgen hypothesis’ asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be

  18. Testosterone Replacement and Cardiovascular Safety: No Straight and Narrow!

    PubMed Central

    Hans, Sartaj S; Dhindsa, Sandeep S; Chemitiganti, Rama

    2015-01-01

    The past decade has seen a tremendous increase in the number of men treated for hypogonadism with the expectation of symptomatic benefit. However, the long-term cardiovascular safety of testosterone replacement remains unknown because retrospective studies of testosterone replacement have been inconsistent, and definitive, prospective, randomized studies are lacking. The purpose of this review is to critically appraise the studies on testosterone replacement and cardiovascular outcomes. PMID:25983562

  19. Recidivous offence in sadistic homosexual pedophile with karyotype 48, XXXY after testicular pulpectomy. A case report.

    PubMed

    Lachman, M; Brzek, A; Mellan, J; Hampl, R; Starka, L; Motlik, K

    1991-01-01

    The case of recidivous sexual offender with genetically caused mental retardation and primary hypogonadism (Klinefelter's syndrome with karyotype 48, XXXY) is described. He was examined after sadistic abuse of a boy aged 13 that he had committed 19 years after performed testicular pulpectomy. Plasmatic level of testosterone was found 4x higher than mean level in men after orchidectomy. Histological examination of residual scrotal tissues proved that the source of androgens were hyperplastic nodules of extratesticular Leydig cells. PMID:1778231

  20. [Premature ovarian failure].

    PubMed

    Assumpção, Carmen Regina Leal de

    2014-03-01

    This article is a review on different aspects of premature ovarian failure (POF) defined as the development of hypogonadism in women before 40 years of age. The review will discuss the etiopathogeny, autoimmune and iatrogenic causes, abnormalities of chromosome X, as well as clinical manifestations, diagnosis, and treatment. Most of the women with this disorder do not have menstrual history, specific of POF development, but infertility associated with the diagnosis is the most problematic aspect of the disease. PMID:24830590

  1. Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men.

    PubMed

    Borst, Stephen E; Yarrow, Joshua F

    2015-06-15

    The value of testosterone replacement therapy (TRT) for older men is currently a topic of intense debate. While US testosterone prescriptions have tripled in the past decade (9), debate continues over the risks and benefits of TRT. TRT is currently prescribed for older men with either low serum testosterone (T) or low T plus accompanying symptoms of hypogonadism. The normal range for serum testosterone is 300 to 1,000 ng/dl. Serum T ≤ 300 ng/dl is considered to be low, and T ≤ 250 is considered to be frank hypogonadism. Most experts support TRT for older men with frank hypogonadism and symptoms. Treatment for men who simply have low T remains somewhat controversial. TRT is most frequently administered by intramuscular (im) injection of long-acting T esters or transdermally via patch or gel preparations and infrequently via oral administration. TRT produces a number of established benefits in hypogonadal men, including increased muscle mass and strength, decreased fat mass, increased bone mineral density, and improved sexual function, and in some cases those benefits are dose dependent. For example, doses of TRT administered by im injection are typically higher than those administered transdermally, which results in greater musculoskeletal benefits. TRT also produces known risks including development of polycythemia (Hct > 50) in 6% of those treated, decrease in HDL, breast tenderness and enlargement, prostate enlargement, increases in serum PSA, and prostate-related events and may cause suppression of the hypothalamic-pituitary-gonadal axis. Importantly, TRT does not increase the risk of prostate cancer. Putative risks include edema and worsening of sleep apnea. Several recent reports have also indicated that TRT may produce cardiovascular (CV) risks, while others report no risk or even benefit. To address the potential CV risks of TRT, we have recently reported via meta-analysis that oral TRT increases CV risk and suggested that the CV risk profile for im TRT

  2. Recent advances in the understanding and management of delayed puberty.

    PubMed

    Wei, Christina; Crowne, Elizabeth Clare

    2016-05-01

    Delayed puberty, especially in boys, is a common presentation in paediatrics. Recent advances have improved our understanding of the neuroendocrine, genetic and environmental factors controlling pubertal development, and hence inform the pathophysiology of delayed puberty. The discovery of kisspeptin signalling through its receptor identified neuroendocrine mechanisms controlling the gonadotrophin-releasing hormone (GnRH) pulse generator at the onset of puberty. Genetic mechanisms from single gene mutations to single nucleotide polymorphism associated with delayed puberty are being identified. Environmental factors, including nutritional factors and endocrine disruptors, have also been implicated in changes in secular trends and abnormal timing of puberty. Despite these advances, the key clinical question is to distinguish delayed puberty associated with an underlying pathology or hypogonadism from constitutional delay in growth and puberty, which remains challenging as biochemical tests are not always discriminatory. The diagnostic accuracies of newer investigations, including 36-hour luteinising hormone releasing hormone (LHRH) tests, GnRH-agonist tests, antimullerian hormone and inhibin-B, require further evaluation. Sex hormone replacement remains the main available treatment for delayed puberty, the choice of which is largely dictated by clinical practice and availability of the various sex steroid preparations. Spontaneous reversal of hypogonadism has been reported in boys with idiopathic hypogonadotrophic hypogonadism after a period of sex steroid treatment, highlighting the importance of reassessment at the end of pubertal induction. Novel therapies with a more physiological basis such as gonadotrophins or kisspeptin-agonist are being investigated for the management of hypogonadotrophic hypogonadism. Careful clinical assessment and appreciation of the normal physiology remain the key approach to patients with delayed puberty. PMID:26353794

  3. Chromosome banding studies in two patients with XXXXY syndrome.

    PubMed Central

    Levy, C L; Sparkes, R S; Carlson, H E

    1978-01-01

    In 2 adult male patients with 49 chromosomes, an XXXXY sex chromosome constitution was confirmed by trypsin-Giemsa banding sites. Clinical findings as well as fingerprint ridge counts were typical of the syndrome. Primary hypogonadism was documented by finding low serum testosterone and raised serum LH and FSH levels. Several radiological abnormalities, not previously described in this syndrome, were seen in 1 patient. Images PMID:568665

  4. Impaired pubertal development and testicular hormone function in males with sickle cell anemia.

    PubMed

    Martins, Paulo Roberto Juliano; Kerbauy, José; Moraes-Souza, Helio; Pereira, Gilberto de Araújo; Figueiredo, Maria Stella; Verreschi, Ieda Therezinha

    2015-01-01

    Changes in weight/height ratio, delayed sexual maturation, hypogonadism and impaired fertility have been demonstrated in sickle cell disease (SCD). This study aimed to evaluate the clinical and laboratory views of the Leydig cells function after stimulation with hCG in adults with sickle cell disease. We studied 15 patients with SCD (18 to 40 years; median=27 years old), fourteen homozygous S, and one with SC disease. The control group, composed by adult males, was divided into two groups: I - 10 relatives (18-39 years, median=26 years) with the same socioeconomic level of the patients, and II - 9 normal individuals (23-28, median=31 years) randomly chosen. Clinically it was observed a slight degree of malnutrition, important puberty delay, rarefaction of chest, underarm and pubic hair, and important reduction of the testis and penis size, featuring a mild hypogonadism in patients with SCD. The hormonal level assessment of testosterone at baseline and at 24, 48 and 72 h after hCG stimulation showed no significant differences between the groups studied. We can presume that adult men with SCD showed clinical hypoandrogenism with normal testicular hormonal function, a fact inconsistent with the hypothesis of primary hypogonadism. PMID:25190051

  5. Male gonadal function in coeliac disease: 1. Sexual dysfunction, infertility, and semen quality.

    PubMed

    Farthing, M J; Edwards, C R; Rees, L H; Dawson, A M

    1982-07-01

    The prevalence of hypogonadism, sexual dysfunction and abnormalities of semen quality was determined in 28 consecutive males with coeliac disease. These observations were related to jejunal morphology and nutritional status, and were compared with findings in 19 men with Crohn's disease of similar age and nutritional status. Two of the 28 coeliacs (7%) had clinical evidence of hypogonadism but impotence and decreased sexual activity occurred more commonly, the latter apparently improving after gluten withdrawal. Of the married coeliacs, 19% had infertile marriages, a value greater than expected in the general population. Hypogonadism and sexual dysfunction were not detected in our patients with Crohn's disease. Seminal analysis in coeliacs revealed marked abnormalities of sperm morphology and motility, but only the former appeared to improve after gluten withdrawal. Similar abnormalities, however, were also detected in patients with Crohn's disease, although, unlike the coeliacs, 46% also had reduced concentrations of spermatozoa. Semen quality in coeliac disease could not be clearly related to general or specific (serum vitamin B(12) and red cell folate) nutritional deficiencies or to fertility, although sperm motility was markedly reduced in two of the three coeliacs with infertile marriages. The presence of antisperm antibodies did not appear to be an important aetiological factor in male infertility in coeliac disease. The pathogenesis of infertility and sexual dysfunction in coeliac disease remains unclear, suggesting that factors such as endocrine dysfunction or other specific nutritional deficiency may be involved. PMID:7200931

  6. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    SciTech Connect

    Faraco, J.; Francke, U.; Toledo, S.

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  7. The laboratory diagnosis of testosterone deficiency.

    PubMed

    Paduch, Darius A; Brannigan, Robert E; Fuchs, Eugene F; Kim, Edward D; Marmar, Joel L; Sandlow, Jay I

    2014-05-01

    The evaluation and treatment of hypogonadal men has become an important part of urologic practice. Fatigue, loss of libido, and erectile dysfunction are commonly reported, but nonspecific symptoms and laboratory verification of low testosterone (T) are an important part of evaluation in addition to a detailed history and physical examination. Significant intraindividual fluctuations in serum T levels, biologic variation of T action on end organs, the wide range of T levels in human serum samples, and technical limitations of currently available assays have led to poor reliability of T measurements in the clinical laboratory setting. There is no universally accepted threshold of T concentration that distinguishes eugonadal from hypogonadal men; thus, laboratory results have to be interpreted in the appropriate clinical setting. This review focuses on clinical, biological, and technological challenges that affect serum T measurements to educate clinicians regarding technological advances and limitations of the currently available laboratory methods to diagnose hypogonadism. A collaborative effort led by the American Urological Association between practicing clinicians, patient advocacy groups, government regulatory agencies, industry, and professional societies is underway to provide optimized assay platforms and evidence-based normal assay ranges to guide clinical decision making. Until such standardization is commonplace in clinical laboratories, the decision to treat should be based on the presence of signs and symptoms in addition to serum T measurements. Rigid interpretation of T ranges should not dictate clinical decision making or define coverage of treatment by third party payers. PMID:24548716

  8. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

    PubMed Central

    Hwang, Kathleen; Miner, Martin

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism. PMID:25652628

  9. The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

    PubMed Central

    Sheridan, Molly B.; Wohler, Elizabeth; Batista, Denise A. S.; Applegate, Carolyn; Hoover-Fong, Julie

    2015-01-01

    Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC). Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified. PMID:26664771

  10. Review of health risks of low testosterone and testosterone administration

    PubMed Central

    Jia, Huanguang; Sullivan, Charles T; McCoy, Sean C; Yarrow, Joshua F; Morrow, Matthew; Borst, Stephen E

    2015-01-01

    Hypogonadism is prevalent in older men and testosterone replacement therapy (TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to a lack of large-scale randomized clinical trials directly comparing the health risks of untreated hypogonadism vs long-term use of TRT. Meta-analyses of clinical trials of TRT as of 2010 have identified three major adverse events resulting from TRT: polycythemia, an increase in prostate-related events, and a slight reduction in serum high-density lipoprotein cholesterol. There are other purported health risks but their incidence can be neither confirmed nor denied based on the small number of subjects that have been studied to date. Furthermore, subsequent literature is equivocal with regard to the safety and utility of TRT and this topic has been subject to contentious debate. Since January 2014, the United States Food and Drug Administration has released two official announcements regarding the safety of TRT and clinical monitoring the risks in TRT users. Additionally, the health risks related to the clinical presentation of low or declining testosterone levels not been resolved in the current literature. Because TRT is prescribed in the context of putative risks resulting from reduced testosterone levels, we reviewed the epidemiology and reported risks of low testosterone levels. We also highlight the current information about TRT utilization, the risks most often claimed to be associated with TRT, and current or emerging alternatives to TRT. PMID:25879005

  11. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

    PubMed

    Kelsey, Thomas W; Li, Lucy Q; Mitchell, Rod T; Whelan, Ashley; Anderson, Richard A; Wallace, W Hamish B

    2014-01-01

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism. PMID:25295520

  12. Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome.

    PubMed

    Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Yehiely-Cohen, Ravit; Maneschi, Elena; Gacci, Mauro; Carini, Marco; Adorini, Luciano; Vannelli, Gabriella B; Maggi, Mario

    2012-10-01

    In the male, metabolic syndrome (MetS) is associated to an increased risk of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). A recently established rabbit model of high fat diet (HFD)-induced MetS showed hypogonadism and the presence of prostate gland alterations, including inflammation, hypoxia and fibrosis. The present study investigated whether HFD-induced MetS might also alter bladder structure and function. Testosterone and the farnesoid X receptor (FXR) agonist INT-747, were evaluated for possible effects on HFD bladder. MetS rabbits develop bladder alterations, including fibrosis (reduced muscle/fiber ratio), hypoxia [2-fold increase as compared to regular diet (RD) group], low-grade inflammation (increased leukocyte infiltration and inflammatory markers) and RhoA/ROCK hyperactivity. Bladder strips from HFD rabbits, pre-contracted with carbachol, showed an overactive response to the selective ROCK inhibitor Y-27632. All these HFD-induced bladder alterations were partially blunted by testosterone and almost completely reverted by INT-747. Both treatments prevented some MetS features (glucose intolerance and visceral fat increase), thus suggesting that their effects on bladder could be ascribed to an improvement of the metabolic and/or hypogonadal state. However, a pathogenetic role for hypogonadism has been ruled out as GnRH analog-induced hypogonadal rabbits, fed a regular diet, did not show any detectable bladder alterations. In addition, INT-747 did not revert the MetS-induced hypogonadal state. FXR mRNA was highly expressed in rabbit bladder and positively associated with visceral fat increase. A direct effect of INT-747 on bladder smooth muscle was further suggested by inhibition of RhoA/ROCK-mediated activity by in vitro experiments on isolated cells. In conclusion, HFD-related MetS features are associated to bladder derangements, which are ameliorated by testosterone or INT-747 administration. INT-747 showed the most marked

  13. Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells.

    PubMed

    Vignozzi, Linda; Cellai, Ilaria; Santi, Raffaella; Lombardelli, Letizia; Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Logiodice, Federica; Carini, Marco; Nesi, Gabriella; Gacci, Mauro; Piccinni, Marie-Pierre; Adorini, Luciano; Maggi, Mario

    2012-07-01

    Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by T-cells, an increase in IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on testosterone cells [corrected]. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses. PMID:22562653

  14. Endocrine dysfunction in patients of leprosy

    PubMed Central

    Singh, Rohit Kumar; Bhasin, Rohit; Bisht, Y. S.; Kumar, K. V. S. Hari

    2015-01-01

    Background: Leprosy is a chronic granulomatous disease and affects many internal organs in addition to the skin and peripheral nerves. Endocrine dysfunction is often silent and is often missed in patients of leprosy leading to significant morbidity. We studied the presence of occult endocrine disorders in leprosy patients and compared the same with disease parameters. Materials and Methods: We evaluated 40 patients of leprosy (aged 18–70 years, any duration) in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, gonadal function, and dynamic testing was done when deemed necessary. The participants were divided into two groups: Group 1 (Leprosy, n = 40) and Group 2 (Controls, n = 20) and the data were analyzed with appropriate statistical tests. Results: The study participants (35 males, 5 females) had a mean age of 36.4 ± 11.3 years, and duration of the disease was 2.5 ± 5.5 years. Eleven out of 40 patients showed results consistent with an endocrine disorder, including subclinical hypothyroidism (n = 4), sick euthyroid syndrome (n = 3), growth hormone (GH) deficiency (n = 2), primary hypogonadism (n = 2) and secondary hypogonadism in one patient. One patient had partial hypopituitarism (GH deficiency and secondary hypogonadism) and none of the controls showed any hormonal dysfunction. Testosterone levels showed inverse correlation with the number of skin patches (P = 0.0006). Conclusion: Occult endocrine dysfunction is seen in a quarter of patients with leprosy. Thyroid and gonadal axes abnormalities are common, and the severity is more in lepromatous forms of the disease. Further large studies are required to confirm the findings observed in our study. PMID:25932392

  15. Kallmann syndrome patient with gender dysphoria, multiple sclerosis, and thrombophilia.

    PubMed

    Renukanthan, Aniruthan; Quinton, Richard; Turner, Benjamin; MacCallum, Peter; Seal, Leighton; Davies, Andrew; Green, Richard; Evanson, Jane; Korbonits, Márta

    2015-11-01

    One of the challenging issues in patients with complex problems is that the various diseases and their treatment can influence each other and present unusual hurdles in management. We investigated one such complex case. A 34-year-old XY male presented with azoospermia, detected on semen analysis for pre-orchidectomy sperm banking. He had a 20-year history of gender dysphoria and bilateral breast swelling. The patient suffered a deep vein thrombosis at the age of 19 years. Examination confirmed clinical features of Kallmann syndrome including unilateral cryptorchidism, micropenis, congenital anosmia, and bimanual synkinesis (mirror movements), with reduced serum testosterone and normal gonadotropin levels demonstrating hypogonadotropic hypogonadism. MRI showed missing olfactory bulbs. Osteopenia and reduced vitamin D levels of 21 nmol/L were identified. He was found to harbor a heterozygous factor-V-Leiden mutation. The genetic basis of Kallmann syndrome remains unknown: his screening tests were negative for mutations in CHD7, FGF8, FGFR1, GNRH1, GNRHR, HS6ST1, KAL1, KISS1R, KISS1, NELF, PROK2, PROKR2, TAC3, and TACR3. The patient initially declined testosterone therapy with a view to undergo gender reassignment. Over the next 2 years, the patient experienced recurrent episodes of weakness and paresthesia, associated with classical MRI appearances of multiple sclerosis-related demyelination in the spinal cord and brain. Although it was difficult to elucidate an association between the patient's gender dysphoria and untreated congenital hypogonadism, his desire to become female together with his co-existing thrombophilia, presented challenges to the administration of hormone treatment. Furthermore, we have considered an association between multiple sclerosis and hypogonadotropic hypogonadism. PMID:25739677

  16. Influence of ghrelin and adipocytokines on bone mineral density in adolescent female athletes with amenorrhea and eumenorrheic athletes.

    PubMed

    Russell, Melissa; Misra, Madhusmita

    2010-01-01

    Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes. PMID:20956863

  17. Zinc in growth and development and spectrum of human zinc deficiency.

    PubMed

    Prasad, A S

    1988-10-01

    Growth retardation is seen in experimental animals as a result of severe dietary restriction of several essential trace elements. However, in humans, the effect of zinc deficiency is most pronounced. Growth failure and hypogonadism in males, related to a deficiency of zinc, have been recognized in many developing countries. A mild deficiency of zinc, affecting growth and development in children and adolescents, has been reported from developed countries as well. Zinc deficiency in humans may manifest as severe, moderate, or mild. The manifestations of severe zinc deficiency include bullous pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections due to cell-mediated immune dysfunctions, hypogonadism in males, neurosensory disorders, and problems with healing of ulcers. This condition can be fatal. A moderate level of zinc deficiency has been reported in a variety of conditions. Clinical manifestations include growth retardation and male hypogonadism in adolescence, rough skin, poor appetite, mental lethargy, delayed wound healing, cell-mediated immune dysfunctions, and abnormal neurosensory changes. A mild level of zinc deficiency may manifest with decreased serum testosterone level and oligospermia in males, decreased lean body mass, hyper-ammonemia, neurosensory changes, anergy, decreased serum thymulin activity, and decreased IL-2 activity. Although the clinical aspects of severe and moderate levels of zinc deficiency are well known, the recognition of mild levels of zinc deficiency has been difficult. Currently plasmas zinc appears to be the most widely used parameter for assessment of human zinc status, and it is known to be decreased in cases of severe and moderate deficiency of zinc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3053862

  18. Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects

    PubMed Central

    Delfino, Michele; Elia, Jlenia; Benedetti, Francesco; Alesi, Laura; Chessa, Luciana; Mazzilli, Fernando

    2015-01-01

    Summary We report the case of a 19-year-old boy, presenting several congenital malformations (facial dysmorphisms, cardiac and musculoskeletal abnormalities), mental retardation, recurrent respiratory infections during growth and delayed puberty. Although previously hospitalised in other medical centres, only psychological support had been recommended for this patient. In our department, genetic, biochemical/hormonal and ultrasound examinations were undertaken. The karyotype was 49,XXXXY, a rare aneuploidy with an incidence of 1/85 000–100 000, characterised by the presence of three extra X chromosomes in phenotypically male subjects. The hormonal/biochemical profile showed hypergonadotropic hypogonadism, insulin resistance and vitamin D deficiency. The patient was then treated with testosterone replacement therapy. After 12 months of treatment, we observed the normalisation of testosterone levels. There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction and the normalisation of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context. Learning points In cases of plurimalformative syndrome, cognitive impairment, recurrent infections during growth and, primarily, delayed puberty, it is necessary to ascertain as soon as possible whether the patient is suffering from hypogonadism or metabolic disorders due to genetic causes. In our case, the diagnosis of hypogonadism, and then of 49,XXXXY syndrome, was unfortunately made only at the age of 19 years.The testosterone replacement treatment, even though delayed, induced positive effects on: i) development of the reproductive system, ii) regulation of the metabolic profile and iii) interaction with the social environment and context.However, earlier and timely hormonal replacement treatment could probably have improved the quality of life of this subject and his family. PMID:26767114

  19. Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

    PubMed

    Yang, Susan Q; DeGuire, Jason R; Lavery, Paula; Mak, Ivy L; Weiler, Hope A; Santosa, Sylvia

    2016-05-01

    We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs. PMID:27101759

  20. Influence of Ghrelin and Adipocytokines on Bone Mineral Density in Adolescent Female Athletes with Amenorrhea and Eumenorrheic Athletes

    PubMed Central

    Russell, Melissa; Misra, Madhusmita

    2013-01-01

    Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and non-athletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotrophin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes. PMID:20956863

  1. AB155. Clinical presentation and its relationship with chromosomal abnormalities in Turner syndrome

    PubMed Central

    Thao, Bui Phuong; Dung, Vu Chi; Khanh, Nguyen Ngoc; Ngoc, Can Thi Bich; Hoan, Nguyen Thi; Phuong, Nguyen Thi

    2015-01-01

    Background Turner syndrome is a relatively common chromosomal disorder. The disease affects only females, causing hypogonadism and short stature. Early treatment can improve short stature and hypogonadism. The study aims to describe chromosomal abnormalities, clinical characteristics and its relationship with chromosomal abnormalities in patients with Turner syndrome. Methods A total of 213 patients with Turner syndrome diagnosed in National Hospital of Pediatrics, Hanoi. A cross section study was used. Results Mean age on diagnosis was 12.2±4.9 years. Monosomy 45,XO occupied 54,31%; 45,X/46,XX was seen in 14.66%; 27.59% had structural disorders of chromosome X. Short stature was found in all patients aged more than 15 years. Severity of short stature and percentage of patients with short stature went up with age. There was no difference in term of height between karyotype groups. In group aged ≥12 years, 95.2% of cases had hypogonadism. Other symptoms frequently seen were nail hypoplasia (77.4%), cubitus valgus (74.7%), broad chest (69.2%)/abnormalities in face and neck were epicanthic fold (55.6%), low posterior line (51.3%), excessive skin in the back of the neck/webbed neck (42.5%). In a group aged <1 year, lymphoedema of hands/feet, epicanthic fold, broad chest, cubitus valgus were found in 100%. Majority of symptoms, congenital defects of heart/kidney were seen more frequently in 45,X group. Conclusions Lymphoedema of hands/feet in infants, low growth velocity, delayed puberty, abnormalities in face and neck, and other symptoms should be checked to early diagnose and treat Turner syndrome. Patients with 45,X had more severe presentation compared to patients with 45,X/46,XX and structural abnormalities of X chromosome.

  2. Treatment of Anabolic-Androgenic Steroid Dependence: Emerging Evidence and Its Implications

    PubMed Central

    Kanayama, Gen; Brower, Kirk J.; Wood, Ruth I.; Hudson, James I.; Pope, Harrison G.

    2010-01-01

    Currently, few users of anabolic-androgenic steroids (AAS) seek substance-abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population—those who initiated AAS as youths in the 1980s—are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance-abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body-image disorders such as “muscle dysmorphia” may become dependent on AAS for their anabolic effects; these body-image disorders may respond to psychological therapies or pharmacologic treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. PMID:20188494

  3. Association of Wolfram syndrome with Fallot tetralogy in a girl.

    PubMed

    Korkmaz, Hüseyin A; Demir, Korcan; Hazan, Filiz; Yıldız, Melek; Elmas, Özlem N; Özkan, Behzat

    2016-06-01

    Wolfram syndrome (DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a rare neurodegenerative disorder. Mutations of the WFS1 (wolframin) on chromosome 4 are responsible for the clinical manifestations in majority of patients with Wolfram syndrome. Wolfram syndrome is also accompanied by neurologic and psychiatric disorders, urodynamic abnormalities, restricted joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotrophic hypogonadism in males and diabetic microvascular disorders. There are very limited data in the literature regarding cardiac malformations associated in children with Wolfram syndrome. A 5-year-old girl with Wolfram syndrome and tetralogy of Fallot is presented herein. PMID:27164349

  4. Multiglandular Hormone Deficiency in a Patient with Systemic Capillary Leak Syndrome

    PubMed Central

    Then, Cornelia; Ritzel, Katrin; Seibold, Christa; Mann, Johannes F. E.; Reincke, Martin

    2015-01-01

    Systemic capillary leak syndrome (SCLS) is a rare but potentially fatal disorder characterized by a loss of fluid and proteins into the interstitial space leading to intravascular hypovolemia up to the point of hypovolemic shock. We report the case of a 64-year-old man with SCLS and multiple hormone abnormalities (primary hypothyroidism, hypoadrenalism, and hypogonadism), deficiency of hormone binding globulins, and hypogammaglobulinemia. The patient was successfully treated with intravenous immunoglobulins, theophylline, and terbutaline. Strikingly, with the dissolution of peripheral edema, hormone levels improved. To our knowledge, this is the first reported case of SCLS associated with polyglandular abnormalities. PMID:25685157

  5. Male sexual dysfunction in Asia

    PubMed Central

    Ho, Christopher CK; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-01-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  6. [Endocrine disorders and osteoporosis].

    PubMed

    Kinoshita, Yuka

    2015-10-01

    Secondary osteoporosis is a bone disease characterized by decreased bone mass that predisposes fractures due to underlying disorders or medication. Disorders of the endocrine system, such as primary hyperparathyroidism, hyperthyroidism, hypogonadism, growth hormone deficiency, Cushing's syndrome, and anorexia nervosa frequently cause secondary osteoporosis. In those diseases, hormone excess or deficiency affects functions of osteoblasts, osteocyte, and osteoclasts, leading to aberrant bone remodeling. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in most patients with secondary osteoporosis along with treatment of the underlying disease. PMID:26529938

  7. [Chronic kidney disease associated with Poems syndrome: Report of one case].

    PubMed

    Vega, Jorge

    2016-04-01

    POEMS syndrome is characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes. We report a woman with the syndrome, who had peripheral polyneuropathy, osteosclerotic myeloma, monoclonal IgA elevation, hypothyroidism, hypogonadotrophic hypogonadism, hyperprolactinemia, adrenal insufficiency, hepatosplenomegaly, lymphadenopathy, thyroid and parotid enlargement, Castleman’s disease, papilledema, stiff and hyperpigmented skin, white nails, clubbing, ascites and chronic diarrhea. She had also a nephropathy characterized by microscopic hematuria, proteinuria, renal insufficiency and a unilateral kidney retraction. She was treated with melphalan and prednisone, achieving remission of the disease and nephropathy. She survived twelve years and died due to a myocardial infarction 20 years after POEMS diagnosis. PMID:27401385

  8. Prader-Labhart-Willi syndrome.

    PubMed

    Anavi, Y; Mintz, S M

    1990-01-01

    Prader-Labhart-Willi Syndrome is a complex, multisystem sporadic disorder which presents during childhood and proceeds into adulthood. The major features include infantile hypotonia, developmental delay, hypogonadism with abnormal sexual maturation, mental retardation and behavior abnormalities, short stature with small hands and feet, massive obesity with diabetes mellitus, dysmorphic facial features, and marked dental caries and enamel hypoplasia. Recently, a deletion of chromosome 15 has been found in a large percentage of these patients, but the exact cause and genetic transmission has not yet been determined. Two cases of Prader-Labhart-Willi Syndrome are presented with emphasis on the differential diagnosis of enamel hypoplasia associated with sexual maturation. PMID:2278477

  9. [GnRH analogs in gynecology. Possibilities for therapeutic use].

    PubMed

    Niesert, S

    1990-09-10

    Gonadotropin releasing hormone (GnRH) agonists are synthetic peptide analogues of the natural gonadotropin releasing hormone with a stronger and more prolonged effect than the natural GnRH. Repeated administration of GnRH agonists induces pituitary desensitization followed by a decrease in gonadotropin secretion and estradiol synthesis. Thus reversible hypogonadotropic hypogonadism is produced. Consequently, estrogen-dependent diseases can be treated successfully with GnRH analogues. The therapeutic results obtained in patients with endometriosis, leiomyoma, pubertas praecox, and metastatic breast cancer are discussed. Furthermore the contraceptive properties of GnRH analogues, and combination treatment with HMG to induce ovulation is reviewed. PMID:2262188

  10. Male sexual dysfunction in Asia.

    PubMed

    Ho, Christopher Ck; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-07-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  11. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  12. Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single‐Use Autoinjector: A Phase II Study

    PubMed Central

    Kaminetsky, Jed; Swerdloff, Ronald S.

    2015-01-01

    Abstract Introduction Hypogonadism is one of the most common male endocrine problems. Although many treatments are currently available, unmet need exists for new testosterone (T) replacement therapies that are simple to administer and use, are safe, and mimic physiologic T levels. Aim The study aim was to determine the pharmacokinetics (PK), safety, and tolerability of T enanthate (TE) administered via a novel single‐use autoinjector system, which was designed to eject high‐viscosity solutions from a prefilled syringe fitted with a five‐eighths‐inch 27‐gauge needle. Methods Thirty‐nine men with hypogonadism entered this dose‐finding, open‐label, parallel‐group study. Patients were washed out of their topical T regimens and randomized to receive 50 or 100 mg of subcutaneous (SC) TE weekly. The reference group were patients with hypogonadism who were maintained on standard 200‐mg intramuscular (IM) TE. Main Outcome Measure The primary outcome measure was the PK profile of SC TE, analyzed in reference to T levels used by the Food and Drug Administration to approve T products. Secondary outcome measures were safety and tolerability assessments. Results Both doses of SC TE achieved normal average concentrations of serum T within a 168‐h dosing interval after injection. Concentration ranges were similar at all time points following 50‐mg SC TE injections and following the third injection in the 100‐mg arm. Mean steady‐state T concentration at week 6 was 422.4 and 895.5 ng/dL for the 50‐ and 100‐mg SC TE arms, respectively. SC TE demonstrated PK dose proportionality. SC TE restored normal serum T with low variation relative to 200‐mg IM without clinically significant adverse events. Conclusions Administration of TE via this novel injection system restored T levels to normal range in men with hypogonadism. SC TE dosed weekly demonstrated steady, dose‐proportional measures of exposure and was well‐tolerated. Kaminetsky J, Jaffe JS

  13. The endocrine pharmacology of testosterone therapy in men

    NASA Astrophysics Data System (ADS)

    Oettel, Michael

    The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.

  14. Endocrine effects of anorexia nervosa.

    PubMed

    Miller, Karen Klahr

    2013-09-01

    A key feature of anorexia nervosa, a disease primarily psychiatric in origin, is chronic starvation, which results in profound neuroendocrine dysregulation, including hypogonadism, relative growth hormone resistance, and hypercortisolemia. A recent area of investigation is appetite hormone dysregulation. Whether such dysregulation is compensatory or plays a role in the pathophysiology of anorexia nervosa is incompletely understood. The primary therapy for anorexia remains psychiatric, and endocrine abnormalities tend to improve with weight restoration, although residual endocrine dysfunction can occur. In addition, therapies directed at specific complications have been a particular focus of research. PMID:24011884

  15. [Gonadal function after treatment for a childhood or adolescent cancer].

    PubMed

    Rousset-Jablonski, Christine; Giscard d'Estaing, Sandrine; Bernier, Valérie; Lornage, Jacqueline; Thomas-Teinturier, Cécile; Aubier, Françoise; Faure-Conter, Cécile

    2015-01-01

    Due to high cure rate in childhood and adolescent cancer, fertility preservation is a major concern. Chemotherapy, radiotherapy and surgery may alter gonadal function, and uterine cavity in women. In women, combined toxicity affecting both endocrine function and ovulation are observed leading to premature ovarian insufficiency. In men, spermatogenesis is frequently affected whereas endocrine function is almost always preserved. The current article focuses on investigations concerning gonadal function after treatment for a cancer during childhood or adolescence and treatment of subsequent infertility or hypogonadism. Nevertheless, those therapeutic are still limited and pretherapeutic preservation of fertility is preferred when possible. PMID:25890827

  16. Two interesting cases highlighting an oblivious specialty of psychoneuroendocrinology.

    PubMed

    Hari Kumar, K V S; Dhull, Pawan; Somasekharan, Manoj; Seshadri, K

    2012-01-01

    Psychoneuroendocrinology deals with the overlap disorders pertaining to three different specialties. Awareness about the somatic manifestations of psychiatric diseases and vice versa is a must for all the clinicians. The knowledge of this interlinked specialty is essential because of the obscure presentation of certain disorders. Our first case was treated as depressive disorder, whereas the diagnosis was hypogonadism with empty sella. Our second patient was managed as schizophrenia and the evaluation revealed bilateral basal ganglia calcification and a diagnosis of Fahr's disease. We report these cases for their unusual presentation and to highlight the importance of this emerging specialty. PMID:23806989

  17. [Syndactylia associated with multiple malformation syndromes. Observation of a new symptomatologic complex in 3 brothers].

    PubMed

    Garau, A; Nurchi, A M; Melis, P; Frau, G; Costa, G

    1988-01-01

    Hand and feet malformations are often part of complex malformation associations. The present paper reports on a family whose three sibs (two males and one female) are affected with symmetric soft tissue syndactyly involving both fingers and toes, fifth finger clinodactyly, a pattern of dysmorphism including down slanting palpebral fissures, long flat nasal saddle, out turned nostril openings ("Greek warrior helmet"-like profile), dysplastic teeth, and, in addition, severe growth retardation, microcephaly, severe mental deficiency with immaturity of cerebral activity of EEG, hypergonadotropic hypogonadism and some skeletal anomalies. All cases show large secondary constriction in one of the chromosome 1 pair (1qh+). PMID:2845373

  18. Hyperprolactinemia and prolactinomas.

    PubMed

    Mancini, Tatiana; Casanueva, Felipe F; Giustina, Andrea

    2008-03-01

    Any process interfering with dopamine synthesis, its transport to the pituitary gland, or its action at the level of lactotroph dopamine receptors can cause hyperprolactinemia. As described in this article, considering the complexity of prolactin regulation, many factors could cause hyperprolactinemia, and hyperprolactinemia can have clinical effects not only on the reproductive axis. Once any drug effects are excluded, prolactinomas are the most common cause of hyperprolactinemia. The most frequent symptom is hypogonadism in both genders. Medical and surgical therapies generally have excellent results, and most prolactinomas are well controlled or even cured in some cases. PMID:18226731

  19. [Osteoporosis in males].

    PubMed

    Audran, M; Legrand, E; Chappard, D; Bigorgne, J C; Basle, M F

    2000-09-01

    A shorter life expectancy, a higher peak bone mass and the absence of distinct menopause equivalent explain the lower incidence of osteoporotic fractures in men. In contrast to women, osteoporosis in younger men is in most cases secondary. Causes such as prolonged glucocorticoid therapy, ethanol abuse, hypogonadism and gastrointestinal disorders are now well recognized. The impact of cigarette smoking, low calcium intake, vitamin D deficiency, hypercalciuria and thyrotoxicosis is more controversial but seems to constitute real risk factors for bone loss. Furthermore increased propensity to fall also plays a major role in fracture risk, particularly in alcoholic patients and in elderly men with neurologic disorders. PMID:11033475

  20. Bardet-Biedl syndrome: A rare genetic disease

    PubMed Central

    Valverde, Diana; Castro-Sánchez, Sheila; Álvarez-Satta, María

    2013-01-01

    Bardet-Biedl syndrome (BBS) is a rare multisystem genetic disease, with high phenotypic and genetic heterogeneity. Rod-cone dystrophy, obesity, polydactyly, hypogonadism, cognitive impairment and renal abnormalities have been established as primary features. There are 17 BBS genes (BBS1-BBS17) described to date, which explain 70–80% of the patients clinically diagnosed, therefore more BBS genes remain to be identified. BBS belongs to a group of diseases known as ciliopathies. In general, ciliopathies and BBS in particular share a partial overlapping phenotype that makes them complicated to diagnose. We present an up-to-date review including clinical, epidemiologic and genetic aspects of the syndrome.

  1. An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

    PubMed Central

    Kuechler, Amla; Hauffa, Berthold P; Köninger, Angela; Kleinau, Gunnar; Albrecht, Beate; Horsthemke, Bernhard; Gromoll, Jörg

    2010-01-01

    Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C>A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163 kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance. PMID:20087398

  2. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use.

    PubMed

    McBride, J Abram; Coward, Robert M

    2016-01-01

    The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use. PMID:26908067

  3. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

    NASA Technical Reports Server (NTRS)

    Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

    2003-01-01

    Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

  4. Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation.

    PubMed

    Barnum, Jessie L; Petryk, Anna; Zhang, Lei; DeFor, Todd E; Baker, K Scott; Steinberger, Julia; Nathan, Brandon; Wagner, John E; MacMillan, Margaret L

    2016-08-01

    A number of endocrinopathies have been described after hematopoietic cell transplantation (HCT), but data are limited in patients with Fanconi anemia (FA). We report several endocrine-based disorders in a cohort of 44 patients with FA after HCT compared with both 74 patients who received HCT for hematologic malignancies and with 275 healthy controls. Endocrinopathies assessed included hypothyroidism, hypogonadism, short stature, dyslipidemia, insulin resistance, abnormalities in body composition, and bone health. Most (86%) patients with FA had at least 1 endocrinopathy, with 11% having 3 or more. Hypothyroidism was seen in 57%, hypogonadism in 27%, short stature in 50%, and reduced total body and lumbar spine bone mineral density (BMD) (height adjusted Z-score < -1) in 57% and 21%, respectively. Vitamin D deficiency was seen in 71%. Short stature was associated with younger age at HCT and gonadal failure was associated with older age at HCT. Insulin resistance was associated with increased percent fat mass and increased android/gynoid ratio by dual energy X-ray absorptiometry. Hypothyroidism, short stature, and reduced total body BMD were more prevalent in patients with FA compared with patients with hematologic malignancies. We recommend an assessment before transplantation and close follow-up afterwards to ensure proper clinical management. Future studies should continue to explore the impact of HCT on endocrinopathies in FA patients. PMID:27180116

  5. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    PubMed Central

    McBride, J Abram; Coward, Robert M

    2016-01-01

    The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use. PMID:26908067

  6. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy. PMID:27050912

  7. Anti-Müllerian Hormone: A Valuable Addition to the Toolbox of the Pediatric Endocrinologist

    PubMed Central

    Josso, Nathalie; Rey, Rodolfo A.; Picard, Jean-Yves

    2013-01-01

    Anti-Müllerian hormone (AMH), secreted by immature Sertoli cells, provokes the regression of male fetal Müllerian ducts. FSH stimulates AMH production; during puberty, AMH is downregulated by intratesticular testosterone and meiotic germ cells. In boys, AMH determination is useful in the clinical setting. Serum AMH, which is low in infants with congenital central hypogonadism, increases with FSH treatment. AMH is also low in patients with primary hypogonadism, for instance in Down syndrome, from early postnatal life and in Klinefelter syndrome from midpuberty. In boys with nonpalpable gonads, AMH determination, without the need for a stimulation test, is useful to distinguish between bilaterally abdominal gonads and anorchism. In patients with disorders of sex development (DSD), serum AMH determination helps as a first line test to orientate the etiologic diagnosis: low AMH is indicative of dysgenetic DSD whereas normal AMH is suggestive of androgen synthesis or action defects. Finally, in patients with persistent Müllerian duct syndrome (PMDS), undetectable serum AMH drives the genetic search to mutations in the AMH gene, whereas normal or high AMH is indicative of an end organ defect due to AMH receptor gene defects. PMID:24382961

  8. In Search for a Common Pathway for Health Issues in Men--the Sign of a Holmesian Deduction.

    PubMed

    Aoun, Fouad; Albisinni, Simone; Chemaly, Anthony Kallas; Zanaty, Marc; Roumeguère, Thierry

    2016-01-01

    The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions. PMID:26838191

  9. Endocrine complications following pediatric bone marrow transplantation.

    PubMed

    Ho, Josephine; Lewis, Victor; Guilcher, Gregory M T; Stephure, David K; Pacaud, Danièle

    2011-01-01

    Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly. PMID:21823531

  10. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice

    PubMed Central

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  11. [Late endocrine and growth sequelae after cancer treatment in children].

    PubMed

    Birkebaek, N H; Helgestad, J E

    1994-08-01

    Growth and endocrinological disturbances are possible late side-effects of cancer treatment in childhood. These side-effects can be treated, thus their discovery is important. The side-effects particularly appear in the years following treatment with irradiation and/or alkylating chemotherapy. After irradiation of the brain or the neck the function of the thyroid and the parathyroid glands should be tested every third month the first year, and later on annually. Two years after the end of treatment, the patient should be examined for growth hormone deficiency. This examination should be carried out annually. One should be alert to symptoms of pubertas praecox the years prior to puberty. At the age when puberty is expected and thereafter one should look for signs of secondary hypogonadism. Primary hypogonadism may follow radiotherapy below the diaphragm and/or treatment with alkylating chemotherapeutics; further, reduced fertility in men and early menopause in women may follow these treatments. The bone structure of the face and the teeth may be damaged by radiation and chemotherapy, so therefore yearly examination by a dentist with specialty in this subject is recommended. Surgery in order to improve function may be a possibility. PMID:7832924

  12. GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis.

    PubMed

    Schorr-Lenz, A M; Alves, J; Henckes, N A C; Seibel, P M; Benham, A M; Bustamante-Filho, I C

    2016-09-01

    Hypogonadism is defined as the inadequate gonadal production of testosterone. Low serum testosterone leads to infertility by impairing spermatogenesis and reducing sperm count, however, the impact of hypogonadism in epididymal sperm maturation is poorly understood. From the testis, spermatozoa are transported into the epididymis where they find a specific microenvironment composed of a complex mixture of proteins that facilitate sperm storage and maturation. Inside the epididymal ductule, spermatozoa undergo several changes, resulting in their becoming capable of fertilizing eggs. Protein disulfide isomerases (PDIs) are known to participate in the folding and assembly of secreted proteins in the endoplasmic reticulum. However, little is known about the control and function of PDIs in the testis and epididymis, particularly during male development. The aim of this work was to compare the expression and distribution of PDI and PDIA3 (ERp57) in the testis and epididymis of healthy and GnRH-immunized boars. We detected higher amounts of PDIA3 and PDI in sperm preparations and fluid from the proximal regions of the epididymis of healthy boars. However, we observed an increase in PDIA3 expression in the testis and cauda epididymis in the immunocastrated group. GnRH-immunized boars showed a marked increase in PDI content in cauda spermatozoa and fluid, indicating a possible endocrine dysregulation of PDI. The results of our study suggest that PDIs are associated with epididymal sperm maturation and may be attractive candidates for monitoring male fertility. PMID:27323298

  13. MCM9 Mutations Are Associated with Ovarian Failure, Short Stature, and Chromosomal Instability

    PubMed Central

    Wood-Trageser, Michelle A.; Gurbuz, Fatih; Yatsenko, Svetlana A.; Jeffries, Elizabeth P.; Kotan, L. Damla; Surti, Urvashi; Ketterer, Deborah M.; Matic, Jelena; Chipkin, Jacqueline; Jiang, Huaiyang; Trakselis, Michael A.; Topaloglu, A. Kemal; Rajkovic, Aleksandar

    2014-01-01

    Premature ovarian failure (POF) is genetically heterogeneous and manifests as hypergonadotropic hypogonadism either as part of a syndrome or in isolation. We studied two unrelated consanguineous families with daughters exhibiting primary amenorrhea, short stature, and a 46,XX karyotype. A combination of SNP arrays, comparative genomic hybridization arrays, and whole-exome sequencing analyses identified homozygous pathogenic variants in MCM9, a gene implicated in homologous recombination and repair of double-stranded DNA breaks. In one family, the MCM9 c.1732+2T>C variant alters a splice donor site, resulting in abnormal alternative splicing and truncated forms of MCM9 that are unable to be recruited to sites of DNA damage. In the second family, MCM9 c.394C>T (p.Arg132∗) results in a predicted loss of functional MCM9. Repair of chromosome breaks was impaired in lymphocytes from affected, but not unaffected, females in both families, consistent with MCM9 function in homologous recombination. Autosomal-recessive variants in MCM9 cause a genomic-instability syndrome associated with hypergonadotropic hypogonadism and short stature. Preferential sensitivity of germline meiosis to MCM9 functional deficiency and compromised DNA repair in the somatic component most likely account for the ovarian failure and short stature. PMID:25480036

  14. Identification of a novel mutation confirms the implication of IFT172 (BBS20) in Bardet-Biedl syndrome.

    PubMed

    Schaefer, Elise; Stoetzel, Corinne; Scheidecker, Sophie; Geoffroy, Véronique; Prasad, Megana K; Redin, Claire; Missotte, Isabelle; Lacombe, Didier; Mandel, Jean-Louis; Muller, Jean; Dollfus, Hélène

    2016-05-01

    Bardet-Biedl syndrome (BBS; MIM 209900) is a recessive heterogeneous ciliopathy characterized by retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. So far, 20 BBS genes have been identified, with the last reported ones being found in one or very few families. Whole-exome sequencing was performed in a consanguineous family in which two affected children presented typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism and cognitive impairment) without any mutation identified in known BBS genes at the time of the study. We identified a homozygous splice-site mutation (NM_015662.2: c.4428+3A>G) in both affected siblings in the last reported BBS gene, namely, Intraflagellar Transport 172 Homolog (IFT172). Familial mutation segregation was consistent with autosomal recessive inheritance. IFT172 mutations were initially reported in Jeune and Mainzer-Saldino syndromes. Recently, mutations have also been found in isolated RP and Bardet-Biedl-like ciliopathy. This is the second report of IFT172 mutations in BBS patients validating IFT172 as the twentieth BBS gene (BBS20). Moreover, another IFT gene, IFT27, was already associated with BBS, confirming the implication of IFT genes in the pathogenesis of BBS. PMID:26763875

  15. Testosterone and benign prostatic hyperplasia

    PubMed Central

    Jarvis, Thomas R; Chughtai, Bilal; Kaplan, Steven A

    2015-01-01

    The use of testosterone to treat the symptoms of late-onset hypogonadal men has increased recently due to patient and physician awareness. However, concerns regarding the effect of testosterone on the prostate, in particular any possible effect on the risk of prostate cancer have prompted further research in this regard. Surprisingly, numerous retrospective or small, randomized trials have pointed to a possible improvement in male lower urinary tract symptoms (LUTS) in patients treated with testosterone. The exact mechanism of this improvement is still debated but may have a close relationship to metabolic syndrome. For the clinician, the results of these studies are promising but do not constitute high levels of evidence. A thorough clinical examination (including history, examination and laboratory testing of testosterone) should be undertaken before considering the diagnosis of late-onset hypogonadism or instigating treatment for it. Warnings still remain on the testosterone supplement product labels regarding the risk of urinary retention and worsening LUTS, and these should be explained to patients. PMID:25337845

  16. Testosterone Replacement Therapy and Cardiovascular Risk: A Review

    PubMed Central

    Corona G, Giovanni; Rastrelli, Giulia; Maseroli, Elisa; Sforza, Alessandra

    2015-01-01

    Recent reports in the scientific and lay press have suggested that testosterone (T) replacement therapy (TRT) is likely to increase cardiovascular (CV) risk. In a final report released in 2015, the Food and Drug Administration (FDA) cautioned that prescribing T products is approved only for men who have low T levels due to primary or secondary hypogonadism resulting from problems within the testis, pituitary, or hypothalamus (e.g., genetic problems or damage from surgery, chemotherapy, or infection). In this report, the FDA emphasized that the benefits and safety of T medications have not been established for the treatment of low T levels due to aging, even if a man's symptoms seem to be related to low T. In this paper, we reviewed the available evidence on the association between TRT and CV risk. In particular, data from randomized controlled studies and information derived from observational and pharmacoepidemiological investigations were scrutinized. The data meta-analyzed here do not support any causal role between TRT and adverse CV events. This is especially true when hypogonadism is properly diagnosed and replacement therapy is correctly performed. Elevated hematocrit represents the most common adverse event related to TRT. Hence, it is important to monitor hematocrit at regular intervals in T-treated subjects in order to avoid potentially serious adverse events. PMID:26770933

  17. More Than Hypomyelination in Pol-III Disorder

    PubMed Central

    Vanderver, Adeline; Tonduti, Davide; Bernard, Genevieve; Lai, Jinping; Rossi, Christopher; Carosso, Giovanni; Quezado, Martha; Wong, Kondi; Schiffmann, Raphael

    2012-01-01

    The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy. The classical form is characterized by the association of hypomyelination, abnormal dentition, and hypogonadotropic hypogonadism, but the recent identification of 2 genes responsible for the syndrome demonstrates that these 3 main characteristics can be variably combined among “Pol-III related leukodystrophies”. The pathophysiology of this group of diseases is still to be elucidated and there are no neuropathological descriptions of brain tissue. We report the clinical, neuroradiological and neuropathological findings of a patient affected by 4H syndrome with confirmed POLR3A mutations. We found a marked loss of oligodendrocytes varying in severity in different brains regions accompanied by severe loss of myelin, moderately severe loss of axons and patchy perivascular regions of better-preserved white matter. There was relatively mild white matter astrogliosis and microgliosis. A macrophage reaction involving viable, normal-appearing oligodendroglia suggests the possibility of an immunologic process in this disorder. Cortical laminar astrogliosis and mineralization of layers I and II in particular was present. Thus, despite the uniformly hypomyelinating pattern seen on magnetic resonance imaging, neuropathological examination reveals a complex heterogeneous leukodystrophy with prominent neuro-axonal and glial involvement in this disorder. PMID:23242285

  18. Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress.

    PubMed

    Wainwright, Steven R; Workman, Joanna L; Tehrani, Amir; Hamson, Dwayne K; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-03-01

    Hypogonadal men are more likely to develop depression, while testosterone supplementation shows antidepressant-like effects in hypogonadal men and facilitates antidepressant efficacy. Depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and testosterone exerts suppressive effects on the HPA axis. The hippocampus also plays a role in the feedback regulation of the HPA axis, and depressed patients show reduced hippocampal neuroplasticity. We assessed the antidepressant-like effects of testosterone with, or without, imipramine on behavioral and neural endophenotypes of depression in a chronic unpredictable stress (CUS) model of depression. A 21-day CUS protocol was used on gonadectomized male Sprague-Dawley rats treated with vehicle, 1mg of testosterone propionate, 10mg/kg of imipramine, or testosterone and imipramine in tandem. Testosterone treatment reduced novelty-induced hypophagia following CUS exposure, but not under non-stress conditions, representing state-dependent effects. Further, testosterone increased the latency to immobility in the forced swim test (FST), reduced basal corticosterone, and reduced adrenal mass in CUS-exposed rats. Testosterone also facilitated the effects of imipramine by reducing the latency to immobility in the FST and increasing sucrose preference. Testosterone treatment had no significant effect on neurogenesis, though the combination of testosterone and imipramine increased PSA-NCAM expression in the ventral dentate gyrus. These findings demonstrate the antidepressant- and anxiolytic-like effects of testosterone within a CUS model of depression, and provide insight into the mechanism of action, which appears to be independent of enhanced hippocampal neurogenesis. PMID:26774465

  19. A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor (GNRHR) presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia

    PubMed Central

    Lin, Lin; Conway, Gerard S.; Hill, Nathan R.; Dattani, Mehul T.; Hindmarsh, Peter C.; Achermann, John C.

    2007-01-01

    Context The GnRH receptor plays a central role in regulating gonadotropin synthesis and release, and several mutations in the GNRHR gene have been reported in patients with idiopathic or familial forms of isolated hypogonadotropic hypogonadism (IHH). Objective To investigate whether partial loss of function mutations in the GnRH receptor might be responsible for delayed puberty phenotypes. Patients Sibling pairs with delayed puberty (n=8) or where one brother had delayed puberty and another had hypogonadotropic hypogonadism (n=3). Methods Mutational analysis of the GNRHR gene. Results A homozygous R262Q mutation in the GnRH receptor was identified in two brothers from one family. In this kindred, the proband presented at 15 years of age with delayed puberty. Following a short course of testosterone, he seemed to be progressing through puberty appropriately and was discharged from follow up. His younger brother was also referred with delayed puberty but showed little progress following treatment. Frequent sampling revealed detectable but apulsatile LH and FSH release. His clinical progress was consistent with IHH and he requires ongoing testosterone replacement. Conclusions Homozygous partial loss of function mutations in the GnRH receptor, such as R262Q, can present with variable phenotypes including apparent delayed puberty. Ongoing clinical vigilance might be required when patients are discharged from follow-up, especially when there is a family history of delayed puberty or IHH, as oligospermia and reduced bone mineralization can occur with time. PMID:16968799

  20. Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.

    PubMed

    El-Khairi, Ranna; Martinez-Aguayo, Alejandro; Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C

    2011-01-01

    The nuclear receptor transcription factors DAX-1 (NR0B1) and SF-1 (NR5A1) regulate many aspects of adrenal and reproductive development and function. Disruption of the genes encoding these factors can be associated with pediatric adrenal disease. DAX-1 mutations are classically associated with X-linked adrenal hypoplasia congenita, hypogonadotropic hypogonadism and impaired spermatogenesis. However, other phenotypes are also being reported, such as isolated mineralocorticoid insufficiency, premature sexual development, primary adrenal insufficiency in a 46, XX patient and late-onset X-linked adrenal hypoplasia congenita and/or hypogonadotropic hypogonadism. SF-1 mutations have also been associated with primary adrenal insufficiency, together with 46, XY disorders of sex development. However it is emerging that SF-1 changes are a relatively rare cause of primary adrenal failure in humans, and most individuals with SF-1 mutations have a spectrum of 46, XY disorders of sex development phenotypes. These conditions range from 46, XY females with streak gonads and müllerian structures, through children with ambiguous genitalia and inguinal testes, to severe penoscrotal hypospadias with undescended testes. Therefore, the human gonad appears to be more sensitive than the adrenal gland to loss of SF-1 function. This review will focus on the expanding range of phenotypes associated with DAX-1 and SF-1 mutations. PMID:21164257

  1. Systemic zinc redistribution and dyshomeostasis in cancer cachexia.

    PubMed

    Siren, Pontus M A; Siren, Matti J

    2010-09-01

    Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia's other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin-proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated. PMID:21475700

  2. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

    PubMed

    Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

    2012-01-01

    Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy. PMID:21748720

  3. Anorexia Nervosa and Its Associated Endocrinopathy in Young People.

    PubMed

    Misra, Madhusmita; Klibanski, Anne

    2016-01-01

    Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin-like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite-regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

  4. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    PubMed Central

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  5. Regulation of Sclerostin Production in Human Male Osteocytes by Androgens: Experimental and Clinical Evidence.

    PubMed

    Di Nisio, Andrea; De Toni, Luca; Speltra, Elena; Rocca, Maria Santa; Taglialavoro, Giuseppe; Ferlin, Alberto; Foresta, Carlo

    2015-12-01

    In this study we aimed to elucidate a possible role of T in the regulation of sclerostin, a glycoprotein secreted by osteocytes known to regulate bone mass. To this end, we evaluated the effect of T stimulation on sclerostin production and gene expression in human cultured osteocytes. In addition, we evaluated serum sclerostin levels in a cohort of 20 hypogonadal male patients, compared with 20 age-matched eugonadal controls. Stimulation with DHT decreased sclerostin expression in cultured osteocytes in a time- and dose-dependent manner. Confirming a direct androgen receptor-mediated effect on sclerostin production, flutamide coincubation and silencing of androgen receptor gene in osteocytes abolished the DHT effects. In addition, hypogonadal patients showed higher serum sclerostin levels with respect to controls (145.87 ± 50.83 pg/mL vs 84.02 ± 32.15 pg/mL; P < .001) and in both probands and controls, serum T levels were negatively correlated with sclerostin (R = -0.664, P = 0.007, and R = -0.447, P = .045, respectively). Finally, multiple stepwise regression analysis showed that T represented the only independent predictor of sclerostin levels. In conclusion, by showing a direct correlation between T and sclerostin, both in vivo and in vitro, this study adds further support to the emerging clinical and experimental studies focusing on sclerostin as a therapeutic target for osteoporosis treatment. PMID:26393301

  6. Men regret anabolic steroid use due to a lack of comprehension regarding the consequences on future fertility.

    PubMed

    Kovac, J R; Scovell, J; Ramasamy, R; Rajanahally, S; Coward, R M; Smith, R P; Lipshultz, L I

    2015-10-01

    We examined whether men with anabolic-steroid-induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic-androgenic steroids (AAS) and what their reasons were for this regret. An anonymous, prospective survey was distributed to 382 men seeking follow-up treatment for hypogonadism. Prior AAS use was confirmed by self-report, and men were categorised based upon whether they regretted (R) or did not regret (NR) their use of AAS. The average patient age was 40 ± 0.9 years (n = 79) and 15.2% expressed regret over AAS use. No demographic differences were identified between those who regretted AAS use (n = 12) and those who did not (n = 67). Regret was not related to ASIH diagnosis or to AAS-related side effects like increased aggression, mood disorders, erectile dysfunction, acne, fluid retention or dyslipidemia. Those who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility (P < 0.030). Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%). A total of 15.2% of men regretted using AAS. A lack of awareness regarding the negative long-term effects on fertility was the primary factor related to regret of AAS use in men with ASIH. PMID:25220690

  7. A summary of the controversy surrounding off-label medications in men’s health

    PubMed Central

    Parker, Adam; Bruha, Matthew; Akinola, Oluwaseun

    2016-01-01

    While there are common and accepted practices in men’s health, barriers exist to treatment of these disorders with Food and Drug Administration (FDA) approved medications. In male factor infertility, these barriers include studies that are often underpowered for desired outcomes. This has led to the use of medications previously examined in females in an off-label fashion for treatment of male infertility. Issues surrounding the treatment of hypogonadism in men are more complex, becoming increasingly so in the last few years. Drug companies have developed compounds for treatment of hypogonadism for particular subgroups of men. However, the indicated groups for these medications are narrow leading to these medications being regularly used for an indication the FDA considers to be part of “normal aging”. This work will examine the controversy surrounding the use of off-label medications in men’s health and how factors like pharma advertising, FDA regulation and difficulties in creating adequate studies has affected the current paradigm. PMID:27141447

  8. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice.

    PubMed

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  9. Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons

    PubMed Central

    Balasubramanian, Ravikumar; Dwyer, Andrew; Seminara, Stephanie B.; Pitteloud, Nelly; Kaiser, Ursula B.; Crowley, William F.

    2010-01-01

    Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management. PMID:20606386

  10. Changes in peripheral blood levels and pulse frequencies of GnRH in patients with hypopituitarism.

    PubMed

    Hayashi, M; Takanashi, N; Yaoi, Y

    1998-09-01

    Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients. PMID:9749566

  11. Corticosteroid-induced bone loss. Prevention and management.

    PubMed

    Picado, C; Luengo, M

    1996-11-01

    Osteoporosis is one of the most serious adverse effects experienced by patients receiving long term corticosteroid therapy. Bone loss occurs soon after corticosteroid therapy is initiated and results from a complex mechanism involving osteoblastic suppression and increased bone resorption. There are a number of factors that may increase the risk of corticosteroid-induced osteoporosis [smoking, excessive alcohol (ethanol) consumption, amenorrhoea, relative immobilisation, chronic obstructive pulmonary disease, inflammatory bowel disease, hypogonadism in men, organ transplantation]. The initial assessment of patients about to start taking corticosteroids should include measurement of spinal bone density, urinary calcium level and plasma calcifediol (25-hydroxycholecalciferol) level; serum testosterone levels should also be measured when hypogonadism is suspected. Many different drugs have been used to prevent osteoporosis in patients receiving long-term corticosteroid therapy, including thiazide diuretics, cholecalciferol (vitamin D) metabolites, bisphosphonates, calcitonin, fluoride, estrogens, anabolic steroids and progesterone. At present, however, published studies have failed to demonstrate a reduction in the rate of fracture using different preventive pharmacological therapies in patients being treated with corticosteroids on a continuous basis. Among the drugs studied, bisphosphonates (pamidronic acid and etidronic acid) and calcitonin appear to be effective in increasing bone density. Cholecalciferol preparations have been reported to be effective in some, but not all, studies. Limited data have shown positive results with thiazide diuretics, estrogen, progesterone and nandrolone. When treating patients with corticosteroids, the lowest effective dose should be used, with topical corticosteroids used whenever possible. Auranofin may be considered in patients with corticosteroid-dependent asthma. Patients should take as much physical activity as possible

  12. Male prolactinomas presenting with normal testosterone levels.

    PubMed

    Shimon, Ilan; Benbassat, Carlos

    2014-06-01

    In men harboring prolactinoma the most common symptoms are related to hypogonadism, including decreased libido, erectile dysfunction, and gynecomastia. These men characteristically present with elevated serum prolactin (PRL) levels, suppressed gonadotropins, and low testosterone levels. We studied a group of 11 unique men with prolactinomas presenting with testosterone levels within the normal range (≥2.6 ng/ml; cohort A), and compared them to 11 prolactinoma men with borderline baseline testosterone (2.1-2.5 ng/ml; cohort B) and to a cohort of 34 prolactinoma patients with low testosterone levels (≤2 ng/ml; cohort C). Mean testosterone levels at presentation were 3.91 ± 0.9 ng/ml in cohort A (range, 2.6-5.2 ng/ml), 2.44 ± 0.16 ng/ml in cohort B and 0.96 ± 0.6 in cohort C (p < 0.001). Mean baseline PRL levels were >20 times above normal in cohort A compared to >100 times above normal in cohorts B and C. Symptoms of hypogonadism were present in 55, 64 and 76% of men in groups A, B and C, respectively. There was a trend towards a larger tumor size in the low testosterone group (p = 0.06). Visual fields defects at presentation were more prevalent in this cohort (C). With cabergoline, testosterone level increased from 3.91 to 6.42 ng/ml (Δ = 2.51 ng/ml) in cohort A, from 2.44 to 5.63 ng/ml (Δ = 3.19 ng/ml) in cohort B, and from 0.96 to 3.30 ng/ml (Δ = 2.34 ng/ml) in cohort C (p < 0.05 for each group). Symptoms of hypogonadism improved following treatment in 83% of symptomatic men in cohort A. Normal testosterone does not exclude the likelihood of prolactinoma in men. When treated with cabergoline, testosterone levels in these men can increase higher within the normal range together with clinical improvement. PMID:23756784

  13. Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

    PubMed

    Giri, N; Vowels, M R; Barr, A L; Mameghan, H

    1992-07-01

    We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI. PMID:1515886

  14. Woodhouse-Sakati Syndrome: Report of the First Tunisian Family with the C2orf37 Gene Mutation

    PubMed Central

    Hdiji, Olfa; Turki, Emna; Bouzidi, Nouha; Bouchhima, Imen; Damak, Mariem; Bohlega, Saeed; Mhiri, Chokri

    2016-01-01

    Woodhouse-Sakati syndrome (WSS) is an infrequent autosomal recessive condition characterized by progressive extrapyramidal signs, mental retardation, hypogonadism, alopecia, and diabetes mellitus. This syndrome belongs to a heterogeneous group of inherited neurodegenerative disorders characterized iron accumulation in the brain, and it is caused by mutations of the C2orf37 gene. We report the first Tunisian family with two affected sisters presenting with a phenotype suggestive of WSS. We examined the index patient presenting with movement disorders and mental retardation and then searched for similar cases in her family, which identified a sister with similar signs. We performed a genetic study that confirmed the diagnosis and revealed a c.436delC mutation of the C2orf37 gene. Therefore, WSS is an important consideration in patients presenting with movement disorders and intellectual disability. A high consanguinity contributes to the clustering of such rare autosomal recessive syndromes. PMID:27240811

  15. Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part I.

    PubMed

    Aikawa, Katsuji; Miyawaki, Toshio; Hitaka, Takenori; Imai, Yumi N; Hara, Takahito; Miyazaki, Junichi; Yamaoka, Masuo; Kusaka, Masami; Kanzaki, Naoyuki; Tasaka, Akihiro; Shiraishi, Mitsuru; Yamamoto, Satoshi

    2015-05-15

    To develop effective drugs for hypogonadism, sarcopenia, and cachexia, we designed, synthesized, and evaluated selective androgen receptor modulators (SARMs) that exhibit not only anabolic effects on organs such as muscles and the central nervous system (CNS) but also neutral or antagonistic effects on the prostate. Based on the information obtained from a docking model with androgen receptor (AR), we modified a hit compound A identified through high-throughput screening. Among the prepared compounds, 1-(4-cyano-1-naphthyl)-2,3-disubstituted pyrrolidine derivatives 17h, 17m, and 17j had highly potent AR agonistic activities in vitro and good tissue selectivity in vivo. These derivatives increased the weight of the levator ani muscle without influencing the prostate and seminal vesicle. In addition, these compounds induced sexual behavior in castrated rats, indicating that the compounds could also act as agonists on the CNS. PMID:25862209

  16. Ten-year follow-up of a giant prolactinoma.

    PubMed

    Fernandes, Vera; Santos, Maria Joana; Almeida, Rui; Marques, Olinda

    2015-01-01

    Giant prolactinomas are rare pituitary tumours of which management can be a challenge. A 28-year-old man presented with headaches, visual impairment and behavioural changes. Clinically, the patient was found to have hypogonadism and bitemporal hemianopsia. A MRI demonstrated a pituitary tumour 76 mm in diameter and blood tests revealed a serum prolactin of 158,700 µU/mL (reference range 58-254). Initially, a craniotomy was performed. Immunohistochemistry of the tumour identified a prolactinoma with a high proliferative index and the patient was started on treatment with a dopamine agonist. A year later, neurological symptoms worsened due to regrowth of the lesion's cystic component, and so further surgery was performed. After 10 years of treatment with dopamine agonists, the prolactin levels decreased by 96.8%, there was an effective reduction in tumour size, and the neurological signs and symptoms resolved. PMID:26590188

  17. Infertility, obstetric and gynaecological problems in coeliac sprue.

    PubMed

    Sher, K S; Jayanthi, V; Probert, C S; Stewart, C R; Mayberry, J F

    1994-01-01

    There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. In women it can also lead to delayed menarche, amenorrhoea, early menopause, recurrent abortions, and a reduced pregnancy rate. In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. The real mechanism by which coeliac sprue produces these changes is unclear, but factors such as malnutrition, iron, folate and zinc deficiencies have all been implicated. In addition in men gonadal dysfunction is believed to be due to reduced conversion of testosterone to dihydrotestosterone caused by low levels of 5 alpha-reductase in coeliac sprue. This leads to derangement of the hypothalamic-pituitary axis. Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women. PMID:7988065

  18. Testosterone levels in an aging population: screen, measure, and restore.

    PubMed

    Kells, John; Dollbaum, Charles M

    2011-01-01

    An insufficient level of testosterone in aging men and women is associated with a constellation of adverse conditions (cognitive decline, loss of muscle mass, osteopenia, decreased libido, changes in fat distribution, fragility, depression, a greater risk of fracture). Research has confirmed that supplementary testosterone can ameliorate those signs and symptoms in hypogonadic individuals, but the benefits and risks of that therapy remain controversial. The treatment of such patients should be based on knowledge of the physiologic effects of testosterone in the elderly, effective screening for testosterone deficiency accurate measurement of bioavailable levels of that hormone, and safe and effective treatment options, all of which are examined in this article. In designing hormone replacement regimens, the skill of a compounding pharmacist who can customize dose and dosage forms to answer individual medical needs and preferences can be instrumental in achieving the desired outcome. PMID:23696079

  19. Systemic sarcoidosis with hypercalcaemia, hypothalamic-pituitary dysfunction and thyroid involvement.

    PubMed

    Alsahwi, Nassib; Blavo, Delali; Karanchi, Harsha

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disorder. The lungs are the principal organs affected, however, extrapulmonary involvement including disorders of the pituitary and thyroid glands has been reported but presentation with multiple endocrine manifestations is rare. We report the case of a 36-year-old African-American woman who presented with hypercalcaemia, abnormal thyroid function studies and secondary amenorrhoea. On workup including laboratory, radiological testing and biopsy she was diagnosed with sarcoidosis with multi-organ involvement. Endocrine manifestations included non-parathyroid hormone mediated hypercalcaemia related to sarcoidosis, thyroid involvement with sarcoidosis and hypothalamic-pituitary involvement with a sellar and suprasellar mass associated with secondary adrenal insufficiency, secondary hypogonadism, growth hormone deficiency and secondary hypothyroidism. We report to the best of our knowledge the first case of simultaneous multiple endocrine manifestations of sarcoidosis that included hypercalcaemia, hypopituitarism and sarcoidosis of the thyroid gland. PMID:27495178

  20. Idiopathic stuttering priapism treated with salbutamol orally: a case report.

    PubMed

    Migliorini, F; Porcaro, A B; Baldassarre, R; Artibani, W

    2016-03-01

    Recurrent ischaemic priapism also known as stuttering priapism is an uncommon form of ischaemic priapism, and its treatment is not yet clearly defined. If left untreated, it may evolve into classic form of acute ischaemic priapism and lead to erectile dysfunction due to fibrosis of corpora cavernosa. Several drugs have been proposed with variable results and only supported with level three or four of evidence. Hormonal therapy such as cyproterone acetate, oestrogen, bicalutamide or Lh-Rh agonist are often effective but can cause side effects such as hypogonadal state and infertility. Other medical options are 5-alpha-reductase and phosphodiesterase-5 inhibitors, ketoconazole, baclofen, digoxin, gabapentin and beta-2-agonist terbutaline. We report the first case of stuttering priapism treated with beta-2-agonist salbutamol. PMID:26032021

  1. Mixed gynecomastia.

    PubMed

    Al Qassabi, Salim S; Al-Harthi, Saud M; Al-Osali, Magdi E

    2015-09-01

    Gynecomastia is an enlargement of male breast resulting from a proliferation of its glandular component, and it is usually due to an altered estrogen-androgen balance. It should be differentiated from pseudogynecomastia, which is characterized by fat deposition without glandular proliferation and from breast carcinoma. Gynecomastia could be physiological in neonates and pubertal or pathological due to drug intake, chronic liver, or renal disease, hyperthyroidism, testicular or adrenal neoplasms, and hypogonadism whether primary, or secondary. Properly organized work-up is needed to reach the cause of gynecomastia. Here, we reported a case of a young Omani man with gynecomastia with the aim of creating awareness of the occurrence of Klinefelter's syndrome (KS) in patients with gynecomastia, to observe any differences in clinical presentation of KS from those reported in the literature, and highlight the needed diagnostic work-up and treatment. PMID:26318471

  2. Congenital disorder of glycosylation type 1a: three siblings with a mild neurological phenotype.

    PubMed

    Coman, D; McGill, J; MacDonald, R; Morris, D; Klingberg, S; Jaeken, J; Appleton, D

    2007-07-01

    We report 3 siblings (1 male and 2 female) recently diagnosed with congenital disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild mental retardation but manage to function independently in society. Their professions are library assistant, professional artistic painter and secretarial work. All three siblings have cerebellar hypoplasia and ataxia, but are able to ambulate easily. Two of the siblings have required strabismus surgical repairs. All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features. Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type 1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been demonstrated. They are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our patients are among the mildest of intellectually affected CDG-Ia patients reported to date. PMID:17451957

  3. The andrologist's contribution to a better life for ageing men: part 1.

    PubMed

    Comhaire, F; Mahmoud, A

    2016-02-01

    The present opinion paper, explores the possibility that optimal hormone treatment and judicious nutraceutical food supplement can help ageing men to gain quality-adjusted life years. Testosterone treatment of patients with late-onset hypogonadism is given via the transdermal route or by intramuscular injections. There is overwhelming evidence that testosterone replacement therapy (TRT) has many beneficial effects and increases longevity by approximately 2% per year. On the basis of knowledge of physiology, animal and human experimental data, we explain why TRT reduces the risk of cardiovascular disease and of prostate cancer. However, the total testosterone load supplied per day should remain within the physiological range, and new galenical formulations should be developed, mimicking normal day-night variations. PMID:26395199

  4. Familial interstitial Xq27.3q28 duplication encompassing the FMR1 gene but not the MECP2 gene causes a new syndromic mental retardation condition

    PubMed Central

    Rio, Marlène; Malan, Valérie; Boissel, Sarah; Toutain, Annick; Royer, Ghislaine; Gobin, Stéphanie; Morichon-Delvallez, Nicole; Turleau, Catherine; Bonnefont, Jean-Paul; Munnich, Arnold; Vekemans, Michel; Colleaux, Laurence

    2010-01-01

    X-linked mental retardation is a common disorder that accounts for 5–10% of cases of mental retardation in males. Fragile X syndrome is the most common form resulting from a loss of expression of the FMR1 gene. On the other hand, partial duplication of the long arm of the X chromosome is uncommon. It leads to functional disomy of the corresponding genes and has been reported in several cases of mental retardation in males. In this study, we report on the clinical and genetic characterization of a new X-linked mental retardation syndrome characterized by short stature, hypogonadism and facial dysmorphism, and show that this syndrome is caused by a small Xq27.3q28 interstitial duplication encompassing the FMR1 gene. This family broadens the phenotypic spectrum of FMR1 anomalies in an unexpected manner, and we suggest that this condition may represent the fragile X syndrome «contre-type». PMID:19844254

  5. [Testosterone therapy].

    PubMed

    Diemer, T; Hauptmann, A; Wagenlehner, F M E

    2016-04-01

    Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency. PMID:27067659

  6. [Urological Diseases in Men and their Prevention].

    PubMed

    Cantieni, Christoph; Gasser, Thomas

    2016-01-01

    The late-onset hypogonadism is defined as a reduction of blood testosterone values in aging males in combination with sexual symptoms. A hormone substitution is only necessary if desired by the patient. Erectile dysfunction is often caused by vasculopathy. Therefore, vascular risk factors should be evaluated. In case of cardiovascular disease a cardiologist should be addressed before initiating treatment. First line therapy consists of phosphodiesterase inhibitors. In lower urinary tract symptoms prostatic enlargement is the likely cause, but other causes have to be ruled out. Symptomatic therapy can be initiated if the patient is bothered. If voiding symptoms are predominant, alpha blockers or alpha reductase inhibitors are the treatment of choice. In case of storage symptoms, treatment can be started with muscarin receptor antagonists. PMID:26732714

  7. [Conservative therapy of erectile dysfunction].

    PubMed

    Trottmann, M; Marcon, J; Pompe, S; Strobach, D; Becker, A J; Stief, C G

    2015-05-01

    The erectile dysfunction (ED) with a prevalence of 19.2% and a steep age-related increase up to 53.4% in men over 70 years is a common sexual disorder. Especially after market launch of the phosphodiesterase 5 inhibitors the possibility of an easy-to-use and well-tolerated therapy is available. In case of nonresponse, vasoactive substances can be applied in different forms. In case of an additional hypogonadism, testosterone substitution is indicated. Simultaneously the causes of ED should always be treated, including a change of lifestyle with elimination of exogenous noxa. The use of mechanic tools as single or combination therapy can lead to improved erection. This article provides a critical overview of the latest conservative therapy options, it explains previous unsuccessful therapeutic trials and gives an outlook into potential ED therapy concepts of the future. PMID:25987332

  8. [Therapeutic issues concerning male fertility].

    PubMed

    Bernard, V; Bouvattier, C; Christin-Maitre, S

    2014-10-01

    Men reproductive health has long been ignored although it is responsible for 50% of couple's infertility. However, in recent years, the understanding of endocrine physiology underlying testis development and spermatogenesis has enabled the development of new therapeutic strategies. Some concern the management of male infertility. Others are dealing with finding an effective male contraceptive. In this review, we first present the management of infertility, in patients with congenital hypogonadotropic hypogonadism. We then describe the major improvements for Klinefelter patient's infertility. Finally, we review the different hormonal and non-hormonal methods for male contraception, currently in development. Efficacy and safety of the some non-hormonal methods remain to be demonstrated so far in humans. PMID:25617918

  9. Exogenous pubertal induction by oral versus transdermal estrogen therapy.

    PubMed

    Kenigsberg, Lisa; Balachandar, Sadana; Prasad, Kris; Shah, Bina

    2013-04-01

    Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction. PMID:22112543

  10. Selective androgen receptor modulators in preclinical and clinical development

    PubMed Central

    Narayanan, Ramesh; Mohler, Michael L.; Bohl, Casey E.; Miller, Duane D.; Dalton, James T.

    2008-01-01

    Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on prostate and other secondary sexual organs. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, or end-stage renal disease, osteoporosis, frailty, and hypogonadism. This review summarizes the current standing of research and development of SARMs, crystallography of AR with SARMs, plausible mechanisms for their action and the potential therapeutic indications for this emerging class of drugs. PMID:19079612

  11. Kennedy's disease and partial androgen insensitivity syndrome. Report of 4 cases and literature review.

    PubMed

    Valera Yepes, Rocío; Virgili Casas, Maria; Povedano Panades, Monica; Guerrero Gual, Mireia; Villabona Artero, Carles

    2015-05-01

    Kennedy's disease, also known as bulbospinal muscular atrophy, is a rare, X-linked recessive neurodegenerative disorder affecting adult males. It is caused by expansion of an unstable cytosine-adenine-guanine tandem-repeat in exon 1 of the androgen-receptor gene on chromosome Xq11-12, and is characterized by spinal motor neuron progressive degeneration. Endocrinologically, these patients often have the features of hypogonadism associated to the androgen insensitivity syndrome, particularly its partial forms. We report 4 cases with the typical neurological presentation, consisting of slowly progressing generalized muscle weakness with atrophy and bulbar muscle involvement; these patients also had several endocrine manifestations; the most common non-neurological manifestation was gynecomastia. In all cases reported, molecular analysis showed an abnormal cytosine-adenine-guanine triplet repeat expansion in the androgen receptor gene. PMID:25857692

  12. Human immunodeficiency virus endocrinopathy

    PubMed Central

    Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

    2011-01-01

    Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

  13. Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency

    PubMed Central

    Mohd Effendy, Nadia; Mohamed, Norazlina; Muhammad, Norliza; Naina Mohamad, Isa; Shuid, Ahmad Nazrun

    2012-01-01

    Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis. PMID:22844328

  14. European Neuroendocrine Association--ninth meeting. 3-7 September 1999, Odense, Denmark.

    PubMed

    Almeida, O F

    1999-12-01

    The Ninth Meeting and Workshops of the European Neuroendocrine Association (ENEA) were held in Odense, Denmark. Training workshops covering topics of interest to basic and clinical neuroendocrinologists occupied the first two days of the meeting; on the remaining 3 days, sessions were organized into meet-the professor sessions, plenary lectures, symposia, and free oral and poster communications. The symposia covered most of the principal areas of neuroendocrinology which have important clinical implications (regulation of growth and metabolism, neuroendocrine tumors, hypogonadism, and hormone resistance syndromes), but some symposia covered more basic research in the field (neuroendocrinology of behavior, mutant mouse models, neuronal plasticity and the molecular biology of pituitary tumors). Papers in the free communication sessions generally interphased well with the themes of the symposia. PMID:16113954

  15. Clinical and molecular genetic analysis of a Chinese family with congenital X-linked adrenal hypoplasia caused by novel mutation 1268delA in the DAX-1 gene*

    PubMed Central

    ZHANG, Zhe; FENG, Ye; YE, Dan; LI, Cheng-jiang; DONG, Feng-qin; TONG, Ying

    2015-01-01

    Congenital X-linked adrenal hypoplasia (AHC) is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism (HHG) during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 (DAX-1) mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation (1268delA) of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype. PMID:26537215

  16. Current status of testosterone replacement therapy in men.

    PubMed

    Winters, S J

    1999-01-01

    Testosterone plays an essential role in the development of the normal male and in the maintenance of many male characteristics, including muscle mass and strength, bone mass, libido, potency, and spermatogenesis. Androgen deficiency occurs with disorders that damage the testes, including traumatic or surgical castration (primary testicular failure) or disorders in which the gonadotropin stimulation of the testes is reduced (hypogonadotropic hypogonadism). The clinical manifestations of androgen deficiency depend on the age at onset and the severity and duration of the deficiency. In adult males, these manifestations may include reduced body hair, decreased muscle mass and strength, increased fat mass, decreased hematocrit, decreased libido, erectile dysfunction, infertility, osteoporosis, and depressed mood. The forms of androgen replacement currently available in the United States are intramuscular depot injections of testosterone esters, oral tablets of testosterone derivatives, and transdermal patches. For most patients, androgen replacement therapy with testosterone is a safe, effective treatment for testosterone deficiency. PMID:10333822

  17. Adrenal insufficiency presenting as bilateral rigid auricles: a case report

    PubMed Central

    2014-01-01

    Introduction Stiff ears appear to be a warning sign for adrenal insufficiency. This remarkable and rare sign has not been described to present in adrenal insufficiency in the setting of critical care. Case presentation We present the case of a 68-year-old Caucasian male who underwent a thymoma resection and suffered from preoperative weight loss and lack of strength. The perioperative phase was characterised by hypotension and sputum stasis due to muscle weakness, which caused two readmissions to the intensive care unit. His physical examination showed two fully rigid auricles. In retrospect, our patient suffered from secondary adrenal insufficiency and hypogonadism. Conclusions The bilateral rigid auricles appeared to be a warning sign for adrenal insufficiency. This remarkable sign is easily checked, and should prompt a higher index of suspicion towards adrenal insufficiency and other hormonal deficiencies. PMID:25209544

  18. Double-stimulation with LH-RH in primary amenorrhea caused by chronic internal hydrocephylus: a case study.

    PubMed

    Moeslein, S; Dericks-Tan, J S; Lorenz, R; Taubert, H D

    1987-06-01

    A 19-year-old female patient with primary amenorrhea and pubertas tarda due to chronic internal hydrocephalus presented with normal hormonal findings except for low estradiol and a prepubertal type of reaction in the double-stimulation test with LH-RH. After successful operative treatment with a Spitz-Holter high-pressure valve, the intracranial decompression was promptly followed by pubertal development, she began to menstruate, and the LH-RH double-stimulation test showed an adult pattern of response. The results of the test support the view that a partial deficiency in the secretion of LH-RH is the cause of hypogonadism in such a case. PMID:3140582

  19. [Recent aspects of therapy with androgenic and anabolic steroids].

    PubMed

    Schambach, H; Nitschke, U; Kröhne, H J

    1983-11-15

    From the pharmacology of the therapeutically available androgen preparations and the clinical experience results that a highly dosed androgen long-term therapy is effectively possible only by testosterone esters which are to be injected intramuscularly (e.g. testosterone oenanthate). It is indicated in all forms of endocrine hypogonadism, certain aplastic anaemias and if necessary in extreme male high growth. In partial androgen deficiency (pubertas tarda, Klinefelter's syndrome, climacterium virile and others) orally applicable androgens such as testosterone-undecanoate (Andriol) and mesterolone (Vistimon) can be used. The latter is to be preferred when a hyperoestrogenism is present, e.g. in liver cirrhosis. When 17-alpha-alkylated oral androgens are used, their often not sufficiently confirmed anabolic effect and their potential liver toxicity should more be taken into consideration. PMID:6666179

  20. Mediastinal mixed germ cell tumor in an infertile male with Klinefelter syndrome:A case report and literature review.

    PubMed

    Pradhan, Dinesh; Kaman, Lileswar; Dhillon, Jasreman; Mohanty, Sambit K

    2015-01-01

    Klinefelter syndrome (KS) is a well-documented abnormality of the sex chromosome, with an incidence of 1 in 600 newborn males. It is characterized by a 47, XXY or a mosaic karyotype, hypergonadotrophic hypogonadism, infertility, reduced body hair, gynecomastia, and tall stature. Different neoplasms such as breast, testicular, and lymphoreticular malignancies may occur in 1% to 2% of the cases with KS. Herein we describe a case of mediastinal mixed germ cell tumor (GCT) in a 40-year-old male with KS. Interestingly, this case also had mitral valve prolapse, and an incidental papillary microcarcinoma of the thyroid gland. In view of the presence of pulmonary nodules, antemortem differential diagnoses considered were mycobacterial infection, lymphoma, thymic carcinoma, and a primary/metastatic neoplasm of the lung. As GCT was not considered, the serum markers of a GCT were not performed. The diagnosis of this rare mediastinal mixed GCT with KS was made at autopsy. PMID:26881632

  1. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness.

    PubMed

    Pan, Michael M; Kovac, Jason R

    2016-04-01

    Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required. PMID:27141449

  2. [Endocrine and other medical causes of abnormal fatigability].

    PubMed

    Bürgi, U

    1991-11-01

    Many endocrine diseases can cause fatigue. Tiredness is a frequent symptom of primary and secondary hypothyroidism, hyperthyroidism, excessive glucocorticoid or mineralocorticoid production, primary and secondary adrenal insufficiency, primary and secondary hypogonadism and hyperprolactinemia in the male, acromegaly, diabetes mellitus and diabetes insipidus. A great number of medical diseases other than those mentioned in the articles on cardiological and pneumological fatigue can also cause abnormal tiredness (infectious diseases, hematological, renal, hepatic, gastrointestinal and rheumatological disturbances, vasculitis and malignant tumors). The pathogenesis of tiredness caused by endocrine or medical illnesses, i.e. how the sensation of fatigue is produced, is not clear. The fatigue of the various endocrine or other medical diseases is not disease-specific, i.e. its characteristics do not differentiate it from the fatigue of other illnesses. PMID:1754971

  3. Ghrelin and reproductive disorders.

    PubMed

    Repaci, Andrea; Gambineri, Alessandra; Pagotto, Uberto; Pasquali, Renato

    2011-06-20

    Ghrelin is an important factor involved in most of the metabolic and hormonal signals which adapt the reproductive functions in conditions of altered energy balance. Moreover, the coordinated role of leptin and ghrelin appears in fact to have a specific role in the regulation of puberty. Systemic action of ghrelin on the reproductive axis involves the control of the hypothalamic-pituitary-gondal axis. In addition, it has been shown that ghrelin may directly act at a gonadal level in both females and males. Available data also demonstrate that sex steroid hormones and gonadotropins may in turn regulate the gonadal effect of ghrelin, as documented by studies performed in females with the polycystic ovary syndrome and in hypogonadal men. Notably, recent studies also confirm a potentially important role for ghrelin in fetal and neonatal energy balance, and specifically in allowing fetal adaptation to an adverse intrauterine environment. PMID:21453749

  4. The evidence for seasonal variations of testosterone in men.

    PubMed

    Smith, Ryan P; Coward, Robert M; Kovac, Jason R; Lipshultz, Larry I

    2013-03-01

    Ample evidence exists to support the concept of diurnal variations in testosterone levels; however, substantiation for seasonal fluctuations is sparse and inconsistent. Since circadian disparities exist, laboratory screening for hypogonadism has traditionally been conducted using serum testosterone levels obtained in the early morning. Should circannual variability of testosterone be confirmed, it would make the monitoring of testosterone levels more difficult while forcing the development of seasonal reference standards to allow for comparison. Moreover, decisions to begin treatment and adjustment of practice patterns would likely follow. This review thoroughly explores all of the available evidence concerning seasonal variations in testosterone levels. The impacts of melatonin, vitamin D, sleep-wake cycles, light exposure, physical activity, BMI, and waist circumference are also discussed. Current research suggests that while some evidence exists to support the notion of seasonal testosterone variations, the discussed inconsistencies preclude the incorporation of this concept into current clinical standards. PMID:23294933

  5. Inhibitory effects of mitotane on viability and secretory activity in mouse gonadotroph cell lines.

    PubMed

    Gentilin, Erica; Molè, Daniela; Gagliano, Teresa; Minoia, Mariella; Ambrosio, Maria Rosaria; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2014-06-01

    Mitotane represents the mainstay medical treatment for metastatic, inoperable or recurrent adrenocortical carcinoma. Besides the well-known adverse events, mitotane therapy is associated also with endocrinological effects, including sexual and reproductive dysfunction. The majority of male patients undergoing adjuvant mitotane therapy show a picture of hypogonadism, characterized by low free testosterone and high sex hormone binding globulin levels and unmodified LH concentrations. Since mitotane has been shown to have direct pituitary effects, we investigated whether mitotane may influence both cell viability and function of gonadotroph cells in the settings of two pituitary cell lines. We found that mitotane reduces cell viability, induces apoptosis, modifies cell cycle phase distribution and secretion of gonadotroph cells. The present data strengthen previous evidence showing a direct mitotane effect at pituitary level and represent a possible explanation of the lack of LH increase following decrease in free testosterone in patients undergoing adjuvant mitotane therapy. PMID:24486453

  6. Role of fibroblast growth factor (FGF) signaling in the neuroendocrine control of human reproduction.

    PubMed

    Miraoui, Hichem; Dwyer, Andrew; Pitteloud, Nelly

    2011-10-22

    Fibroblast growth factor (FGF) signaling is critical for a broad range of developmental processes. In 2003, Fibroblast growth factor receptor 1 (FGFR1) was discovered as a novel locus causing both forms of isolate GnRH Deficiency, Kallmann syndrome [KS with anosmia] and normosmic idiopathic hypogonadotropic hypogonadism [nIHH] eventually accounting for approximately 10% of gonadotropin-releasing hormone (GnRH) deficiency cases. Such cases are characterized by a broad spectrum of reproductive phenotypes from severe congenital forms of GnRH deficiency to reversal of HH. Additionally, the variable expressivity of both reproductive and non-reproductive phenotypes among patients and family members harboring the identical FGFR1 mutations has pointed to a more complex, oligogenic model for GnRH deficiency. Further, reversal of HH in patients carrying FGFR1 mutations suggests potential gene-environment interactions in human GnRH deficiency disorders. PMID:21664428

  7. [USE OF SILDENAFIL CITRATE FOR TREATMENT OF ERECTILE DYSFUNCTION OF VARIOUS ETIOLOGY].

    PubMed

    Efremov, E A; Kasatonova, E V; Mel'nik, Ja I

    2015-01-01

    Erectile dysfunction is closely linked to the general state of both physical and psychological wellness. Among the major risk factors are heart disease, arterial hypertension, diabetes, hyperlipidemia, as well as sedentary lifestyle, smoking and alcohol abuse. Also, the disease is more frequently found in men undergoing radiation therapy or surgery for prostate cancer. Psychological correlates include anxiety, depression and irritability. Despite a higher prevalence among older men, erectile dysfunction is not considered an inevitable part of aging. Due to polyetiology of the disease, sildenafil is regarded as the gold standard of treatment, and new high quality generic drugs are marketed. The article covers the use of sildenafil in patients with diseases of the cardiovascular system, diabetes, hypogonadism. Effectiveness of sildenafil in patients on chronic hemodialysis as well as in patients undergoing radical prostatectomy is discussed. The issue of addiction to sildenafil is outlined. PMID:26237819

  8. How do you monitor the patient with Turner's syndrome in adulthood?

    PubMed

    Conway, Gerard S; Band, Margaret; Doyle, Jacqueline; Davies, Melanie C

    2010-12-01

    Within endocrinology, the long-term management of Turner syndrome (TS) in adults is fast becoming a specialist subject in its own right. The complications of TS can affect every system in the body, and the main reason why it falls to endocrinologists to coordinate health care is that many features are clearly within the endocrine remit: hypothyroidism, diabetes, hypertension, osteoporosis, hypogonadism. Endocrinologists as general physicians can often cover surveillance of problems in other areas such as congenital heart disease, inflammatory bowel disease and deafness, calling upon specialist input only if the need arises. In this way, a simple 'one stop shop' can offer a well-woman service for women with TS in a cost-effective manner. Such a service requires a multidisciplinary approach. PMID:20718775

  9. Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation

    PubMed Central

    Raju, Gottumukkala Achyuta Rama; Chavan, Rahul; Deenadayal, Mamata; Gunasheela, Devika; Gutgutia, Rohit; Haripriya, Geetha; Govindarajan, Mirudhubashini; Patel, Nayana Hitesh; Patki, Ameet Shashikant

    2013-01-01

    Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART. PMID:24672160

  10. Prader-Willi syndrome.

    PubMed Central

    Cassidy, S B

    1997-01-01

    Prader-Willi syndrome is a complex disorder affecting multiple systems with many manifestations relating to hypothalamic insufficiency. Major findings include infantile hypotonia, developmental delay and mental retardation, behaviour disorder, characteristic facial appearance, obesity, hypogonadism, and short stature. Obesity and the behavioural problems are the major causes of morbidity and mortality. Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process. Diagnostic identification of all causes has become available in recent years, permitting early detection and institution of appropriate management. This testing has permitted recent identification of some phenotypic differences among affected subjects of different race and between those with deletions and uniparental disomy as a cause. Images PMID:9391886

  11. Male osteoporosis: A review.

    PubMed

    Herrera, Antonio; Lobo-Escolar, Antonio; Mateo, Jesús; Gil, Jorge; Ibarz, Elena; Gracia, Luis

    2012-12-18

    Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. The etiology can be idiopathic or secondary to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic and every disease or drug use that alters bone metabolism.Risk factors such as a previous history of fragility fracture should be assessed for the diagnosis. However, risk factors in men are very heterogeneous. There are significant differences in the pharmacological treatment of osteoporosis between men and women fundamentally due to the level of evidence in published trials supporting each treatment. New treatments will offer new therapeutic prospects. The goal of this work is a revision of the present status knowledge about male osteoporosis. PMID:23362466

  12. [Osteoporosis: a clinical perspective].

    PubMed

    Matikainen, Niina

    2016-01-01

    Osteoporosis is defined by decreased bone density and microarchitectural deterioration that predispose to fragility fractures. The WHO diagnostic criteria of osteoporosis require bone densitometry but treatment is possible on the basis of high clinical fracture risk and can be assessed by the FRAX risk algorithm. All those subject to fracture risk should be advised about proper basic treatment of osteoporosis, including exercise, prevention of falls, smoking cessation, avoidance of alcohol intake, and dietary or supplemental abundance of calcium and vitamin D. Underlying diseases must be studied after diagnosis of osteoporosis even if treatment is initiated without densitometry. When indicated, specific osteoporosis therapy includes bisphosphonates, denosumab, teriparatide, strontium ranelate or SERMs. In hypogonadism, gonadal steroids may be indicated alone or in addition to a specific treatment. Treatment effect and continuation are assessed after 2 to 5 years. PMID:27400591

  13. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report.

    PubMed

    Mutlu, Gül Yesiltepe; Kırmızıbekmez, Heves; Aydın, Hatip; Çetiner, Handan; Moralıoğlu, Serdar; Celayir, Ayşenur Cerrah

    2015-01-01

    46,XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. This syndrome is caused by a defect in the determination of sex during embryogenesis and is characterised with female external genitalia, normal or rudimentary uterus, and streak gonads, despite the presence of the 46,XY karyotype. Most of the studied cases presented with leak of secondary sex characteristics and primary amenorrhea during adolescence. Laboratory findings reveal hypergonadotropic hypogonadism. Herein we present the case of a female with a 46,XY karyotype who was admitted with delayed puberty and detected to have a microdeletion in the SRY gene and diagnosed to have Swyer syndrome. We highlight the importance of karyotype analysis in patients with delayed puberty and primary amenorrhea. Once the diagnosis of 46,XY complete gonadal dysgenesis is established, early laparoscopic removal of the dysgenetic gonads is crucial to prevent the development of gonadal malignancy. PMID:25153220

  14. Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory.

    PubMed

    Mitchell, Anna L; Dwyer, Andrew; Pitteloud, Nelly; Quinton, Richard

    2011-07-01

    Idiopathic hypogonadotropic hypogonadism (IHH) is defined by absent or incomplete puberty and characterised biochemically by low levels of sex steroids, with low or inappropriately normal gonadotropin hormones. IHH is frequently accompanied by non-reproductive abnormalities, most commonly anosmia, which is present in 50-60% of cases and defines Kallmann syndrome. The understanding of IHH has undergone rapid evolution, both in respect of genetics and breadth of phenotype. Once considered in monogenic Mendelian terms, it is now more coherently understood as a complex genetic condition. Oligogenic and complex genetic-environmental interactions have now been identified, with physiological and environmental factors interacting in genetically susceptible individuals to alter the clinical course and phenotype. These potentially link IHH to ancient evolutionary pressures on the ancestral human genome. PMID:21511493

  15. [Bone metabolism and fracture risk in anorexia nervosa].

    PubMed

    Fernández Soto, María Luisa; González Jiménez, Amalia; Varsavsky, Mariela

    2010-07-17

    The prevalence of anorexia nervosa has increased in recent years and a large proportion of patients with this disorder have low bone density at diagnosis and, therefore, an increased risk of early and late fractures. The mechanism of bone loss in anorexia nervosa is not well understood, yet it likely includes hypogonadism, alterations of the GH-IGF-1 axis and hypercortisolism. DEXA is the most effective tool for assessing and monitoring bone density in these patients, and it is important to improve or at least stabilize bone metabolism in those with low bone mass. No agent has yet been proven to be effective in improving bone density. However, sustained weight recovery and menses besides an adequate intake of calcium and vitamin D are recommended to optimize the conditions in which bone mass accrual may occur. PMID:19631350

  16. An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome.

    PubMed

    Balraj, Pauline; Concannon, Pat; Jamal, Rahman; Beghini, Alessandro; Hoe, T S; Khoo, Alan Soobeng; Volpi, Ludovica

    2002-10-31

    Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations. PMID:12379465

  17. Anticancer treatment and fertility: Effect of therapeutic modalities on reproductive system and functions.

    PubMed

    Vassilakopoulou, Maria; Boostandoost, Erfaneh; Papaxoinis, George; de La Motte Rouge, Thibault; Khayat, David; Psyrri, Amanda

    2016-01-01

    The significant improvement of cancer treatments entailed a longer life in cancer survivors and raised expectations for higher quality of life with minimized long-term toxicity. Infertility and gonadal dysfunction are adverse effects of anticancer therapy or may be related to specific tumors. In female cancer survivors, premature ovarian failure is common after antineoplastic treatments resulting in infertility and other morbidities related to oestrogen deficiency such as osteoporosis. In male cancer survivors, infertility and persistent a zoospermia is a more common long-term adverse effect than hypogonadism because germ cells are more sensitive to chemotherapy and radiotherapy than leydig cells. Gonadal toxicity and compromise of reproductive functions will be more efficiently prevented and treated if addressed before treatment initiation. This review focuses on these issues in young cancer survivors of childbearing age, where methods of protecting or restoring endocrine function and fertility need to be considered. PMID:26481950

  18. Transdermal delivery of testosterone.

    PubMed

    Hadgraft, Jonathan; Lane, Majella E

    2015-05-01

    Male hypogonadism has been treated with exogenous testosterone since the 1930s. The early transdermal patches of testosterone became available in the 1980s with gel and solution preparations following subsequent decades. This review focusses on the skin permeation characteristics of testosterone, pharmacokinetics following application of transdermal formulations and formulations currently available. At present, gels dominate the market for transdermal testosterone replacement therapy, presumably because of their greater patient acceptability and non-occlusive nature compared with patches. However, specific incidences of secondary transfer of gels to children with consequent unwanted effects such as precocious puberty have been reported. A regulatory review of all testosterone replacement therapies is currently underway which may have implications for future prescribing practices of transdermal testosterone products. PMID:25709060

  19. [Kallmann syndrome].

    PubMed

    Mokosch, A; Bernecker, C; Willenberg, H S; Neumann, N J

    2011-10-01

    The Kallmann syndrome is a very rare congenital association of gonadotropin-releasing hormone deficiency and hyposmia or anosmia. Clinically it is characterized by low serum concentrations of testosterone and inadequate low levels of luteinizing hormone and follicle-stimulating hormone as well as incomplete sexual maturation, lack of secondary sexual features (facial and body hair growth, deepening of the voice), micropenis and sometimes even cryptorchidism. The reduced or absent sense of smell is typical for the Kallmann syndrome and distinguishes this syndrome from other causes of hypogonadotropic hypogonadism. Additional findings may include synkinesia, hearing loss, unilateral renal aplasia, brachy- or syndactyly, agenesis of corpus callosum, cleft palate and dental agenesis. A 19-year-old man presented to our male infertility clinic with delayed sexual maturation, eunuchoid habitus, micropenis, cryptorchidism, erectile dysfunction and absence of ejaculation, anemia and osteoporosis as well as low serum concentrations of luteinizing hormone, follicle-stimulating hormone and testosterone in combination with hyposmia. PMID:21918848

  20. Rothmund-Thomson syndrome: two case reports show heterogeneous cutaneous abnormalities, an association with genetically programmed ageing changes, and increased chromosomal radiosensitivity.

    PubMed Central

    Kerr, B; Ashcroft, G S; Scott, D; Horan, M A; Ferguson, M W; Donnai, D

    1996-01-01

    Rothmund-Thomson syndrome is a rare, autosomal recessive disorder associated with characteristic cutaneous changes, sparse hair, juvenile cataracts, short stature, skeletal defects, dystrophic teeth and nails, and hypogonadism. Mental retardation is unusual. An increased incidence of certain malignancies has been reported. Clonal or mosaic chromosome abnormalities and abnormalities in DNA repair mechanisms have been reported in some cases. We report two cases of Rothmund-Thomson syndrome, both with intellectual handicap, associated in one with a previously undescribed histological appearance of involved skin, suggesting that the spectrum of abnormalities is even more heterogeneous than previously presumed. Both cases exhibited chromosomal radiosensitivity of lymphocytes which may be an indication of a DNA repair defect. This is the first report of an association between Rothmund-Thomson syndrome and unique, intrinsic, age related skin changes. Images PMID:8950673

  1. Battle of the sex steroids in the male skeleton: and the winner is....

    PubMed

    Weber, Thomas J

    2016-03-01

    Male osteoporosis is a multifactorial disease, although it is often in part related to hypogonadism. While testosterone replacement therapy has been shown to improve bone mineral density, studies have also linked bone loss and higher fracture risk in men to low estrogen levels. In this issue of the JCI, Finkelstein and colleagues report the results of a clinical study in a cohort of healthy adult men aimed at further discerning the specific roles of androgen and estrogen deficiency in bone loss. The results of their study support previous findings that estrogen deficiency has a dramatic effect on bone homeostasis in men. Future studies to corroborate and expand on these findings have potential to influence the clinical management of male osteoporosis. PMID:26901810

  2. Testosterone and Cardiovascular Disease.

    PubMed

    Kloner, Robert A; Carson, Culley; Dobs, Adrian; Kopecky, Stephen; Mohler, Emile R

    2016-02-01

    Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety. PMID:26846952

  3. Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

    PubMed Central

    Jones, Kea M.; Niaz, Mohammad S.; Brooks, Cynthia M.; Roberson, Shannon I.; Aguinaga, Maria P.; Hills, Edward R.; Rice, Valerie Montgomery; Bourne, Phillip; Bruce, Donald; Archibong, Anthony E.

    2009-01-01

    Two experiments were conducted to determine: 1) whether the adult male transgenic sickle cell mouse (Tg58 × Tg98; TSCM), exhibits the patterns of reproductive endpoints (hypogonadism) characteristic of men with sickle cell disease (SCD) and 2) whether hydroxyurea (HU) exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM) (N = 10/group) for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline) as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ± 0.004g) that was further decreased on day 56 (0.06 ± 0.003g; treatment x time interaction) compared with controls (day 28, 0.15 ± 0.01g; day 56, 2, 0.16 ± 0.01g). Concomitant with a 52% shrinkage (P<0.001) in area of testes in 56 days of HU treatment, testes from HU-treated TSCM exhibited significant atrophic degeneration

  4. Prader–Willi syndrome

    PubMed Central

    Cassidy, Suzanne B; Driscoll, Daniel J

    2009-01-01

    Prader–Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2–q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect. PMID:18781185

  5. Chronic obstructive pulmonary disease and the metabolic syndrome: Consequences of a dual threat

    PubMed Central

    Naik, Dukhabandhu; Joshi, Anjali; Paul, Thomas Vizhalil; Thomas, Nihal

    2014-01-01

    The metabolic syndrome is found to be more frequent in chronic obstructive pulmonary disease (COPD). The presence of inflammatory markers in circulation, sputum, and broncho-alveolar fluid suggest systemic inflammation is one of the potential mechanisms responsible for both COPD and metabolic syndrome. Physical inactivity, skeletal muscle dysfunction, hypogonadism, and steroid use are also important causes of the metabolic syndrome in COPD. Obesity and insulin resistance is found to be more common in mild to moderate stages (I and II) of COPD. Patients with COPD and the metabolic syndrome have increase risk of morbidity and mortality due to cardiovascular disease. This review describes in details the various components of metabolic syndrome and its impact on long outcomes in COPD patients. PMID:25285275

  6. A successful laparoscopic neovaginoplasty using peritoneum in Müllerian agenesis with inguinal ovaries accompanied by primary ovarian insufficiency

    PubMed Central

    Gweon, Seonghye; Lee, Jisun; Hwang, Suna; Hwang, Kyoung Joo

    2016-01-01

    The combination of Müllerian agenesis with inguinal ovaries accompanied by primary ovarian insufficiency is extremely rare. A 21-year-old Korean woman was referred to our center with primary amenorrhea. The patient was diagnosed with Müllerian agenesis with inguinal ovaries. Her hormonal profile showed hypergonadotrophic hypogonadism suggesting primary ovarian insufficiency. We performed laparoscopic neovaginoplasty using modified Davydov's procedure and reposition inguinal ovaries in the pelvic cavity. Oral estrogen replacement was applied for the treatment of primary ovarian insufficiency. This is a rare case report on Mayer-Rokitansky-Kuster-Hauser syndrome accompanied not only by inguinal ovaries but also with primary ovarian insufficiency. We present our first experience on the laparoscopic neovaginoplasty performed on the patient with müllerian agenesis accompanied by inguinal ovaries and primary ovarian insufficiency. PMID:27462606

  7. Diagnostic evaluation of erectile dysfunction.

    PubMed

    Miller, T A

    2000-01-01

    Erectile dysfunction, the persistent inability to attain or maintain penile erection sufficient for sexual intercourse, affects millions of men to various degrees. The majority of cases have an organic etiology, most commonly vascular disease that decreases blood flow into the penis. Regardless of the primary cause, erectile dysfunction can have a negative impact on self-esteem, quality of life and interpersonal relationships. The initial step in evaluation is a detailed medical and social history, including a review of medication use. Discussion with the patient's sexual partner may clarify exacerbating issues. The physical examination focuses on the cardiovascular, neurologic and urogenital systems. Laboratory tests are useful to screen for common etiologic factors and, when indicated, to identify hypogonadal syndromes. Appropriate evaluation of erectile dysfunction leads to accurate advice, management and referral of patients with erectile dysfunction. PMID:10643952

  8. Male osteoporosis: A review

    PubMed Central

    Herrera, Antonio; Lobo-Escolar, Antonio; Mateo, Jesús; Gil, Jorge; Ibarz, Elena; Gracia, Luis

    2012-01-01

    Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. The etiology can be idiopathic or secondary to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic and every disease or drug use that alters bone metabolism. Risk factors such as a previous history of fragility fracture should be assessed for the diagnosis. However, risk factors in men are very heterogeneous. There are significant differences in the pharmacological treatment of osteoporosis between men and women fundamentally due to the level of evidence in published trials supporting each treatment. New treatments will offer new therapeutic prospects. The goal of this work is a revision of the present status knowledge about male osteoporosis. PMID:23362466

  9. Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders

    PubMed Central

    Clarke, Holly; Dhillo, Waljit S.

    2015-01-01

    Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field. PMID:26194072

  10. [Sexuality in overweight and obesity].

    PubMed

    Abrahamian, Heidemarie; Kautzky-Willer, Alexandra

    2016-03-01

    The association between obesity and sexual dysfunction has been described in many studies. Neurobiological, hormonal, vascular and mental disturbances are the main reasons in male and in female gender. Sexual interest and desire, sexual arousal, orgasm, painful intercourse and premature ejaculation can be involved. Data for prevalence of sexual function disturbances in obese people are scarce and most studies were small. For screening of sexual function we recommend the International Index of Erectile Function (IIEF)-Score, which contains 15 Items for males and the Female Sexual Function Index (FSFI), which contains 19 items for females. Treatment of sexual function disturbances include lifestyle changes with an increase of physical activity, weight control, healthy eating and smoking cessation. Testosterone substitution in cases of real hypogonadism and treatment with PDE-5 inhibitors are well documented treatment options in male individuals. New treatment options for female patients with variable effectiveness are fibanserin, testosterone, bupropione and oxytocin. PMID:26811242

  11. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness

    PubMed Central

    Pan, Michael M.

    2016-01-01

    Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required. PMID:27141449

  12. Partial trisomy 14q and monosomy 20q due to an unbalanced familial translocation

    SciTech Connect

    Menasse-Palmer, L; Leo, J.; Cannizaro, L.

    1994-09-01

    Partial trisomy of distal 14q and monosomy of 20q are rare. There have been several reports of a partial distal trisomy 14q with characteristic clinical findings, including hypogonadism and a conotruncal cardiac anomaly. There is no deletion distal 20q syndrome. We have recently examined a newborn with this unique duplication/deletion syndrome. Case report: J.S. was the 2980 gm product of a term uneventful pregnancy delivered to a 24-year-old gravida 2, para 1001 mother. The newborn exam revealed a dysmorphic newborn male with a sloping forehead, bitemporal narrowing, glabellar furrowing and micrognathia. A systolic murmur was audible. The genital abnormalities were micropenis, hypospadias with chordee and bifid scrotum with prominent raphe, and gonads were palpable. A CAT scan of the head revealed grade I IVH. An echocardiogram showed a VSD, ASD and an AP window. A sonogram of the liver showed absence of the gallbladder. Chromosome analysis revealed an abnormal male karyotype containing a derivative 20, subsequently shown to be inherited as a result of malsegregation of a paternal translocation: 46,XY,-20,+der(20)t(14;20)(q32.1;q13.3)pat. The infant fed poorly and required tube feedings and was treated for congestive heart failure with Digoxin, Lasix and oxygen. A decreased cortisol level and cholestasis were noted. The infant died after a cardiopulmonary arrest at one month of age. No post-mortem was obtained. Clinical cytogenetic correlation (conotruncal abnormality and hypogonadism) with partial duplication of distal 14q was positive. This case helps to further delineate duplication 14q and a syndrome due to partial deletion 20q.

  13. Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem.

    PubMed

    Rahnema, C D; Crosnoe, L E; Kim, E D

    2015-03-01

    Colloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace. PMID:25684733

  14. A New Look at XXYY Syndrome: Medical and Psychological Features

    PubMed Central

    Tartaglia, Nicole; Davis, Shanlee; Hench, Alison; Nimishakavi, Sheela; Beauregard, Renee; Reynolds, Ann; Fenton, Laura; Albrecht, Lindsey; Ross, Judith; Visootsak, Jeannie; Hansen, Robin; Hagerman, Randi

    2011-01-01

    XXYY syndrome occurs in approximately 1:18,000–1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multicenter study of 95 males age 1–55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall

  15. Androgens and prostate disease

    PubMed Central

    Cooper, Lori A; Page, Stephanie T

    2014-01-01

    A growing body of literature has established the anabolic benefits of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease. PMID:24407178

  16. Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly

    PubMed Central

    Schaefer, E.; Zaloszyc, A.; Lauer, J.; Durand, M.; Stutzmann, F.; Perdomo-Trujillo, Y.; Redin, C.; Bennouna Greene, V.; Toutain, A.; Perrin, L.; Gérard, M.; Caillard, S.; Bei, X.; Lewis, R.A.; Christmann, D.; Letsch, J.; Kribs, M.; Mutter, C.; Muller, J.; Stoetzel, C.; Fischbach, M.; Marion, V.; Katsanis, N.; Dollfus, H.

    2011-01-01

    The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1–2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for

  17. Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

    PubMed

    Schaefer, E; Zaloszyc, A; Lauer, J; Durand, M; Stutzmann, F; Perdomo-Trujillo, Y; Redin, C; Bennouna Greene, V; Toutain, A; Perrin, L; Gérard, M; Caillard, S; Bei, X; Lewis, R A; Christmann, D; Letsch, J; Kribs, M; Mutter, C; Muller, J; Stoetzel, C; Fischbach, M; Marion, V; Katsanis, N; Dollfus, H

    2011-09-01

    The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for

  18. Management of the cardinal features of andropause.

    PubMed

    Mooradian, Arshag D; Korenman, Stanley G

    2006-01-01

    There are several problems facing aging men, especially sexual dysfunction, hypogonadism, and psychologic changes. This constellation of changes is sometimes referred to as "manopause" or "andropause." Unlike the dramatic changes in the hormonal milieu occurring during menopause in women, the age-related changes in reproductive hormones of men are subtle and occur gradually throughout the years of mature life. It has been estimated that circulating testosterone (T) declines longitudinally from age 19 at an average rate of 1% per year. The free or dialyzable fraction of serum T and the bioavailable (the sum of free fraction and loosely bound to albumin fraction) T decline more rapidly with age. Although the essential role of androgens in reproductive tissue development and emergence of secondary sex characteristics is well known, their role in adult sexual function seems to be primarily facultative. The effect of T on the central nervous system extends beyond sexual behavior. T has been shown to alter mood, memory, ability to concentrate, and the overall sense of vigor and well being that may interact with a host of other psychologic changes associated with aging. Disordered erectile function is not generally an endocrine problem but rather vascular, neurologic, and psychogenic in origin. It also may be the first sign of systemic vascular disease. The clinical management of andropause requires an individualized approach. In some men, the main problem may be psychologic, whereas in others, hypogonadism may play an important role. Many with erectile failure, suffer silently regardless of its etiology. In this review, we suggest some practical guidelines for the management of these conditions. PMID:16645432

  19. Study of trabecular bone microstructure using spatial autocorrelation analysis

    NASA Astrophysics Data System (ADS)

    Wald, Michael J.; Vasilic, Branimir; Saha, Punam K.; Wehrli, Felix W.

    2005-04-01

    The spatial autocorrelation analysis method represents a powerful, new approach to quantitative characterization of structurally quasi-periodic anisotropic materials such as trabecular bone (TB). The method is applicable to grayscale images and thus does not require any preprocessing, such as segmentation which is difficult to achieve in the limited resolution regime of in vivo imaging. The 3D autocorrelation function (ACF) can be efficiently calculated using the Fourier transform. The resulting trabecular thickness and spacing measurements are robust to the presence of noise and produce values within the expected range as determined by other methods from μCT and μMRI datasets. TB features found from the ACF are shown to correlate well with those determined by the Fuzzy Distance transform (FDT) in the transverse plane, i.e. the plane orthogonal to bone"s major axis. The method is further shown to be applicable to in-vivo μMRI data. Using the ACF, we examine data acquired in a previous study aimed at evaluating the structural implications of male hypogonadism characterized by testosterone deficiency and reduced bone mass. Specifically, we consider the hypothesis that eugonadal and hypogonadal men differ in the anisotropy of their trabecular networks. The analysis indicates a significant difference in trabecular bone thickness and longitudinal spacing between the control group and the testosterone deficient group. We conclude that spatial autocorrelation analysis is able to characterize the 3D structure and anisotropy of trabecular bone and provides new insight into the structural changes associated with osteoporotic trabecular bone loss.

  20. A girl with incomplete Prader-Willi syndrome and negative MS-PCR, found to have mosaic maternal UPD-15 at SNP array.

    PubMed

    Morandi, Anita; Bonnefond, Amélie; Lobbens, Stéphane; Carotenuto, Marco; Del Giudice, Emanuele Miraglia; Froguel, Philippe; Maffeis, Claudio

    2015-11-01

    The Prader-Willi syndrome (PWS) is caused by lack of expression of paternal allele of the 15q11.2-q13 region, due to deletions at paternal 15q11.2-q13 (<70%), maternal uniparental disomy of chromosome 15 (mat-UPD 15) (30%) or imprinting defects (1%). Hyperphagia, intellectual disabilities/behavioral disorders, neonatal hypotonia, and hypogonadism are cardinal features for PWS. Methylation sensitive PCR (MS-PCR) of the SNRPN locus, which assesses the presence of both the unmethylated (paternal) and the methylated (maternal) allele of 15q11.2-q13, is considered a sensitive reference technique for PWS diagnosis regardless of genetic subtype. We describe a 17-year-old girl with severe obesity, short stature, and intellectual disability, without hypogonadism and history of neonatal hypotonia, who was suspected to have an incomplete PWS. The MS-PCR showed a normal pattern with similar maternal and paternal electrophoretic bands. Afterwards, a SNP array showed the presence of iso-UPD 15, that is, UPD15 with two copies of the same chromosome 15, in about 50% of cells, suggesting a diagnosis of partial PWS due to mosaic maternal iso-UPD15 arisen as rescue of a post-fertilization error. A quantitative methylation analysis confirmed the presence of mosaic UPD15 in about 50% of cells. We propose that complete clinical criteria for PWS and MS-PCR should not be considered sensitive in suspecting and diagnosing partial PWS due to mosaic UPD15. In contrast, clinical suspicion based on less restrictive criteria followed by SNP array is a more powerful approach to diagnose atypical PWS due to UPD15 mosaicism. PMID:26109092

  1. Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin-releasing hormone deficiency caused by mutations in the KAL1 gene

    PubMed Central

    Li, Juan; Li, Niu; Ding, Yu; Huang, Xiaodong; Shen, Yongnian; Wang, Jian; Wang, Xiumin

    2015-01-01

    Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) pertains to a group of genetic disorders consisting of anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). KS is genetically heterogeneous. We hereby present 5 young male patients with GnRH deficiency caused by mutations in the KAL1 gene. Their ages ranged from 9 months to 16 years. They were referred to our department for an endocrine consultation for micropenis. Hormone assays showed low circulating gonadotropins and testosterone. Molecular studies revealed KAL1 mutations in all cases, three reported nonsense sequence variants in the KAL1 gene were detected in 4 patients, respectively (c.784C > T (p.Arg 262*), c.1267C > T (p.Arg423*), and c.1270C > T (p.Arg424*)), and one patient harbored a novel hemizygous sequence variant [c.227G > A (p.Trp76*)]. Only one patient presented short stature without growth hormone deficiency and anosmia. Another patient had bilateral eyelid ptosis, trichiasis, and refractive error. This is the first report on the co-occurrence of a KAL1 gene mutation and tent-like upper lip in four patients. All of our cases had normal olfactory bulbs and showed no renal agenesis, cleft lip/palate, and hearing impairment. These cases expand our knowledge of the phenotype associated with KAL1 sequence variations, although the precise mechanism by which KAL1 gene influences the development of this phenotype is still unknown. PMID:26862482

  2. Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model.

    PubMed

    Audran, M; Chappard, D; Legrand, E; Libouban, H; Baslé, M F

    2001-10-01

    In men, the risk of fragility fractures increases as bone mineral declines but there is an overlap in the bone mineral density (BMD) measurements between patients with and those without fractures. Biomechanical competence of trabecular (Tb) bone depends on the amount of bone and on microarchitecture. We have developed new histomorphometric methods for evaluating microarchitecture on histological sections. These methods were used in the orchidectomized male rat (ORX--a model of hypogonadism-induced osteoporosis) and on transiliac bone biopsies performed in male osteoporotic patients. ORX rats were studied at 2, 4, 8, and 16 weeks post-ORX. Bone mineral content (BMC) was reduced at 16 weeks. Trabecular bone volume (BV/TV) was significantly decreased from the 4th week. Differences in the sensitivity of the methods were found. Fractal dimension was modified as early as 2 weeks and appeared the most potent descriptor of Tb disorganization. The architectural changes in this model mimic those observed in hypogonadic men. We examined the relationships among BMD, micro-architecture, and vertebral fracture in 108 men with lumbar osteopenia (T-score <-2.5). At least one vertebral fracture was observed in 62 patients and none in 46 patients. After adjusting for age, body mass index (BMI), and BMD, there was no significant difference between the two groups in BV/TV, Tb.Th, and Star volume. In contrast, the mean values of ICI and Tb.Sp were significantly higher whereas Tb.N and nodes were lower in patients with vertebral fracture. Logistic regression analysis showed that ICI, strut analysis, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of I SD ranged from 1.7 for nodes to 3.2 for ICI. These results strongly suggest that bone Tb microarchitecture is a major and independent determinant of vertebral fracture in men with osteoporosis. PMID:11730253

  3. Impact of genotype on endocrinal complications in β-thalassemia patients

    PubMed Central

    AL-AKHRAS, AHMED; BADR, MOHAMED; EL-SAFY, USAMA; KOHNE, ELISABETH; HASSAN, TAMER; ABDELRAHMAN, HADEEL; MOURAD, MOHAMED; BRINTRUP, JOAQUIN; ZAKARIA, MARWA

    2016-01-01

    In β-thalassemia, certain mutations cause a complete absence of β-globin chain synthesis, termed β0-thalassemia, while others may allow certain β-globin production and are termed β+- or β++-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in β-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the β0β0 genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the β0β+ and β+β+ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption. PMID:27284414

  4. Endocrine dysfunction in hereditary hemochromatosis.

    PubMed

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies. PMID:26951056

  5. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

    PubMed Central

    Oduwole, Olayiwola O.; Vydra, Natalia; Wood, Nicholas E. M.; Samanta, Luna; Owen, Laura; Keevil, Brian; Donaldson, Mandy; Naresh, Kikkeri; Huhtaniemi, Ilpo T.

    2014-01-01

    Testosterone (T), alone or in combination with progestin, provides a promising approach to hormonal male contraception. Its principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the testicular T production needed for spermatogenesis, while simultaneously maintaining the extragonadal androgen actions, such as potency and libido, to avoid hypogonadism. A serious drawback of the treatment is that a significant proportion of men do not reach azoospermia or severe oligozoospermia, commensurate with contraceptive efficacy. We tested here, using hypogonadal luteinizing hormone/choriongonadotropin receptor (LHCGR) knockout (LHR−/−) mice, the basic principle of the T-based male contraceptive method, that a specific T dose could maintain extragonadal androgen actions without simultaneously activating spermatogenesis. LHR−/− mice were treated with increasing T doses, and the responses of their spermatogenesis and extragonadal androgen actions (including gonadotropin suppression and sexual behavior) were assessed. Conspicuously, all dose responses to T were practically superimposable, and no dose of T could be defined that would maintain sexual function and suppress gonadotropins without simultaneously activating spermatogenesis. This finding, never addressed in clinical contraceptive trials, is not unexpected in light of the same androgen receptor mediating androgen actions in all organs. When extrapolated to humans, our findings may jeopardize the current approach to hormonal male contraception and call for more effective means of inhibiting intratesticular T production or action, to achieve consistent spermatogenic suppression.—Oduwole, O. O., Vydra, N., Wood, N. E. M., Samanta, L., Owen, L., Keevil, B., Donaldson, M., Naresh, K., Huhtaniemi, I. T. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception. PMID:24599970

  6. Potential Diagnostic Utility of Intermittent Short-Acting GnRH Agonist Administration in Gonadotropin Deficiency

    PubMed Central

    Zimmer, Carrie A.; Ehrmann, David A; Rosenfield, Robert L.

    2010-01-01

    Objective The objective was to determine if intermittent, low-dose, short-acting GnRH agonist (GnRHag) administration up-regulates pituitary-gonadal function in gonadotropin deficiency (GnD) sufficiently to be of diagnostic or therapeutic value. Design/Intervention Low-dose leuprolide acetate was administered SC at 4–5 d intervals up to one year. Patients Adult volunteers and GnD patients were studied. Setting The studies were performed in a General Clinical Research Center. Main Outcome Measures LH, FSH, and sex steroid responses were determined. Results In normal men and women, low-dose GnRHag repetitively transiently stimulated gonadotropins in a gender-dimorphic manner. In congenitally GnD deficient men (n=6) and women (n=1), none of whom had a normal LH response to an initial GnRHag test dose, this regimen consistently stimulated LH to the normal baseline range within two weeks. Long-term GnRHag administration to a partially GnD man did not alleviate hypogonadism, however. Women with hypothalamic amenorrhea (n=2) responded normally to a single GnRHag injection; however, repeated dosing did not seem to induce the normal priming effect. Conclusions The subnormal LH response to GnRHag of congenital GnD normalized in response to repetitive intermittent GnRHag, but not sufficiently to improve hypogonadism. Hypothalamic amenorrhea patients lacked the priming response to repeated GnRHag, but otherwise had normal hormonal responses to GnRHag. We conclude that intermittent administration of a short-acting GnRHag is of potential diagnostic value in distinguishing hypothalamic from pituitary causes of GnD. PMID:20553679

  7. Enhanced transdermal delivery of sex hormones in swine with a novel topical aerosol.

    PubMed

    Morgan, T M; Parr, R A; Reed, B L; Finnin, B C

    1998-10-01

    This study investigated the enhanced transdermal delivery of testosterone (Tes) and estradiol (E2) in swine in vivo with novel metered-dose topical aerosols containing the penetration enhancer padimate O (PadO) and predicted the dose deliverable in humans from the calculated drug flux across the skin. Weanling swine were catheterized and castrated under general anaesthesia and used as a conscious hypogonadal model. Tes and E2 (with and without PadO) were applied once, and venous blood samples were taken over 24 h. Tes and E2 plasma levels were determined by radioimmunoassay. After daily topical dosing of Tes for 6 days, the plasma Tes levels were determined and the transdermal flux was calculated by correcting the pseudo steady-state plasma concentration versus time profile with the clearance of an iv dose within the same swine. After a single application of the E2 aerosol over 30 cm2, or the Tes aerosol over 180 cm2, the mean AUC0-24 h when PadO was included in the spray was 14.1- and 2.0-fold greater than control, respectively (p < 0.03). After the sixth application of the Tes spray with PadO, the mean flux (+/-SE, n = 4) across swine skin in vivo was 2.12 +/- 0.35 microg/cm2.h, which gave a predicted flux in humans of 0.95 microg/cm2.h. From these data the expected plasma levels of Tes in hypogonadal men would compare well with the normal diurnal Tes profile in healthy men. These novel topical aerosols are capable of enhanced transdermal delivery of sex hormones in vivo, and they have the potential to deliver clinically relevant doses to humans. PMID:9758680

  8. Mechanism of Testosterone Deficiency in the Transgenic Sickle Cell Mouse

    PubMed Central

    Musicki, Biljana; Zhang, Yuxi; Chen, Haolin; Brown, Terry R.; Zirkin, Barry R.; Burnett, Arthur L.

    2015-01-01

    Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease. PMID:26023917

  9. Total Testosterone and Calculated Estimates for Free and Bioavailable Testosterone: Influence of Age and Body Mass Index and Establishment of Sex-Specific Reference Ranges.

    PubMed

    Deutschbein, T; Mann, K; Petersenn, S

    2015-10-01

    Measurement of sex steroids is required to evaluate gonadal function, but normative data are lacking (especially for estimates of physiologically active testosterone). Using modern immunoassays, this study established sex-specific reference ranges (2.5% and 97.5% percentiles) for total testosterone (TOT), bioactive testosterone Vermeulen (BTV), free androgen index (FAI), free testosterone Sartorius (FTS), free testosterone Vermeulen (FTV), and sex hormone binding globulin (SHBG). In the comparative study, subjects were grouped by age (18-30; 31-50; >50 years), BMI (<25; 25-30; >30 kg/m(2)), and sex. Study participants were selected in such a way that each group comprised 12 subjects (e.g., 12 males between 18 and 30 years with a BMI of <25 kg/m(2), and so on), resulting in a total of 216 controls (108 males, 108 females; age: 40.3 ± 1.0; BMI: 27.8 ± 0.4). Multiple stepwise regression analyses were performed (covariates: age, BMI, sex), and sex-specific reference ranges were applied to 50 males (age: 46.1 ± 2.3; BMI: 27.4 ± 0.7) with suspected hypogonadism. Regression analysis identified the strongest predictor of each parameter apart from sex, resulting in age-specific (males: FAI, SHBG, BTV, FTV; females: TOT, FTS, SHBG), BMI-specific (males: TOT, FTS; females: FAI, BTV, FTV) and overall cutoffs for both sexes. In male patients, overall agreement between the results derived from the estimates (i.e., BTV, FTS, FTV) was high (with discordant results in only 4%). In summary, if both the endocrine workup and the clinical presentation were taken into account, the newly established reference ranges allowed reliable identification of hypogonadal males. PMID:25565093

  10. Bone mineral density and disorders of mineral metabolism in chronic liver disease

    PubMed Central

    George, Joe; Ganesh, Hosahithlu K; Acharya, Shrikrishna; Bandgar, Tushar R; Shivane, Vyankatesh; Karvat, Anjana; Bhatia, Shobna J; Shah, Samir; Menon, Padmavathy S; Shah, Nalini

    2009-01-01

    AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS: The study was performed on 72 Indian patients with cirrhosis (63 male, nine female; aged < 50 years). Etiology of cirrhosis was alcoholism (n = 37), hepatitis B (n = 25) and hepatitis C (n = 10). Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density (BMD) was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS: Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium: protein ratio and calcium: phosphorus ratio. Vitamin D deficiency was highly prevalent (92%). There was a high incidence of hypogonadism (41%). Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor (IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low (68%) and urinary deoxypyridinoline to creatinine ratio was high (79%), which demonstrated low bone formation with high resorption. CONCLUSION: Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level. PMID:19630107

  11. Anabolic effects of testosterone are preserved during inhibition of 5alpha-reductase.

    PubMed

    Borst, Stephen E; Conover, Christine F; Carter, Christy S; Gregory, Chris M; Marzetti, Emanuele; Leeuwenburgh, Christiaan; Vandenborne, Krista; Wronski, Thomas J

    2007-08-01

    At replacement doses, testosterone produces only modest increases in muscle strength and bone mineral density in older hypogonadal men. Although higher doses of testosterone are more anabolic, there is concern over increased adverse effects, notably prostate enlargement. We tested a novel strategy for obtaining robust anabolic effects without prostate enlargement. Orchiectomized (ORX) male rats were treated for 56 days with 1.0 mg testosterone/day, with and without 0.75 mg/day of the 5alpha-reductase inhibitor MK-434. Testosterone administration elevated the prostate dihydrotestosterone concentration and caused prostate enlargement. Both effects were inhibited by MK-434. ORX produced a catabolic state manifested in reduced food intake, blunted weight gain, reduced hemoglobin concentration, decreased kidney mass, and increased bone resorption, and in the proximal tibia there was both decreased cancellous bone volume and a decreased number of trabeculae. In soleus and extensor digitorum longus muscles, ORX reduced both the percentage of type I muscle fibers and the cross-sectional area of type 1 and 2 fibers. Testosterone administration caused a number of anabolic effects, including increases in food intake, hemoglobin concentration, and grip strength, and reversed the catabolic effects of ORX on bone. Testosterone administration also partially reversed ORX-induced changes in muscle fibers. In contrast to the prostate effects of testosterone, the effects on muscle, bone, and hemoglobin concentration were not blocked by MK-434. Our study demonstrates that the effects of testosterone on muscle and bone can be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men. PMID:17488806

  12. Neuroendocrine mechanisms mediating awakening of the human gonadotropic axis in puberty.

    PubMed

    Veldhuis, J D

    1996-06-01

    The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator presides over the pulsatile and feedback-regulated activities of the pituitary-gonadal axis. Awakening of synchronous activity of the GnRH neuronal ensemble in the earliest stages of puberty heralds the onset of full activation of the reproductive axis in girls and boys. Progression from prepuberty to adulthood in boys is directed by marked (30-fold) amplitude enhancement of pulsatile luteinizing hormone (LH) secretion, as assessed by an ultrasensitive immunofluorometric assay and deconvolution analysis. There is a much less apparent rise in LH secretory burst frequency (approximately 1.3-fold increase). Consequently, human puberty is an amplitude-driven neuroendocrine maturational process. However, less is known about pulsatile follicle-stimulating hormone (FSH) release in puberty. Multiple pathophysiologies that result in hypogonadotropic hypogonadism can converge on a final common mechanism of attenuated hypothalamic GnRH pulse generator output and hence reduced LH (and FSH) secretion. Disturbances may take the form of reduced GnRH pulse frequency and/or attenuated GnRH secretory burst mass. When the pathophysiology of hypogonadism originates exclusively in a failed GnRH pulse generator, then either treatment of the primary disease process where possible (e.g., by refeeding in starvation, improved metabolic control in diabetes mellitus, dopamine agonist treatment in hyperprolactinemia, etc) and/or treatment with pulsatile GnRH (e.g., in Kallmann's syndrome, isolated hypothalamic lesions, etc.) can provide relevant therapeutic options in children and adults. PMID:8792395

  13. Flavor perception test: evaluation in patients with Kallmann syndrome.

    PubMed

    Maione, Luigi; Cantone, Elena; Nettore, Immacolata Cristina; Cerbone, Gaetana; De Brasi, Davide; Maione, Nunzia; Young, Jacques; Di Somma, Carolina; Sinisi, Antonio Agostino; Iengo, Maurizio; Macchia, Paolo Emidio; Pivonello, Rosario; Colao, Annamaria

    2016-05-01

    In Kallmann syndrome (KS), congenital hypogonadism is associated with olfactory impairment. To evaluate flavor perception-related disability in KS patients, 30 patients with KS, 12 with normosmic hypogonadism (nIHH), 24 with acquired anosmia (AA), and 58 healthy controls entered the study. All participants completed questionnaires concerning dietary habits, olfaction-related quality of life (QoL), and self-determined olfactory, flavor, and taste abilities prior to undergoing standardized olfactometry and gustometry. Each subject underwent flavor testing, using orally administered aqueous aromatic solutions, identifying 21 different compounds by choosing each out of 5 alternative items. Flavor score (FS) was calculated as the sum of correct answers (range 0-21). Flavor perception by self-assessment was similar between KS, nIHH, and controls, and was mostly reduced only in AA. FS was similar between KS (5.4 ± 1.4) and AA (6.4 ± 1.9), and lower than in nIHH (16.2 ± 2.4, p < 0.001) and controls (16.8 ± 1.7, p < 0.0001). FS showed strong reproducibility, and correlated with olfactory scores in the overall population. KS and AA patients identified aromatics eliciting trigeminal stimulation better than pure odorants. Olfaction-related QoL was more impaired in AA than in KS. We report significant flavor impairment in KS. This contrasts with routine clinic evidence; KS patients, in contrast with AA, do not complain of flavor perception impairment, perhaps owing to the congenital nature of the dysfunction. Flavor perception impairment should be considered a specific KS disability, because of important detrimental effects on physical and mental health and on QoL. KS patients should also be advised of this impairment in order to prevent accidental and life-threatening events. PMID:26209039

  14. Analysis of the relationship between the blood concentration of several metals, macro- and micronutrients and endocrine disorders associated with male aging.

    PubMed

    Rotter, Iwona; Kosik-Bogacka, Danuta I; Dołęgowska, Barbara; Safranow, Krzysztof; Kuczyńska, Magdalena; Laszczyńska, Maria

    2016-06-01

    Beyond 30 years of age, men experience a decline in the production of testosterone, yet only a few develop late-onset hypogonadism. This study was designed to determine the relationship between blood concentrations of metals, macro- and micronutrients and age-related testosterone deficiency and associated hormonal changes in aging men. The research involved 313 men aged 50-75 years. We used ELISA to determine the concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG). We calculated free androgen index (FAI). With the use of emission spectrometry in inductively coupled argon plasma, we determined the whole-blood concentrations of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As) and tungsten (W), as well as serum concentrations of magnesium (Mg), iron (Fe), calcium (Ca), copper (Cu), zinc (Zn), selenium (Se), chromium (Cr), manganese (Mn) and molybdenum (Mo). The study showed no relationship between TT and FT and the concentrations of metals. Men with TT deficiency had significantly lower concentrations of Mg and Fe and increased Mn. Men with FT deficiency had higher W and Cr levels and lower Fe. Assessing the correlation between the concentrations of hormones, SHBG and FAI, and the concentration of metals and macro- and microelements in the blood of the men, we found positive correlations between the concentrations of TT-Mg, TT-Fe, TT-Mo, FT-Fe, E2-As, SHBG-Mn, FAI-W, FAI-As, FAI-Zn and FAI-Ca, and negative correlations between the concentrations of TT-Mn, FT-Cd, FT-Cr, E2-Hg, E2-Cr, SHBG-W, SHBG-As, SHBG-Zn, SHBG-Ca, FAI-Pb and FAI-Mn. Positive correlations between As and E2 and between As and FAI may suggest a lack of association between this metal and hypogonadism in people not exposed to excess As levels. Our research indicates a positive relationship between the concentrations of Mg, Fe and Zn and endocrine system in aging men, in contrast to Mn and

  15. Gender differences in macroprolactinomas: a single centre experience

    PubMed Central

    Khare, Shruti; Lila, Anurag R; Patt, Hiren; Yerawar, Chaitanya; Goroshi, Manjunath; Bandgar, Tushar; Shah, Nalini S

    2015-01-01

    Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29±10.39 years) presented at younger mean age than males (35.23±9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36±6863.01 ng/ml) than males (7927.07±16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49±1.48 cm) was smaller than males (3.93±1.53 cm) (P<0.001). In 88 treatment naïve patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1–2 cm, 2.1–4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females. PMID:26682970

  16. Turner syndrome: contemporary thoughts and reproductive issues.

    PubMed

    Reindollar, Richard H

    2011-07-01

    Turner syndrome is a common genetic disorder that has been classically associated with a 45,X karyotype. Several X-chromosomal abnormalities have been identified in these patients, many of which involve mosaicism. These patients have variable but predictable phenotypic findings and are at risk for development of endocrine, autoimmune, and structural abnormalities. As many as 1.5% of the population with Turner syndrome may develop dissection and rupture of the ascending aorta; the presence of abnormalities of the cardiac tree and hypertension increase this risk, but their absence does not preclude it. Rupture has occurred at aortic diameters smaller than previously reported for other patient populations. Five percent or more of women with Turner syndrome may have abbreviated menstrual function before developing amenorrhea and hypergonadotropic hypogonadism. An estimated 1 to 2% of all patients may become pregnant. Only three patients with Turner syndrome (and two of them with streak ovaries) have ever been reported to become pregnant after developing amenorrhea and elevated gonadotropin levels. Pregnancy, either spontaneous or more commonly from donor oocyte, increases maternal mortality rate for these women by an estimated ≥100 fold. It appears that all Turner women are at risk of rupture; neither prior spontaneous menses nor age >30 years provides protection. In addition, the literature suggests that the physiological changes of pregnancy may increase the risk of rupture in future years after delivery for those Turner women who seemingly made it safely through pregnancy. The use of the term PRIMARY OVARIAN INSUFFICIENCY (POI) for Turner syndrome gives me some discomfort. For women with 46,XX hypergonadotropic hypogonadism, POI accurately provides the suggestion that follicular depletion is often not complete (although remissions are usually self-limiting and the vast majority of patients will not spontaneously become pregnant). I clearly understand the need to

  17. Severity and pattern of bone mineral loss in endocrine causes of osteoporosis as compared to age-related bone mineral loss

    PubMed Central

    Dutta, D; Dharmshaktu, P; Aggarwal, A; Gaurav, K; Bansal, R; Devru, N; Garga, UC; Kulshreshtha, B

    2016-01-01

    Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD) loss in endocrinopathies [Graves’ disease (GD), type 1 diabetes mellitus (T1DM), hypogonadotrophic hypogonadism (HypoH), hypergonadotropic hypogonadism (HyperH), hypopituitarism, primary hyperparathyroidism (PHPT)] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO), andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126) were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%), HyperH (85%), and HypoH (79.59%) compared to age-related BMD loss (60.02%; P < 0.001). The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%), HyperH (85%), and HypoH (59.26%) compared to PMO (49.34%; P < 0.001). Z score at LS, TF, NOF, and greater trochanter (GT) was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67%) and HypoH (54.55%) compared to andropause (45.45%; P = 0.001). Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI) and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting. PMID:27241810

  18. Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts

    PubMed Central

    2014-01-01

    Background Mutations in the gene STUB1, encoding the protein CHIP (C-terminus of HSC70-interacting protein), have recently been suggested as a cause of recessive ataxia based on the findings in few Chinese families. Here we aimed to investigate the phenotypic and genotypic spectrum of STUB1 mutations, and to assess their frequency in different Caucasian disease cohorts. Methods 300 subjects with degenerative ataxia (n = 167) or spastic paraplegia (n = 133) were screened for STUB1 variants by whole-exome-sequencing (n = 204) or shotgun-fragment-library-sequencing (n = 96). To control for the specificity of STUB1 variants, we screened an additional 1707 exomes from 891 index families with other neurological diseases. Results We identified 3 ataxia patients (3/167 = 1.8%) with 4 novel missense mutations in STUB1, including 3 mutations in its tetratricopeptide-repeat domain. All patients showed evidence of pyramidal tract damage. Cognitive impairment was present only in one and hypogonadism in none of them. Ataxia did not start before age 48 years in one subject. No recessive STUB1 variants were identified in families with other neurological diseases, demonstrating that STUB1 variants are not simply rare polymorphisms ubiquitous in neurodegenerative disease. Conclusions STUB1-disease occurs also in Caucasian ataxia populations (1.8%). Our results expand the genotypic spectrum of STUB1-disease, showing that pathogenic mutations affect also the tetratricopeptide-repeat domain, thus providing clinical evidence for the functional importance of this domain. Moreover, they further delineate the phenotypic core features of STUB1-ataxia. Pyramidal tract damage is a common accompanying feature and can include lower limb spasticity, thus adding STUB1-ataxia to the differential diagnosis of “spastic ataxias”. However, STUB1 is rare in subjects with predominant spastic paraplegia (0/133). In contrast to previous reports, STUB1-ataxia can start even above age 40

  19. Pituitary Involvement in Granulomatosis With Polyangiitis

    PubMed Central

    De Parisot, Audrey; Puéchal, Xavier; Langrand, Corinne; Raverot, Gerald; Gil, Helder; Perard, Laurent; Le Guenno, Guillaume; Berthier, Sabine; Tschirret, Olivier; Eschard, Jean Paul; Vinzio, Stephane; Guillevin, Loïc; Sève, Pascal

    2015-01-01

    Abstract Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database. Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been

  20. Giant prolactinomas: are they really different from ordinary macroprolactinomas?

    PubMed

    Espinosa, Etual; Sosa, Ernesto; Mendoza, Victoria; Ramírez, Claudia; Melgar, Virgilio; Mercado, Moisés

    2016-06-01

    Giant prolactinomas (gPRLomas) are rare tumors of the lactotroph defined by an unusually large size (>4 cm) and serum PRL levels >1000 ng/mL. The purpose of this study is to characterize the clinical spectrum of gPRLomas comparing them with non-giant prolactinomas. This is a retrospective study at a large referral center. Data from patients harboring gPRLomas and macroprolactinomas were retrieved from medical records of the Prolactinoma Clinic. Analysis was focused on clinical, biochemical, and tumor volume characteristics, as well as on the response to treatment with dopamine agonists. Among 292 patients with prolactinomas followed between 2008 and 2015, 47 (16 %) met the diagnostic criteria for gPRLomas (42 males). The most common complaint was a visual field defect; headache was reported by 79 % and sexual dysfunction was present in over half of the patients. Median basal PRL level and tumor volume were 6667 ng/mL (3750-10,000) and 32 cm(3) (20-50), respectively; hypogonadotropic hypogonadism was documented in 87 %. Cabergoline treatment resulted in the normalization of PRL levels in 68 % and in the reduction of >50 % in tumor volume in 87 % of the gPRLoma patients. The composite goal of PRL normalization and >50 % tumor reduction was achieved by 55 % (n = 26) of patients with gPRL and by 66 % (n = 100) of patients with no giant macroprolactinomas (p = 0.19). Recovery of hypogonadism and improvement of visual fields defects occurred in 32 % and 68 % of the patients, respectively. Cabergoline treatment was equally effective in patients with gPRLoma and those with macroprolactinomas in regard of achieving treatment goals, although the median CBG dose was slightly higher in the gPRLoma group (2 vs. 1.5 mg/w). Six patients required surgery. Beyond their impressive dimensions and the huge amount of PRL they secrete, the clinical behavior of gPRLoma is not different from macroprolactinomas. These tumors are highly responsive to cabergoline

  1. Clinical, endocrinological and biochemical effects of zinc deficiency.

    PubMed

    Prasad, A S

    1985-08-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been

  2. Clinical, endocrinologic, and biochemical effects of zinc deficiency.

    PubMed

    Prasad, A S

    1985-01-01

    The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell

  3. The role of zinc in gastrointestinal and liver disease.

    PubMed

    Prasad, A S

    1983-09-01

    Zinc is essential for many metabolic and enzymatic functions in man. Deficiency of zinc in man has now been recognized to occur not only as a result of nutritional factors, but also in various disease states, including malabsorption syndromes, acrodermatitis enteropathica, Crohn's disease, alcoholism and cirrhosis of the liver. The deficiency state in human subjects exists as a spectrum extending from mild to severe degree. The clinical manifestations of mild zinc deficiency include oligospermia, weight loss and hyperammonaemia. Moderate zinc deficiency is characterized clinically by growth retardation, hypogonadism in males, skin changes, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In severe zinc deficiency states, bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorders, weight loss, intercurrent infections, hypogonadism in males and, if unrecognized, death have been observed. Zinc is needed for the functions of over 100 enzymes. It is essential for DNA, RNA and protein synthesis and, as such, is important for cell division. Zinc is an inducer of mRNA of metallothionein, a protein which may have an important role in the regulation of intestinal zinc absorption. Zinc has a specific effect on testes in animals and man. Recent reports indicate that in human subjects thymopoietin may be zinc dependent and in animal studies somatomedin may be affected adversely due to dietary zinc restriction. Zinc plays an important role in the protection of cell membrane integrity and may be protective against free radical injury. Zinc is known to compete with cadmium, lead, copper, iron and calcium for similar binding sites. In the future, a potential use of zinc may be to alleviate toxic effects of cadmium and lead in human subjects. Recent evidence suggests that thymic-dependent lymphocytes (T cells are zinc dependent. T-helper and suppressor cells, T-effector cells and T-natural killer cells appear to be

  4. Clinical manifestations of zinc deficiency.

    PubMed

    Prasad, A S

    1985-01-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present

  5. Comparison of the Effects of Testosterone Gels, Injections, and Pellets on Serum Hormones, Erythrocytosis, Lipids, and Prostate-Specific Antigen

    PubMed Central

    Pastuszak, Alexander W; Gomez, Lissette P; Scovell, Jason M; Khera, Mohit; Lamb, Dolores J; Lipshultz, Larry I

    2015-01-01

    Introduction Numerous testosterone (T) formulations are available, each with differing effects on serum parameters. Aim The aim of this study was to compare the long-term effects of topical, injectable, and implantable pellet T formulations in hypogonadal men. Methods Retrospective review of hypogonadal men treated with a single T formulation was performed: 47 men on T gels, 57 on injectable T, and 74 on T pellets were identified. Total T (TT), calculated free T (FT), estradiol (E), hemoglobin (Hgb), hematocrit (Hct), prostate-specific antigen (PSA), total cholesterol (Tchol), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were evaluated at baseline and every 3–6 months for 3 years. Serum parameters were compared using a mixed model linear regression for repeated measures. Main Outcome Measures Effects of topical, injectable, and pellet T formulations on serum hormone levels, Hgb, Hct, lipid parameters and PSA. Results Men in the injectable T group were younger (42.5 ± 12.3 years) than in the gel (54.1 ± 9.8 years) or pellet groups (53.8 ± 13.0 years), and baseline FT, Hgb, and Hct were higher in the injectable T group than in gel or pellet groups. Increases in TT and FT were observed throughout follow-up in all groups. Increases in E were observed at in all T groups and throughout follow-up in injectable and gel groups. No PSA increases were observed. Erythrocytosis (Hct > 50%) was more common with injectable T (66.7%) than with T gels (12.8%) or pellets (35.1%, P < 0.0001). Transient changes in cholesterol, TG, and LDL were observed, and no significant changes were seen in HDL for any group. Conclusions All T formulations increase serum T and FT. More significant increases in E occur with injectable T and T gels. Changes in Hgb and Hct are most significant with injectable T, and effects on lipids are variable and inconsistent. Selection of T formulations must account for individual

  6. Gender differences in macroprolactinomas: a single centre experience.

    PubMed

    Khare, Shruti; Lila, Anurag R; Patt, Hiren; Yerawar, Chaitanya; Goroshi, Manjunath; Bandgar, Tushar; Shah, Nalini S

    2016-01-01

    Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29±10.39 years) presented at younger mean age than males (35.23±9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36±6863.01 ng/ml) than males (7927.07±16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49±1.48 cm) was smaller than males (3.93±1.53 cm) (P<0.001). In 88 treatment naïve patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1-2 cm, 2.1-4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females. PMID:26682970

  7. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction.

    PubMed

    Anawalt, B D; Bebb, R A; Matsumoto, A M; Groome, N P; Illingworth, P J; McNeilly, A S; Bremner, W J

    1996-09-01

    We used a recently developed ELISA format to test the hypothesis that inhibin B is the physiologically active form of inhibin in men. We measured and compared inhibin A, inhibin B, and pro-alpha-C-related immunoreactive peptides (pro-alpha-C-RI) in normal men before and after perturbations of their gonadotropin levels and baseline values in normal men and men with various disturbances of the hypothalamic-pituitary-testicular axis including men with idiopathic hypogonadotropic hypogonadism, infertile men with elevated FSH, men with Klinefelter's syndrome, and orchidectomized men. Mean serum inhibin concentrations were significantly higher in normal men than untreated men with idiopathic hypogonadotropic hypogonadism, infertile men with elevated FSH, untreated men with Klinefelter's syndrome, and orchidectomized men (187 +/- 28 vs 45 +/- 11, 37 +/- 6, 11 +/- 3, and < or = 10 pg/mL, respectively; P < 0.05). Inhibin B levels were below the limit of detection in all of the orchidectomized men. Pro-alpha-C-RI levels were detectable in all men studied including the orchidectomized men, and no significant differences in the pro-alpha-C-RI levels were noted between the normal men and men with various testicular diseases were noted except that orchidectomized men had significantly lower pro-alpha-C-RI levels than all other groups (P < 0.05). Inhibin A was undetectable in all men tested in this study. Six normal men who were administered exogenous levonorgestrel and testosterone had significantly lower serum gonadotropin, inhibin B, and pro-alpha-C-RI levels during the treatment period than the control and recovery periods (P < 0.05). Ten normal men who were administered human recombinant FSH had significantly higher peak serum FSH (21.85 +/- 3.23 IU/L vs. 3.01 +/- 0.51 IU/L), inhibin B (311 +/- 88 pg/mL vs. 151 +/- 23 pg/mL) and pro-alpha-C-RI (646 +/- 69 vs. 402 +/- 38 pg/mL) levels during the treatment period than the baseline values (P < 0.05). We conclude that inhibin B

  8. AB69. Phyto-androgenic androgens in men’s health, sex and aging FX

    PubMed Central

    Adimoelja, Arif; Siauw, Ali Fuchih

    2014-01-01

    Protodioscin is a Herbal Steroid Saponin extract derived mainly from Tribulus terristris L. grown mainly in Bulgaria. This herbal plant begun well known in main stream medicine since the periods around 1972 in Indonesia when this phyto-steroid compound has been proven of having the ability to be converted to DHEA and further to another androgenic androgen (T) in hypogonadal men in the presence of 5-alpha-dehydrogenase (A. Adimoelja, 1976, 1978). Biogenic androgens and androgenic androgens Testosterone as a product of the male gonads from blood serum cholesterol. Cholesterol is further converted to DHEA. This product is identified as one of the biogenic or endogenic androgens (testosterone, pregnenolone, progesterone, aldosterone, androstendione). Health disorders are often hampered by the tendencies of men or women to conceal their health (sexual health) conditions due to fear and/or embarrassments. If these conditions are not being soonest medically diagnosed and left to be untreated, another un-healthy condition may appear. (hypertension, high blood serum cholesterol, decrease HDL, CVD). Decrease libido, sex arousal and ED are the first expression of the down-degraded health conditions which may appear (A. Adimoelja 1985). Prescription of phytopharmaceuticals in mainstream medicine Surprisingly more phyto-pharmaceuticals in mainstream medicine were unconsciously prescribed by physicians (25% of prescriptions, WHO, 1908). Prescriptions were made to support health conditions and promote sexual health problems, most common as aphrodisiacs. Prtodioscin and health enhancers Protodioscin indeed promote health condition in hypogonadic men (A.Adimoelja and Tjahjo Djojo Tanojo, 2009). Regretfully most herbal products whih has been promoted as health foods in the market, or sex-tonics are combined with other chemical product(s), some of which combined with erectogenics (W. Pangkahila, 2010). Sharlip ID (USA) too reported in the “Newark Star Ledger in 2002” that 9 out

  9. Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats.

    PubMed

    Giovambattista, Andrés; Suescun, María O; Nessralla, Claudio C D L; França, Luiz R; Spinedi, Eduardo; Calandra, Ricardo S

    2003-11-01

    Neonatal L-monosodium glutamate (MSG) administration in rats induces several neuroendocrine and metabolic disruptions. Leptin, the adipocyte product, modulates several neuroendocrine systems including the hypothalamic-pituitary-gonadal (HPG) axis in mammals. The aim of the present study was to determine whether MSG-induced chronic hyperleptinemia could play any relevant role in the hypogonadism developed by male rats when examined in adulthood. We found that 120-day-old MSG male rats displayed significant hyperleptinemia, hypogonadism, and undisturbed basic testis structure and spermatogenesis. In vitro studies in purified Leydig cells from normal (CTR) and MSG-damaged rats revealed that basal and human chorionic gonadotropin (hCG)-stimulated 17-hydroxy-progesterone (17-HO-P(4)), Delta(4)-androstenedione (Delta(4)A) and testosterone (T) secretions were significantly lower in MSG than in CTR cells. Exposure to murine leptin (Mleptin, 10(-8)M) significantly inhibited hCG-elicited T secretion by CTR cells after 180 min incubation. While Mleptin significantly inhibited hCG-stimulated Delta(4)A output and the Delta(4)A:17-OH-P(4) ratio of secretion, conversely, it failed to modify the ratio T:Delta(4)A release by CTR Leydig cells. Interestingly, the effects of Mleptin found on CTR Leydig cells were absent in MSG Leydig cells. Finally, endogenous hyperleptinemia was associated with a significant decrease in Leydig cell expression of Ob-Rb mRNA in MSG rats. In summary, this study demonstrates that: (1) Mleptin inhibited testicular steroidogenesis in CTR rats; (2) MSG-treated rats showed lower in vitro 17-OH-P(4), Delta(4)A and T production under basal and post-hCG stimulation conditions; (3) purified Leydig cells from MSG-treated rats displayed resistance to the inhibitory action of Mleptin on T release, and (4) endogenous leptin exerts a modulatory effect on Leydig cell Ob-Rb mRNA expression. The inhibitory effect of leptin on testicular function is thus abrogated in MSG

  10. PEYRONIE’S DISEASE: A REVIEW OF ETIOLOGY, DIAGNOSIS, AND MANAGEMENT

    PubMed Central

    Bilgutay, Aylin N.; Pastuszak, Alexander W.

    2015-01-01

    Peyronie’s Disease (PD) is a superficial fibrosing disorder of the penis resulting in plaque formation and penile deformity. Once considered rare, PD has more recently been found in up to 13% of men, and can negatively affect sexual and psychosocial function of both patients and their partners. While the etiology of PD is unclear, it is thought to result from an inciting traumatic event followed by aberrant fibrosis or dysregulated wound healing. The evaluation of men presenting with PD includes a detailed history and physical exam, focusing on the penis in both the flaccid and erect states. PD is often associated with erectile dysfunction (ED), as well as several other comorbidities. Laboratory testing is not needed to diagnose PD, although given the associations between PD and systemic diseases including hypogonadism, diabetes, and cardiovascular disease, screening and work-up for these conditions in men with PD may be warranted. Treatment modalities for PD are diverse and include oral, topical, intralesional, mechanical, and surgical therapies. Oral, topical, and mechanical therapies generally have little evidence supporting their efficacy. Several intralesional therapies, including interferon α2b and collagenase Clostridium hystiolyticum have demonstrated efficacy in the treatment of PD. Surgical treatment, indicated in men with significant, stable deformity, includes plication of the tunica albuginea, plaque incision/excision and grafting, and placement of inflatable penile prosthesis (IPP) with or without additional maneuvers to achieve desired results, and has high success rates. PMID:26279643

  11. Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria.

    PubMed

    Hale, Caitlin L; Niederriter, Adrienne N; Green, Glenn E; Martin, Donna M

    2016-02-01

    CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary anomalies, and Ear malformations, including deafness and vestibular disorders) is a genetic condition characterized by a specific and recognizable pattern of features. Heterozygous pathogenic variants in the chromodomain helicase DNA-binding protein 7 (CHD7) are the major cause of CHARGE syndrome, and have been identified in 70-90% of individuals fulfilling clinical diagnostic criteria. Since 2004, when CHD7 was discovered as the causative gene for CHARGE syndrome, the phenotypic spectrum associated with pathogenic CHD7 variants has expanded. Predicted pathogenic CHD7 variants have been identified in individuals with isolated features of CHARGE including autism and hypogonadotropic hypogonadism. Here, we present genotype and phenotype data from a cohort of 28 patients who were considered for a diagnosis of CHARGE syndrome, including one patient with atypical presentations and a pathogenic CHD7 variant. We also summarize published literature on pathogenic CHD7 variant positive individuals who have atypical clinical presentations. Lastly, we propose a revision to current clinical diagnostic criteria, including broadening of the major features associated with CHARGE syndrome and addition of pathogenic CHD7 variant status as a major criterion. PMID:26590800

  12. Zinc: An Essential Micronutrient

    PubMed Central

    SAPER, ROBERT B.; RASH, REBECCA

    2009-01-01

    Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children. Zinc in combination with antioxidants may be modestly effective in slowing the progression of intermediate and advanced age-related macular degeneration. Zinc is an effective treatment for Wilson disease. Current data do not support zinc supplementation as effective for upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc is well tolerated at recommended dosages. Adverse effects of long-term high-dose zinc use include suppressed immunity, decreased high-density lipoprotein cholesterol levels, anemia, copper deficiency, and possible genitourinary complications. PMID:20141096

  13. First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic.

    PubMed

    Pomahačová, Renata; Sýkora, Josef; Zamboryová, Jana; Paterová, Petra; Varvařovská, Jana; Šubrt, Ivan; Dort, Jiří; Dortová, Eva

    2016-06-01

    We characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory results. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The enzymatic block was found at the beginning of steroidogenesis. The mutation was confirmed in the CYP11A1 gene. The patient is compound heterozygote for the novel CYP11A1 missense mutation c.412G>A (p.Gly138Arg) in exon 2 and frameshift mutation c.508_509delCT (p.Leu170Valfs*30) in exon 3. The CYP11A1: c.412G>A (p.Gly138Arg) was predicted as pathogenic by in silico analysis. So far, only 19 patients with CYP11A1 mutations causing P450scc deficiency have been reported worldwide. There are no related reports in the Czech Republic. PMID:27008691

  14. Bardet-Biedl syndrome: Mapping of a new locus to chromosome 3 and fine-mapping of the chromosome 16 linked locus

    SciTech Connect

    Kwitek-Black, A.E.; Rokhlina, T.; Nishimura, D.Y.

    1994-09-01

    Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by mental retardation, post-axial polydactyly, obesity, retinitis pigmentosa, and hypogonadism. Other features of this disease include renal and cardiovascular abnormalities and an increased incidence of hypertension and diabetes mellitus. The molecular etiology for BBS is not known. We previously linked BBS to chromosome 16q13 in a large inbred Bedouin family, and excluded this locus in a second large inbred Bedouin family. We now report linkage of this second family to markers on chromosome 3q, proving non-allelic, genetic heterogeneity in the Bedouin population. A third large inbred Bedouin family was excluded from the 3q and 16q BBS loci. In addition to the identification of a new BBS locus on chromosome 3, we have identified and utilized additional short tandem repeat polymorphisms (STRPs) in the 16q BBS region to narrow the candidate interval to 3 cM. Additional recombinant individuals will allow further refinement of the interval. Identification of genes causing BBS has the potential to provide insight into diverse genetic traits and disease processes including obesity, hypertension, diabetes, retinal degeneration, and abnormal limb, renal and cardiac development.

  15. Leptin inhibits the reproductive axis in adult male Syrian hamsters exposed to long and short photoperiod.

    PubMed

    Boggio, Veronica; Cutrera, Rodolfo; Carbone, Silvia; Scacchi, Pablo; Ponzo, Osvaldo J

    2013-09-01

    The aim of the study was to investigate the effects of acute leptin treatment of adult Syrian hamsters exposed to a long (LP, eugonadal males) and short photoperiod (SP, hypogonadal males). Animals were exposed to LP (L:D 14:10) or SP (L:D 10:14) for 10 weeks. Afterwards, both LP and SP hamsters were allocated to a control (SP-C, LP-C) or leptin-treated group (SP 3, SP 10, SP 30 or LP3, LP 10, LP 30). One hour before sacrifice, a single dose of leptin (3, 10 or 30 μg/kg) or vehicle was administered (i.p.) to the males. Testis weight, serum and pituitary luteinizing hormone (LH) concentrations, as well as the hypothalamic concentration of gonadotropin-releasing hormone (GnRH) were recorded. Histological analysis of the testis was performed and GnRH concentration in the culture medium of hypothalamic explants was examined. A dramatic regression of testicular weight and histological atrophy of seminiferous tubules, as well as a decrease in serum and pituitary LH concentrations were found in SP males. All doses of leptin significantly reduced serum LH levels and medium GnRH concentrations in both photoperiod groups. Pituitary LH and hypothalamic GnRH concentrations were not affected by leptin. In conclusion, we demonstrated that leptin inhibited the reproductive axis of Syrian male hamsters exposed to LP and SP and fed ad libitum. PMID:24011191

  16. Novel homozygous deletion of segmental KAL1 and entire STS cause Kallmann syndrome and X-linked ichthyosis in a Chinese family.

    PubMed

    Xu, H; Li, Z; Wang, T; Wang, S; Liu, J; Wang, D W

    2015-12-01

    Kallmann syndrome (KS) is a genetically heterogeneous disease characterised by hypogonadotrophic hypogonadism in association with anosmia or hyposmia. This condition affects 1 in 10 000 men and 1 in 50,000 women. Defects in seventeen genes including KAL1 gene contribute to the molecular basis of KS. We report the clinical characteristics, molecular causes and treatment outcome of two Chinese brothers with KS and X-linked ichthyosis. The phenotypes of the patients were characterised by bilateral cryptorchidism, unilateral renal agenesis in one patient but normal kidney development in another. The patients had low serum testosterone, follicle-stimulating hormone and luteinising hormone levels and a blunt response to the gonadotrophin-releasing hormone stimulation test. After human chorionic gonadotrophin treatment, the serum testosterone levels were normalized, and the pubic hair, penis length and testicular volumes were greatly improved in both of the patients. The two affected siblings had the same novel deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene. Our study broadens the mutation spectrum in the KAL1 gene associated with KS and facilitates the genetic diagnosis and counselling for KS. PMID:25597551

  17. The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis.

    PubMed

    Martinez, M Elena; Karaczyn, Aldona; Stohn, J Patrizia; Donnelly, William T; Croteau, Walburga; Peeters, Robin P; Galton, Valerie A; Forrest, Douglas; St Germain, Donald; Hernandez, Arturo

    2016-03-01

    Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis. PMID:26727108

  18. Current State of Practice Regarding Testosterone Supplementation Therapy in Men with Prostate Cancer

    PubMed Central

    Kovac, Jason R.; Pan, Michael M.; Lipshultz, Larry I.; Lamb, Dolores J.

    2014-01-01

    Hypogonadal men are characterized by low serum testosterone and symptoms of low energy, decreased libido, and muscle mass as well as impaired concentration and sexual functioning. Men with prostate cancer (PCa) currently on active surveillance or post-therapy, have traditionally been excluded from management paradigms given the decade-old concern that testosterone caused PCa growth. However, there appears to be little or no relationship between serum testosterone concentration and PCa. Androgen action in the prostate has long been known to be affected by the kinetics of receptor saturation and, as such, testosterone beyond a certain baseline is unable to stimulate prostatic growth due to complete intra-prostatic androgen receptor binding. Given this physiologic concept, many clinical investigators have begun to promote testosterone supplementation therapy (TST) as safe in men with PCa. This review examines the basics of testosterone physiology and summarizes the most recent findings on the use of TST in men with PCa on active surveillance and following treatment with external beam radiotherapy, brachytherapy and radical prostatectomy. PMID:25072793

  19. Diabetes in the young - a case of Alström syndrome with myopathy.

    PubMed

    Bronson, S C; Anand Moses, C R; Periyandavar, I; Dharmarajan, P; Suresh, E; Shanmugam, A; Vasuki, R; Venkatesh, D; Amudha, J

    2015-03-01

    Alström syndrome is a rare ciliopathy affecting about 1 in 1,000,000 individuals. It is characterised by cone-rod dystrophy, insulin resistance, diabetes mellitus, cardiomyopathy, renal failure and hypogonadism. Progressive multi-organ dysfunction eventually leads to death. Only about 800 patients with this disorder have been identified so far. The diagnosis of Alström syndrome is critical as it can easily be overlooked because of the many features it shares with metabolic syndrome. The gene affected in this autosomal recessive disease is ALMS1, the protein product of which is involved in intracellular trafficking and ciliary function. Alström syndrome is being studied as a model which would potentially shed light on the pathophysiology of diabetes mellitus. In this report, we describe a patient with features of Alström syndrome and a clinical picture suggestive of a recurrent, severe, steroid responsive myopathy which, to the best of our knowledge, has not been reported so far. PMID:25874828

  20. Loss of Function of Glucocerebrosidase GBA2 Is Responsible for Motor Neuron Defects in Hereditary Spastic Paraplegia

    PubMed Central

    Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L.; Gonzalez, Michael A.; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

    2013-01-01

    Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. PMID:23332916

  1. Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.

    PubMed

    Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L; Gonzalez, Michael A; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

    2013-02-01

    Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. PMID:23332916

  2. Conflict of interest in online point-of-care clinical support websites.

    PubMed

    Amber, Kyle T; Dhiman, Gaurav; Goodman, Kenneth W

    2014-08-01

    Point-of-care evidence-based medicine websites allow physicians to answer clinical queries using recent evidence at the bedside. Despite significant research into the function, usability and effectiveness of these programmes, little attention has been paid to their ethical issues. As many of these sites summarise the literature and provide recommendations, we sought to assess the role of conflicts of interest in two widely used websites: UpToDate and Dynamed. We recorded all conflicts of interest for six articles detailing treatment for the following conditions: erectile dysfunction, fibromyalgia, hypogonadism, psoriasis, rheumatoid arthritis and Crohn's disease. These diseases were chosen as their medical management is either controversial, or they are treated using biological drugs which are mostly available by brand name only. Thus, we hypothesised that the role of conflict of interest would be more significant in these conditions than in an illness treated with generic medications or by strict guidelines. All articles from the UpToDate articles demonstrated a conflict of interest. At times, the editor and author would have a financial relationship with a company whose drug was mentioned within the article. This is in contrast with articles on the Dynamed website, in which no author or editor had a documented conflict. We offer recommendations regarding the role of conflict of interest disclosure in these point-of-care evidence-based medicine websites. PMID:24493079

  3. Rapid height growth after liver transplantation in adulthood.

    PubMed

    Szili, Balázs; Görög, Dénes; Gerlei, Zsuzsanna; Győri, Gabriella; Lakatos, Péter; Takács, István

    2016-08-01

    Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation. PMID:27041087

  4. Rare coding variants and X-linked loci associated with age at menarche.

    PubMed

    Lunetta, Kathryn L; Day, Felix R; Sulem, Patrick; Ruth, Katherine S; Tung, Joyce Y; Hinds, David A; Esko, Tõnu; Elks, Cathy E; Altmaier, Elisabeth; He, Chunyan; Huffman, Jennifer E; Mihailov, Evelin; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Stolk, Lisette; Teumer, Alexander; Thompson, Deborah J; Traglia, Michela; Wang, Carol A; Yerges-Armstrong, Laura M; Antoniou, Antonis C; Barbieri, Caterina; Coviello, Andrea D; Cucca, Francesco; Demerath, Ellen W; Dunning, Alison M; Gandin, Ilaria; Grove, Megan L; Gudbjartsson, Daniel F; Hocking, Lynne J; Hofman, Albert; Huang, Jinyan; Jackson, Rebecca D; Karasik, David; Kriebel, Jennifer; Lange, Ethan M; Lange, Leslie A; Langenberg, Claudia; Li, Xin; Luan, Jian'an; Mägi, Reedik; Morrison, Alanna C; Padmanabhan, Sandosh; Pirie, Ailith; Polasek, Ozren; Porteous, David; Reiner, Alex P; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia F; Schlessinger, David; Scott, Robert A; Stöckl, Doris; Visser, Jenny A; Völker, Uwe; Vozzi, Diego; Wilson, James G; Zygmunt, Marek; Boerwinkle, Eric; Buring, Julie E; Crisponi, Laura; Easton, Douglas F; Hayward, Caroline; Hu, Frank B; Liu, Simin; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Strauch, Konstantin; Streeten, Elizabeth A; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Wellons, Melissa; Franceschini, Nora; Chasman, Daniel I; Thorsteinsdottir, Unnur; Murray, Anna; Stefansson, Kari; Murabito, Joanne M; Ong, Ken K; Perry, John R B

    2015-01-01

    More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait. PMID:26239645

  5. Snapin interacts with G-protein coupled receptor PKR2.

    PubMed

    Song, Jian; Li, Jie; Liu, Hua-die; Liu, Wei; Feng, Yong; Zhou, Xiao-Tao; Li, Jia-Da

    2016-01-15

    Mutations in Prokineticin receptor 2 (PKR2), a G-protein-coupled receptor, have been identified in patients with Kallmann syndrome and/or idiopathic hypogonadotropic hypogonadism, characterized by delayed puberty and infertility. In this study, we performed yeast two-hybrid screening by using PKR2 C-terminus (amino acids 333-384) as a bait, and identified Snapin as a novel interaction partner for PKR2. The interaction of Snapin and PKR2 was confirmed in GST pull-down and co-immunoprecipitation studies. We further demonstrated that two α-helix domains in Snapin are required for the interaction. And the interactive motifs of PKR2 were mapped to YFK (343-345) and HWR (351-353), which shared a similar sequence of two aromatic amino acids followed by a basic amino acid. Disruption of Snapin-PKR2 interaction did not affect PKR2 signaling, but increased the ligand-induced degradation, implying a role of Snapin in the trafficking of PKR2. PMID:26687946

  6. Early menopause: A hazard to a woman's health.

    PubMed

    Hernández-Angeles, Claudio; Castelo-Branco, Camil

    2016-04-01

    Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI. PMID:27377497

  7. Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence From Neuroimaging Studies

    PubMed Central

    Lenroot, Rhoshel K.; Lee, Nancy Raitano; Giedd, Jay N.

    2010-01-01

    Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the effects of different dosages of sex chromosome genes on brain development may help to understand the basis for functional differences in affected individuals. It may also be informative regarding how sex chromosomes contribute to typical sexual differentiation. Studies of 47,XXY males make up the bulk of the current literature of neuroimaging studies in individuals with supernumerary sex chromosomes, with a few small studies or case reports of the other SCAs. Findings in 47,XXY males typically include decreased gray and white matter volumes, with most pronounced effects in the frontal and temporal lobes. Functional studies have shown evidence of decreased lateralization. Although the hypogonadism typically found in 47,XXY males may contribute to the decreased brain volume, the observation that 47,XXX females also show decreased brain volume in the presence of normal pubertal maturation suggests a possible direct dosage effect of X chromosome genes. Additional X chromosomes, such as in 49,XXXXY males, are associated with more markedly decreased brain volume and increased incidence of white matter hyperintensities. The limited data regarding effects of having two Y chromosomes (47,XYY) do not find significant differences in brain volume, although there are some reports of increased head size. PMID:20014372

  8. Management and rehabilitation of neurologic patients with sexual dysfunction.

    PubMed

    Basson, Rosemary; Bronner, Gila

    2015-01-01

    Neurologic disease frequently negatively affects sexual experience in multiple ways. The patient's sexual self-image, sexual function, propensity to sexual pain, and motivation to be sexually active may be impacted, as may the sexual experiences of the partner. Difficulties with mobility can limit both partners' sexual arousal and pleasure. Conditions associated with chronic pain or continence concerns add further distress. Thus sexual rehabilitation needs to address many areas. Comorbid depression is common and needs to be stabilized before definitive treatment of sexual dysfunction. Management strategies include cognitive behavioral therapy, mindfulness-based cognitive therapy, and sex therapy and, for erectile dysfunction and premature ejaculation, pharmacotherapy can be added. Benefit from all these modalities is confirmed in the general population but only pharmacologic treatment of erectile dysfunction has been studied in neurologic patients, where benefit is also seen. Testosterone is indicated only for comorbid testosterone deficit: very occasionally the neurologic condition causes secondary male hypogonadism. No androgen deficiency state has been identified in women. Results of testosterone treatment in women are conflicting: recruited women were not clearly dysfunctional and women with neurologic conditions have not been studied. Future research involving both partners using combined medical and psychologic therapy as followed in clinical practice is advocated. PMID:26003258

  9. Chronic kidney disease and erectile dysfunction.

    PubMed

    Suzuki, Etsu; Nishimatsu, Hiroaki; Oba, Shigeyoshi; Takahashi, Masao; Homma, Yukio

    2014-11-01

    Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack. PMID:25374815

  10. Genetic linkage analysis in 26 families with Bardet-Biedl syndrome

    SciTech Connect

    Wright, A.F.; Bruford, E.A.; Mansfield, D.C.

    1994-09-01

    Bardet-Biedl syndrome is an autosomal recessive disorder characterized by polydactyly, obesity, hypogonadism, retinitis pigmentosa, renal anomalies and mental retardation. Clinical heterogeneity is quite marked both within and between families. Linkage has been reported between Bardet-Biedl syndrome and the D16408 marker in chromosomal region 16q21 in an extended Bedouin kindred and, more recently, in a subset of 17 out of 31 families using the PYGM/D11S913 markers in chromosomal region 11q13. We have analyzed linkage to the 16q21 and 11q13 regions and used markers covering chromosomes 2, 3, 17 and 18 in a set of 26 Bardet-Biedl families, each containing at least two affected individuals, with a total of 57 affected members. Evidence of linkage to the D11S527 locus has been identified assuming linkage homogeneity with a lod score of 2.72 at a recombination fraction of 0.11 (95% limits 0.03-0.25).

  11. C8orf37 is mutated in Bardet-Biedl syndrome and constitutes a locus allelic to non-syndromic retinal dystrophies.

    PubMed

    Khan, Arif O; Decker, Eva; Bachmann, Nadine; Bolz, Hanno J; Bergmann, Carsten

    2016-09-01

    Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features. PMID:26854863

  12. Genetic evaluation of male infertility

    PubMed Central

    2014-01-01

    Men with severe oligospermia (<5 million sperm/mL ejaculate fluid) or azoospermia should receive genetic testing to clarify etiology of male infertility prior to treatment. Categorization by obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is critical since genetic testing differs for the former with normal testicular function, testicular volume (~20 mL), and follicle-stimulating hormone (FSH) (1-8 IU/mL) when compared to the latter with small, soft testes and increased FSH. History and physician examination along with laboratory testing (following appropriate genetic counseling) is critical to accurate selection of genetic testing appropriate for azoospermia due to primary testicular failure as compared with congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be warranted depending on the clinical context of severe oligospermia or NOA. The results of genetic testing guide management options. The most recent techniques for genetic analysis, including sperm microRNA (miRNA) and epigenetics, are forming the foundation for future genetic diagnosis and therapeutic targets in male infertility. PMID:26813518

  13. Kallmann Syndrome: Mutations in the Genes Encoding Prokineticin-2 and Prokineticin Receptor-2

    PubMed Central

    Dodé, Catherine; Teixeira, Luis; Levilliers, Jacqueline; Fouveaut, Corinne; Bouchard, Philippe; Kottler, Marie-Laure; Lespinasse, James; Lienhardt-Roussie, Anne; Mathieu, Michèle; Moerman, Alexandre; Morgan, Graeme; Murat, Arnaud; Toublanc, Jean-Edmont; Wolczynski, Slawomir; Delpech, Marc; Petit, Christine; Young, Jacques; Hardelin, Jean-Pierre

    2006-01-01

    Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases. In a cohort of 192 patients we took a candidate gene strategy and identified ten and four different point mutations in the genes encoding the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2), respectively. The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state. In addition, one of the patients heterozygous for a PROKR2 mutation was also carrying a missense mutation in KAL1, thus indicating a possible digenic inheritance of the disease in this individual. These findings reveal that insufficient prokineticin-signaling through PROKR2 leads to abnormal development of the olfactory system and reproductive axis in man. They also shed new light on the complex genetic transmission of Kallmann syndrome. PMID:17054399

  14. Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581

    PubMed Central

    Nakhai Pour, Hamid Reza; Emmelot-Vonk, Marielle H; Sukel-Helleman, Marja; Verhaar, Harald JJ; Grobbee, Diederick E; van der Schouw, Yvonne T

    2006-01-01

    In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2 and 10.72 nmol/L, respectively. PMID:16887030

  15. A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

    PubMed

    Brenig, Bertram; Schütz, Ekkehard; Hardt, Michael; Scheuermann, Petra; Freick, Markus

    2015-01-01

    Aristaless-like homeobox 4 (ALX4) gene is an important transcription regulator in skull and limb development. In humans and mice ALX4 mutations or loss of function result in a number of skeletal and organ malformations, including polydactyly, tibial hemimelia, omphalocele, biparietal foramina, impaired mammary epithelial morphogenesis, alopecia, coronal craniosynostosis, hypertelorism, depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, and body agenesis. Here we show that a complex skeletal malformation of the hind limb in Galloway cattle together with other developmental anomalies is a recessive autosomal disorder most likely caused by a duplication of 20 bp in exon 2 of the bovine ALX4 gene. A second duplication of 34 bp in exon 4 of the same gene has no known effect, although both duplications result in a frameshift and premature stop codon leading to a truncated protein. Genotyping of 1,688 Black/Red/Belted/Riggit Galloway (GA) and 289 White Galloway (WGA) cattle showed that the duplication in exon 2 has allele frequencies of 1% in GA and 6% in WGA and the duplication in exon 4 has frequencies of 23% in GA and 38% in WGA. Both duplications were not detected in 876 randomly selected German Holstein Friesian and 86 cattle of 21 other breeds. Hence, we have identified a candidate causative mutation for tibial hemimelia syndrome in Galloway cattle and selection against this mutation can be used to eliminate the mutant allele from the breed. PMID:26076463

  16. The Spermatogenic Effect of Yacon Extract and Its Constituents and Their Inhibition Effect of Testosterone Metabolism

    PubMed Central

    Park, Jeong Sook; Han, Kun

    2013-01-01

    We screened the pharmacological effects of a 50% ethanol extract of Yacon tubers and leaves on spermatogenesis in rats. As a result, we found that Yacon tuber extracts increased sperm number and serum testosterone level in rats. It has been reported that the crude extract of Yacon tubers and leaves contain phenolic acids, such as, chlorogenic acid, ferulic acid and caffeic acid by HPLC/MS analysis. We were interested in the contributions made by phenolic acid, particularly chlorogenic acid of Yacon tuber extract to the spermatogenic activity. After administering Yacon tuber extract or chlorogenic acid to rats for 5 weeks, numbers of sperm in epididymis were increased by 34% and 20%, respectively. We also administered ferulic acid, which has been reported to be a metabolite of chlorogenic acid and a constituent of Yacon tuber extract to investigate its spermatogenic activity in rats. Yacon tuber extract and ferulic acid increased sperm numbers by 43% and 37%, respectively. And, Yacon tuber extract, and chlorogenic acid showed significantly inhibition effect of testoeterone degradation in rat liver homogenate. We considered that the spermatogenic effect of Yacon tuber extract might be related to phenolic compounds and their inhibitory effect of testosterone degradation. Yacon showed the possibility as ameliorable agents of infertility by sperm deficiency and late onset hypogonadism syndrome with low level of testosterone. PMID:24009874

  17. The spermatogenic effect of yacon extract and its constituents and their inhibition effect of testosterone metabolism.

    PubMed

    Park, Jeong Sook; Han, Kun

    2013-03-01

    We screened the pharmacological effects of a 50% ethanol extract of Yacon tubers and leaves on spermatogenesis in rats. As a result, we found that Yacon tuber extracts increased sperm number and serum testosterone level in rats. It has been reported that the crude extract of Yacon tubers and leaves contain phenolic acids, such as, chlorogenic acid, ferulic acid and caffeic acid by HPLC/MS analysis. We were interested in the contributions made by phenolic acid, particularly chlorogenic acid of Yacon tuber extract to the spermatogenic activity. After administering Yacon tuber extract or chlorogenic acid to rats for 5 weeks, numbers of sperm in epididymis were increased by 34% and 20%, respectively. We also administered ferulic acid, which has been reported to be a metabolite of chlorogenic acid and a constituent of Yacon tuber extract to investigate its spermatogenic activity in rats. Yacon tuber extract and ferulic acid increased sperm numbers by 43% and 37%, respectively. And, Yacon tuber extract, and chlorogenic acid showed significantly inhibition effect of testoeterone degradation in rat liver homogenate. We considered that the spermatogenic effect of Yacon tuber extract might be related to phenolic compounds and their inhibitory effect of testosterone degradation. Yacon showed the possibility as ameliorable agents of infertility by sperm deficiency and late onset hypogonadism syndrome with low level of testosterone. PMID:24009874

  18. The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications.

    PubMed

    Kyriakakis, Nikolaos; Lynch, Julie; Ajjan, Ramzi; Murray, Robert D

    2016-04-01

    Disturbances of coagulation and fibrinolysis are usually multifactorial and growing evidence suggests that endocrinopathies modulate the haemostatic balance. The thrombotic alterations in endocrine disorders range from mild laboratory clotting abnormalities with little clinical significance to serious thrombotic and bleeding disorders directly related to hormonal disturbances. This literature review focuses on presenting the current data on the effects of thyroid and pituitary disorders on various parameters of the haemostatic system. With the exception of overt hypothyroidism which appears to cause a bleeding tendency, the rest of the endocrinopathies discussed in this review (subclinical hypothyroidism, hyperthyroidism, endogenous hypercortisolaemia, growth hormone deficiency, acromegaly, prolactinoma/hyperprolactinaemia and hypogonadotrophic hypogonadism) are associated with a hypercoagulable and hypofibrinolytic state, increasing the overall cardiovascular risk and thromboembolic potential in these patients. In most studies, the haemostatic abnormalities seen in endocrine disorders are usually reversible with successful treatment of the underlying condition and biochemical disease remission. High-quality studies on larger patient cohorts are needed to produce robust evidence on the effects of endocrine disorders and their therapeutic interventions on coagulation and fibrinolysis, as well as on the long-term mortality and morbidity outcomes in association with endocrine-related haemostatic imbalance. Given the rarity of some of the endocrine disorders, multicentre studies are required to achieve this target. PMID:25753252

  19. Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma.

    PubMed

    Beatty, Norman; Medina-Garcia, Luis; Al Mohajer, Mayar; Zangeneh, Tirdad T

    2016-01-01

    Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID:27006841

  20. Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma

    PubMed Central

    Beatty, Norman; Medina-Garcia, Luis; Al Mohajer, Mayar; Zangeneh, Tirdad T.

    2016-01-01

    Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID:27006841

  1. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).

    PubMed

    Chiang, Annie P; Beck, John S; Yen, Hsan-Jan; Tayeh, Marwan K; Scheetz, Todd E; Swiderski, Ruth E; Nishimura, Darryl Y; Braun, Terry A; Kim, Kwang-Youn A; Huang, Jian; Elbedour, Khalil; Carmi, Rivka; Slusarski, Diane C; Casavant, Thomas L; Stone, Edwin M; Sheffield, Val C

    2006-04-18

    The identification of mutations in genes that cause human diseases has largely been accomplished through the use of positional cloning, which relies on linkage mapping. In studies of rare diseases, the resolution of linkage mapping is limited by the number of available meioses and informative marker density. One recent advance is the development of high-density SNP microarrays for genotyping. The SNP arrays overcome low marker informativity by using a large number of markers to achieve greater coverage at finer resolution. We used SNP microarray genotyping for homozygosity mapping in a small consanguineous Israeli Bedouin family with autosomal recessive Bardet-Biedl syndrome (BBS; obesity, pigmentary retinopathy, polydactyly, hypogonadism, renal and cardiac abnormalities, and cognitive impairment) in which previous linkage studies using short tandem repeat polymorphisms failed to identify a disease locus. SNP genotyping revealed a homozygous candidate region. Mutation analysis in the region of homozygosity identified a conserved homozygous missense mutation in the TRIM32 gene, a gene coding for an E3 ubiquitin ligase. Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci data set demonstrate that TRIM32 is a BBS gene. This study shows the value of high-density SNP genotyping for homozygosity mapping and the use of expression correlation data for evaluation of candidate genes and identifies the proteasome degradation pathway as a pathway involved in BBS. PMID:16606853

  2. Giant, thrombosed, sellar-suprasellar internal carotid artery aneurysm with persistent, primitive trigeminal artery causing hypopituitarism.

    PubMed

    Tungaria, Arun; Kumar, Vijendra; Garg, Pallav; Jaiswal, Awadhesh K; Behari, Sanjay

    2011-05-01

    A rare case of a giant, thrombosed, sellar-suprasellar paraclinoid internal carotid artery (ICA) aneurysm with persistent primitive trigeminal artery (PPTA) causing hypopituitarism that manifested as hypogonadism, hypothyroidism, and hypocortisolism is reported. There were no visual/neurological deficits, diabetes insipidus, or episodes of subarachnoid hemorrhage. The alteration in the flow dynamics of the circle of Willis due to the presence of PPTA may have been responsible for both the genesis of the giant aneurysm as well as for the induction of thrombogenesis within its lumen. As the digital subtraction angiogram showed complete thrombosis within the aneurysm and hormonal replacement therapy was effective in ensuring complete normalization of symptoms, the patient was unwilling to undergo surgical clipping of the aneurysm and removal of the suprasellar clot in an attempt to restore pituitary functions. Hypopituitarism recurred when the patient stopped her hormonal supplementation therapy after 7 years, and she again became symptom-free on restarting the therapy. To the best of the authors' knowledge, this represents the first reported case in the literature of hypopituitarism consequent to a giant, thrombosed, sellar-suprasellar ICA aneurysm with an associated PPTA on the side of the aneurysm. PMID:21234615

  3. A case of GH deficiency and beta-thalassemia.

    PubMed

    Smacchia, M P; Mercuri, V; Antonetti, L; Bassotti, G; D'Amico, T; Pietrobono, D; Gargiulo, P

    2012-06-01

    A 23-year-old male patient, who suffers from beta-thalassemia major, came to us for an endocrine-metabolic evaluation. Medical history showed a diagnosis of heart disease with heart failure since the age of 16, type 1 diabetes mellitus diagnosed at the age of 18, treated with an intensive insulin therapy with a poor glycometabolic control. Patient performed regular blood transfusions and iron chelation with deferasirox. An echocardiogram revealed an enlarged left ventricle. Patient had undergone a comprehensive study of buoyancy both basal and hormone-stimulated and it was therefore carried out a diagnosis of GH deficiency and hypogonadotropic hypogonadism. A recombinant GH replacement therapy was then prescribed. After six months of therapy, the patient reported a net improvement of asthenic symptoms. Physical examination showed a reduction in abdominal adiposity in waist and an increase of 5 cm in stature. Laboratory tests showed an amelioration of glycometabolic control, such as to justify a reduction in daily insulin dose. The stature observed was thought appropriate to begin the administration of testosterone. Moreover, the cardiological framework showed a reduction of left ventricular dilatation, good ventricular motility, global minimum persistent tricuspid but not mitral regurgitation and no alteration on ECG. PMID:22691893

  4. Helq acts in parallel to Fancc to suppress replication-associated genome instability

    PubMed Central

    Luebben, Spencer W.; Kawabata, Tsuyoshi; Akre, Monica K.; Lee, Wai Long; Johnson, Charles S.; O’Sullivan, M. Gerard; Shima, Naoko

    2013-01-01

    HELQ is a superfamily 2 DNA helicase found in archaea and metazoans. It has been implicated in processing stalled replication forks and in repairing DNA double-strand breaks and inter-strand crosslinks. Though previous studies have suggested the possibility that HELQ is involved in the Fanconi anemia (FA) pathway, a dominant mechanism for inter-strand crosslink repair in vertebrates, this connection remains elusive. Here, we investigated this question in mice using the Helqgt and Fancc− strains. Compared with Fancc−/− mice lacking FANCC, a component of the FA core complex, Helqgt/gt mice exhibited a mild of form of FA-like phenotypes including hypogonadism and cellular sensitivity to the crosslinker mitomycin C. However, unlike Fancc−/− primary fibroblasts, Helqgt/gt cells had intact FANCD2 mono-ubiquitination and focus formation. Notably, for all traits examined, Helq was non-epistatic with Fancc, as Helqgt/gt;Fancc−/− double mutants displayed significantly worsened phenotypes than either single mutant. Importantly, this was most noticeable for the suppression of spontaneous chromosome instability such as micronuclei and 53BP1 nuclear bodies, known consequences of persistently stalled replication forks. These findings suggest that mammalian HELQ contributes to genome stability in unchallenged conditions through a mechanism distinct from the function of FANCC. PMID:24005041

  5. A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle

    PubMed Central

    Brenig, Bertram; Schütz, Ekkehard; Hardt, Michael; Scheuermann, Petra; Freick, Markus

    2015-01-01

    Aristaless-like homeobox 4 (ALX4) gene is an important transcription regulator in skull and limb development. In humans and mice ALX4 mutations or loss of function result in a number of skeletal and organ malformations, including polydactyly, tibial hemimelia, omphalocele, biparietal foramina, impaired mammary epithelial morphogenesis, alopecia, coronal craniosynostosis, hypertelorism, depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, and body agenesis. Here we show that a complex skeletal malformation of the hind limb in Galloway cattle together with other developmental anomalies is a recessive autosomal disorder most likely caused by a duplication of 20 bp in exon 2 of the bovine ALX4 gene. A second duplication of 34 bp in exon 4 of the same gene has no known effect, although both duplications result in a frameshift and premature stop codon leading to a truncated protein. Genotyping of 1,688 Black/Red/Belted/Riggit Galloway (GA) and 289 White Galloway (WGA) cattle showed that the duplication in exon 2 has allele frequencies of 1% in GA and 6% in WGA and the duplication in exon 4 has frequencies of 23% in GA and 38% in WGA. Both duplications were not detected in 876 randomly selected German Holstein Friesian and 86 cattle of 21 other breeds. Hence, we have identified a candidate causative mutation for tibial hemimelia syndrome in Galloway cattle and selection against this mutation can be used to eliminate the mutant allele from the breed. PMID:26076463

  6. Kisspeptin Signaling in the Brain

    PubMed Central

    Oakley, Amy E.; Clifton, Donald K.; Steiner, Robert A.

    2009-01-01

    Kisspeptin (a product of the Kiss1 gene) and its receptor (GPR54 or Kiss1r) have emerged as key players in the regulation of reproduction. Mutations in humans or genetically targeted deletions in mice of either Kiss1 or Kiss1r cause profound hypogonadotropic hypogonadism. Neurons that express Kiss1/kisspeptin are found in discrete nuclei in the hypothalamus, as well as other brain regions in many vertebrates, and their distribution, regulation, and function varies widely across species. Kisspeptin neurons directly innervate and stimulate GnRH neurons, which are the final common pathway through which the brain regulates reproduction. Kisspeptin neurons are sexually differentiated with respect to cell number and transcriptional activity in certain brain nuclei, and some kisspeptin neurons express other cotransmitters, including dynorphin and neurokinin B (whose physiological significance is unknown). Kisspeptin neurons express the estrogen receptor and the androgen receptor, and these cells are direct targets for the action of gonadal steroids in both male and female animals. Kisspeptin signaling in the brain has been implicated in mediating the negative feedback action of sex steroids on gonadotropin secretion, generating the preovulatory GnRH/LH surge, triggering and guiding the tempo of sexual maturation at puberty, controlling seasonal reproduction, and restraining reproductive activity during lactation. Kisspeptin signaling may also serve diverse functions outside of the classical realm of reproductive neuroendocrinology, including the regulation of metastasis in certain cancers, vascular dynamics, placental physiology, and perhaps even higher-order brain function. PMID:19770291

  7. Classification of trabeculae into three-dimensional rodlike and platelike structures via local inertial anisotropy

    PubMed Central

    Vasilić, Branimir; Rajapakse, Chamith S.; Wehrli, Felix W.

    2009-01-01

    Trabecular bone microarchitecture is a significant determinant of the bone’s mechanical properties and is thus of major clinical relevance in predicting fracture risk. The three-dimensional nature of trabecular bone is characterized by parameters describing scale, topology, and orientation of structural elements. However, none of the current methods calculates all three types of parameters simultaneously and in three dimensions. Here the authors present a method that produces a continuous classification of voxels as belonging to platelike or rodlike structures that determines their orientation and estimates their thickness. The method, dubbed local inertial anisotropy (LIA), treats the image as a distribution of mass density and the orientation of trabeculae is determined from a locally calculated tensor of inertia at each voxel. The orientation entropies of rods and plates are introduced, which can provide new information about microarchitecture not captured by existing parameters. The robustness of the method to noise corruption, resolution reduction, and image rotation is demonstrated. Further, the method is compared with established three-dimensional parameters including the structure-model index and topological surface-to-curve ratio. Finally, the method is applied to data acquired in a previous translational pilot study showing that the trabecular bone of untreated hypogonadal men is less platelike than that of their eugonadal peers. PMID:19673224

  8. [Intrasellar arachnoid cyst. A case report and review of the literature].

    PubMed

    Zieliński, Grzegorz; Podgórski, Jan Krzysztof; Koziarski, Andrzej; Potakiewicz, Ziemowit

    2006-01-01

    Intrasellar arachnoid cyst (IAC) is a very rare pathological lesion occurring in 5 of 1000 autopsy cases, and constitutes 9% of all arachnoid cysts. As a space-occupying mass, IAC may cause headaches, visual disturbances, hypopituitarism, precocious puberty, and the "bobble-head doll" syndrome. The pathogenesis of IAC remains controversial. Magnetic resonance imaging (MRI) is the neurodiagnostic tool of choice to evaluate IAC. The authors presented a 38 year-old woman suffering from severe chronic headaches, dysmenorrhea, and visual disturbance. MRI revealed an intrasellar cystic lesion that had compressed the optic chiasma. Preoperative endocrinological assessment revealed hyperprolactinemia and hypogonadotropic hypogonadism. The patient underwent transsphenoidal surgery. The cyst membrane was opened and clear, serous fluid was evacuated. The postoperative course was complicated by CSF leakage, which was corrected by an autologous fat graft placement. Visual field defects improved immediately after surgery but a transient panhypopituitarism and diabetes insipidus occurred. Postoperative MRI revealed no recurrence of the lesion during the four-year follow-up. PMID:16967358

  9. Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

    PubMed

    Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

    2016-05-01

    Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients. PMID:26924790

  10. 10q26.1 Microdeletion: Redefining the critical regions for microcephaly and genital anomalies.

    PubMed

    Choucair, Nancy; Abou Ghoch, Joelle; Fawaz, Ali; Mégarbané, André; Chouery, Eliane

    2015-11-01

    Distal 10q deletion syndrome is a well-characterized chromosomal disorder consisting of neurodevelopmental impairment, facial dysmorphism, cardiac malformations, genital and urinary tract defects, as well as digital anomalies. Patients with interstitial deletions involving band 10q26.1 present a phenotype similar to the ones with the distal 10q deletion syndrome, which led to the definition of a causal 600 kb smallest region of overlap (SRO). In this report, we describe a male patient with an interstitial 4.5 Mb deletion involving exclusively the 10q26.1 segment. He had growth and psychomotor retardation, microcephaly, flat feet, micropenis, and cryptorchidism. The patient's deleted region does not overlap the 10q SRO. We reviewed the clinical phenotype of patients with similar deletions and suggest the presence of two new SROs, one associated with microcephaly, growth and psychomotor retardation, and the other associated to genital anomalies. Interestingly, we narrowed those regions to segments encompassing five and two genes, respectively. FGFR2, NSMCE4A, and ATE1 were suggested as candidates for facial dysmorphism, growth cessation, and heart defects, respectively. WDR11 was linked to idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Its haploinsufficiency could play a crucial role in the genital anomalies of these patients. PMID:26114870

  11. Testosterone deficiency and mood in aging men: pathogenic and therapeutic interactions.

    PubMed

    Seidman, Stuart N

    2003-01-01

    In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in hypothalamic-pituitary-gonadal (HPG) function in aging men: testosterone (T) levels decline through both central (pituitary) and peripheral (testicular) mechanisms and there is a loss of the circadian rhythm of T secretion. In cohorts of men 75 years of age, mean plasma T levels are 35% lower than comparable young men, and more than 25% of men over 75 appear to be T-deficient. Such age-associated T deficiency, which has been termed 'andropause', is thought to be responsible for a variety of symptoms experienced by elderly men, such as weakness, fatigue, reduced muscle and bone mass, impaired haematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia and memory impairment. However, it has been difficult to establish correlations between these symptoms and plasma T levels. Nevertheless, there is some evidence that T replacement leads to symptom relief, particularly with respect to muscle strength, bone mineral density, and haematopoiesis. Studies to date on the specific association between psychiatric symptoms, such as depressed mood, and T levels have been methodologically flawed. Overall, data suggest that although hypogonadism is not central to major depressive disorder (MDD), HPG hypofunction may have aetiological importance in mild depressive conditions, such as dysthymia. PMID:12582972

  12. Stereotactic fractionated radiotherapy for the treatment of benign meningiomas

    SciTech Connect

    Candish, Charles; McKenzie, Michael . E-mail: mmckenzi@bccancer.bc.edu; Clark, Brenda G.; Ma, Roy; Lee, Richard; Vollans, Emily; Robar, James; Gete, Ermias; Martin, Monty

    2006-11-15

    Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm{sup 3} and 18.9 cm{sup 3}, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45-50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective.

  13. Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

    PubMed Central

    Lanfranco, Fabio; Motta, Giovanna; Minetto, Marco Alessandro; Baldi, Matteo; Balbo, Marcella; Ghigo, Ezio; Arvat, Emanuela; Maccario, Mauro

    2010-01-01

    Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH) secretion coupled to reduced insulin-like growth factor-I (IGF-I) concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL) rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA) axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH) secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death. PMID:20182553

  14. Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.

    PubMed

    Mejlachowicz, Dan; Nolent, Flora; Maluenda, Jérome; Ranjatoelina-Randrianaivo, Hanitra; Giuliano, Fabienne; Gut, Ivo; Sternberg, Damien; Laquerrière, Annie; Melki, Judith

    2015-10-01

    Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.1996delC, p.Gln666Serfs∗36) and inherited from the father was identified in the probands. In another family, a distinct heterozygous truncating mutation leading to frameshift (c.2118delT, p.Leu708Trpfs∗7) and occurring de novo on the paternal allele of MAGEL2 was identified in the affected individual. In both families, RNA analysis identified the mutated paternal MAGEL2 transcripts only in affected individuals. MAGEL2 is one of the paternally expressed genes within the Prader-Willi syndrome (PWS) locus. PWS is associated with, to varying extents, reduced fetal mobility, severe infantile hypotonia, childhood-onset obesity, hypogonadism, and intellectual disability. MAGEL2 mutations have been recently reported in affected individuals with features resembling PWS and called Schaaf-Yang syndrome. Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene. PMID:26365340

  15. Prader-Willi Syndrome: A spectrum of anatomical and clinical features.

    PubMed

    Hurren, Bradley J; Flack, Natasha A M S

    2016-07-01

    Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation, involving Chromosome 15. The phenotypical appearance of individuals with the syndrome follows a similar developmental course. During infancy, universal hypotonia accompanied by feeding problems, hypogonadism, and dolichocephaly are evident. Characteristic facial features such as narrow bifrontal diameter, almond-shaped eyes, and small mouth (with downturned corners and thin upper lip) may also be evident at this stage. In early childhood, the craniofacial features become more obvious and a global developmental delay is observed. Simultaneously, individuals develop hyperphagia that leads to excessive or rapid weight gain, which, if untreated, exists throughout their lifespan and may predispose them to numerous, serious health issues. The standard tool for differential diagnosis of PWS is genetic screening; however, clinicians also need to be aware of the characteristic features of this disorder, including differences between the genetic subtypes. As the clinical manifestations of the syndrome vary between individuals and become evident at different developmental time points, early assessment is hindered. This article focuses on the clinical and anatomical manifestations of the syndrome and highlights the areas of discrepancy and limitations within the existing literature. Clin. Anat. 29:590-605, 2016. © 2016 Wiley Periodicals, Inc. PMID:26749552

  16. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

    PubMed Central

    Thiffault, Isabelle; Wolf, Nicole I.; Forget, Diane; Guerrero, Kether; Tran, Luan T.; Choquet, Karine; Lavallée-Adam, Mathieu; Poitras, Christian; Brais, Bernard; Yoon, Grace; Sztriha, Laszlo; Webster, Richard I.; Timmann, Dagmar; van de Warrenburg, Bart P.; Seeger, Jürgen; Zimmermann, Alíz; Máté, Adrienn; Goizet, Cyril; Fung, Eva; van der Knaap, Marjo S.; Fribourg, Sébastien; Vanderver, Adeline; Simons, Cas; Taft, Ryan J.; Yates III, John R.; Coulombe, Benoit; Bernard, Geneviève

    2015-01-01

    A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy. PMID:26151409

  17. The endocrine spectrum of intracranial cysts in childhood and review of the literature.

    PubMed

    Savas Erdeve, Senay; Ocal, Gonul; Berberoglu, Merih; Siklar, Zeynep; Hacihamdioglu, Bulent; Evliyaoglu, Olcay; Fitoz, Suat

    2011-01-01

    Intracranial cysts (ICC) may cause a wide spectrum of endocrinological disorders. We evaluated 27 patients who were diagnosed with ICC during investigation for neuroendocrine dysfunctions and reviewed the relevant literature. The types of ICC in the patients were arachnoid cysts (n = 13); Rathke cleft cysts (n = 7); pineal cysts (n = 5); an ependymal cyst (n = 1) and a cavum septum pellucidum cyst (n = 1). The neuroendocrine dysfunctions of the patients were obesity (n = 7), isolated growth hormone deficiency (n = 6), central precocious puberty (n = 6), multiple pituitary hormone deficiency (n = 3), central diabetes insipidus (n = 1), growth hormone deficiency and central precocious puberty (n = 1), obesity and galactorrhea (n = 1), obesity and hypogonadotropic hypogonadism (n = 1) and growth hormone neurosecretory dysfunction (n = 1). Only three patients, who had arachnoid cysts, showed neurologic symptomatology. Although three patients underwent surgery, no improvements in endocrinological dysfunctions were observed. ICC should be considered when evaluating patients with endocrinological problems and patients with coincidental ICC should be recommended for follow-up. PMID:22308834

  18. [Estrogens and pharmacological modulation of estrogen receptors].

    PubMed

    Sanidize, T V; Ratiani, L R; Gabuniia, L Iu; Tortladze, M L; Kuridze, N N

    2009-02-01

    Estrogens belong to more or less frequently prescribed preparations. Main fields of application of these preparations (as in monotherapy as well as in combination) are contraception and hormone replacement therapy during menopause. More uncommon indications of estrogens are growth inhibition and hypogonadism (in this case they are prescribed along with gonadotropic hormones). Synthesis and metabolism of estrogens, as well as their intracellular receptors are well studied these days, which allow us to understand physiology and pharmacology of these hormones. In pharmacology the main stage is detection of estrogen receptors inside of cells of targets. There are two types of estrogen receptors alpha- and beta- coded by different genes. A number of steroid and non-steroid compounds have characteristics of estrogens. Likely in the future their popularity will increase, as by the aging of population number of those women, who receive replacement therapy, will increase. Investigations to find an ideal elective modulator of estrogen receptors, that will possess anti-estrogenic activity in connection with mammal gland and develop indifference in connection with endometrium and at the same time will display ability to reduce hot flushes, bone resorption, atrophy of mucous membranes of vagina and urinary bladder, as well as it will favorably effect on metabolism of lipoproteins are carried out. PMID:19276483

  19. Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease.

    PubMed

    Pierce, Sarah B; Gulsuner, Suleyman; Stapleton, Gail A; Walsh, Tom; Lee, Ming K; Mandell, Jessica B; Morales, Augusto; Klevit, Rachel E; King, Mary-Claire; Rogers, R Curtis

    2016-07-01

    Mutations in nuclear genes required for the replication and maintenance of mitochondrial DNA cause progressive multisystemic neuromuscular disorders with overlapping phenotypes. Biallelic mutations in C10orf2, encoding the Twinkle mitochondrial DNA helicase, lead to infantile-onset cerebellar ataxia (IOSCA), as well as milder and more severe phenotypes. We present a 13-year-old girl with ataxia, severe hearing loss, optic atrophy, peripheral neuropathy, and hypergonadotropic hypogonadism. Whole-exome sequencing revealed that the patient is compound heterozygous for previously unreported variants in the C10orf2 gene: a paternally inherited frameshift variant (c.333delT; p.L112Sfs*3) and a maternally inherited missense variant (c.904C>T; p.R302W). The identification of novel C10orf2 mutations extends the spectrum of mutations in the Twinkle helicase causing recessive disease, in particular the intermediate IOSCA phenotype. Structural modeling suggests that the p.R302W mutation and many other recessively inherited Twinkle mutations impact the position or interactions of the linker region, which is critical for the oligomeric ring structure and activity of the helicase. This study emphasizes the utility of whole-exome sequencing for the genetic diagnosis of a complex multisystemic disorder. PMID:27551684

  20. Hypoparathyroidism and subclinical hypothyroidism with secondary hemochromatosis.

    PubMed

    Jeong, Hyung Ki; An, Joon Hwan; Kim, Hyoung Sang; Cho, Eun Ae; Han, Min Gui; Moon, Jung Sik; Kim, Hee Kyung; Kang, Ho-Cheol

    2014-03-01

    Hemochromatosis is an inherited genetic disorder of iron metabolism which can also occur as a secondary result of iron-overload. It leads to organ damage such as cardiomyopathy, liver cirrhosis, hypogonadism, and diabetes. This paper discusses a case of secondary hemochromatosis associated with repeated transfusions, presenting as asymptomatic hypoparathyroidism and subclinical hypothyroidism with multiple organ involvement. The 29-year-old female, who had severe aplastic anemia, received multiple transfusions totaling approximately 1,400 units of red blood cells over 15 years. During her routine laboratory examination, hypocalcemia was detected with decreased intact parathyroid hormone and increased thyroid stimulating hormone. Serum ferritin, iron, and total iron binding capacity had increased to 27,583.03 ng/mL, 291 µg/dL, and 389 µg/dL, respectively. She had unusually bronze skin and computed tomography revealed iron deposition in the thyroid, liver, and heart. Multiorgan involvement as seen in this case is rare in hemochromatosis associated with secondary transfusions. To the best of the author's knowledge, this is the first case report in Korea of hypoparathyroidism and subclinical hypothyroidism due to iron deposition in the parathyroid and thyroid gland. PMID:24741460

  1. Late endocrine effects of childhood cancer.

    PubMed

    Rose, Susan R; Horne, Vincent E; Howell, Jonathan; Lawson, Sarah A; Rutter, Meilan M; Trotman, Gylynthia E; Corathers, Sarah D

    2016-06-01

    The cure rate for paediatric malignancies is increasing, and most patients who have cancer during childhood survive and enter adulthood. Surveillance for late endocrine effects after childhood cancer is required to ensure early diagnosis and treatment and to optimize physical, cognitive and psychosocial health. The degree of risk of endocrine deficiency is related to the child's sex and their age at the time the tumour is diagnosed, as well as to tumour location and characteristics and the therapies used (surgery, chemotherapy or radiation therapy). Potential endocrine problems can include growth hormone deficiency, hypothyroidism (primary or central), adrenocorticotropin deficiency, hyperprolactinaemia, precocious puberty, hypogonadism (primary or central), altered fertility and/or sexual function, low BMD, the metabolic syndrome and hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer should be delivered in a multidisciplinary setting, providing continuity from acute cancer treatment to long-term follow-up of late endocrine effects throughout the lifespan. Endocrine therapies are important to improve long-term quality of life for survivors of childhood cancer. PMID:27032982

  2. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy.

    PubMed

    Østergren, Peter Busch; Kistorp, Caroline; Bennedbæk, Finn Noe; Faber, Jens; Sønksen, Jens; Fode, Mikkel

    2016-06-01

    Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking. PMID:27112391

  3. Primary Hyperparathyroidism and Hyperthyroidism in a Patient with Myotonic Dystrophy: A Case Report and Review of the Literature

    PubMed Central

    Cherif, Yosra; Zantour, Baha; Alaya, Wafa; Berriche, Olfa; Younes, Samia; Sfar, Mohamed Habib

    2015-01-01

    Various endocrine manifestations are commonly described in myotonic dystrophy (MD), including primary hypogonadism, diabetes mellitus, and thyroid and parathyroid dysfunction. We describe a 46-year-old woman with a family history of MD with her son. She was diagnosed with cardiac arrhythmia and required the implantation of a pacemaker. She was noted to have a bilateral cataract. She complained of muscle weakness, diffuse myalgia, and palpitation. The electromyography (EMG) showed myotonic discharges. Laboratory tests showed high serum calcium 2.83 mmol/L, serum phosphate 1.2 mmol/L, parathormone 362.5 pg/mL, thyroid stimulating hormone TSH 0.02 mIU/L (normal range: 0.34–5.6 mIU/L), FT4 21.17 ng/mL, and negative anti-thyroperoxidase antibodies. Cervical ultrasound revealed a multinodular goiter. The 99mTc-MIBI scintigraphy localized a lower right parathyroid adenoma. The clinical data, the family history of MD, EMG data, and endocrine disturbances were strongly suggestive of MD associated with hyperthyroidism and primary hyperparathyroidism. PMID:26175917

  4. Langerhans cell histiocytosis - a case report.

    PubMed

    Jeunon, Thiago; Sousa, Maria Auxiliadora Jeunon; Santos-Rodrigues, Nilton; Lopes, Raquel

    2012-01-01

    A 17-year-old male presented for dermatologic consultation with slightly elevated reddish papules covered by yellowish scales in the scalp for the last two years and reddish and indurated ulcers in the perineum lasting six months. Additional complaints included polyuria, polydipsia, delay in the development of secondary sexual characteristics and hearing loss of the right ear secondary to a medium otitis. Lesions from scalp and perineum were sampled for histopathologic examination and revealed a dense cellular infiltrate made up of mononuclear cells with conspicuous eosinophilic cytoplasm and large cleaved vesicular nucleus, some of them with shapes resembling the format of a kidney and others reminiscent of coffee beans. Numerous intermingling eosinophils were present. The diagnosis of Langerhans cell histiocytosis was then rendered and confirmed by positive immunostaining of neo-plastic cells for anti-CD1a and anti-S100 protein antibodies. The work-up revealed diabetes insipidus, hypogonadotropic hypogonadism, hiperprolactenemia, growing-hormone deficiency and thickness of the pituitary stalk. The patient was treated with prednisone and vinblastin based chemotherapy regimen for six months with complete remission, but presented recurrence of some lesions in the scalp, which were handled with topical mustard and corticosteroids. After chemotherapy, the endocrinologic disturbances were corrected with hormonal replacement therapy. The patient is currently in good health with a follow-up of five years. PMID:24765546

  5. Effects of sex chromosome aneuploidies on brain development: evidence from neuroimaging studies.

    PubMed

    Lenroot, Rhoshel K; Lee, Nancy Raitano; Giedd, Jay N

    2009-01-01

    Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the effects of different dosages of sex chromosome genes on brain development may help to understand the basis for functional differences in affected individuals. It may also be informative regarding how sex chromosomes contribute to typical sexual differentiation. Studies of 47,XXY males make up the bulk of the current literature of neuroimaging studies in individuals with supernumerary sex chromosomes, with a few small studies or case reports of the other SCAs. Findings in 47,XXY males typically include decreased gray and white matter volumes, with most pronounced effects in the frontal and temporal lobes. Functional studies have shown evidence of decreased lateralization. Although the hypogonadism typically found in 47,XXY males may contribute to the decreased brain volume, the observation that 47,XXX females also show decreased brain volume in the presence of normal pubertal maturation suggests a possible direct dosage effect of X chromosome genes. Additional X chromosomes, such as in 49,XXXXY males, are associated with more markedly decreased brain volume and increased incidence of white matter hyperintensities. The limited data regarding effects of having two Y chromosomes (47,XYY) do not find significant differences in brain volume, although there are some reports of increased head size. PMID:20014372

  6. Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis.

    PubMed

    Francavilla, S; D'Abrizio, P; Rucci, N; Silvano, G; Properzi, G; Straface, E; Cordeschi, G; Necozione, S; Gnessi, L; Arizzi, M; Ulisse, S

    2000-08-01

    In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes. PMID:10946867

  7. Phytotherapy: emerging therapeutic option in urologic disease

    PubMed Central

    2012-01-01

    Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists. PMID:26816707

  8. Anabolic steroids abuse and male infertility.

    PubMed

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage. PMID:26855782

  9. Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.

    PubMed

    Brayman, Melissa J; Pepa, Patricia A; Mellon, Pamela L

    2012-11-01

    Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic-pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated by gonadal steroid hormones. Disruptions in androgen levels are involved in a number of reproductive defects, including hypogonadotropic hypogonadism and polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites in the proximal promoter. In this study, we show AR also represses GnRH transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766 region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791, resulted in decreased basal activity and a loss of AR-mediated repression. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive regions, including the site at -1792/-1791. PMID:22877652

  10. Nutritional and Pubertal Disorders.

    PubMed

    Muñoz-Calvo, M Teresa; Argente, Jesús

    2016-01-01

    Caloric-protein malnutrition can slow growth and cause pubertal delay. This chapter focuses on endocrine abnormalities and pubertal alterations in patients with eating disorders, childhood obesity, the female athlete triad and children cancer survivors. Patients with anorexia nervosa (AN) exhibit multiple endocrine abnormalities, including isolated hypogonadotropic hypogonadism. The delay in pubertal development and reduction in growth seen in AN patients may be a direct result of malnutrition. Appropriate psychiatric, nutritional and hormonal therapy is necessary. It is suggested that obesity during childhood can accelerate pubertal onset and these children usually exhibit accelerated linear growth during puberty. In girls the relationship between childhood obesity and early pubertal onset could be related to their insulin resistance and/or hyperinsulinemia. The female athlete triad is often observed in physically active girls and women in whom low energy availability with or without disordered eating, menstrual dysfunction and low bone mineral density can be present. In prepubertal girls excess exercise can cause delayed menarche with no effects on adult height, while in postpubertal females it results in menstrual cycle irregularities. The consequences of childhood cancer depend on the type of cancer, its location, the age at which the disease was diagnosed, the dose of radiotherapy, and the type and dose of chemotherapy. PMID:26680577

  11. Turner syndrome presented with tall stature due to overdosage of the SHOX gene

    PubMed Central

    Seo, Go Hun; Kang, Eungu; Cho, Ja Hyang; Lee, Beom Hee; Choi, Jin-Ho; Kim, Gu-Hwan; Seo, Eul-Ju

    2015-01-01

    Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the SHOX gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by SHOX overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the PPP2R3 gene near the 5'-end of the SHOX gene through the FANCD gene at Xp22.2. PMID:26191517

  12. A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis

    PubMed Central

    Weinberg-Shukron, Ariella; Renbaum, Paul; Kalifa, Rachel; Zeligson, Sharon; Ben-Neriah, Ziva; Dreifuss, Amatzia; Abu-Rayyan, Amal; Maatuk, Noa; Fardian, Nilly; Rekler, Dina; Kanaan, Moien; Samson, Abraham O.; Levy-Lahad, Ephrat; Gerlitz, Offer; Zangen, David

    2015-01-01

    Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure. PMID:26485283

  13. IGF-I Signaling Is Essential for FSH Stimulation of AKT and Steroidogenic Genes in Granulosa Cells

    PubMed Central

    Zhou, Ping; Baumgarten, Sarah C.; Wu, Yanguang; Bennett, Jill; Winston, Nicola; Hirshfeld-Cytron, Jennifer

    2013-01-01

    FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR. PMID:23340251

  14. Male gonadal axis function in patients with type 2 diabetes.

    PubMed

    Costanzo, Pablo R; Knoblovits, Pablo

    2016-05-01

    Patients with type 2 diabetes have lower serum testosterone levels and a higher prevalence of hypogonadism than non-diabetic patients, independently of the metabolic control of disease. The mechanisms underlying a decrease in testosterone might be related to age, obesity and insulin resistance, often present in patients with type 2 diabetes. The increase in estrogens due to higher aromatase enzyme activity in increased adipose tissue might exert negative-feedback inhibition centrally. Insulin stimulates gonadal axis activity at all three levels and therefore insulin resistance might account for the lower testosterone production. Leptin exerts a central stimulatory effect but inhibits testicular testosterone secretion. Thus, resistance to leptin in obese subjects with type 2 diabetes determines lower central effects of leptin with lower gonadotropin-releasing hormone (GnRH) secretion and, on the other hand, hyperleptinemia secondary to leptin resistance inhibits testosterone secretion at the testicular level. However, lower testosterone levels in patients with diabetes are observed independently of age, weight and body mass index, which leads to the assumption that hyperglycemia per se might play a role in the decrease in testosterone. Several studies have shown that an overload of glucose results in decreased serum testosterone levels. The aim of this review is to assess changes in the male gonadal axis that occur in patients with type 2 diabetes. PMID:27071157

  15. Classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults.

    PubMed

    Bachelot, Anne; Chakthoura, Zeina; Rouxel, Agnès; Dulon, Jérome; Touraine, Philippe

    2008-01-01

    During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization and to attain normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. The aims here are to review the multiple clinical, hormonal and metabolic abnormalities that could be found in adult CAH patients as such a decrease in bone mineral density, overweight and disturbed reproductive functions. In women with classic CAH, a low fertility rate is reported, and is probably the consequence of multiple factors including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. Therefore a multidisciplinary team with knowledge of CAH should carefully follow up these patients, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens. PMID:18204267

  16. Insulin-like growth factor- I and factors affecting it in thalassemia major

    PubMed Central

    Soliman, Ashraf T.; Sanctis, Vincenzo De; Elalaily, Rania; Yassin, Mohamed

    2015-01-01

    Despite improvement of blood transfusion regimens and iron chelation therapy growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis still occur in good number of thalassemic patients. Decreased IGF-1 secretion occurs in the majority of the thalassemic patients particularly those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including disturbed growth hormone (GH) - insulin-like growth factor - I (IGF-I) axis. The possible factors contributing to low IGF-I synthesis in thalassemia and the possible interaction between low IGF-I secretion and the occurrence of these complications is discussed in this mini-review. Improvement of IGF-I secretion in thalassemic patients should be intended to improve linear growth and bone mineral accretion in thalassemic patients. This can be attained through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake), correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism at the proper time and treating GH deficiency. This review paper provides a summary of the current state of knowledge regarding IGF-I and factors affecting it in patients with thalassaemia major (TM). Search on PubMed and reference lists of articles with the term ‘IGF-I, GH, growth, thalassemia, thyroxine, anemia, vitamin D, and zinc’ was carried out. A hundred and forty-eight articles were found and used in the write up and the data analyzed was included in this report. PMID:25729686

  17. Endocrine Dysregulation in Anorexia Nervosa Update

    PubMed Central

    2011-01-01

    Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

  18. Prader-Willi Syndrome and Growth Hormone Deficiency

    PubMed Central

    Aycan, Zehra; Baş, Veysel Nijat

    2014-01-01

    Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient’s life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures. PMID:24932597

  19. A microRNA switch regulates the rise in hypothalamic GnRH production before puberty.

    PubMed

    Messina, Andrea; Langlet, Fanny; Chachlaki, Konstantina; Roa, Juan; Rasika, Sowmyalakshmi; Jouy, Nathalie; Gallet, Sarah; Gaytan, Francisco; Parkash, Jyoti; Tena-Sempere, Manuel; Giacobini, Paolo; Prevot, Vincent

    2016-06-01

    A sparse population of a few hundred primarily hypothalamic neurons forms the hub of a complex neuroglial network that controls reproduction in mammals by secreting the 'master molecule' gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH expression are essential for puberty and adult fertility. Here we report that a multilayered microRNA-operated switch with built-in feedback governs increased GnRH expression during the infantile-to-juvenile transition and that impairing microRNA synthesis in GnRH neurons leads to hypogonadotropic hypogonadism and infertility in mice. Two essential components of this switch, miR-200 and miR-155, respectively regulate Zeb1, a repressor of Gnrh transcriptional activators and Gnrh itself, and Cebpb, a nitric oxide-mediated repressor of Gnrh that acts both directly and through Zeb1, in GnRH neurons. This alteration in the delicate balance between inductive and repressive signals induces the normal GnRH-fuelled run-up to correct puberty initiation, and interfering with this process disrupts the neuroendocrine control of reproduction. PMID:27135215

  20. Excitatory effects of the puberty-initiating peptide kisspeptin and group I metabotropic glutamate receptor agonists differentiate two distinct subpopulations of GnRH neurons

    PubMed Central

    Dumalska, Iryna; Wu, Min; Morozova, Elena; Liu, Rongjian; van den Pol, Anthony; Alreja, Meenakshi

    2008-01-01

    Activation of the G protein-coupled receptor, GPR54 by kisspeptins during normal puberty promotes the central release of gonadotropin releasing hormone (GnRH) that in turn leads to reproductive maturation. In humans and mice, a loss of function mutations of GPR54 prevents the onset of puberty and leads to hypogonadotropic hypogonadism and infertility. Using electrophysiological, morphological, molecular and retrograde-labeling techniques in brain slices prepared from vGluT2-GFP and GnRH-GFP mice, we demonstrate the existence of two physiologically distinct subpopulations of GnRH neurons. The first subpopulation is comprised of septal GnRH neurons that co-localize vGluT2 and GFP and is insensitive to metabotropic glutamate receptor agonists, but is exquisitely sensitive to kisspeptin which closes potassium channels to dramatically initiate a long-lasting activation in neurons from pre- and post-pubertal mice of both sexes. A second subpopulation is insensitive to kisspeptin but is uniquely activated by group I metabotropic glutamate receptor agonists. These two physiologically distinct classes of GnRH cells may subserve different functions in the central control of reproduction and fertility. PMID:18685025