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Sample records for hypogonadism

  1. Male hypogonadism.

    PubMed

    Basaria, Shehzad

    2014-04-01

    Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal amounts of sperm, or both. Hypogonadism may arise from testicular disease (primary hypogonadism) or dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical presentations vary dependent on the time of onset of androgen deficiency, whether the defect is in testosterone production or spermatogenesis, associated genetic factors, or history of androgen therapy. The clinical diagnosis of hypogonadism is made on the basis of signs and symptoms consistent with androgen deficiency and low morning testosterone concentrations in serum on multiple occasions. Several testosterone-replacement therapies are approved for treatment and should be selected according to the patient's preference, cost, availability, and formulation-specific properties. Contraindications to testosterone-replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment should be monitored for benefits and adverse effects. PMID:24119423

  2. Male hypogonadism.

    PubMed

    Isidori, Andrea M; Giannetta, Elisa; Lenzi, Andrea

    2008-01-01

    The hypothalamic-pituitary-gonadal (HPG) axis regulates the development, endocrine and reproductive function of the gonads throughout all phases of life. Male hypogonadism is defined an inadequate gonadal function, as manifested by deficiency in gametogenesis and/or secretion of gonadal hormones. In most cases, male hypogonadism is diagnosed through detailed history, physical examination and a few basic hormonal evaluations. In selected cases, however, additional tests are needed to define the aetiology and the extent of HPG axis dysfunction. These include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography, testicular biopsy and hormonal dynamic testing. The stimulation tests of the HPG are of particular importance in the differential diagnosis of congenital delayed puberty versus pre-pubertal hypogonadism in children. This review will focus on the methods, indications and limitations of endocrine testing in the characterisation and differential diagnosis of male hypogonadism at various ages. A practical hands-on guide on how to perform these tests is also provided.

  3. Hypothalamic hypogonadism.

    PubMed

    Bhasin, S; Swerdloff, R S

    1985-01-01

    The reproductive system consists of a series of feedback loops involving the higher centers, the hypothalamus, the pituitary, and the gonads. The factors involved in physiologic restraint of the hypothalamic pituitary gonadal axis until the time of puberty are complex. The pattern (frequency and amplitude) of GnRH signal is important in regulating pituitary LH and FSH secretion. This signal can be amplified and modulated at the pituitary level at least in part by the sex steroids. Hypothalamic hypogonadism can be considered a disorder of the hypothalamic GnRH pulse generator that results in deficient or dysrhythmic GnRH release. The mechanisms underlying the abnormal GnRH release in acquired, functional disorders such as anorexia nervosa and amenorrhea of joggers remain controversial. Evaluation of patients with hypothalamic hypogonadism involves exclusion of hyperprolactinemia, space-occupying lesions, and other systemic disorders. The pulsatile administration of GnRH for induction of fertility represents a major advance in the treatment of these patients.

  4. 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

  5. Opioids and hypogonadism.

    PubMed

    2012-04-01

    Detailed reports of hypogonadotropic hypogonadism in patients receiving morphine analgesia were published in 2010. Symptoms included flushing and sweating, amenorrhoea, impotence and decreased libido. Epidemiological studies have examined a possible link between hypogonadism and opioid use, in both patients and drug addicts. Statistically significant decreases in plasma hormone concentrations were found, with lower testosterone and LH levels in men, and lower oestradiol, progesterone, LH and FSH levels in women. Animal studies have provided consistent results. It is suspected that opioids affect the hypothalamic-pituitary axis, inhibiting LH secretion. Patients should be warned of this risk. If signs of hypogonadism occur in a patient taking an opioid, the benefits and harms of treatment should be reassessed. If possible, the dose should be reduced or the opioid withdrawn.

  6. Osteopenia and Male Hypogonadism

    PubMed Central

    Dupree, Kendall; Dobs, Adrian

    2004-01-01

    A 34-year-old male, with a history of chronic myelogenous lymphoma (CML) previously successfully treated 20 years earlier with chemotherapy, bone marrow transplants, and donor lymphocyte infusion therapy, presented with fatigue and low serum testosterone level. Evaluation revealed male hypogonadism from primary testicular failure due to prior CML therapy in addition to osteopenia. The patient received supplementary calcium, vitamin D, and testosterone; improvement in serum testosterone level was noted in 6 weeks, along with increased energy level and good libido and erectile function. Dual-energy x-ray absorptiometry (DEXA) scan showed improvement in bone status. Male hypogonadism is associated with increased risk for osteopenia and osteoporosis. Supplemental testosterone therapy, because of its direct effect and its aromatization to estrogen, can improve bone density in these patients. PMID:16985910

  7. 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

  8. 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.

  9. Micropenis. II. Hypogonadotropic hypogonadism.

    PubMed

    Danish, R K; Lee, P A; Mazur, T; Amrhein, J A; Migeon, C J

    1980-05-01

    This paper documents the case histories of 14 patients with hypogonadotropic hypogonadism and micropenis (penile length below 2.5 SD from the mean for the patient's chronlogical age, or for age corresponding to stage of sexual development). Nine of the patients were raised as males. Five of them received androgen for the purpose of stimulating penile growth: two realized normal adult penile length (-0.2 and -2.1 SD from normal mean length) whereas the other three had penile lengths significantly below the mean (-3.6, -4.6 and -5.2 SD from normal mean length). These data suggest that among hypogonadotropic patients with micropenis, those with prepubertal penile lengths between 2.5 and 3 SD below the mean may develop an adult penis of a length within the normal range. However, for those presenting with a shorter phallus, the expectation is that penile length will remain greater than 2 SD below the mean.

  10. 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.

  11. Genetics and hypogonadotrophic hypogonadism.

    PubMed

    Hay, Cathy; Wu, Frederick

    2002-06-01

    Hypothalamic pulsatile gonadotrophin-releasing hormone secretion, stimulating pituitary gonadotrophin secretion, is essential for adult reproductive function. This neuroendocrine drive to the reproductive axis is critically dependent on a sequence of developmental events in utero. During early foetal life, gonadotrophin-releasing hormone neurones migrate from the nasal placode to the medial basal hypothalamus where gonadotrophin-releasing hormone can be transported down portal vessels to the anterior pituitary. Gonadotrophin-releasing hormone secretion is active fleetingly neonatally but soon becomes quiescent throughout childhood. At the time of puberty activation of gonadotrophin-releasing hormone secretion reawakens the hypothalamic pituitary-gonadal axis and secondary sexual maturation is triggered. Any disruption in gonadotrophin-releasing hormone secretion will result in hypogonadotrophic hypogonadism. The clinical manifestations of this become apparent with secondary sexual maturation. Genetic mutations have been identified in a minority of cases. These include Kallmann syndrome, adrenal hypoplasia congenital, gonadotropin-releasing hormone receptor and luteinizing hormone or follicle-stimulating hormone beta-subunit gene mutations. The importance of these discoveries is important not only in relation to the conditions that result, but also for our better understanding of normal reproductive function.

  12. Endocrine studies in primary hypogonadism.

    PubMed

    Ross, H; Hasen, J; Boyar, R M

    1978-01-01

    Two 15-year-old boys with primary hypogonadism had evaluation of their hypothalamic-pituitary-gonadal axis. Testicular biopsies and chromsomal studies were also performed. Both patients presented with delayed puberty and short stature and had prepubertal LH, FSH and testosterone concentrations. Serial 24-hour frequent-interval blood studies over a 2-year period in one patient (R.F.) showed a gradual progression from a normal early pubertal LH secretory pattern to one characteristic of 'primary' testicular failure. The testicular biopsies showed prepubertal tests with no significant germinal cell maturation. Although both patients had some somatic stigmata of Noonan's syndrome, they had different karyotypes (XY and xyq-). These studies show that elevated levels of LH and FSH in primary hypogonadism syndrome may not become apparent until after the onset of CNS puberty.

  13. 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

  14. Hypogonadism and renal failure: An update.

    PubMed

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  15. Etiology and treatment of hypogonadism in adolescents.

    PubMed

    Viswanathan, Vidhya; Eugster, Erica A

    2011-10-01

    Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown.

  16. Etiology and treatment of hypogonadism in adolescents.

    PubMed

    Viswanathan, Vidhya; Eugster, Erica A

    2009-12-01

    Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown.

  17. 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

  18. Hypogonadism

    MedlinePlus

    ... in loss of sex drive and may cause: Impotence Infertility Osteoporosis Weakness Men normally have lower testosterone ... Breast discharge Breast enlargement (men) Hot flashes (women) Impotence Loss of body hair Loss of menstrual period ...

  19. 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

  20. 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.

  1. The genetics of hypogonadotropic hypogonadism.

    PubMed

    Bhagavath, Balasubramanian; Layman, Lawrence C

    2007-07-01

    An up-to-date review of the genetic aspects of idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS) is presented. Because proper development of the neuroendocrine axis must occur for normal puberty and reproductive function, gonadotropin-releasing hormone (GnRH) neuron migration is outlined first, followed by an introduction to the in vitro analysis of GnRH neuron migration. The normal hypothalamic-pituitary-gonadal (HPG) axis at different ages is discussed, along with a brief overview of normal and delayed puberty in both boys and girls. The phenotype of IHH/KS is discussed in detail, with its relation to Mendelian inheritance and chromosomal translocations. The molecular basis of IHH/KS is reviewed, with particular emphasis on the three most common genes ( KAL1, FGFR1, and GNRHR) that possess mutations in these patients. However, all other known genes for which mutations occur are also addressed briefly. The goal of this review is to provide a comprehensive discussion of IHH/KS, and to include both basic science and clinical findings that should allow a more complete understanding of hypothalamic-pituitary neuroendocrinology that is important in puberty and reproduction.

  2. 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

  3. TRANSITION IN ENDOCRINOLOGY: Hypogonadism in adolescence.

    PubMed

    Dwyer, Andrew A; Phan-Hug, Franziska; Hauschild, Michael; Elowe-Gruau, Eglantine; Pitteloud, Nelly

    2015-07-01

    Puberty is a remarkable developmental process with the activation of the hypothalamic-pituitary-gonadal axis culminating in reproductive capacity. It is accompanied by cognitive, psychological, emotional, and sociocultural changes. There is wide variation in the timing of pubertal onset, and this process is affected by genetic and environmental influences. Disrupted puberty (delayed or absent) leading to hypogonadism may be caused by congenital or acquired etiologies and can have significant impact on both physical and psychosocial well-being. While adolescence is a time of growing autonomy and independence, it is also a time of vulnerability and thus, the impact of hypogonadism can have lasting effects. This review highlights the various forms of hypogonadism in adolescence and the clinical challenges in differentiating normal variants of puberty from pathological states. In addition, hormonal treatment, concerns regarding fertility, emotional support, and effective transition to adult care are discussed.

  4. Anosmia and hypogonadism with ovarian mosaicism.

    PubMed

    Jones, J R; Kemmann, E; Cresci, J; Solish, G I

    1975-04-01

    An 18-year-old woman with anosmia and hypogonadotropic hypogonadism is presented. In addition endocrinologic evaluation revealed an apparent deficiency in pituitary growth hormone secretion in response to hypoglycemia and an ovarian insensitivity to exogenous gonadotropins. The ovaries, which on histologic examination appeared to be normal, upon karyotyping showed a chromosomal mosaicism, probably 46, XX/47, XXF+.

  5. The role of hypogonadism in Klinefelter Syndrome

    PubMed Central

    Høst, Christian; Skakkebæk, Anne; Groth, Kristian A; Bojesen, Anders

    2014-01-01

    Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be difficult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome. PMID:24407186

  6. Hypothalamic and pituitary function in hypogonadotropic hypogonadism.

    PubMed

    Paulson, D F; Wiebe, H R; Hammond, C B

    1975-09-01

    Hypogonadotropic hypogonadism has been identified as a cause of partial or complete failure of puberty, may be familial and may have other associated abnormalities of hyposmia, intellectual retardation, perceptive deafness, color blindness, skeletal deformities, and gynecomastia. Pituitary function is usually normal with the primary defect believed to be hypothalamic. A twenty-year-old white male with a clinical diagnosis of hypogonadotropic hypogonadism and anosmia under-went complete endocrine evaluation with evaluation of the pituitary response to luteinizing hormone-releasing hormone. FSH (follicle-stimulating hormone) and LH (luteinizing hormone) release after luteinizing hormone-releasing hormone did occur, but the response was less than that seen in normal controls. Evaluation demonstrated that the pituitary-gonadal axis was intact with the hypothalamic-pituitary axis being defective. Therapy with the synthetic decapeptide (luteinizing hormone-releasing hormone) is correct theoretically and may be superior to therapy with exogenous gonadotropins.

  7. 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.

  8. 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.

  9. Male partial hypogonadotrophic hypogonadism with gynaecomastia and metabolic syndrome.

    PubMed

    Ahsan, Tasnim; Banu, Zeenat

    2012-02-01

    The causal association of childhood obesity and hypogonadotrophic hypogonadism needs to be studied to unravel the cause and effect relationship between the two conditions. The relationship of hypogonadism to the Metabolic Syndrome (MetS) remains valid even when using different definitions of MetS, and following the patients prospectively for over 10 years. This is a case of 19 years male who presented with micropenis, marked gynaecomastia and weight gain. Childhood obesity and family history of diabetes predisposed him to future MetS. Presence of micropenis reflects intrauterine hypogonadotrophic hypogonadism. Both entities exacerbated each other.

  10. Plasma kisspeptin levels in male cases with hypogonadism.

    PubMed

    Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

    2014-08-22

    The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/ml in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/ml in a male with Kallmann's syndrome, 40.7 fmol/ml in a male with azoospermia, 323.2 fmol/ml in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/ml (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

  11. Plasma kisspeptin levels in male cases with hypogonadism.

    PubMed

    Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

    2014-01-01

    The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

  12. Complex genetics in idiopathic hypogonadotropic hypogonadism.

    PubMed

    Pitteloud, Nelly; Durrani, Sadia; Raivio, Taneli; Sykiotis, Gerasimos P

    2010-01-01

    Idiopathic hypogonadotropic hypogonadism (IHH) is an important human disease model. Investigations of the genetics of IHH have facilitated insights into critical pathways regulating sexual maturation and fertility. IHH has been traditionally considered a monogenic disorder. This model holds that a single gene defect is responsible for the disease in each patient. In the case of IHH, 30% of cases are explained by mutations in one of eleven genes. In recent years, several lines of evidence have challenged the monogenic paradigm in IHH. First, disease-associated mutations display striking incomplete penetrance and variable expressivity within and across IHH families. Second, each locus is responsible for only a small percentage of cases. Third, more than one disease-associated mutation seems to be segregating in some families with IHH, and their combined or separate presence in individuals accounts for the variability in disease severity. Finally, IHH is not strictly a congenital and life-long disorder; occasionally it manifests itself during adulthood (adult-onset IHH); in other cases, the disease is not permanent, as evidenced by normal activity of the hypothalamic-pituitary-gonadal axis after discontinuation of treatment in adulthood (IHH reversal). Together, these observations suggest that IHH is not strictly a monogenic mendelian disease, as previously thought. Rather, it is emerging as a digenic, and potentially oligogenic disease, in which hormonal and/or environmental factors may critically influence genetic predisposition and clinical course. Future investigations of IHH should characterize the extent of the involvement of multiple genes in disease pathogenesis, and elucidate the contributions of epigenetic factors.

  13. Female hypogonadism: evaluation of the hypothalamic-pituitary-ovarian axis.

    PubMed

    Rothman, Micol S; Wierman, Margaret E

    2008-01-01

    Female hypogonadism refers to deficient or abnormal function of the hypothalamic-pituitary-ovarian axis that clinically presents with menstrual cycle disturbances. Female hypogonadism can be due to a congenital or acquired cause, and the defect can be at the level of the hypothalamus, pituitary or ovary. A careful history, physical exam and selected laboratory testing can often determine the locus of the defect and whether it results from a structural or hormonal problem. Laboratory testing generally relies on basal hormone levels; however, timing of blood sampling in relation to menses is important to interpretation of the data.

  14. Preserving fertility in the hypogonadal patient: an update.

    PubMed

    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

  15. Preserving fertility in the hypogonadal patient: an update.

    PubMed

    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.

  16. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis.

    PubMed

    Seftel, A

    2006-01-01

    Male hypogonadism has a multifactorial etiology that includes genetic conditions, anatomic abnormalities, infection, tumor, and injury. Defects in the hypothalamic-pituitary-gonadal axis may also result from type II diabetes mellitus and treatment with a range of medications. Circulating testosterone levels have been associated with sexual function, cognitive function, and body composition. Apart from reduced levels of testosterone, clinical hallmarks of hypogonadism include absence or regression of secondary sex characteristics, reduced fertility (oligospermia, azoospermia), anemia, muscle wasting, reduced bone mass (and bone mineral density), and/or abdominal adiposity. Some patients, particularly those with partial androgen deficiency of the aging male, also experience sexual dysfunction, reduced sense of vitality, depressed mood, increased irritability, difficulty concentrating, and/or hot flushes in certain cases of acute onset. As many patients with male hypogonadism-like patients with erectile dysfunction-do not seek medical attention, it is important for clinicians to be acquainted with the signs and symptoms of hypogonadism, and to conduct appropriate laboratory testing and other assessments to determine the causes and inform the treatment of this condition.

  17. 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

  18. 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

  19. [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

  20. Outcomes associated with hypogonadism in men with chronic kidney disease.

    PubMed

    Palmer, Biff F

    2004-10-01

    Chronic kidney disease is commonly accompanied by disturbances in the hypothalamic-pituitary-gonadal axis. Such disturbances in men give rise to hypogonadism and low circulating testosterone levels. The deficiency in testosterone can contribute to clinical outcomes such as sexual dysfunction, decreased bone mineralization, malnutrition and decreased muscle mass, and anemia. The administration of androgens to nonuremic hypogonadal men is usually effective in treating such outcomes. By contrast, the response to therapy in uremic men tends to be much less predictable. This variability in response is not surprising, because these same clinical outcomes can be the result of other aspects of the uremic state or the comorbid conditions that are frequently present in men with chronic kidney disease. Although further studies are needed, testosterone therapy may prove most useful as an adjunct to other more general therapies designed to address the uremic state.

  1. Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

    PubMed

    Zacharin, Margaret

    2015-06-01

    Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized.

  2. 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

  3. Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

    PubMed

    Zacharin, Margaret

    2015-06-01

    Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized. PMID:26051297

  4. 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

  5. [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.

  6. Hypogonadism and endocrine metabolic disorders in Prader-Willi syndrome.

    PubMed

    Müller, J

    1997-11-01

    Disturbances of the hypothalamic-pituitary-gonadal axis are reviewed in patients with Prader-Willi syndrome, and a brief account is given of thyroid function, adrenal function and glucose metabolism in such patients. Cryptorchidism, hypoplastic external genitalia and delayed or incomplete pubertal development in most patients with Prader-Willi syndrome suggest dysfunction of the hypothalamic-pituitary-gonadal axis. Decreased levels of gonadotrophins, consistent with hypogonadotrophic hypogonadism, have been found in some patients, whereas others appear to have hypergonadotrophic hypogonadism secondary to cryptorchidism and its treatment. Gonadal function is normal in a small number of patients with the syndrome. Although most clinicians agree that cryptorchidism should be corrected in early childhood, in practice the surgery is often not performed. In addition, most patients do not receive sex hormone replacement therapy. It is therefore suggested that more aggressive endocrine treatment strategies for hypogonadism are warranted in both children and adults with Prader-Willi syndrome. Both thyroid function and adrenal function appear to be normal in most patients, and glucose metabolism is similar to that in normal obese individuals.

  7. [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

  8. Clinicopathologic assessment of hypogonadism in men with type 2 diabetes mellitus

    PubMed Central

    Ugwu, Theophilus E.; Ikem, Rosemary T.; Kolawole, Babatope A.; Ezeani, Ignatius U.

    2016-01-01

    Objective: To determine the prevalence of hypogonadism in men with type 2 diabetes mellitus and evaluate its clinical and pathologic correlates. Subjects and Methods: In a cross-sectional survey of 200 type 2 diabetic males aged 32–69 years, total testosterone (TT), follicle stimulating hormone, luteinizing hormone, waist circumference (WC), glycated hemoglobin, and lipids were measured. Clinical assessment of androgen deficiency was done using the androgen deficiency in aging male (ADAM) questionnaire. Overt hypogonadism was defined as a combination of positive ADAM score and TT < 8 nmol/L while possible hypogonadism was defined as positive ADAM score with TT 8–12 nmol/L. Results: Overt and possible hypogonadism occurred in 29.5% and 23% of the participants, respectively. Majority (76.3%) of the subjects who had overt hypogonadism had the hypogonadotrophic pattern. Hypogonadal subjects were significantly older (P = 0.014) and had higher mean WC (P = 0.009) than eugonadal ones. Erectile dysfunction was the most common symptom, occurring in 79.7% of overtly hypogonadal subjects. There was a significant negative correlation between WC and serum TT (r = −0.41, P = 0.001). Conclusion: There is a high frequency of symptomatic hypogonadism in men with type 2 diabetes and the frequency increases with advancing age and visceral adiposity. PMID:27730078

  9. Metabolic syndrome and hypogonadism--two peas in a pod.

    PubMed

    Ebrahimi, Fahim; Christ-Crain, Mirjam

    2016-01-01

    Testosterone deficiency is highly prevalent in up to 50% of men with the metabolic syndrome and type 2 diabetes mellitus. Low testosterone levels in men appear to be an independent cardiovascular risk factor and predictor of subsequent development of the metabolic syndrome. Reciprocally, the metabolic syndrome leads to a decrease in testosterone levels. This review provides an account of the pathophysiological mechanisms in the bidirectional relationship between hypogonadism and body composition, inflammation and insulin sensitivity as well as the effects of testosterone replacement on diverse metabolic parameters.

  10. 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.

  11. Testosterone in men with hypogonadism and high cardiovascular risk, Pros.

    PubMed

    Rosano, Giuseppe M C; Vitale, Cristiana; Fini, Massimo

    2015-11-01

    Although numerous randomized studies have shown that testosterone replacement therapy (TRT) improves intermediate outcomes in patients at risk and in those with proven cardiovascular disease (CVD), results derived mainly from registries and observational studies have suggested an increased cardiovascular risk in elderly men receiving often supra-therapeutic doses of testosterone. Recent meta-analyses have shown that when testosterone has been used in patients with pre-existing cardiovascular conditions, the effect on the disease has been either beneficial or neutral. Similar results have been reported in hypo- and eugonadal men. Contrasting results have been reported by two trials of testosterone treatment in frail elderly men. Reports from poorly analyzed databases have reported an increased risk of cardiovascular events with testosterone use. More recently, a population-based study showed no increased cardiovascular risk of testosterone replacement in hypogonadal men. Available data from controlled clinical trials suggest that the use of testosterone in elderly men does not increase cardiovascular risk nor the risk of events. Studies in men with CVD, angina, or heart failure report a benefit from testosterone replacement in men with or without hypogonadism. Therefore, at present, the cardiovascular benefits of TRT in elderly men outweigh the risks. This is particularly evident in those men with pre-existing CVD.

  12. 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.

  13. Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

    PubMed

    Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

    2007-02-01

    Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

  14. 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

  15. Clomiphene citrate and enclomiphene for the treatment of hypogonadal androgen deficiency.

    PubMed

    Kaminetsky, Jed; Hemani, Micah L

    2009-12-01

    Hypogonadism has a number of important clinical consequences related to androgen deficiency and impaired spermatogenesis. The cause of this condition is multifactorial and can result from hypothalamic, pituitary or gonadal dysfunction as well as factors that affect hormonal signaling along the hypothalamic-pituitary-gonadal axis. While testosterone replacement is the most common treatment, it can paradoxically lead to infertility, and may be a less physiologic therapy for patients with secondary hypogonadism due to pituitary dysfunction. Clomiphene citrate, and its derivatives, may allow for restoration of gonadal function by restoring physiologic pituitary function in a subset of patients with hypogonadism.

  16. [Male hypogonadism in children and adolescents: diagnostic assessment and therapy indications].

    PubMed

    Braggion, F; Gargantini, L; Calzi, P; Chiumello, G

    1989-01-01

    Testicular hormones, produced by hypothalamic-pituitary-gonadal axis activation, induce male development during embryogenesis and sexual maturation at puberty. As a consequence, any lesion at different levels of the axis is responsible for different clinical alterations, depending on the phase of life in which it develops, from early gestation to adult life. The evaluation of a hypogonadic male is complex and often diagnostic procedures only discriminate the level of damage but not the cause. Standardized and widely accepted therapies for specific forms of hypogonadism are briefly exposed. Three cases of hypogonadotropic hypogonadism are reported.

  17. 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

  18. [The aging male: a global approach to late onset hypogonadism and erectile dysfunction].

    PubMed

    Vlamopoulos, Yannis; Jichlinski, Patrice; Tawadros, Thomas

    2014-12-01

    The concept of aging male is defined by an age in which might appear some clinical symptoms. These symptoms, including erectile dysfunction (ED), are sometimes similar to those met in the late onset hypogonadism. Simultaneously, cardiovascular diseases increase with age and are associated with ED. The diagnosis of ED, associated or not with late onset hypogonadism, is mostly clinical. Its management will include PDE-5 which are generally well tolerated. Early detection of late onset hypogonadism is recommended as testosterone substitution improves quality of life. Although testosterone substitution needs to be carefully monitored, there is no clear evidence of increased risk of prostate cancer or cardiovascular disease. PMID:25626250

  19. Hypogonadism following long-term treatment with diethylstilbestrol.

    PubMed

    Wortsman, J; Hamidinia, A; Winters, S J

    1989-06-01

    The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.

  20. Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men.

    PubMed

    Jockenhövel, F; Blum, W F; Vogel, E; Englaro, P; Müller-Wieland, D; Reinwein, D; Rascher, W; Krone, W

    1997-08-01

    The ob gene product leptin (OB) is a feedback signal from the adipocyte to the hypothalamus and is involved in regulation of food intake and energy expenditure in rodents. A major determinant of serum OB levels is fat mass. Several studies suggest that men have lower OB levels than women even after adjustment for percent body fat. We, therefore, investigated the influence of testosterone (T) substitution in hypogonadal men on serum OB levels. Hypogonadal men with T levels of 3.6 nmol/L or less and off substitution therapy for at least 3 months were assigned to two treatment groups: testosterone enanthate (TE; 250 mg, i.m., every 21 days; n = 10) or a single s.c. implantation of 1200 mg crystalline T (TPEL; n = 12). Blood samples for determination of T, 5 alpha-dihydrotestosterone (DHT), sex hormone-binding globulin, and 17 beta-estradiol were obtained before therapy and then every 21 days until day 189 and at follow-up visits on days 246 and 300. Serum OB levels were assessed on days 0, 42, 84, 126, 168, and 300. OB levels were referred to a normal range for men based on the analysis of OB levels in 393 adult men. Substitution with T led to a large rise in T and DHT in both groups compared to baseline values (average T, days 21-189: TE, 14.33 +/- 2.63 nmol/L; TPEL, 24.98 +/- 1.64; average DHT, days 21-189: TE, 4.20 +/- 0.57 nmol/L; TPEL, 5.11 +/- 0.56; P < or = 0.05). Concomitantly, 17 beta-estradiol increased in both groups, and sex hormone-binding globulin levels were significantly decreased. At baseline, serum OB levels in hypogonadal men were 3-fold elevated compared to those in normal men (12.39 +/- 2.93 micrograms/L vs. 4.28 +/- 0.52; P < 0.01) and not different between groups (TE, 13.7 +/- 5.6; TPEL, 11.3 +/- 2.9 micrograms/L). This elevation was retained after adjustment for body mass index in the normal control group [TE, 1.45 +/- 0.51 SD score (P < 0.0001); TPEL, 0.98 +/- 0.35 SD score (P < 0.0008)]. During T substitution serum OB was completely

  1. 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

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

    PubMed Central

    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

  3. 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

  4. 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.

  5. Selective androgen receptor modulators for the treatment of late onset male hypogonadism

    PubMed Central

    Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

    2014-01-01

    Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism. PMID:24407183

  6. 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)

  7. Selective androgen receptor modulators for the treatment of late onset male hypogonadism.

    PubMed

    Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

    2014-01-01

    Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

  8. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach.

    PubMed

    Rey, R A; Grinspon, R P; Gottlieb, S; Pasqualini, T; Knoblovits, P; Aszpis, S; Pacenza, N; Stewart Usher, J; Bergadá, I; Campo, S M

    2013-01-01

    Normal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving

  9. 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.

  10. 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

  11. Advances in the molecular genetics of hypogonadotropic hypogonadism.

    PubMed

    Achermann, J C; Jameson, J L

    2001-01-01

    Mutations in several genes have been shown to cause hypogonadotropic hypogonadism (HHG) in humans. This condition may result from abnormalities in hypothalamic gonadotropin-releasing hormone (GnRH) secretion, impaired pituitary gonadotropin release, or both. Here, we consider mutations in KAL in X-linked Kallmann syndrome; DAX1 in X-linked adrenal hypoplasia congenita; the related orphan nuclear receptor, steroidogenic factor-1; leptin and prohormone convertase-1, which may influence GnRH release and processing; the GnRH receptor; the pituitary transcription factors, HESX-1, LHX3 and PROP-1; and the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Identifying naturally occurring mutations in these genes provides important information about the role of these factors in the development and function of the hypothalamic-pituitary gonadal axis in humans. Different approaches to treatment and counseling may be needed, depending on the condition. Furthermore, the pathophysiological basis of HHG in the majority of individuals remains unclear, despite recent advances. Other candidate genes may be involved in these patients.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Spreading the clinical window for diagnosing fetal-onset hypogonadism in boys.

    PubMed

    Grinspon, Romina P; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M; Rey, Rodolfo A

    2014-01-01

    In early fetal development, the testis secretes - independent of pituitary gonadotropins - androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic-pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic-pituitary-gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3-6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic-pituitary-testicular axis in boys suspected of fetal-onset hypogonadism.

  18. Micropenis. III. Primary hypogonadism, partial androgen insensitivity syndrome, and idiopathic disorders.

    PubMed

    Lee, P A; Danish, R K; Mazur, T; Migeon, C J

    1980-11-01

    This paper, the third in a series, presents data from 28 patients with micropenis categorized as primary hypogonadism (11 subjects), partial androgen insensitivity (1 subject), idiopathic (6 subjects), and etiology undetermined (10 subjects). Among the 11 patients with primary hypogonadism, 8 presented with various degrees of gonadal dysgenesis, 1 was a true hermaphrodite and 2 had the Robinow syndrome. Nine of the 28 patients were raised as females: 5 with primary hypogonadism and 4 with undetermined etiology. Eleven of the 19 patients raised as males received androgen stimulation during prepubertal years and responded with penile growth. However, this growth response was temporary and did not appear to be predictive of eventual adult size of the penis. Generally, the prestimulation size of this group of patients is more predictive of adult penile size. Only 7 of the patients raised as males have attained adult somatic growth. Three out of the three with primary hypogonadism, the subject with partial androgen insensitivity, and one of three with idiopathic micropenis have below-normal adult penile length. These limited data suggest that growth potential of the micropenis may be greater among the patients with an idiopathic state than among those with primary hypogonadism and partial androgen insensitivity.

  19. Testosterone treatment comes of age: new options for hypogonadal men.

    PubMed

    Nieschlag, Eberhard

    2006-09-01

    Male hypogonadism is one of the most frequent, but also most underdiagnosed, endocrinopathies. However, the required testosterone treatment is simple and very effective if properly administered. Although testosterone has been available for clinical use for seven decades, until quite recently the treatment modalities were far from ideal. Subdermal testosterone pellets require minor surgery for insertion and often cause local problems. The injectable testosterone enanthate, for a long period the most frequently used mode of administration, lasts for two to four weeks, but produces supraphysiological levels initially and low levels before the next injection. The oral testosterone undecanoate has to be taken three times daily, has an uncertain absorption pattern and results in peaks and valleys of serum testosterone levels throughout the day. With the advent of transdermal testosterone preparations, the desired physiological serum levels could be achieved for the first time. Scrotal testosterone patches were the first to fulfil this requirement. These were followed by nonscrotal skin patches, which, however, cause considerable skin reactions including erythema and blisters. Recently introduced, invisible transdermal testosterone gels increased the intervals of application and are now slowly replacing other modalities. A mucoadhesive buccal testosterone tablet with sustained release is also a recent competing modality. Finally, injectable testosterone undecanoate in castor oil was made into a real depot preparation requiring only four injections per year for replacement therapy. These new preparations with a desired pharmacokinetic testosterone profile give the patient a real choice and make treatment easier. Based on pharmacogenetic considerations taking the androgen receptor polymorphism into account, treatment may be individualized for each patient in the future. PMID:16918944

  20. Characterization of the male ApcMin/+ mouse as a hypogonadism model related to cancer cachexia

    PubMed Central

    White, James P.; Puppa, Melissa J.; Narsale, Aditi; Carson, James A.

    2013-01-01

    Summary Cancer cachexia, the unintentional loss of lean body mass, is associated with decreased quality of life and poor patient survival. Hypogonadism, involving a reduction in circulating testosterone, is associated with the cachectic condition. At this time there is a very limited understanding of the role of hypogonadism in cancer cachexia progression. This gap in our knowledge is related to a lack of functional hypogonadal models associated with cancer cachexia. The ApcMin/+ mouse is an established colorectal cancer model that develops an IL-6 dependent cachexia which is physiologically related to human disease due to the gradual progression of tumor development and cachexia. The purpose of this study was to assess the utility of the ApcMin/+ mouse for the examination of hypogonadism during cancer cachexia and to investigate if IL-6 has a role in this process. We report that ApcMin/+ mice that are weight stable have comparable testosterone levels and gonad size compared to wild type mice. Cachectic ApcMin/+ mice exhibit a reduction in circulating testosterone and gonad size, which has a significant association with the degree of muscle mass and functional strength loss. Circulating testosterone levels were also significantly associated with the suppression of myofibrillar protein synthesis. Skeletal muscle and testes androgen receptor expression were decreased with severe cachexia. Although testes STAT3 phosphorylation increased with severe cachexia, systemic IL-6 over-expression for 2 weeks was not sufficient to reduce either testes weight or circulating testosterone. Inhibition of systemic IL-6 signaling by an IL-6 receptor antibody to ApcMin/+ mice that had already initiated weight loss was sufficient to attenuate a reduction in testes size and circulating testosterone. In summary, the ApcMin/+ mouse becomes hypogonadal with the progression of cachexia severity and elevated circulating IL-6 levels may have a role in the development of hypogonadism during

  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 and Kallmann syndrome in males].

    PubMed

    Ghervan, Cristina; Young, Jacques

    2014-02-01

    Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are a group of rare disorders responsible for complete or partial pubertal failure due to lack or insufficient secretion of the pituitary gonadotropins LH and FSH. The underlying neuroendocrine abnormalities are classically divided into two main groups: molecular defects of the gonadotrope cascade leading to isolated normosmic CHH (nCHH), and developmental abnormalities affecting the hypothalamic location of GnRH neurons, but also olfactory bulbs and tracts morphogenesis and responsible for KS. Identification of genetic abnormalities related to CHH/KS has provided major insights into the pathways critical for the development, maturation and function of the gonadotrope axis. In patients affected by nCHH, particularly in familial cases, genetic alterations affecting GnRH secretion (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GnRH sensitivity of gonadotropic cells (GNRHR) have been found. Mutations in KAL1, FGFR1/FGF8/FGF17, PROK2/PROKR2, NELF, CHD7, HS6ST1, WDR11, SEMA3A, SOX10, IL17RD2, DUSP6, SPRY4, and FLRT3 have been associated with KS but sometimes also with its milder hyposmic/normosmic CHH clinical variant. A number of observations, particularly in sporadic cases, suggest that CHH/KS is not always a monogenic mendelian disease as previously thought but rather a digenic or potentially oligogenic condition. Before the age of 18 years, the main differential diagnosis of isolated nCHH is the relatively frequent constitutional delay of growth and puberty (CDGP). However, in male patients with pubertal delay and low gonadotropin levels, the presence of micropenis and/or cryptorchidism argues strongly in favor of CHH and against CDGP. CHH/KS are not always congenital life-long disorders as initially thought, because in nearly 10 % of patients the disease seems not permanent, as evidenced by partial recovery of the pulsatile activity of the hypothalamic-pituitary-gonadal axis

  3. Effects of endurance exercise on the reproductive system of men: the "exercise-hypogonadal male condition".

    PubMed

    Hackney, A C

    2008-10-01

    An increasing number of investigative research studies point to participation in endurance exercise training as having significant detrimental effects upon reproductive hormonal profiles in men. Specifically, men chronically exposed to this type of exercise training exhibit persistently reduced basal (resting-state) free and total testosterone concentrations without concurrent LH elevations. Men displaying these symptoms have been deemed to exhibit the "exercise-hypogonadal male condition". The exact physiological mechanism inducing the reduction of testosterone in these men is currently unclear, but is postulated to be a dysfunction (or perhaps a readjustment) within the hypothalamic-pituitary-testicular regulatory axis. The potential exists for the reduced testosterone concentrations within exercise-hypogonadal men to be disruptive and detrimental to some anabolic-androgenic testosterone- dependent physiological processes. Findings on this point are limited, but do suggest spermatogenesis problems may exist in some cases. Alternatively, reductions in circulating testosterone concentrations could have cardiovascular protective effects and thus be beneficial to the health of these men. Present evidence suggests the exercise-hypogonadal condition is limited to men who have been persistently involved in chronic endurance exercise training for an extended period time (i.e., years), and it is not a highly prevalent occurrence (although, a thorough epidemiological investigation on the topic is lacking in the literature). Many questions regarding the male reproductive endocrine adaptive process to exercise training still remain unanswered, necessitating the need for much further investigation on the topic, especially with respect to the exercise-hypogonadal condition.

  4. Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency

    PubMed Central

    Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T.

    2016-01-01

    Context: Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Case Description: Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. Conclusions: The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism. PMID:27533310

  5. Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

    PubMed

    Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

    2016-01-01

    Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

  6. Impaired emotional state, quality of life and cognitive functions in young hypogonadal men.

    PubMed

    Lašaitė, L; Ceponis, J; Preikša, R T; Zilaitienė, B

    2014-12-01

    The study aimed to analyse emotional state, quality of life and cognitive functions in young hypogonadal men. Thirty-four males with hypogonadism (age 29.1 ± 10.5 years) and 34 age-matched healthy males (age 30.5 ± 11.0 years) were recruited. Their emotional state was evaluated by Profile of Mood States, quality of life - by WHO Brief Quality of Life Questionnaire - and cognitive functioning - by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale. It was found that young men with hypogonadism had higher depression-dejection (13.1 ± 8.8 versus 7.4 ± 5.9, P = 0.003), fatigue-inertia (10.0 ± 5.8 versus 7.0 ± 4.9, P = 0.030), confusion-bewilderment (5.1 ± 4.6 versus 2.3 ± 3.1, P = 0.004) and lower vigour-activity (14.3 ± 5.1 versus 17.7 ± 4.3, P = 0.008) levels than age- and sex-matched controls. Quality of life psychological (13.1 ± 2.8 versus 15.1 ± 1.9, P = 0.005) and social (13.6 ± 2.4 versus 15.7 ± 2.0, P < 0.001) domains were significantly worse in men with hypogonadism than in controls. Cognitive functions were significantly worse (P < 0.001) in men with hypogonadism than in controls, showing worse executive function, attention, visual scanning abilities and psychomotor speed. A significant correlation was found between testosterone concentration and quality of life psychological domain. Cognitive functioning scores were significantly related with FT4 concentration. It is concluded that young hypogonadal patients have impaired emotional state and quality of life, but the most severe impairment was found in cognitive functioning.

  7. A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

    PubMed

    Macchiaroli, Annamaria; Kelberman, Daniel; Auriemma, Renata Simona; Drury, Suzanne; Islam, Lily; Giangiobbe, Sara; Ironi, Gabriele; Lench, Nicholas; Sowden, Jane C; Colao, Annamaria; Pivonello, Rosario; Cavallo, Luciano; Gasperi, Maurizio; Faienza, Maria Felicia

    2014-01-25

    Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.

  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. Comparison of questionnaires used for screening and symptom identification in hypogonadal men.

    PubMed

    Bernie, Aaron M; Scovell, Jason M; Ramasamy, Ranjith

    2014-12-01

    Late-onset hypogonadism (LOH) is typically defined as the cluster of symptoms appearing in aging men and accompanied by a decrease in serum testosterone levels. The identification of a simple screening tool with a high level of sensitivity and specificity to predict LOH has remained a challenge. To identify men with LOH, a variety of self-administered questionnaires have been developed including The Saint Louis University Androgen Deficiency in the Aging Male (ADAM) Questionnaire, The Quantitative ADAM (qADAM) Questionnaire, The Aging Male Symptoms (AMS) rating scale, The Massachusetts Male Aging Study (MMAS) questionnaire and The New England Research Institutes (NERI) hypogonadism questionnaire. The applicability of these questionnaires in the clinical setting is debated because some of the symptoms associated with LOH could be attributed to the natural process of aging and comorbidities. The goal of this review is to compare the utility and the validity of the different LOH questionnaires.

  10. 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

  11. Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone.

    PubMed

    Hwang, T I-S; Chen, H-E; Tsai, T-F; Lin, Y C

    2006-01-01

    To investigate the therapeutic effect of androgen on hypogonadal patients unresponsive to sildenafil alone. In total, 32 hypogonadal patients with erectile dysfunction (ED), initially had an inadequate response to sildenafil (100 mg). Oral testosterone undecanoate (Restandol, 80 mg, bid or tid) alone was supplied for 2 months, and if patients could not achieve a satisfactory erection, combined use of testosterone and sildenafil was continued thereafter. Total testosterone (TT), free testosterone (FT), and the parameters of the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), and uroflow rate (UFR) were assessed. Eleven patients (34.3%) achieved satisfactory erectile function after testosterone replacement only. Another 12 (37.5%) patients experienced satisfactory intercourse after combined therapy. Serum TT and FT levels significantly increased after the use of testosterone alone (415+/-163 vs 220+/-101 ng/dl, P<0.01; 10.4+/-4.6 vs 5.1+/-1.9 ng/dl; P<0.01, respectively) and the combined use of testosterone and sildenafil (498+/-178 vs 220+/-101 ng/dl, P<0.01; 11.7+/-4.6 vs 5.1+/-1.9 ng/dl, P<0.001, respectively); as did the IIEF score (14.8+/-6.8 vs 12.6+/-7.5, P<0.01, 17.5+/-5.2 vs 12.6+/-7.5, P<0.001, respectively). However, no statistical differences were demonstrated for IPSS or UFR. In conclusions, one-third of hypogonadal patients with ED who failed to respond to sildenafil, responded to testosterone alone, another third responded to sildenafil again after normalization of testosterone. So, in hypogonadal patients with ED, androgen supplementation is first-line therapy. If patients are unresponsive to androgen alone or sildenafil alone, combined use may improve erectile function and enhance the therapeutic effect of PDE-5 inhibitors. PMID:16395321

  12. 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.

  13. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism.

    PubMed

    Counts, D R; Pescovitz, O H; Barnes, K M; Hench, K D; Chrousos, G P; Sherins, R J; Comite, F; Loriaux, D L; Cutler, G B

    1987-06-01

    Adrenarche is a developmental change of the adrenal gland that results in increased secretion of adrenal androgens. This maturational process generally begins several years before activation of the hypothalamic-pituitary-gonadal axis (gonadarche). To study further the relationship between adrenarche and gonadarche, we examined adrenarche in patients with precocious puberty and in patients with isolated hypogonadotropic hypogonadism. Plasma dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and cortisol were measured basally and during an infusion of ACTH in 50 children with precocious puberty, 5 patients with isolated hypogonadotropic hypogonadism, 7 preadrenarchal children with constitutional short stature, 44 normal pubertal children, and 40 normal adults. Children with precocious puberty did not have a corresponding advance in the timing of adrenarche. Their basal and ACTH-stimulated adrenal androgen levels were markedly lower than those of normal children matched for pubertal stage (P less than 0.05) and were only slightly greater than those reported for normal children of the same age. Similarly, patients with isolated hypogonadotropic hypogonadism and delayed puberty had no corresponding delay of adrenarche. Their adrenal androgen levels were appropriate for chronological age. Thus, these data provide further support for the hypothesis that adrenarche and gonadarche are independent maturational events controlled by separate mechanisms.

  14. 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.

  15. Hypogonadism in males with chronic kidney disease: another cause of resistance to erythropoiesis-stimulating agents?

    PubMed

    Stenvinkel, Peter; Bárány, Peter

    2012-01-01

    Anemia, inflammation, resistance to erythropoiesis-stimulating agents (ESA) and hypogonadism (testosterone deficiency) are highly prevalent conditions, which heralds poor prognosis, in chronic kidney disease (CKD). It has been speculated that testosterone stimulates erythropoiesis via production of hematopoietic growth factors and possibly improvement of iron bioavailability. Where as inflammation stimulates synthesis of the liver-derived iron regulatory protein hepcidin, a recent study suggests that testosterone inhibits hepcidin synthesis, thus offering a possible novel mechanism for testosterone-induced erythropoiesis. As any agent that lowers hepcidin may be an effective strategy to normalize iron homeostasis and overcome renal anemia, testosterone deficiency should be considered in this patient group. Indeed, a recent study in males with CKD showed that hypogonadism may be an additional cause of anemia and reduced ESA responsiveness. Thus, a randomized controlled trial is needed to test the possibility that restoration of testosterone levels in hypogonadal CKD males may translate into lower prevalence of anemia, better ESA responsiveness and better quality of life.

  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. Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins.

    PubMed

    Spratt, D I; Bigos, S T; Beitins, I; Cox, P; Longcope, C; Orav, J

    1992-12-01

    Previous reports of hypogonadotropic hypogonadism in critically ill men may not reflect the complexity of changes in the hypothalamic-pituitary-gonadal (HPG) axis during acute illness. We sampled blood throughout hospitalization in 55 men admitted to acute care units to delineate the spectrum of changes in circulating gonadotropin and sex steroid levels at the onset and during recovery from acute illness. Bioactive LH and FSH were measured in a subset of patients. Percent free testosterone was measured to assess changes in binding to sex hormone binding globulin. Medications and serum estrogen and prolactin levels were monitored as potential causes of hypogonadotropism. Sustained suppression of serum testosterone levels below the normal range occurred in 62% of men with varying diagnoses and disease severity. Percent free testosterone remained constant. Hypogonadotropism was observed in most men (60%) and occurred independently from head injury, surgery, medications, or hyperprolactinemia. In a subset of men (n = 16), LH and/or FSH rose transiently above the normal range. Bioactivity of both LH and FSH remained constant while serum testosterone levels decreased. In contrast to serum testosterone levels, mean serum levels of E1, E2 and androstenedione were not less than control values. We conclude that both primary and secondary hypogonadism occur transiently in acutely ill men and cannot be explained solely by medications, hyperprolactinemia, or hyperestrogenemia. Neither biopotency of gonadotropins nor binding of testosterone to SHBG change across the course of acute illness. The hypogonadism, often severe and prolonged, may contribute to the persistent catabolic state observed in many critically ill patients.

  19. Testosterone and endurance exercise: development of the "exercise-hypogonadal male condition".

    PubMed

    Hackney, A C; Moore, A W; Brownlee, K K

    2005-01-01

    During the last 30 years a large number of research studies have been conducted examining reproductive endocrine dysfunction in exercising women. The number of similar studies examining men is still relatively small. Nevertheless, an increasing amount of research studies in men indicate endurance exercise training has significant effects upon the major male reproductive hormone, testosterone, and the hypothalamic-pituitary-testicular axis that regulates reproductive hormones. This review article addresses one reproductive endocrine dysfunction found in exercising men, what has been deemed the "exercise-hypogonadal male condition". Specifically, men with this condition exhibit basal (resting-state) free and total testosterone levels that are significantly and persistently reduced. The exact physiological mechanism inducing the reduction of testosterone is currently unclear, but is postulated to be a dysfunction (or perhaps a readjustment) within the hypothalamic-pituitary-testicular regulatory axis. The time course for the development of the "exercise-hypogonadal condition" or the threshold of exercise training necessary to induce the condition remains unresolved. The potential exists for these reduced testosterone levels within the exercise-hypogonadal male to disrupt and be detrimental to some anabolic or androgenic testosterone-dependent physiological processes. Unfortunately, extremely few research studies have addressed whether such processes are affected, and thus findings are inconclusive. Conversely, the alterations in testosterone levels brought about by endurance exercise training have the potential for cardiovascular protective effects and thus could be beneficial to the health of these men. Current evidence suggests this condition is limited to men who have been persistently involved in chronic endurance exercise training for extended periods of time (i.e., years). Many questions, however, regarding the male reproductive endocrine adaptive process to

  20. Modeling Testosterone Circadian Rhythm in Hypogonadal Males: Effect of Age and Circannual Variations.

    PubMed

    González-Sales, Mario; Barrière, Olivier; Tremblay, Pierre-Olivier; Nekka, Fahima; Desrochers, Julie; Tanguay, Mario

    2016-01-01

    The objective of this study was to characterize the baseline circadian rhythm of testosterone levels in hypogonadal men. A total of 859 baseline profiles of testosterone from hypogonadal men were included in this analysis. The circadian rhythm of the testosterone was described by a stretched cosine function. Model parameters were estimated using NONMEM(®) 7.3. The effect of different covariates on the testosterone levels was investigated. Model evaluation was performed using non-parametric bootstrap and predictive checks. A stretched cosine function deeply improved the data goodness of fit compared to the standard trigonometric function (p < 0.001; ΔOFV = -204). The effect of the age and the semester, defined as winter and spring versus summer and fall, were significantly associated with the baseline levels of testosterone (p < 0.001, ΔOFV = -15.6, and p < 0.001, ΔOFV = -47.0). Model evaluation procedures such as diagnostic plots, visual predictive check, and non-parametric bootstrap evidenced that the proposed stretched cosine function was able to model the time course of the diurnal testosterone levels in hypogonadal males with accuracy and precision. The circadian rhythm of the testosterone levels was better predicted by the proposed stretched cosine function than a standard cosine function. Testosterone levels decreased by 5.74 ng/dL (2.4%) every 10 years and were 19.3 ng/dL (8.1%) higher during winter and spring compared to summer and fall.

  1. Association between megestrol acetate treatment and symptomatic adrenal insufficiency with hypogonadism in male patients with cancer.

    PubMed

    Dev, Rony; Del Fabbro, Egidio; Bruera, Eduardo

    2007-09-15

    Patients with advanced cancer may develop cachexia, which is often treated with megestrol acetate (MA). In addition to thromboembolic disease, MA may cause symptomatic suppression of the hypothalamic pituitary adrenal axis. In male patients with cancer, treatment with MA may also suppress the gonadal axis, resulting in symptomatic androgen deficiency. Three cases are presented to highlight the symptomatic burden of adrenal insufficiency and hypogonadism. Clinicians need an increased awareness of the complication of adrenal insufficiency secondary to MA treatment and a low threshold to test for adrenal and gonadal dysfunction in symptomatic male patients with advanced cancer.

  2. Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin.

    PubMed

    Yura, S; Ogawa, Y; Sagawa, N; Masuzaki, H; Itoh, H; Ebihara, K; Aizawa-Abe, M; Fujii, S; Nakao, K

    2000-03-01

    Excess or loss of body fat can be associated with infertility, suggesting that adequate fat mass is essential for proper reproductive function. Leptin is an adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure, and its synthesis and secretion are markedly increased in obesity. Short-term administration of leptin accelerates the onset of puberty in normal mice and corrects the sterility of leptin-deficient ob/ob mice. These findings suggest a role for leptin as an endocrine signal between fat depots and the reproductive axis, but the effect of hyperleptinemia on the initiation and maintenance of reproductive function has not been elucidated. To address this issue, we examined the reproductive phenotypes of female transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. With no apparent adipose tissue, female transgenic skinny mice exhibit accelerated puberty and intact fertility at younger ages followed by successful delivery of healthy pups. However, at older ages, they develop hypothalamic hypogonadism characterized by prolonged menstrual cycles, atrophic ovary, reduced hypothalamic gonadotropin releasing hormone contents, and poor pituitary luteinizing hormone secretion. This study has demonstrated for the first time to our knowledge that accelerated puberty and late-onset hypothalamic hypogonadism are associated with chronic hyperleptinemia, thereby leading to a better understanding of the pathophysiological and therapeutic implication of leptin.

  3. Evaluation of the isokinetic muscle strength, balance and anaerobic performance in patients with young male hypogonadism.

    PubMed

    Aydogan, Umit; Eroglu, Ali; Akbulut, Halil; Yildiz, Yavuz; Gok, Deniz Engin; Sonmez, Alper; Aydin, Taner; Bolu, Erol; Saglam, Kenan

    2012-01-01

    Hypogonadism is a clinical condition that occurs due to infrequent abnormalities in the hypothalamic-pituitary-gonadal (HPG) axis in adolescence. Symptoms include weakening of muscle and bone strength. 30 young male patients with congenital hypogonadotropic hypogonadism (CHH) and 20 healthy young males were included in the present study. Quadriceps and hamstring muscle strength, balance and anaerobic performance capacities of the study group were measured both before and six months after Testosterone replacement therapy (TRT). The strength of the extensor and flexor muscles of both legs showed a statistically significant increase in the isokinetic test values at 60(0)/sec and 180(0)/sec angular velocity (p < 0.05). When the parameters related to balance were investigated, a statistically significant difference was found for stability indices of left and right between pre-TRT and post-TRT (p = 0.001 for both comparisons). According to the patients' anaerobic performance measurement results, a statistically significant improvement (p < 0.001) was also found between pre-TRT and post-TRT values for each parameter. It was shown that TRT significantly increases muscle strength, balance, and anaerobic performance of patients with male CHH. As a result, we absolutely recommend the use of TRT in patients with male CHH.

  4. Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene.

    PubMed

    Good, D J; Porter, F D; Mahon, K A; Parlow, A F; Westphal, H; Kirsch, I R

    1997-04-01

    The family of basic helix-loop-helix (bHLH) genes comprises transcription factors involved in many aspects of growth and development. We have previously described two bHLH transcription factors, Nhlh1 and Nhlh2 (originally named NSCL1 and NSCL2). The nucleotide and predicted protein sequences of Nhlh1 and Nhlh2 are homologous within their bHLH domain where there are only three conservative amino acid differences. During murine embryogenesis, Nhlh1 and Nhlh2 share an overlapping but distinct pattern of expression in the developing nervous system. To improve our understanding of the role of these genes during neurogenesis, we have generated mice containing targeted deletions of both genes and here describe our results for Nhlh2. Loss of Nhlh2 results in a disruption of the hypothalamic-pituitary axis in mice. Male Nhlh2-/- mice are microphallic, hypogonadal and infertile with alterations in circulating gonadotropins, a defect in spermatogenesis and a loss of instinctual male sexual behaviour. Female Nhlh2-/- mice reared alone are hypogonadal, but when reared in the presence of males, their ovaries and uteri develop normally and they are fertile. Both male and female homozygotes exhibit progressive adult-onset obesity. Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary. Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism.

  5. Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

    PubMed

    Witek, Barbara; El Wakil, Abeer; Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A; Hallberg, Bengt; Palmer, Ruth H

    2015-01-01

    Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

  6. Normal neonatal surge of gonadotrophins and sex steroids in infants of men with isolated hypogonadotrophic hypogonadism.

    PubMed

    Rose, S R; Cassorla, F; Sherins, R J

    1988-12-01

    The inheritance of isolated hypogonadotrophic hypogonadism (IHH) is not fully determined. Although men with this diagnosis can be treated to induce fertility, it is not known whether their offspring will inherit the hormonal deficiency. We evaluated the hypothalamic-pituitary-gonadal axis in nine children (born to men with IHH) during the first few months of life. This axis normally shows activation in infancy similar to that which occurs at puberty. Luteinizing hormone (LH) releasing hormone stimulated a peak LH response in excess of prepubertal levels (39.0 +/- 11 mIU/ml [mean +/- SD]). Testosterone in males (6.2 +/- 2.8 nmol/l and oestradiol in two of the females (320 and 100 pmol/l) were also in excess of prepubertal levels. These infants of men with IHH showed no evidence of inheriting hypogonadotrophic hypogonadism. While further studies will be conducted at the usual age of puberty to confirm spontaneous activation of the hypothalamic-pituitary-gonadal axis, our studies suggest that it may be possible to assess the integrity of this axis at a much younger age.

  7. Adrenal Hypoplasia Congenita: A Rare Cause of Primary Adrenal Insufficiency and Hypogonadotropic Hypogonadism

    PubMed Central

    Loureiro, Marta; Reis, Filipa; Robalo, Brígida; Pereira, Carla; Sampaio, Lurdes

    2015-01-01

    Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC) was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG), confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism. PMID:26500747

  8. [Osteoporosis fracture in a male patient secondary to hypogonadism due to androgen deprivation treatment for prostate cancer].

    PubMed

    Verdú Solans, J; Roig Grau, I; Almirall Banqué, C

    2014-01-01

    A 84 year-old patient, in therapy with androgen deprivation during the last 5 years due a prostate cancer, is presented with a osteoporotic fracture of the first lumbar vertebra. The pivotal role of the primary care physician, in the prevention of the osteoporosis secondary to the hypogonadism in these patients, is highlighted.

  9. 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. ...

  10. Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

    PubMed

    Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

    2011-07-01

    Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

  11. 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.

  12. Hypothalamic function in women with secondary hypogonadism and unresponsive to clomiphene therapy.

    PubMed

    Vaughan Williams, C A

    1987-01-01

    Seven women with secondary hypogonadism who had been previously unresponsive to two 5-d courses of clomiphene citrate, were treated with clomiphene citrate 100 mg daily for 10 d. LH and FSH concentrations were measured in serum collected at 15-min intervals for 5 h before and on the 10th day of treatment and oestradiol was measured in the first two samples on each day. Four women responded with an increase in the amplitude of LH pulses and in mean LH values and in three there was a marked increase in serum oestradiol concentrations. Three women who showed no gonadotrophin response were subsequently unresponsive to pulsatile LHRH therapy. These preliminary data are consistent with the hypothesis that hypothalamic hypogonadotrophism may result from hypersensitivity of the hypothalamus to oestrogen negative feedback and that the hypothalamic potential for secretion of LHRH is unimpaired. Prolonged treatment with clomiphene may provide a simple test of hypothalamic function in women with normal pituitary function.

  13. 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

  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. [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

  16. Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

    PubMed

    Shimon, Ilan; Lubina, Alexandra; Gorfine, Malka; Ilany, Jacob

    2006-01-01

    Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

  17. Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation.

    PubMed

    Yin, Anthony Y; Htun, Michelle; Swerdloff, Ronald S; Diaz-Arjonilla, Maruja; Dudley, Robert E; Faulkner, Sandra; Bross, Rachelle; Leung, Andrew; Baravarian, Sima; Hull, Laura; Longstreth, James A; Kulback, Steven; Flippo, Gregory; Wang, Christina

    2012-01-01

    Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsifying drug delivery system formulation. Pharmacokinetics studies were conducted in 3 parts: 12 hypogonadal men were enrolled in 2 centers for a 1-day dosing study; 29 participants were enrolled from 3 centers for a 7-day dosing study; and 15 participants were enrolled from 1 center for a 28-day dosing study. Serial blood samples for serum sex hormone measurements by liquid chromatography-tandem mass spectrometry were drawn for up to 36 hours after oral TU administration. Mean serum T levels (C(avg)) after oral dosing of T 200 mg as TU twice daily with food were within the adult male range in most participants in the 1-, 7-, and 28-day dosing studies but were much lower in the fasting state. The dose-proportional increase in C(avg) of serum T after oral T 300 mg twice daily resulted in more participants with supraphysiologic serum T levels. In the 28-day study, trough serum T reached a steady state at day 7. Serum dihydrotestosterone and estradiol levels tracked serum T concentration. Dihydrotestosterone-testosterone ratios increased 3-fold after oral TU administration. Oral T 200 mg twice daily as TU in a new SEDDS formulation may be a viable therapy for hypogonadal men. PMID:21474786

  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. 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

  20. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

    PubMed Central

    Huhtaniemi, Ilpo

    2014-01-01

    Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%–40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T <11 nmol l−1 and free T <220 pmol l−1) and three sexual symptoms (erectile dysfunction, and reduced frequency of sexual thoughts and morning erections). By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short

  1. 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

  2. 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

  3. Estrogen receptor alpha single nucleotide polymorphism as predictor of diabetes type 2 risk in hypogonadal men.

    PubMed

    Linnér, Carl; Svartberg, Johan; Giwercman, Aleksander; Giwercman, Yvonne Lundberg

    2013-06-01

    Estradiol (E2) is, apart from its role as a reproductive hormone, also important for cardiac function and bone maturation in both genders. It has also been shown to play a role in insulin production, energy expenditure and in inducing lipolysis. The aim of the study was to investigate if low circulating testosterone or E2 levels in combination with variants in the estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) genes were of importance for the risk of type-2 diabetes. The single nucleotide polymorphisms rs2207396 and rs1256049, in ESR1 and ESR2, respectively, were analysed by allele specific PCR in 172 elderly men from the population-based Tromsø study. The results were adjusted for age. In individuals with low total (≤11 nmol/L) or free testosterone (≤0.18 nmol/L) being carriers of the variant A-allele in ESR1 was associated with 7.3 and 15.9 times, respectively, increased odds ratio of being diagnosed with diabetes mellitus type 2 (p = 0.025 and p = 0.018, respectively). Lower concentrations of E2 did not seem to increase the risk of being diagnosed with diabetes. In conclusion, in hypogonadal men, the rs2207396 variant in ESR1 predicts the risk of type 2 diabetes.

  4. Isolated cryptorchidism: no evidence for involvement of genes underlying isolated hypogonadotropic hypogonadism.

    PubMed

    Laitinen, Eeva-Maria; Tommiska, Johanna; Virtanen, Helena E; Oehlandt, Heidi; Koivu, Rosanna; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

    2011-07-20

    Mutations in FGFR1, GNRHR, PROK2, PROKR2, TAC3, or TACR3 underlie isolated hypogonadotropic hypogonadism (IHH) with clinically variable phenotypes, and, by causing incomplete intrauterine activation of the hypothalamic-pituitary-gonadal axis, may lead to cryptorchidism. To investigate the role of defects in these genes in the etiology of isolated cryptorchidism, we screened coding exons and exon-intron boundaries of these genes in 54 boys or men from 46 families with a history of cryptorchidism. Control subjects (200) included 120 males. None of the patients carried mutation(s) in FGFR1, PROK2, PROKR2, TAC3 or TACR3. Two of the 46 index subjects with unilateral cryptorchidism were heterozygous carriers of a single GNRHR mutation (Q106R or R262Q), also present in male controls with a similar frequency (3/120; p=0.62). No homozygous or compound heterozygous GNRHR mutations were found. In conclusion, cryptorchidism is not commonly caused by defects in genes involved in IHH.

  5. Ethanol-induced hypogonadism is not dependent on activation of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Emanuele, N V; LaPaglia, N; Benefield, J; Emanuele, M A

    2001-11-01

    The well-characterized suppression of the male reproductive unit after ethanol (EtOH) exposure has been speculated to be partially due to activation of the hypothalamic-pituitary-adrenal (HPA) axis. The subsequent corticosterone elevation could result in hypogonadism via suppression of hypothalamic LHRH, pituitary LH, or a direct gonadal effect. To directly examine this possibility, adult male Sprague Dawley rats were either adrenalectomized (ADX) or sham ADX. The ADX animals were given low dose corticosterone via replacement pellet, resulting in a steady level of serum corticosterone. The sham ADX (adrenal intact) animals were implanted with placebo pellets. Half of both groups were then exposed to EtOH by I.P. injection on two consecutive days to mimic an acute binge-drinking model. The other half was given saline I.P., serving as controls. In the adrenal intact animals, EtOH caused the expected rise in corticosterone, and fall in luteinizing hormone (LH) and testosterone. In the ADX animals, where constant levels of corticosterone were maintained by pellet implantation, EtOH resulted in similar LH and testosterone reduction. These results suggest that suppression of the reproductive axis is independent of the activation of the HPA unit.

  6. The recent genetics of hypogonadotrophic hypogonadism - novel insights and new questions.

    PubMed

    Semple, Robert K; Topaloglu, A Kemal

    2010-04-01

    The complex organization and regulation of the human hypothalamic-pituitary-gonadal axis render it susceptible to dysfunction in the face of a variety of genetic insults, leading to different degrees of hypogonadotrophic hypogonadism (HH). Although the genetic basis of some HH was recognized more than 60 years ago the first specific pathogenic defect, in the KAL1 gene, was only identified within the last 20 years. In the past decade, the rate of genetic discovery has dramatically accelerated, with defects in more than 10 genes now associated with HH. Several themes have emerged as the genetic basis of HH has gradually been uncovered, including the association of some genes such as FGFR1, FGF8, PROK2 and PROKR2, both with HH in association with hyposmia/anosmia (Kallmann syndrome) and with normosmic HH, thus blurring the clinical distinction between ontogenic and purely functional defects in the axis. Many examples of digenic inheritance of HH have also been reported, sometimes producing variable reproductive and accessory phenotypes within a family with non-Mendelian inheritance patterns. In strictly normosmic HH, human genetics has made a particularly dramatic impact in the past 6 years through homozygosity mapping in consanguineous families, first through identification of a key role for kisspeptin in triggering GnRH release, and very recently through demonstration of a critical role for neurokinin B in normal sexual maturation. This review summarises current understanding of the genetic architecture of HH, as well as its diagnostic and mechanistic implications.

  7. Cognitive effects of testosterone and finasteride administration in older hypogonadal men

    PubMed Central

    Borst, Stephen E; Yarrow, Joshua F; Fernandez, Carmen; Conover, Christine F; Ye, Fan; Meuleman, John R; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J

    2014-01-01

    Serum concentrations of neuroactive androgens decline in older men and, in some studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥60 years with a serum testosterone concentration of ≤300 ng/dL or bioavailable testosterone ≤70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains. PMID:25143719

  8. The genetics of idiopathic hypogonadotropic hypogonadism:unraveling the biology of human sexual development.

    PubMed

    Bhangoo, Amrit; Jacobson-Dickman, Elka

    2009-03-01

    Idiopathic Hypogonadotropic Hypogonadism (IHH), a syndrome of GnRH deficiency, is characterized by varying degrees of sexual development disruption. When associated with anosmia, it is termed Kallmann Syndrome (KS). Although it was identified as a hereditary disorder over half a century ago, only during the last two decades have specific putative IHH genes been revealed, including: KAL1, GnRHR, FGFR1, GPR54, PROK2, PROKR2, FGF8, CHD7, TAC3 and TAC3R. Human mutations have shed light on the molecular control of GnRH neuronal embryogenesis and have elucidated elements critical in sexual development. Furthermore, the newly proposed oligogenic model has challenged the dogma of IHH being a single gene disorder and has heightened appreciation for the functional overlap of distinct signaling systems. This review offers an historical perspective to gene discoveries in IHH, genotype-phenotype correlations, and finally, discussion of the evolving complexity of the new IHH genetic model, no longer simply characterized by Mendelian inheritance. PMID:19396025

  9. 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

  10. 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

  11. [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.

  12. 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

  13. 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

  14. Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling.

    PubMed

    Fichna, Piotr; Fichna, Marta; Zurawek, Magdalena; Nowak, Jerzy

    2011-01-01

    Hypogonadotropic hypogonadism (HH) is characterised by delayed puberty and infertility. Congenital HH comprises Kallmann syndrome with hypo-/anosmia and idiopathic HH (IHH). The genetic origin remains unknown in most cases, but the defective GnRH receptor gene (GNRHR) accounts for a considerable proportion of IHH. Here we describe a pair of siblings diagnosed with IHH. Aged 17 years, the boy was referred because of short stature (162 cm) and overweight (62.5 kg). He presented no signs of puberty, bone age of 14.5 years and insulin resistance. His sister, aged 16 years, also displayed delayed puberty. She was 166 cm tall and weighed 52 kg; her bone age was 12.5 years. Pelvic ultrasonography showed an infantile uterus and fibrous ovaries. In both siblings, serum gonadotropins were extremely low, and non-responsive to GnRH. Testosterone (1.38 nmol/l) and IGF1 (273 ng/ml) were decreased in the boy, although the girl did not present IFG1 deficiency. Her serum oestradiol was 10 pg/ml. MRIs of the hypothalamo-pituitary region and olfactory bulbs revealed them to be normal. The patients' sense of smell was unaltered. Their parents appeared to be first degree cousins. Considering the clinical data and potentially autosomal recessive HH transmission, the GNRHR gene was screened. The siblings turned out to be homozygous for the G416A transition, which had previously been identified in other HH individuals. The parents were heterozygous mutation carriers. The proband, moderately responding to LH, was started on low dose testosterone replacement, and his sister on transdermal oestradiol. Molecular data indicative of GnRH resistance could guide their future therapy should they desire fertility restoration. Further observations of the male patient may provide insights into androgen's influence on body mass, growth and insulin sensitivity. PMID:21717411

  15. 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.

  16. 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

  17. 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism.

    PubMed

    Nieschlag, Eberhard; Kumar, Narender; Sitruk-Ware, Régine

    2013-03-01

    Testosterone is an essential part of all regimens for hormonal male contraception tested to date. Initial efficacy trials revealed that the half-life of the testosterone preparations available at that time was too short to be used for male contraception. The ensuing search for long-acting preparations yielded testosterone buciclate and undecanoate as well as 7α-methyl-19-nortestosterone (MENT). Following description of the principle of male hormonal contraception and the efficacy trials performed to date, the systematic development of MENT for substitution of male hypogonadism and use in male contraception by the Population Council is reviewed here.

  18. Testosterone Replacement Therapy in Adolescents With Sickle Cell Disease Reverses Hypogonadism Without Promoting Priapism: A Case Report.

    PubMed

    Morrison, Belinda F; Madden, Wendy; Clato-Day, Stephanie; Gabay, Leslie

    2015-11-01

    Delayed puberty secondary to hypogonadism is commonly seen in sickle cell disease (SCD), affecting normal growth and development. The condition is rarely treated in SCD for fear of inducing priapism episodes. We present a case report of an Afro-Jamaican adolescent male at 16 years of age who presented with symptoms of delayed puberty as well as frequent stuttering priapism episodes. Endocrinological assessment revealed low serum total testosterone levels. Treatment was commenced monthly with testosterone enanthate which resulted in improved symptoms of delayed puberty, improvement in anthropometric parameters while apparently ameliorating priapism episodes. PMID:26793544

  19. Bilateral pulmonary emboli after bilateral mastectomy in a 15-year-old boy with hypogonadism: A case report

    PubMed Central

    Piggott, JR; Yazdani, Arjang

    2010-01-01

    Pulmonary emboli are rare, yet serious, complications of body contouring surgery. When they occur, they more often follow as complications of long, invasive procedures in adults. The present report details a case of bilateral pulmonary emboli in an obese 15-year-old boy with hypogonadism undergoing bilateral mastectomy for gynecomastia. The diagnosis of bilateral pulmonary emboli was made on the basis of clinical presentation and positive ventilation/perfusion scan. The patient responded well to heparin anticoagulation treatment. The relevance of pediatric obesity, pediatric body contouring surgery and the risk of thromboembolic events in pediatric patients are discussed. PMID:22131848

  20. 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 (pre- vs. post-pubertal HH: 5 ± 4 mL vs

  1. 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

  2. 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

  3. Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients.

    PubMed

    Strollo, Felice; Strollo, Giovanna; Morè, Massimo; Magni, Paolo; Macchi, Chiara; Masini, Maria Angela; Carucci, Iarba; Celotti, Fabio; Ruscica, Massimiliano; Gentile, Sandro

    2013-06-01

    An open-label follow-up study of low-to-intermediate dose testosterone replacement therapy (TRT) was conducted in 64 overweight patients (aged 65-75 years) with late onset hypogonadism (LOH) and increased fasting plasma glucose (FPG). Patients were subdivided into four treatment groups: oral testosterone (T) (T undecanoate, 80 mg/d), transmucosal T (60 mg/d), transdermal T (30 mg/d) or no treatment (control), and evaluated at 0 and 6 months. FPG, hemoglobin (Hb), prostate-specific antigen (PSA) and total T were measured and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body mass index (BMI), waist circumference, fitness level (6-min walking test), Aging Males' Symptoms (AMS) scale, handgrip strength and energy expenditure with physical activity (Minnesota questionnaire for Leisure Time Physical Activity (LTPA)) were evaluated and a "frailty score" (based on: grip strength, gait speed and LTPA) was calculated. T levels increased in all treatment groups; the oral T group had values still in the hypogonadal range (5.9 ± 1.1 nmol/L). PSA and Hb concentrations did not change in any group. BMI, waist circumference, FPG and HOMA-IR improved in all T-treated groups after 6 months, with a greater effect seen with transmucosal and transdermal T compared with oral T. This study indicates that low-to-intermediate dose TRT may be safely utilized in LOH patients to ameliorate somatic and psychological frailty symptoms in association with improved anthropometric and glycometabolic parameters in aging, overweight men with LOH and impaired fasting glucose. PMID:23517433

  4. Evidence-based medicine update on testosterone replacement therapy (TRT) in male hypogonadism: focus on new formulations.

    PubMed

    Giagulli, V A; Triggiani, V; Corona, G; Carbone, D; Licchelli, B; Tafaro, E; Resta, F; Sabbà, C; Maggi, M; Guastamacchia, E

    2011-01-01

    Until the 2000s Testosterone (T) Replacement Therapy (TRT) wasn't very satisfactory for male hypogonadic patients because the available T formulations weren't able to reproduce the physiological pattern of T secretion in man. In fact, oral formulations (oral undecanoate T) showed very short half-life (<24 hours), requiring the administration of several daily doses, whereas the old injection products (T esters) were characterized by very long half-life (>7 days) because of their adipose tissue storage, requiring to be administered every 2-3 weeks but determining remarkable and quick fluctuations (in 2-3 weeks) of the testosteronemia with variations in a few days from over-physiological levels (> 2000 ng/dl) to very low levels (< 200 ng/dl). Nowadays, several compounds can attain the standards of suitability and effectiveness of TRT in hypogonadal men. Both transcutaneous (gel) T and long-acting injectable formulations are the most modern preparations that can satisfy the criteria of an ideal chronic replacement therapy. In fact, they keep the serum T levels in the physiological range imitating its circadian rhythm, leading to the development and/or the preservation of male sexual characteristics and, finally, positively influencing bone mass, skeletal muscle and adipose tissue distribution. In particular, the availability and use of long-acting injectable undecanoate T can really improve the patients' compliance as requested for a life-long treatment. However, definitive and conclusive evidence regarding the main end-points, such as the diminished recurrence of falls in elderly men, the decrease in fractures in osteoporotic subjects, the reduction in disabling conditions and the extension of life, have not been reached so far. Therefore, the aim of this review is to sum up the most important evidence that has been collected regarding TRT, highlighting in particular those concerning both transcutaneous and long-acting injectable T compounds. PMID:21521164

  5. 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

  6. 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

  7. 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

  8. Postnatal ovarian follicle development in hypogonadal (hpg) and normal mice and associated changes in the hypothalamic-pituitary ovarian axis.

    PubMed

    Halpin, D M; Jones, A; Fink, G; Charlton, H M

    1986-05-01

    Significant uterine growth occurred in normal and hypogonadal (hpg) mice between Days 7 and 21 but thereafter no further growth was observed in hpg mice. The ovaries of hpg mice were significantly smaller than those of normals at all ages, but there was no significant difference between the number of non-growing follicles in the ovaries of mutants and their normal littermates at any age studied, and normal and hpg mice showed a marked reduction in the number of non-growing follicles during the first month of life. The size and composition of the growing follicle population in hpg mice, however, differed markedly from those in normal animals and by 21 days of age the number of growing follicles in mutants was significantly reduced. There was no significant difference in the number of Type 3b follicles before 60 days of age, but the number of all other follicle types was significantly less in hpg mice at all ages studied. Follicles in which the antrum is fully developed (Type 7 and 8) were never seen in the ovaries of mutants and corpora lutea were never observed. Interstitial tissue development was also very poor in hpg ovaries. The hypothalamic GnRH content in normal mice remained low until Day 20, before rising sharply to adult levels (approximately 800 pg) between Days 20 and 30. The pituitary FSH content increased over the first 10 days of life to reach a peak of about 5000 ng, before declining to the adult value of about 2000 ng by Day 30, whilst the plasma FSH concentration was high in the first 10 days, but fell to adult levels over the next 20 days. Pituitary LH content increased significantly between Days 5 and 10 to reach the adult level of about 600 ng. Hypothalamic GnRH was undetectable at all ages in hypogonadal mice, but the pituitary content of FSH and LH had risen to the attenuated mutant adult value by Day 15, and unlike normals, plasma FSH concentrations were not elevated during the neonatal period. These results suggest that minimal gonadotrophic

  9. Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men.

    PubMed

    Yin, Anthony; Alfadhli, Eman; Htun, Michelle; Dudley, Robert; Faulkner, Sandra; Hull, Laura; Leung, Andrew; Bross, Rachelle; Longstreth, James; Swerdloff, Ronald; Wang, Christina

    2012-01-01

    This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically

  10. 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

  11. 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.

  12. 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

  13. A Novel Syndrome of Mandibular Hypoplasia, Deafness, and Progeroid Features Associated with Lipodystrophy, Undescended Testes, and Male Hypogonadism

    PubMed Central

    Shastry, Savitha; Simha, Vinaya; Godbole, Koumudi; Sbraccia, Paolo; Melancon, Serge; Yajnik, Chittaranjan S.; Novelli, Giuseppe; Kroiss, Matthias; Garg, Abhimanyu

    2010-01-01

    Context: Mandibuloacral dysplasia (MAD) is an autosomal recessive progeroid disorder associated with type A (partial) or B (generalized) lipodystrophy and is due to mutations in lamin A/C (LMNA) or zinc metalloproteinase (ZMPSTE24) genes. Objective: The objective of the study was to report a novel syndrome with some overlapping features with MAD. Results: We report seven patients with mandibular hypoplasia, deafness, progeroid features (MDP), and associated lipodystrophy. These patients have similar features to MAD patients such as hypoplastic mandible, beaked nose, stiff joints, and sclerodermatous skin. However, the patients did not harbor any disease causing variants in LMNA or ZMPSTE24 and showed distinct characteristics such as sensorineural hearing loss and absence of clavicular hypoplasia and acroosteolysis. All males with MDP had undescended testes and were hypogonadal. One adult female showed lack of breast development. Skinfold thickness, dual-energy X-ray absorptiometry and whole-body magnetic resonance imaging for body fat distribution revealed a lack of lipodystrophy in a prepubertal female but a progressive loss of sc fat presenting with partial lipodystrophy in young adults and generalized lipodystrophy in older patients. Conclusions: Patients with MDP syndrome have a few overlapping but some distinct clinical features as compared with MAD, suggesting that it is a novel syndrome. The molecular basis of MDP syndrome remains to be elucidated. PMID:20631028

  14. 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

  15. 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

  16. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial.

    PubMed

    Borst, Stephen E; Yarrow, Joshua F; Conover, Christine F; Nseyo, Unyime; Meuleman, John R; Lipinska, Judyta A; Braith, Randy W; Beck, Darren T; Martin, Jeffrey S; Morrow, Matthew; Roessner, Shirley; Beggs, Luke A; McCoy, Sean C; Cannady, Darryl F; Shuster, Jonathan J

    2014-02-15

    Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue. PMID:24326421

  17. Clinical, endocrinological, and molecular characterization of Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: a single center experience

    PubMed Central

    Shin, Sun-Jeong; Sul, Yeonah; Kim, Ja Hye; Cho, Ja Hyang; Kim, Gu-Hwan; Kim, Jae Hyun; Choi, Jin-Ho

    2015-01-01

    Purpose Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified as Kallmann syndrome (KS) with anosmia and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). This study was undertaken to investigate the clinical, endocrinological, and molecular characteristics in Korean patients with KS and nIHH. Methods Twenty-six patients from 25 unrelated families were included. Their clinical, endocrinological, and radiological findings were analyzed retrospectively. Mutation analysis of the GNRH1, GNRHR, KISS1, KISS1R, PROK2, PROKR2, TAC3, TACR3, FGF8, FGFR1, and KAL1 genes was performed in all patients. CHD7 and SOX10 were analyzed in patients with CHARGE (Coloboma, Heart defects, choanae Atresia, Growth retardation, Genitourinary abnormality, Ear abnormality) features or deafness. Results Of the 26 patients, 16 had KS and 10 had nIHH. At diagnosis, mean chronologic age was 18.1 years in males and 18.0 years in females; height SDS were -0.67±1.35 in males, -1.12±1.86 in females; testis volume was 2.0±1.3 mL; and Tanner stage was 1.5. There were associated anomalies in some of the KS patients: hearing loss (n=6) and congenital heart disease (n=4). Absence or hypoplasia of the olfactory bulb/sulci was found in 84.62% of patients with KS. Molecular defects in KAL1, SOX10, and CHD7 were identified in 5 patients from 4 families (16.0%, 4/25 pedigrees). After sex hormone replacement therapy, there were improvement in sexual characteristics and the sexual function. Conclusion This study described the clinical, endocrinological, and molecular genetic features in IGD patients in Korea. Although the mutation screening was performed in 10 genes that cause IGD, molecular defects were identified in relatively small proportions of the cohort. PMID:25883924

  18. Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight.

    PubMed

    Calderón, Berniza; Gómez-Martín, Jesús M; Vega-Piñero, Belén; Martín-Hidalgo, Antonia; Galindo, Julio; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F; Botella-Carretero, José I

    2016-01-01

    To study the prevalence of male obesity-secondary hypogonadism (MOSH) in patients with moderate to severe obesity, we performed a prospective prevalence study including 100 male patients with moderate to severe obesity at a university tertiary hospital. Total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations among others were assayed in all patients. Serum-free testosterone (FT) concentration was calculated from TT and SHBG levels. Semen analysis was conducted in 31 patients. We found a prevalence of 45% (95% CI: 35-55%) when considering decreased TT and/or FT concentrations. Serum concentrations of TT were correlated negatively with glucose (r = -0.328, p < 0.001) and insulin resistance (r = -0.261, p = 0.011). The same occurred with FT and glucose (r = -0.340, p < 0.001) and insulin resistance (r = -0.246, p = 0.016). Sixty-two percent (95% CI: 39-85%) of the patients with seminogram also presented abnormal results in semen analysis. The frequencies of low TT or low FT values were similar in patients with abnormal or normal semen analysis (p = 0.646 and p = 0.346, respectively). Ejaculate volume inversely correlated with BMI (ρ = -0.400, p = 0.029) and with excess body weight (ρ = -0.464, p = 0.010). Our data show the prevalence of MOSH in patients with moderate to severe obesity is high. Low circulating testosterone is associated with insulin resistance and low ejaculate volume with higher BMI and excess body weight. Semen analysis must be performed in these patients when considering fertility whether or not presenting low circulating testosterone. PMID:26663756

  19. Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men.

    PubMed

    Smith, K W; Feldman, H A; McKinlay, J B

    2000-12-01

    To design a self-administered screening questionnaire to inform men about their risk for testosterone deficiency. The screener was developed in two phases. First was a construction phase in which relevant risk factors and a scoring algorithm were defined from multiple logistic regression analyses of survey data. In the second phase, the screener's accuracy (based on sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves) was tested using patients from a primary care clinic. All subjects provided blood samples for endocrine testing. Survey data from 1660 men aged 40-79 years participating in the Massachusetts Male Ageing Study (MMAS) were analysed in the first phase. The clinic sample consisted of 304 men aged 40-79 years presenting at a large Massachusetts primary health care clinic for routine check-ups or minor medical problems. The primary outcome was testosterone deficiency, defined as serum total testosterone below 12.1 nmol/l. Self-reported variables considered as potential risk factors included age, obesity, chronic diseases, health behaviour, the Jackson dominance scale, and symptoms of stress. The prevalence of testosterone deficiency was 20.4% in the MMAS and 42.1% in the clinic sample. An eight-item screener was developed based on age, body mass index, diabetes, asthma, headaches, sleep patterns, dominance preferences, and smoking status. The screener performed significantly better than chance in identifying men with low testosterone levels; the area under the ROC curve was 0.66 in the MMAS sample and 0.67 in the clinic sample. The self-scored screener developed in this study reliably detects men at risk of hypogonadism. The screener encourages at risk men to seek professional evaluation of their testosterone levels.

  20. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism?

    PubMed

    Tambi, M I B M; Imran, M K; Henkel, R R

    2012-05-01

    In most countries, millions of people are relying on herbal medicines as remedy for numerous ailments. In South-East Asia, Eurycoma longifolia Jack, also known as 'Malaysian ginseng' or Tongkat ali, is used to combat stress and disease and to improve physical strength. Moreover, the compounds of the roots of this plant are reported to have aphrodisiac and testosterone enhancing effects in the rat. Considering that human studies are not available, 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardised water-soluble extract of Tongkat ali for 1 month. The Ageing Males' Symptoms (AMS) according to the standardised rating scale and the serum testosterone concentration were taken. Results show that treatment of LOH patients with this Tongkat ali extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration. While before treatment only 10.5% of the patients did not show any complaint according to the AMS scale and 35.5% had normal testosterone levels, after the completed treatment 71.7% and 90.8% of the patients showed normal values, respectively. Thus, Tongkat ali extract appears to be useful as a supplement in overcoming the symptoms of LOH and for the management of hypogonadism. PMID:21671978

  1. 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

  2. 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

  3. 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

  4. 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

  5. The Response to Gonadotropin-Releasing Hormone and hCG in Men with Prior Chronic Androgen Steroid Abuse and Clinical Hypogonadism.

    PubMed

    Flanagan, J N; Lehtihet, M

    2015-08-01

    Androgens were initially developed to improve anabolism for therapeutic purposes. An observed side effect is a sustained inability to regain normal gonadal function after long-term use. This study was designed to evaluate the response to a standard GnRH (gonadotropin-releasing hormone) test (100 μg) followed by an hCG (human chorionic gonadotropin) test to evaluate the HPG (hypothalamic-pituitary-gonadal) axis in a subgroup of men with former androgen use (FAU, n=13, mean age 38±8 years) with secondary hypogonadotropic hypogonadism and total serum testosterone levels below 10 nmol/l. For comparison, healthy men (n=8, mean age 41±5 years) and untreated men with idiopathic hypogonadotropic hypogonadism (IHH, n=5, mean age 26±8 years) were included. Five of 13 FAU males had an LH (luteinizing hormone) peak after GnRH over 9.6 U/l, the 5(th) percentile of normal reference controls. None of the 13 FAU males reached a testosterone response above 16.0 nmol/l after the 72-h hCG stimulation test, the lowest recorded value for healthy male controls. The IHH patients responded to GnRH with an LH peak after 45 min, while the FAU males and healthy controls had an LH peak after 30 min. After hCG stimulation, the IHH patients increased mean testosterone level to 16.8 nmol/l (median 15.0 nmol/l), significantly higher than the FAU males, p<0.05. Current data support that GnRH and 72-h hCG stimulation tests may be valuable clinical tools to evaluate the HPG axis in adults with previous history of complex androgen abuse, and may provide valuable information in clinical management of these men.

  6. 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

  7. 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

  8. 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

  9. Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility

    PubMed Central

    Hoffmann, Hanne M.; Trang, Crystal; Gong, Ping; Kimura, Ikuo; Pandolfi, Erica C.

    2016-01-01

    Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates mammalian fertility. Herein we demonstrate a critical role for the homeodomain transcription factor ventral anterior homeobox 1 (VAX1) in GnRH neuron maturation and show that Vax1 deletion from GnRH neurons leads to complete infertility in males and females. Specifically, global Vax1 knock-out embryos had normal numbers of GnRH neurons at 13 d of gestation, but no GnRH staining was detected by embryonic day 17. To identify the role of VAX1 specifically in GnRH neuron development, Vax1flox mice were generated and lineage tracing performed in Vax1flox/flox:GnRHcre:RosaLacZ mice. This identified VAX1 as essential for maintaining expression of Gnrh1. The absence of GnRH staining in adult Vax1flox/flox:GnRHcre mice led to delayed puberty, hypogonadism, and infertility. To address the mechanism by which VAX1 maintains Gnrh1 transcription, the capacity of VAX1 to regulate Gnrh1 transcription was evaluated in the GnRH cell lines GN11 and GT1-7. As determined by luciferase and electrophoretic mobility shift assays, we found VAX1 to be a direct activator of the GnRH promoter through binding to four ATTA sites in the GnRH enhancer (E1) and proximal promoter (P), and able to compete with the homeoprotein SIX6 for occupation of the identified ATTA sites in the GnRH promoter. We conclude that VAX1 is expressed in GnRH neurons where it is required for GnRH neuron expression of GnRH and maintenance of fertility in mice. SIGNIFICANCE STATEMENT Infertility classified as idiopathic hypogonadotropic hypogonadism (IHH) is characterized by delayed or absent sexual maturation and low sex steroid levels due to alterations in neuroendocrine control of the hypothalamic-pituitary-gonadal axis. The incidence of IHH is 1–10 cases per 100,000 births. Although extensive efforts have been invested in identifying genes giving rise to IHH, >50% of cases have unknown

  10. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis.

    PubMed

    Guo, W; Burris, T P; McCabe, E R

    1995-10-01

    DAX-1, an orphan member of the nuclear hormone receptor superfamily, is responsible for X-linked adrenal hypoplasia congenita (AHC) and the frequently associated hypogonadotropic hypogonadism (HH). The entire DAX-1 genomic region has been sequenced and a putative steroidogenic factor-1 response element has been identified in the promoter region of the gene. The purpose of these investigations was to determine if DAX-1 was expressed in the central nervous system, particularly the hypothalamus and pituitary, in order to better understand the relationship of mutations in this gene to HH associated with AHC. We used Northern blot analysis and reverse transcription PCR to demonstrate that DAX-1 was expressed in the hypothalamus and the pituitary, and to confirm its expression in adrenal cortex and gonads. The expression of DAX-1 in these tissues indicates the involvement of DAX-1 in the development of the reproductive system at multiple levels within the hypothalamic-pituitary-adrenal/gonadal axis. We also observed the expression of DAX-1 in a human adrenocortical carcinoma cell line, NCI-H295, that has features characteristic of the fetal adrenal cortex. Therefore, NCI-H295 cells will be a useful cellular model for investigating the involvement of DAX-1 in the regulation of steroidogenesis.

  11. X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family.

    PubMed

    Van Esch, Hilde; Zanni, Ginevra; Holvoet, Maureen; Borghgraef, Martine; Chelly, Jamel; Fryns, Jean-Pierre; Devriendt, Koenraad

    2005-01-01

    X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism. Two-point linkage analysis with 24 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 6 cM interval in Xp22.1-p21.3, with a maximum LOD score of 2.61 for markers DXS989 and DXS1061 at theta = 0.00. No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1. These data indicate that the interval Xp22.1-p21.3 contains at least one additional MRXS gene.

  12. To treat or not to treat with testosterone replacement therapy: a contemporary review of management of late-onset hypogonadism and critical issues related to prostate cancer.

    PubMed

    Kava, Bruce R

    2014-07-01

    Over the last 10 years there has been a dramatic increase in the number of patients identified and treated with testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH). By virtue of age, race, and family history, many of these patients are concurrently at risk for harboring indolent prostate cancer. Other men are at increased risk for prostate cancer as a result of an elevated serum PSA level or having had a prior prostate biopsy showing prostatic intraepithelial neoplasia (PIN) or atypical small acinar proliferation (ASAP). The clinician is often challenged with the decision whether to initiate TRT in these patients. This review presents a contemporary overview of the rationale for TRT, as well as the relationship between testosterone (endogenous and exogenous) and premalignant and malignant lesions of the prostate. We will discuss preliminary data from several recent series demonstrating that TRT may be safely administered in select patients with certain premalignant and bona fide malignant tumors of the prostate. In the absence of a large randomized clinical trial with long-term outcome data evaluating TRT, we hope that this overview will provide clinicians with an evidence-based approach to managing these anxiety-provoking - and often frustrating - clinical scenarios.

  13. Effects of Long-Term Testosterone Therapy on Patients with “Diabesity”: Results of Observational Studies of Pooled Analyses in Obese Hypogonadal Men with Type 2 Diabetes

    PubMed Central

    Haider, Ahmad; Yassin, Aksam; Doros, Gheorghe; Saad, Farid

    2014-01-01

    To investigate effects of long-term testosterone (T) therapy in obese men with T deficiency (TD) and type 2 diabetes mellitus (T2DM), data were collected from two observational, prospective, and cumulative registry studies of 561 men with TD receiving T therapy for up to 6 years. A subgroup of obese hypogonadal men with T2DM was analyzed. Weight, height, waist circumference (WC), fasting blood glucose (FBG), glycated haemoglobin (HbA1c) blood pressure, lipid profile, C-reactive protein (CRP), and liver enzymes were measured. A total of 156 obese, diabetic men with T deficiency, aged 61.17 ± 6.18 years, fulfilled selection criteria. Subsequent to T therapy, WC decreased by 11.56 cm and weight declined by 17.49 kg (15.04%). Fasting glucose declined from 7.06 ± 1.74 to 5.59 ± 0.94 mmol/L (P < 0.0001 for all). HbA1c decreased from 8.08 to 6.14%, with a mean change of 1.93%. Systolic and diastolic blood pressure, lipid profiles including total cholesterol: HDL ratio, CRP, and liver enzymes all improved (P < 0.0001). Long-term T therapy for up to 6 years resulted in significant and sustained improvements in weight, T2DM, and other cardiometabolic risk factors in obese, diabetic men with TD and this therapy may play an important role in the management of obesity and diabetes (diabesity) in men with T deficiency. PMID:24738000

  14. Boucher-Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature.

    PubMed

    Tarnutzer, A A; Gerth-Kahlert, C; Timmann, D; Chang, D I; Harmuth, F; Bauer, P; Straumann, D; Synofzik, M

    2015-01-01

    The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhäuser syndrome (BNS), which has recently been linked to autosomal-recessive mutations in the PNPLA6 gene in four index patients. Here we present two novel unrelated patients with BNS, where we identified four recessive PNPLA6 mutations (3 of them novel) as the genetic cause, using a targeted high-throughput approach. This finding provides the first replication from independent families that BNS is caused by PNPLA6 and, moreover, highlights PNPLA6 as the major gene leading to BNS. Given the fact that the major gene causing BNS has thus now been identified, we summarize the spectrum of clinical presentations and phenotype evolution of BNS based on a systematic in-depth review of the literature of previously published cases (n = 40). Both the two cases presented here and our review of the literature propose that the clinical presentation of BNS can be variable regarding both the age (ranging from 1 to 40 years) and the clinical symptoms at onset (cerebellar ataxia in 38 %; vision loss in 36 %; delayed puberty in 26 %). A substantial fraction of BNS cases may present with relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres on MRI, while brainstem or cortical changes on MRI seem to be present only in small fractions. Also in the literature, no other major genetic causes of BNS other than PNPLA6 mutations were identified.

  15. 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

  16. 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

  17. Lack of sexual dimorphism in femora of the eusocial and hypogonadic naked mole-rat: a novel animal model for the study of delayed puberty on the skeletal system.

    PubMed

    Pinto, M; Jepsen, K J; Terranova, C J; Buffenstein, R

    2010-01-01

    Sex steroid hormones are major determinants of bone morphology and quality and are responsible for sexually dimorphic skeletal traits. Hypogonadism results in suboptimal skeletal development and may lead to an increased risk of bone fracture later in life. The etiology of delayed puberty and/or hypothalamic amenorrhea is poorly understood, and experimental animal models addressing this issue are predominantly based upon short-term experimental induction of hormonal suppression via gonadotropin releasing hormone antagonists (GnRH-a). This acute change in hormone profile does not necessarily emulate the natural progression of hypogonadic bone disorders. We propose a novel animal model with which to explore the effects of chronic hypogonadism on bone quality, the naked mole-rat (NMR; Heterocephalus glaber). This mouse-size rodent may remain reproductively suppressed throughout its life, if it remains as a subordinate within the eusocial mole-rat colony. NMRs live in large colonies with a single dominant breeding female. She, primarily by using aggressive social contact, naturally suppresses the hypothalamic gonadotropic axis of subordinate NMRs and thereby their reproductive expression. However, should an NMR be separated from the dominant breeder, within less than a week reproductive hormones may become elevated and the animal attains breeding status. We questioned if sexual suppression of subordinates impact upon the development and maintenance of the femora and lead to a sexually indistinct monomorphic skeleton. Femora were obtained from male and female NMRs that were either non-breeders (subordinate) or breeders at the time of sacrifice. Diaphyseal cross-sectional morphology, metaphyseal trabecular micro-architecture and tissue mineral density of the femur were measured using microcomputed tomography and diaphyseal mechanical properties were assessed by four-point bending tests to failure. Subordinates were sexually monomorphic and showed no significant

  18. Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support

    PubMed Central

    2014-01-01

    Background Patients with rare diseases such as congenital hypogonadotropic hypogonadism (CHH) are dispersed, often challenged to find specialized care and face other health disparities. The internet has the potential to reach a wide audience of rare disease patients and can help connect patients and specialists. Therefore, this study aimed to: (i) determine if web-based platforms could be effectively used to conduct an online needs assessment of dispersed CHH patients; (ii) identify the unmet health and informational needs of CHH patients and (iii) assess patient acceptability regarding patient-centered, web-based interventions to bridge shortfalls in care. Methods A sequential mixed-methods design was used: first, an online survey was conducted to evaluate health promoting behavior and identify unmet health and informational needs of CHH men. Subsequently, patient focus groups were held to explore specific patient-identified targets for care and to examine the acceptability of possible online interventions. Descriptive statistics and thematic qualitative analyses were used. Results 105 male participants completed the online survey (mean age 37 ± 11, range 19–66 years) representing a spectrum of patients across a broad socioeconomic range and all but one subject had adequate healthcare literacy. The survey revealed periods of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%) exceeding one year. Patient focus groups identified lasting psychological effects related to feelings of isolation, shame and body-image concerns. Survey respondents were active internet users, nearly all had sought CHH information online (101/105, 96%), and they rated the internet, healthcare providers, and online community as equally important CHH information sources. Focus group participants were overwhelmingly positive regarding online interventions/support with links to reach expert healthcare providers and for peer-to-peer support. Conclusion The web

  19. Of Mice and Men-Warning: Intact Versus Castrated Adult Male Mice as Xenograft Hosts Are Equivalent to Hypogonadal Versus Abiraterone Treated Aging Human Males, Respectively

    PubMed Central

    Sedelaar, J.P. Michiel; Dalrymple, Susan S.; Isaacs, John T.

    2014-01-01

    BACKGROUND Immune deficient male mice bearing human prostate cancer xenografts are used to evaluate therapeutic response to novel androgen ablation approaches and the results compared to surgical castration based upon assumption that testosterone microenvironment in intact and castrated adult male mice mimics eugonadal and castrated aging adult human males. METHODS To test these assumptions, serum total testosterone (TT) and free testosterone (FT) were determined longitudinally in groups (n > 20) of intact versus castrated adult male nude, NOG, and immune competent C57BL/6 mice. RESULTS In adult male mice, TT and FT varies by 30- to 100-fold within the same animal providing a microenvironment that is only equivalent to hypogonadal, not eugonadal, adult human males (TT is 1.7 ± 1.2 ng/ml [5.8 ± 4.1 nM] in nude and 2.5 ± 1.3 ng/ml [8.7 ± 4.4 nM] in NOG mice versus >4.2 ng/ml [14.7 nM] in eugonadal humans). This was confirmed based upon enhanced growth of androgen dependent human prostate cancer xenografts inoculated into mice supplemented with exogenous testosterone to elevate and chronically maintain serum TT at a level (5 ng/ml [18 nM]) equivalent to a 50-year-old eugonadal human male. In castrated mice, TT and FT range from 2 to 20 pg/ml (7–70 pM) and <0.8 pg/ml (<2.6 pM), respectively, which is equivalent to castrate resistant prostate cancer (CRPC) patients treated with abiraterone. This was confirmed based upon the inability of another CYP17A1 inhibitor, ketoconazole, to inhibit the growth of CRPC xenografts in castrated mice. CONCLUSIONS Adult male mice supplemented with testosterone mimic eugonadal human males, while unsupplemented animals mimic standard androgen ablation and castrated animals mimic abiraterone treated patients. These studies confirm what is claimed in Robert Burns’ poem “To a Mouse” that “The best laid schemes of mice and men/often go awry. PMID:23775398

  20. 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

  1. 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

  2. Hypothalamic hypogonadism in myotonic dystrophy.

    PubMed

    Ulloa-Aguirre, A; Larrea, F; Shkurovich, M

    1981-06-01

    Hypothalamic-pituitary-ovarian axis function was assessed in a postpubertal female patient with myotonic dystrophy and secondary amenorrhea. The results suggested a hypothalamic basis for the amenorrhea, confirming previous reports regarding the nature of gonadal failure in women with this multisystemic disorder.

  3. Gonadotropin-releasing hormone agonist analog (nafarelin): a useful diagnostic agent for the distinction of constitutional growth delay from hypogonadotropic hypogonadism.

    PubMed

    Kletter, G B; Rolfes-Curl, A; Goodpasture, J C; Solish, S B; Scott, L; Henzl, M R; Beitins, I Z

    1996-01-01

    To determine the usefulness of a GnRH agonist analog as a diagnostic test to distinguish between constitutional delay of growth (CGD) in boys with Tanner stage I of sexual development and patients with hypogonadotropic hypogonadism (HH), we evaluated six boys (mean age 15 yr 4 m) and five HH patients (mean age 20 yr 4 m). In addition, 20 normal healthy men aged 21 yr to 50 yr received either nafarelin or GnRH followed two weeks later by the other test in order to compare the efficacy of each of these tests and to evaluate the optimal sampling times for the nafarelin test. All subjects were healthy, and had not received hormonal replacement for at least 2 months prior to enrollment in the study. Each man had four baseline blood samples before and at timed intervals following the administration of either GnRH or nafarelin. Each of the patients had blood withdrawn every 15 min during 12 h overnight followed by a single s.c. injection of nafarelin (1 microgram(s)/kg up to 100 microgram(s)), except two HH patients who did not have an overnight study. Blood samples were obtained at timed intervals for 24 h. LH, FSH, T and E2 were measured by RIA. Baseline concentrations of plasma LH, FSH and T were similar before the administration of either GnRH or nafarelin in the group of normal men. Peak stimulation of plasma LH, FSH and T released by nafarelin was significantly higher, and it took a longer time to reach the peak maximum, than after GnRH (p < 0.001). Mean nocturnal LH was 5.5 +/- 0.9 IU/I for the CGD group, and 2.7 +/- 0.7 IU/I for HH (p < 0.02). Mean nocturnal FSH was 5.1 +/- 1.0 and 2.5 +/- 0.2 IU/I whereas mean nocturnal T concentrations were 4.2 +/- 0.8 and 0.7 +/- 0.2 nmol/I (CGD vs HH, respectively, p < 0.02). Peak LH responses to nafarelin were 36.9 +/- 8.9 IU/I for the CGD group, and 7.0 +/- 2.0 IU/I for the HH group (p < 0.001). Peak FSH released by nafarelin was 14.2 +/- 2.4 IU/I for the CGD group and 4.8 +/- 2.0 IU/I for the HH group (p < 0.02). Peak T was

  4. Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study.

    PubMed

    Aversa, Antonio; Bruzziches, Roberto; Francomano, Davide; Greco, Emanuela A; Fornari, Rachele; Di Luigi, Luigi; Lenzi, Andrea; Migliaccio, Silvia

    2012-06-01

    We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD=1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD=0.989 ± 0.109; p < 0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2) = 0.66, p < 0.0001) and femoral (r(2) =0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications. PMID:22439807

  5. 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.

  6. The Ability of Lumbar Spine DXA and Phalanx QUS to Detect Previous Fractures in Young Thalassemic Patients With Hypogonadism, Hypothyroidism, Diabetes, and Hepatitis-B: A 2-Year Subgroup Analysis From the Taranto Area of Apulia Region

    PubMed Central

    Neglia, Cosimo; Peluso, Angelo; di Rosa, Salvatore; Ferrarese, Antonio; Di Tanna, Gianluca; Caiaffa, Vincenzo; Benvenuto, Marco; Cozma, Alexandru; Chitano, Giovanna; Agnello, Nadia; Paladini, Daniele; Baldi, Nicola; Distante, Alessandro; Piscitelli, Prisco

    2013-01-01

    Background: Osteoporosis is a leading cause of morbidity in patients affected by β-thalassemia major or intermediate; we aimed to assess the association between demineralization observed in young thalassemic patients. Methods: A total of 88 patients with β-thalassemia were recruited at Microcitemia Center of Taranto Hospital under the Prevention Osteoporosis and Fractures research project from 2008 to 2010. All the patients were screened with both dual energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). T score and Z score values were obtained for each subject. Results: The overall prevalence of demineralization was 84% with DXA and 70% with QUS, whereas normality was found in 16% of patients screened with DXA and in 30% of cases with QUS. Hypogonadism, hypothyroidism, diabetes mellitus, hepatitis-B, and the presence of previous fragility fractures were significantly associated with the demineralization status (lower T scores values) both with DXA and QUS. Conclusion: Our data confirm that DXA and QUS examinations are both useful for detecting bone demineralization in thalassemic patients. PMID:23652868

  7. 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

    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

    2007-02-01

    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

  8. Clinical and genetic analysis of a Korean patient with late-onset X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism: identification of a novel mutation in the NR0B1 gene.

    PubMed

    Lee, Y-W; Won, J C; Ki, C-S; Lee, H Y; Ahn, H S; Lee, Y K; Kim, Y H; Kim, C-H

    2008-01-01

    Adrenal hypoplasia congenita (AHC) is caused by mutations in the NR0B1 gene on chromosome Xp21.3-p21.2. It manifests as X-linked primary adrenal failure in early infancy or childhood and as hypogonadotropic hypogonadism (HHG) at puberty. Although studies of AHC patients and mutations in the NR0B1 gene have been reported throughout the world, there has previously been only one other case report from Korea. We encountered a 23-year old Korean male with delayed-onset AHC/HHG who had been previously diagnosed with adrenal insufficiency of unknown aetiology at age 13 years. Delayed puberty and incomplete HHG were observed. Direct sequencing of the NR0B1 gene revealed the patient to have a novel insertion mutation (c.959_960insT; Leu321ProfsX68). Although AHC is believed to be rare, it should be considered in a differential diagnosis of patients showing late-onset primary adrenal insufficiency.

  9. Pituitary gonadotrophic hormone synthesis, secretion, subunit gene expression and cell structure in normal and follicle-stimulating hormone β knockout, follicle-stimulating hormone receptor knockout, luteinising hormone receptor knockout, hypogonadal and ovariectomised female mice.

    PubMed

    Abel, M H; Widen, A; Wang, X; Huhtaniemi, I; Pakarinen, P; Kumar, T R; Christian, H C

    2014-11-01

    To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic-pituitary-gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle-stimulating hormone β knockout (FSHβKO), follicle-stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild-type or heterozygote female mice. Serum levels of LH were elevated in FSHβKO and FSHRKO compared to heterozygote females, reflecting the likely decreased oestrogen production in KO females, as demonstrated by the threadlike uteri and acyclicity. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSHβ subunit gene in FSHβKO mice. However, there was a significant increase in expression of the FSHβ and LHβ subunit genes in FSHRKO female mice. The morphology of FSHβKO and FSHRKO gonadotrophs was not significantly different from the control, except that secretory granules in FSHRKO gonadotrophs were larger in diameter. In LuRKO and ovariectomised mice, stimulation of LHβ and FSHβ mRNA, as well as serum protein concentrations, were reflected in subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticula and fewer, larger secretory granules. In the gonadotophin-releasing hormone deficient hpg mouse, gonadotrophin mRNA and protein levels were significantly lower than in control mice and gonadotrophs were correspondingly smaller with less abundant endoplasmic reticula and reduced numbers of secretory granules. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH were found between control and mutant female mice. These changes were

  10. 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

  11. 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

  12. Hypogonadism in chronically lead-poisoned men.

    PubMed

    Braunstein, G D; Dahlgren, J; Loriaux, D L

    1978-01-01

    The hypothalamic-pituitary-testicular axis was evaluated in 10 men with occupational lead exposure, 9 of whom had noted a decrease in libido and frequency of intercourse following this exposure. 6 of these men had clinically apparent lead poisoning while 4 were classified as being only lead-exposed. Results of the endocrine evaluation of these patients were compared to those obtained on 9 age and socioeconomically matched control patients. Both lead poisoned and lead-exposed patients had reduced basal serum testosterone levels and normal basal serum testosterone-estradiol-binding globulin capacity, estradiol, LH, FSH, and prolactin levels. Both groups demonstrated an appropriate rise in serum testosterone following hCG stimulation and a normal increment in serum FSH in response to clomiphene citrate and gonadotropin-releasing hormone in comparison to the control group. The lead poisoned patients demonstrated a significantly reduced increment in serum LH after clomiphene citrate and gonadotropin-releasing hormone administration while the lead-exposed patients had normal LH dynamics. Testicular biopsies carried out on the 2 most severely lead-poisoned men showed peritubular fibrosis, oligospermia, and vacuolization of the Sertoli cells. These results suggest that lead poisoning may lead to a pituitary-hypothalamic defect in LH secretion and may also result in direct testicular seminiferous tubular injury.

  13. Hypogonadism in Prader-Willi syndrome.

    PubMed

    Wannarachue, N; Ruvalcaba, R H

    1975-03-01

    Sexual development was evaluated in 9 female and 2 male subjects with Prader-Willi syndrome. The process of sexual development and degree of genital development attained were found to be variable but abnormal in all subjects. Hypothalamic-pituitary-gonadal functions were evaluated by measurement of serum Luteinizing Hormone and plasma testosterone responses to stimulation by clomiphene citrate and plasma testosterone responses to stimulation by human chorionic gonadotrophin. The degree of vaginal estrogenization was variable. The testicular biopsies showed abnormalities mainly in the germinal epithelium. In agreement with previous studies, it was concluded that the abnormalities of sexual development in this syndrome are mainly due to a defect in the hypothalamic pituitary axis. Adrenal function was not found to be grossly abnormal. The 17 ketosteroid excretion values were low, probably explaining the rather sparse pubic and axillary hair observed in these patients. The urinary 17-hydroxycorticosteroid creatinine ratios were found to be elevated, probably due to decreased creatinine excretion, reflecting the muscular abnormalities of these subjects.

  14. Anorexia nervosa: hypogonadotrophic hypogonadism and bone mineral density.

    PubMed

    Muñoz, M T; Argente, J

    2002-01-01

    Anorexia nervosa is a chronic illness that involves a reduction in caloric intake, loss of weight and amenorrhoea, either primary or secondary. In addition to prolonged amenorrhoea, osteopenia and osteoporosis are the most frequent complications. Patients exhibit an alteration in the hypothalamic-pituitary-gonadal axis, which is responsible for the menstrual disorders. The increase in gonadotrophin secretion that can be observed after ponderal recuperation suggests that malnutrition could be the most important mechanism involved in the decrease in gonadotrophin secretion. The loss of fat tissue, as a consequence of the restriction of nutrients, has been associated with hypoleptinaemia, abnormal secretion of peptides implicated in food control (neuropeptide Y, melanocortins and corticotrophin-releasing hormone, among others) and diminution of the amount of total body fat. Despite oestrogen therapy, the severe loss of bone mass may progress. Other factors such as weight loss, duration of amenorrhoea and low insulin-like growth factor-I (IGF-I) levels could contribute to the loss of bone mass in women with anorexia nervosa. The recuperation of weight and, in particular, the amount of total body fat could lead to the spontaneous recuperation of menstruation.

  15. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.

    PubMed

    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

    2007-06-19

    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 (beta-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.

  16. 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

  17. Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty.

    PubMed

    Hadziselimovic, Faruk; Gegenschatz-Schmid, Katharina; Verkauskas, Gilvydas; Docampo-Garcia, Maria J; Demougin, Philippe; Bilius, Vytautas; Malcius, Dalius; Dasevicius, Darius; Stadtler, Michael B

    2016-01-01

    The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups. Seven were classified as belonging to the high infertility risk (HIR) and 8 to the low infertility risk (LIR) group. Cryptorchid boys in the HIR group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini-puberty. This group of patients will be infertile despite successful surgery. The new important finding was a decreased PROK2, CHD7, FGFR1, and SPRY4 gene expression in the HIR group. Furthermore, identification of multiple differences in gene expression between HIR and LIR groups underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. Our RNA profiling data strongly support the theory that in the HIR group of cryptorchid boys insufficient PROK2/CHD7/FGFR1/SPRY4 gene expression induces deficient LH secretion, resulting in impaired mini-puberty and infertility. We therefore recommend hormonal treatment for this cohort of cryptorchid boys with defective mini-puberty following a seemingly successful orchidopexy.

  18. 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

  19. 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

  20. 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

  1. Disrupted Kisspeptin Signaling in GnRH Neurons Leads to Hypogonadotrophic Hypogonadism

    PubMed Central

    Sonko, Momodou L.; Hoffman, Gloria; Koo, Yongbum; Ko, Chemyong; Wolfe, Andrew; Radovick, Sally

    2014-01-01

    Landmark studies have shown that mutations in kisspeptin and the kisspeptin receptor (Kiss1r) result in reproductive dysfunction in humans and genetically altered mouse models. However, because kisspeptin and its receptor are present in target cells of the central and peripheral reproductive axis, the precise location(s) for the pathogenic signal is unknown. The study described herein shows that the kisspeptin-Kiss1r signaling pathway in the GnRH neuron is singularly critical for both the onset of puberty as well as the attainment of normal reproductive function. In this study, we directly test the hypothesis that kisspeptin neurons regulate GnRH secretion through the activation of Kiss1r on the plasma membrane of GnRH neurons. A GnRH neuron–specific Kiss1r knockout mouse model (GKirKO) was generated, and reproductive development and phenotype were assessed. Both female and male GKirKO mice were infertile, having low serum LH and FSH levels. External abnormalities such as microphallus and decreased anogenital distance associated with failure of preputial gland separation were present in GKirKO males. A delay in pubertal onset and abnormal estrous cyclicity were observed in female GKirKO mice. Taken together, these data provide in vivo evidence that Kiss1r in GnRH neurons is critical for reproductive development and fertility. PMID:24422632

  2. Natural antisense LHCGR could make sense of hypogonadism, male-limited precocious puberty and pre-eclampsia.

    PubMed

    Chambers, Anne E; Banerjee, Subhasis

    2005-09-28

    The pleiotropic effects of human chorionic gonadotrophin (hCG), the key regulator of human pregnancy, are dependent upon cell surface expression of its functional cognate receptor LHCGR in the placental trophoblasts, corpus luteum, uterus, vascular endothelial and smooth muscle cells. Additionally, lutenizing hormone-mediated signalling failure has often been linked to activating/inactivating mutations in LHCGR. One of the intriguing aspects of these studies is that the mutations are most frequently located within C-terminal 200-350 residues of the receptor protein. In an attempt to reconcile the mechanistic basis of LHCGR regulation and mutations, we have carried out bioinformatic analyses to identify the CpG-rich regions and the major potential scaffold/matrix attachment sites (S/MARs) in LHCGR and neighbouring gene (ALF) at human chromosome 2p21. Based on these analyses, we propose a chromatin-loop model, which may explain the temporal regulation and susceptibility to mutation of the human LHCGR. One of the characteristic features of the model, is that the major potential S/MAR sequences of the human LHCGR gene (68 kb) are located at the 3' end of the gene, and unlike mouse, the transmembrane and C-terminal protein coding sequences at exon 11 are embedded in this S/MAR site. Moreover, this region is subject to antisense transcription from the neighbouring gene ALF, which is gonad-specific and is only activated in meiotic spermatocytes and oocytes. Together, these analyses suggest that exon 11 of human LHCGR could be more susceptible to mutation than the other 10 exons together and that activation of LHCGR, contingent to the somatic silencing of neighbouring ALF, could be linked to male-limited precocious puberty and pre-eclampsia. PMID:16087288

  3. Obesity-induced hypogonadism in the male: premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms.

    PubMed

    Sánchez-Garrido, Miguel Angel; Ruiz-Pino, Francisco; Manfredi-Lozano, Maria; Leon, Silvia; Garcia-Galiano, David; Castaño, Justo P; Luque, Raul M; Romero-Ruiz, Antonio; Castellano, Juan M; Diéguez, Carlos; Pinilla, Leonor; Tena-Sempere, Manuel

    2014-03-01

    Reproduction is sensitive to insufficient body energy reserves, especially in females. Metabolic regulation of the male reproductive axis is less obvious, and the impact of conditions of persistent energy excess has received moderate attention. Yet, the escalating prevalence of obesity and the clinical evidence of its deleterious effects on male fertility have raised considerable concerns. We report here phenotypic and mechanistic studies of the reproductive impact of postnatal nutritional manipulations (mainly overnutrition) coupled to a high-fat diet (HFD) after weaning. Metabolic and hormonal analyses in young (4 months old) and middle-aged (10 months old) animals revealed that HFD caused profound metabolic perturbations, including glucose intolerance, which were worsened by precedent postnatal overfeeding; these were detectable already in young males but aggravated in 10-month-old rats. Impairment of reproductive parameters took place progressively, and HFD alone was sufficient to explain most of these alterations, regardless of postnatal under- or overnutrition. In young males, testosterone (T) levels and steroidogenic enzyme expression were suppressed by HFD, without compensatory increases of LH levels, which were in fact partially inhibited in heavier males. In addition, obese males displayed suppressed hypothalamic Kiss1 expression despite low T, and HFD inhibited LH responses to kisspeptin. Overweight anticipated some of the neuroendocrine effects of aging, such as the suppression of hypothalamic Kiss1 expression and the decline in serum T and LH levels. Nonetheless, HFD per se caused a detectable worsening of key reproductive indices in middle-aged males, such as basal LH and FSH levels as well as LH responses to kisspeptin. Our study demonstrates that nutritional stress, especially HFD, has a profound deleterious impact on metabolic and gonadotropic function as well as on the Kiss1 system and precipitates neuroendocrine reproductive senescence in the male.

  4. Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism.

    PubMed

    Mäkinen, Juuso I; Perheentupa, Antti; Irjala, Kerttu; Pöllänen, Pasi; Mäkinen, Juha; Huhtaniemi, Ilpo; Raitakari, Olli T

    2011-12-01

    In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40?69 years (mean 55.9 ± 7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r = -0.38, p = 0.0004), alcohol consumption (r = -0.22, p = 0.047) and serum testosterone (r = -0.27, p = 0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (β = -0.17, p = 0.0226), high density lipoprotein cholesterol (β = 4.17, p = 0.0312) and vessel diameter (β = -4.37, p < 0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.

  5. 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.

  6. Congenital hypogonadotropic hypogonadism and micropenis: effect of testosterone treatment on adult penile size why sex reversal is not indicated.

    PubMed

    Bin-Abbas, B; Conte, F A; Grumbach, M M; Kaplan, S L

    1999-05-01

    Micropenis is commonly due to fetal testosterone deficiency. The clinical management of this form of micropenis has been contentious, with disagreement about the capacity of testosterone treatment to induce a functionally adequate adult penis. As a consequence, some clinicians recommend sex reversal of affected male infants. We studied 8 male subjects with micropenis secondary to congenital pituitary gonadotropin deficiency from infancy or childhood to maturity (ages 18 to 27 years). Four patients were treated with testosterone before 2 years of age (group I) and four between age 6 and 13 years (group II). At presentation, the mean penile length in group I was 1.1 cm (-4 SD; range, 0.5 to 1.5 cm) and in group II it was 2.7 cm (-3.4 SD; range, 1.5 to 3.5 cm). All patients received one or more courses of 3 intramuscular injections of testosterone enanthate (25 or 50 mg) at 4-week intervals in infancy or childhood. At the age of puberty the dose was gradually increased to 200 mg monthly and later to an adult replacement regimen. As adults, both group I and II had attained a mean final penile length of 10.3 cm 2.7 cm with a range of 8 to 14 cm (mean adult stretched penile length for Caucasians is 12.4 2.7 cm). Six of 8 men were sexually active, and all reported normal male gender identity and psychosocial behavior. We conclude that 1 or 2 short courses of testosterone therapy in infancy and childhood augment penile size into the normal range for age in boys with micropenis secondary to fetal testosterone deficiency; replacement therapy at the age of puberty results in an adult size penis within 2 SD of the mean. We found no clinical, psychologic, or physiologic indications to support conversion of affected male infants to girls. Further, the results of this study do not support the notion, derived from data in the rat, that testosterone treatment in infancy or childhood impairs penile growth in adolescence and compromises adult penile length.

  7. 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 ...

  8. Acromegaly Presenting as Erectile Dysfunction: Case Reports and Review of the Literature.

    PubMed

    Raju, Jerry A; Shipman, Kate E; Inglis, John A; Gama, Rousseau

    2015-01-01

    Erectile dysfunction (ED) is a common yet complex condition. The authors report two cases of acromegaly presenting with ED and hypogonadotropic hypogonadism. Surgical cure of the acromegaly was associated with either an improvement or resolution of hypogonadotropic hypogonadism-associated ED. Active acromegaly should be considered in the differential diagnosis of ED presenting with supporting clinical features, particularly hypogonadotropic hypogonadism. PMID:26839523

  9. Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function.

    PubMed

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

    2015-01-01

    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.

  10. 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) ...

  11. 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.

  12. 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. PMID:27625840

  13. 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 ...

  14. 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

  15. Low testosterone in a male adolescent bodybuilder: Which diagnosis holds more weight?

    PubMed

    Woodhill, Ineke; Cooper, Chris; Zacharin, Margaret; Cukier, Kimberly; Vuillermin, Peter

    2014-09-01

    We present the case of a 16-year-old male who presented reporting a 6-month history of lowered mood, fatigue, anhedonia, disturbed sleep and heightened anxiety. On further questioning he reported restricted eating and weightlifting for at least 1 h on a daily basis. Investigations revealed findings compatible with secondary hypogonadism. The potential causes of secondary hypogonadism including structural lesions, muscle dysmorphia and use of illicit anabolic steroids are discussed.

  16. Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy.

    PubMed

    Carroll, Richard W; Christodoulou, Polyxeni; Baynes, Kevin C R; Kahn, David A

    2012-03-01

    Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

  17. 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

  18. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma.

    PubMed

    Lee, Cheng-Chi; Chen, Chung-Ming; Lee, Shih-Tseng; Wei, Kuo-Chen; Pai, Ping-Ching; Toh, Cheng-Hong; Chuang, Chi-Cheng

    2015-01-01

    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of <2.4 ng/mL. The tumor volume was calculated based on the pre- and post-operative magnetic resonance images. We prescribed testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement. PMID:26537232

  19. Hormonal modulation in aging patients with erectile dysfunction and metabolic syndrome.

    PubMed

    Costa, Inês Campos; Carvalho, Hugo Nogueira; Pacheco-Figueiredo, Luís; Tomada, Inês; Tomada, Nuno

    2013-01-01

    Erectile dysfunction (ED), metabolic syndrome (MetS), and hypogonadism are closely related, often coexisting in the aging male. Obesity was shown to raise the risk of ED and hypogonadism, as well as other endocrinological disturbances with impact on erectile function. We selected 179 patients referred for ED to our andrology unit, aiming to evaluate gonadotropins and estradiol interplay in context of ED, MetS, and hypogonadism. Patients were stratified into groups in accordance with the presence (or not) of MetS and/or hypogonadism. Noticeable differences in total testosterone (TT) and free testosterone (FT) levels were found between patients with and without MetS. Men with MetS evidenced lower TT circulating levels with an increasing number of MetS parameters, for which hypertriglyceridemia and waist circumference strongly contributed. Regarding the hypothalamic-pituitary-gonadal axis, patients with hypogonadism did not exhibit raised LH levels. Interestingly, among those with higher LH levels, estradiol values were also increased. Possible explanations for this unexpected profile of estradiol may be the age-related adiposity, other estrogen-raising pathways, or even unknown mechanisms. Estradiol is possibly a molecule with further interactions beyond the currently described. Our results further enlighten this still unclear multidisciplinary and complex subject, raising new investigational opportunities.

  20. Luteinizing hormone and follicle stimulating hormone-releasing hormone test in patients with hypothalamic-pituitary-gonadal dysfunction.

    PubMed

    Mortimer, C H; Besser, G M; McNeilly, A S; Marshall, J C; Harsoulis, P; Tunbridge, W M; Gomez-Pan, A; Hall, R

    1973-10-13

    A standard intravenous 100 mug luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH) test was used to assess the pituitary gonadotrophin responses in 155 patients with a variety of diseases of the hypothalamic-pituitary-gonadal axis. In all but nine patients there was an increase in circulating levels of either LH or FSH in response to the releasing hormone though 137 (88%) were clinically hypogonadal. It was not possible with this test to distinguish between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism, since a variety of LH and FSH responses emerged within the disease groups. However, primary gonadal failure characteristically resulted in exaggerated gonadotrophin response. The potential therapeutic use of the gonadotrophin releasing decapeptide is suggested in certain patients with hypogonadotrophic hypogonadism.

  1. [Diagnosis of delayed puberty].

    PubMed

    Busiah, K; Belien, V; Dallot, N; Fila, M; Guilbert, J; Harroche, A; Leger, J

    2007-09-01

    Puberty is the phenomenon that conducts once to reproductive maturation. Delayed puberty (DP) is defined by the absence of testicular development in boys beyond 14 years old (or a testicular volume lower than 4 ml) and by the absence of breast development in girls beyond 13 years old. DP occurs in approximatively 3% of cases. Most cases are functional DP, with a large amount of constitutional delay of puberty. Others etiologies are hypogonadotrophic hypogonadism like Kallmann syndrome, or hypergonadotrophic hypogonadism. Turner syndrome is a diagnostic one should not forget by its frequency. Treatment is hormonal replacement therapy and of the etiology. During the last decade, many genes have been identified and elucidated the etiological diagnosis of some hypogonadotrophic hypogonadism syndrome. Further studies are required in collaboration with molecular biologists to better understand the mechanism of hypothalamic pituitary gonadal axis abnormalities and of the neuroendocrine physiology of the onset of puberty.

  2. 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.

  3. The aging male: androgens, erectile dysfunction, and depression.

    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) axis activity in aging men: testosterone levels decline and there is a loss of the circadian rhythm of testosterone secretion. Such progressive HPG-axis hypofunctioning is thought to be responsible for some signs and symptoms that are common in elderly men such as fatigue, reduced muscle and bone mass, sexual dysfunction, and depression. Yet, such presumed hypogonadal sequelae have not been correlated with testosterone levels. Unlike the profound effects of replacement therapy in young men with frank hypogonadism, testosterone replacement in men with age-related mild hypogonadism is not apparently effective in reversing these symptoms. This article reviews the relationship between androgens, sexual function, and depression in aging men.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. [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

  9. Bosma arrhinia microphthalmia syndrome in a Mexican patient with a molecular analysis of PAX6.

    PubMed

    Becerra-Solano, Luis E; Chacón, Liliana; Morales-Mata, Dinorah; Zenteno, Juan C; Ramírez-Dueñas, Maria L; García-Ortiz, Jose E

    2016-01-01

    The association of anophthalmia, arrhinia, and hypogonadism constitutes the major clinical features for Bosma arrhinia microphthalmia syndrome. However, there is variability in the presentation of this disease; arrhinia is the most constant clinical feature, which is then combined with a spectrum of anophthalmia/microphthalmia and/or hypogonadism. This rare entity is not associated with any specific genes, but the genes that are related to arrhinia and anophthalmia have been studied in an attempt to explain this phenomenon. We analyzed the PAX6 gene in a Bosma arrhinia microphthalmia syndrome patient but found no variation or mutation that could constitute or establish a causal association in our patient.

  10. 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.

  11. Impotence is not always psychogenic. Newer insights into hypothalamic-pituitary-gonadal dysfunction.

    PubMed

    Spark, R F; White, R A; Connolly, P B

    The concept that impotence is psychogenic in 95% of cases is reconsidered. Screening serum testosterone levels of 105 consecutive patients with impotence showed that 37 patients had previously unsuspected disorders of the hypothalamic-pituitary-gonadal axis. Twenty patients had hypogonadotropic-hypogonadism, seven had hypergonadotropic-hypogonadism, eight had hyperprolactinemia, and two had occult hyperthyroidism. Once the specific defect was defined, appropriate therapy was instituted, and potency was restored in 33 patients. Screening serum testosterone levels is useful in identifying hypothalamic-pituitary-gonadal dysfunction in patients with impotence.

  12. 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

  13. 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

  14. 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

  15. 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

  16. [Suprasellar germinoma: two case reports].

    PubMed

    Ben Abdallah, Néjib; Cherif, Lotfi; Khiari, Karima; Hadj Ali, Insaf; Turki, Sami; Mezni, Faouzi; Ben Jilani, Sarrah; Ben Maïz, Hédi

    2002-03-01

    Suprasellar germinomas are frequent in childhood and adolescence, particularly in male sex. The clinical and neuroendocrine abnormalities depend of tumor localization: Increased intracranial pressure, visual disturbances, hypopituitarism, Parinaud syndrome. We report two cases of suprasellar germinoma in young male patients (16 and 18 years old). The first patient hrad corticotorpin insufficiency and clinical signs of hypothyroïdism and hypogonadism. The second had central hypocorticism, hypothyroïdism and hypogonadism associated with central diabetes insipidus and hyperprolactinemia. The diagnosis of germinoma was confirmed after surgery by anatomopathologic examination in the first case and by stereotaxic biopsy in the second case. Treatment by radiotherapy improves prognosis of this disease.

  17. SOX2 regulates the hypothalamic-pituitary axis at multiple levels

    PubMed Central

    Jayakody, Sujatha A.; Andoniadou, Cynthia L.; Gaston-Massuet, Carles; Signore, Massimo; Cariboni, Anna; Bouloux, Pierre M.; Le Tissier, Paul; Pevny, Larysa H.; Dattani, Mehul T.; Martinez-Barbera, Juan P.

    2012-01-01

    Sex-determining region Y (SRY) box 2 (SOX2) haploinsufficiency causes a form of hypopituitarism in humans that is characterized by gonadotrophin deficiency known as hypogonadotrophic hypogonadism. Here, we conditionally deleted Sox2 in mice to investigate the pathogenesis of hypogonadotrophic hypogonadism. First, we found that absence of SOX2 in the developing Rathke pouch of conditional embryos led to severe anterior lobe hypoplasia with drastically reduced expression of the pituitary-specific transcription factor POU class 1 homeobox 1 (POU1F1) as well as severe disruption of somatotroph and thyrotroph differentiation. In contrast, corticotrophs, rostral-tip POU1F1-independent thyrotrophs, and, interestingly, lactotrophs and gonadotrophs were less affected. Second, we identified a requirement for SOX2 in normal proliferation of periluminal progenitors; in its absence, insufficient precursors were available to produce all cell lineages of the anterior pituitary. Differentiated cells derived from precursors exiting cell cycle at early stages, including corticotrophs, rostral-tip thyrotrophs, and gonadotrophs, were generated, while hormone-producing cells originating from late-born precursors, such as somatotrophs and POU1F1-dependent thyrotrophs, were severely reduced. Finally, we found that 2 previously characterized patients with SOX2 haploinsufficiency and associated hypogonadotrophic hypogonadism had a measurable response to gonadotropin-releasing hormone (GnRH) stimulation, suggesting that it is not the absence of gonadotroph differentiation, but rather the deficient hypothalamic stimulation of gonadotrophs, that underlies typical hypogonadotrophic hypogonadism. PMID:22945632

  18. Prader-Willi Disease: A Case Study.

    ERIC Educational Resources Information Center

    Forbus, William R., III

    A case study focuses on the characteristics and physical management of a 15-year-old with Prader-Willi Syndrome, a birth defect associated with hypotonia, insatiable appetite, hypogonadism, central nervous system dysfunction, and abnormal growth and development . A literature review addresses studies dealing with behavior modification of obesity…

  19. 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.

  20. Endocrine investigation and therapy.

    PubMed

    McClure, R D

    1987-08-01

    The most commonly investigated testicular disorder is male infertility. Although endocrine causes are uncommon, they are potentially curable. A careful history and examination for subtle features of hypogonadism are important initiating steps. Understanding the appropriate use of both baseline and dynamic testing of the hypothalamic-pituitary-gonadal axis (and, in certain instances, the adrenal and thyroid glands) is extremely important.

  1. Minipuberty of infancy and adolescent pubertal function in adrenal hypoplasia congenita.

    PubMed

    Kaiserman, K B; Nakamoto, J M; Geffner, M E; McCabe, E R

    1998-08-01

    An infant and his uncle, both with adrenal hypoplasia congenita, shared the same DAX1 mutation. The adolescent uncle had hypogonadotropic hypogonadism, but the infant had a normal minipuberty of infancy. These observations suggest differences in the physiologic mechanisms regulating the hypothalamic-pituitary-gonadal axis in infancy and adolescence.

  2. Hypothalamic-pituitary function in the Bardet-Biedl syndrome.

    PubMed

    Leroith, D; Farkash, Y; Bar-Ziev, J; Spitz, I M

    1980-07-01

    Four siblings with classic Bardet-Biedl syndrome were studied. The brother had hypogonadism of testiculr origin, with high gonadotropin levels and exaggerated responses to luteinizing-hormone-releasing hormone, whereas the three sisters showed a normal hypothalamic-pituitary-gonadal axis. The remaining pituitary hormone function was intact.

  3. 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

  4. The genetic basis of female reproductive disorders: Etiology and clinical testing ☆

    PubMed Central

    Layman, Lawrence C.

    2013-01-01

    With the advent of improved molecular biology techniques, the genetic basis of an increasing number of reproductive disorders has been elucidated. Mutations in at least 20 genes cause hypogonadotropic hypogonadism including Kallmann syndrome in about 35–40% of patients. The two most commonly involved genes are FGFR1 and CHD7. When combined pituitary hormone deficiency includes hypogonadotropic hypogonadism as a feature, PROP1 mutations are the most common of the six genes involved. For hypergonadotropic hypogonadism, mutations in 14 genes cause gonadal failure in 15% of affected females, most commonly in FMR1. In eugonadal disorders, activating FSHR mutations have been identified for spontaneous ovarian hyperstimulation syndrome; and WNT4 mutations have been described in mullerian aplasia. For other eugonadal disorders, such as endometriosis, polycystic ovary syndrome, and leiomyomata, specific germline gene mutations have not been identified, but some chromosomal regions are associated with the corresponding phenotype. Practical genetic testing is possible to perform in both hypogonadotropic and hypergonadotropic hypogonadism and spontaneous ovarian hyperstimulation syndrome. However, clinical testing for endometriosis, polycystic ovary syndrome, and leiomyomata is not currently practical for the clinician. PMID:23499866

  5. 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

  6. [Observation of a male patient with the empty sella turcica syndrome].

    PubMed

    Bozadzhieva, E; Platonova, E; Sivchev, S; Dashev, G; Chavrakov, G

    1975-01-01

    One case with secondary developed syndrome of sell turcica is described, after hypophysis radiation on the occasion of acromegaly. Of special interest is the preserved tropic hypophysis secretion with a clinical picture of hypopituitarism (secondary developed hypogonadism, hypothyroidism and hypocorticism) as well as the combination with another brain neoplasm--astrocytoma.

  7. 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…

  8. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

  9. [A case of micropenis with strong genetic basis].

    PubMed

    Bolla, G; Mammi, I

    2013-01-01

    The early hormonotherapy of micropenis takes on a diagnostic significance too. The very good tolerance gives value to this behaviour. The Author shows the condition of a male infant 46,XY eighteen months old; the child appeared with a micropenis completely expressed and resulting from hypogonadotropic hypogonadism. He confirms the good response to hormonotherapy for this child.

  10. 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…

  11. 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…

  12. Cryptorchidism due to chromosome 5q inversion duplication.

    PubMed

    Dutta, M K; Gundgurthi, A; Garg, M K; Pakhetr, R

    2013-12-01

    We present a 15 year old boy who was born out of a non consanguineous marriage, and presented with bilateral cryptorchidism, mental retardation, facial dysmorphism, hypergonadotrophic hypogonadism with failure of anatomical and biochemical localisation of testes. Karyotype analysis showed 46 XY with inverted duplication on chromosome 5q22-31.

  13. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction.

    PubMed

    Traish, Abdulmaged M; Guay, Andre; Feeley, Robert; Saad, Farid

    2009-01-01

    The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. These factors increase the risk of cardiovascular disease (CVD) and/or type 2 diabetes. Although the etiology of this syndrome is thought to stem from obesity and physical inactivity, the extent of interactions of the individual MetS components with one another remains poorly defined. Obesity, diabetes, hypogonadism, and specific hormone and metabolic profiles have been implicated in the pathophysiology of CVD. The evolving role of androgens in MetS and CVD is of paramount importance. Reduced androgen levels associated with hypogonadism or androgen deprivation therapy increase cardiovascular risk factors and produce marked adverse effects on cardiovascular function. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. It is suggested that MetS, diabetes, and CVD will increase in the upcoming decades. Thus, it is critically important to develop a better understanding of how obesity, diabetes and hypogonadism contribute to androgen deficiency and the various pathophysiologic states of vascular disease. In this review we discuss the current literature pertaining to androgen deficiency, MetS, and ED, because the relationship of these factors is of scientific and clinical importance. Specifically, we will focus on exploring the relationships between hypogonadism, obesity, MetS, and ED. PMID:18641413

  14. Assessment of thyroid and gonadal function in liver diseases

    PubMed Central

    Kharb, Sandeep; Garg, M. K.; Puri, Pankaj; Brar, Karninder S.; Pandit, Aditi; Srivastava, Sharad

    2015-01-01

    Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH), chronic liver disease (CLD), and those who had undergone liver transplantation (LT). Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1) and Child-Pugh stage B or C (CLD-2), and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16%) and 24 (28%) patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%), followed by subclinical hypothyroidism in three patients (3.5%), subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3%) and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50%) followed by LT (3; 33%), CLD-1 (4; 20%), and AH (3; 14%). Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism. PMID:25593833

  15. Testosterone therapy--what, when and to whom?

    PubMed

    Jockenhövel, F

    2004-12-01

    Testosterone therapy has been used for more than 60 years in the treatment of male hypogonadism. The classical forms of hypogonadism are comprised of primary testicular failure or insufficient testicular stimulation due to the lack of pituitary gonadotropins. Typical causes of primary hypogonadism are Klinefelter's syndrome, anorchia or acquired disturbances of testicular function. Secondary hypogonadism is characterized by insufficient production of pituitary gonadotropins, due either to pituitary failure or defects at the hypothalamic level. It is unequivocally accepted in clinical practice that any male with inadequately low testosterone production for his age will require androgen therapy. In addition to the classical forms of hypogonadism, the past decade of research has clearly demonstrated that, with increasing age, many men will suffer from decreasing testosterone production. About 15-25% of men over the age of 50 years will experience serum testosterone levels well below the threshold considered normal for men between 20 and 40 years of age. Studies substituting testosterone in elderly men with low serum testosterone have shown that men with clinical symptoms identical to the symptomatology of classical hypogonadism will benefit most from such therapy. Therefore, it is the general consensus to treat men with age-related hypogonadism only when clinical symptoms are present that can be potentially corrected by testosterone administration. Until recently, intramuscular injections of esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. The introduction of testosterone patches has not challenged this approach, since many users of patches suffer from moderate to severe skin reactions. Some oral testosterone formulations have proven to be problematic, as absorption can be variable, bioavailability is frequently poor, due to the first-pass effect of the liver, and frequent administration is often required. Oral testosterone

  16. 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

  17. 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

  18. 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

  19. Further clinical delineation of the Börjeson-Forssman-Lehmann syndrome in patients with PHF6 mutations.

    PubMed

    Carter, Melissa T; Picketts, David J; Hunter, Alasdair G; Graham, Gail E

    2009-02-01

    Börjeson-Forssman-Lehmann syndrome is an X-linked condition caused by PHF6 mutations. The classical description of males with this disorder includes severe intellectual disability with epilepsy, microcephaly, short stature, obesity, hypogonadism, and gynecomastia. We present three males with PHF6 mutations whose features included deep-set eyes, large ears, coarse face, tapering fingers, and truncal obesity. Unlike the original description of the syndrome; however, the males described herein had varying degrees of intellectual disability and hypogonadism, were of normal to tall stature, had normal to large head sizes, and did not have seizures. This departure from the usual clinical description of Börjeson-Forssman-Lehmann syndrome is consistent with recent reports of males with mutations in PHF6. In addition, we describe the phenotype and X-inactivation pattern in two females heterozygous for PHF6 mutations, both of whom have mild features of the syndrome.

  20. 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

  1. 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

  2. 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

  3. Mutations affecting gonadotropin secretion and action.

    PubMed

    Huhtaniemi, Ilpo

    2003-01-01

    A number of mutations are known to disturb the development and function of the hypothalamic-pituitary-gonadal axis. They affect hypothalamic-pituitary-gonadal function at multiple levels, from the migration of gonadotropin releasing hormone neurons to the hypothalamus right through to gonadotropin action in the ovary and testis. Most of the mutations are inactivating, causing various forms of hypogonadism. Exceptions are the activating mutations of the luteinizing hormone receptor, causing male-limited gonadotropin-independent precocious puberty. The human mutations and genetically modified animal models have clarified the molecular pathogenesis of hypogonadism and such disorders can now be diagnosed using molecular biological techniques, enabling selection of specific treatments and appropriate counselling of patients and their families.

  4. 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

  5. The effect of testosterone on cardiovascular disease: a critical review of the literature.

    PubMed

    Su, Jeannie J; Park, Samuel K; Hsieh, T Mike

    2014-11-01

    Cardiovascular disease is the leading cause of death in the United States. Testosterone is the principal male sex hormone and plays an important role in men's health and well-being. Historically, testosterone was believed to adversely affect cardiovascular function. However, contemporary literature has refuted this traditional thinking; testosterone has been suggested to have a protective effect on cardiovascular function through its effects on the vascular system. Data from modern research indicate that hypogonadism is closely related to the development of various cardiovascular risk factors, including hyperlipidemia and insulin resistance. Several studies have demonstrated beneficial effects of testosterone supplementation therapy on reversing symptoms of hypogonadism and improving cardiovascular disease risk profiles. In this review, we perform a critical analysis on the association between testosterone and cardiovascular disease.

  6. A young male adolescent with feminine appearance: diagnosis of 46, XX syndrome neglected for 4 years with gynaecomastia presentation.

    PubMed

    Fu, C-P; Sheu, W H-H; Tseng, J-J; Lin, S-Y

    2014-04-01

    Gynaecomastia is common in infancy and adolescent boys, but other inciting causes should be kept in mind and necessitate further evaluation should be conducted to determine any underlying conditions. A 22-year-old unmarried male adolescent visited our endocrinology clinic for feminine appearance despite operations for bilateral gynaecomastia 4 years ago. Physical examination showed inverted triangular distribution of pubic hair, sparse beard, small-sized testes, flaccid short penis and surgical scar of the chest wall. Serum hormones study revealed primary hypergonadotropic hypogonadism, and cytogenetic study disclosed female complement (46, XX). The authors recommend that sexual chromosome abnormality should be considered in patients with hypogonadism to avert androgen deficiency-related complications early and that long-term team care should be provided to improve the patient's health-related quality of life.

  7. Metabolic bone diseases in kidney transplant recipients.

    PubMed

    Zhang, Rubin; Chouhan, Kanwaljit K

    2012-10-01

    Metabolic bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Each patient may have multiple risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism (HPT), poor allograft function, metabolic acidosis, hypophosphatemia, vitamin D deficiency, aging, immobility and chronic disease. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D, bisphosphonates, calcitonin as well as treatment of hypogonadism and HPT. Novel approach to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fracture rate in kidney transplant recipients. PMID:24175250

  8. Kallmann syndrome in a female adolescent: a new mutation in the FGFR1 gene

    PubMed Central

    Novo, Ana; Guerra, Isabel Couto; Rocha, Felisbela; Gama-de-Sousa, Susana; Borges, Teresa; Cerqueira, Rita; Tavares, Purificação; Fonseca, Paula

    2012-01-01

    The Kallmann syndrome is characterised by the association of hypogonadotropic hypogonadism and hypo/anosmia. It represents a phenotypically and genotypically heterogeneous clinical entity, with six genes identified so far in the literature—KAL1, FGFR1, PROKR2, PROK2, CHD7 and FGF8. Mutations in the FGFR1 gene can be found in approximately 10% of the patients. The authors present the case of a female adolescent with hypogonadotropic hypogonadism and impaired olfactory acuity in the presence of hypoplasia of the nasal sulcus and agenesis of the olfactory bulbs. The molecular analysis of the fibroblast growth factor receptor 1 identified a heterozygous mutation c.1377_78insA (p.V460SfsX3) in exon 10 of FGFR1 gene. This mutation has not yet been reported in the literature. A theoretical review of clinical features and therapeutic approach of this syndrome is also presented. PMID:22751423

  9. 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

  10. 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

  11. Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

    PubMed Central

    Amore, Mario; Innamorati, Marco; Costi, Sara; Sher, Leo; Girardi, Paolo; Pompili, Maurizio

    2012-01-01

    The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths). PMID:22719760

  12. 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

  13. 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

  14. [Micropenis in children: etiology, diagnosis and therapy].

    PubMed

    Massa, G G; Langenhorst, V; Oostdijk, W; Wit, J M

    1997-03-15

    The term 'micropenis' is applied if the measured penile length is more than 2.5 standard deviations below the mean for the age; in neonates born at term this means a penile length of less than 2 cm. Micropenis is the consequence of a defect which develops after the 14th week of pregnancy. The cause may be hormonal (hypothalamo-hypophysial (hypogonadotropic hypogonadism), testicular (hypergonadotropic hypogonadism) or end organ resistance), but also iatrogenic (medication during the pregnancy). In addition, micropenis occurs as a part of a number of syndromes. The diagnostic investigation comprises history-taking, physical examination, specific hormonal testing and, if considered necessary, chromosomal and imaging examinations. In the treatment of micropenis, a trial treatment with testosterone plays an important part.

  15. Micropenis. I. Criteria, etiologies and classification.

    PubMed

    Lee, P A; Mazur, T; Danish, R; Amrhein, J; Blizzard, R M; Money, J; Migeon, C J

    1980-04-01

    A micropenis is an abnormally small penis with a normal configuration. This finding constitues a sign not a diagnosis. The etiologies may be classified as hypogonadotropic hypogonadism, primary hypogonadism, androgen insensitivity, or idiopathic; among 45 patients, the respective percentages in these categories were 31, 24, 2 and 7% with 36% as yet undiagnosed. Various clinical syndromes may include a micropenis and can be classified in one of the etiologic categories. This paper provides the criteria for determining the presence of a micropenis. A phallic length which is 2.5 or more standard deviations below the mean should be considered as abnormal; for an infant of 0 to 5 months of age, the lower limit is 1.9 cm. The technique of penile measurement, determination of etiology, guidelines for sex of rearing and psychologic, surgical and medical management are discussed.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Testosterone and Sexual Function.

    PubMed

    Gannon, John R; Walsh, Thomas J

    2016-05-01

    Testosterone and sexual function are related. Current evidence suggests that testosterone replacement therapy (TRT) may improve sexual dysfunction. Sexual dysfunction in men who are hypogonadal, mixed, or eugonadal have all been examined through numerous studies. The most recent large analysis showed an overall improvement in sexual function outcomes in men treated with TRT. This improvement is difficult to measure and seems to differ based on the baseline hormonal status of the patient at the beginning of treatment. PMID:27132579

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

    PubMed

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

    2015-12-01

    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 offered

  2. The Relationship between Testosterone Deficiency and Men's Health.

    PubMed

    Tsujimura, Akira

    2013-08-01

    Testosterone is important in the physiology of various organs and tissues. The serum testosterone concentration gradually declines as one of the processes of aging. Thus, the concept of late-onset hypogonadism has gained increasing attention in the last few years. Reported symptoms of late-onset hypogonadism are easily recognized and include diminished sexual desire and erectile quality, particularly in nocturnal erections, changes in mood with concomitant decreases in intellectual activity and spatial orientation, fatigue, depression and anger, a decrease in lean body mass with associated decreases in muscle volume and strength, a decrease in body hair and skin alterations, and decreased bone mineral density resulting in osteoporosis. Among these various symptoms, sexual dysfunction has been the most common and necessary to treat in the field of urology. It is well known that a low serum testosterone level is associated with erectile dysfunction and hypoactive sexual libido and that testosterone replacement treatment can improve these symptoms in patients with hypogonadism. Recently, in addition to sexual dysfunction, a close relationship between metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, and late-onset hypogonadism has been highlighted by several epidemiologic studies. Several randomized control trials have shown that testosterone replacement treatment significantly decreases insulin resistance in addition to its advantage for obesity. Furthermore, metabolic syndrome is one of the major risk factors for cardiovascular disease, and a low serum testosterone level is closely related to the development of atherosclerosis. Presently, it is speculated that a low serum testosterone level may increase the risk for cardiovascular disease. Thus, testosterone is a key molecule in men's health, especially that of elderly men. PMID:24044107

  3. Biology of kisspeptins.

    PubMed

    Hameed, Saira; Dhillo, Waljit S

    2010-01-01

    In recent years, a substantial body of evidence has accumulated suggesting that the hypothalamic peptide hormone kisspeptin and its cognate receptor, G-protein-coupled receptor 54, play a fundamental role both as gatekeepers for the initiation of puberty and in the regulation of the hypothalamic-pituitary-gonadal axis. This review discusses the physiology of the kisspeptin signalling system and examines how findings from animal and human studies have contributed to our understanding of the pathophysiology of idiopathic hypogonadotropic hypogonadism.

  4. 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

  5. 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.

  6. Testosterone Replacement and Bone Mineral Density in Male Pituitary Tumor Patients

    PubMed Central

    Lee, Min Jeong; Ryu, Hyoung Kyu; An, So-Yeon; Jeon, Ja Young; Lee, Ji In

    2014-01-01

    Background Hypopituitarism is associated with osteoporosis and osteopenia especially when hypogonadotropic hypogonadism is present. Despite hypopituitarism being an important cause of secondary osteoporosis, osteoporosis in patients receiving surgery for pituitary tumors in Korea has not been studied. In this study, we evaluated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) in postoperative hypogonadal patients with pituitary tumors. Methods To examine the effect of TRT on BMD, we performed a retrospective observational study in 21 postoperative male patients who underwent pituitary tumor surgery between 2003 and 2012 at the Ajou University Hospital. Testosterone was replaced in postoperative hypogonadal patients by regular intramuscular injection, daily oral medication, or application of transdermal gel. BMD (g/cm2) measurements of central skeletal sites (lumbar spine, femoral neck, and total femur) were obtained using dual-energy X-ray absorptiometry (GE Lunar). For lumbar spine BMD, L1 to L4 values were chosen for analysis. Femur neck and total femur were also analyzed. Results During the follow-up period (mean, 56 months; range, 12 to 99 months) serum testosterone levels increased with the administration of TRT (P=0.007). There was significant improvement (4.56%±9.81%) in the lumbar spine BMD compared to baseline BMD. There were no significant changes in the femur neck BMD or total femur BMD. We did not find any statistically significant relationships between changes in testosterone levels and BMD using Spearman correlation analysis. Conclusion Our results indicated that TRT used in the postoperative period for hypogonadal pituitary tumor surgery patients may have beneficial effects on the BMD of the spine. PMID:24741454

  7. Risks of testosterone replacement therapy in men

    PubMed Central

    Osterberg, E. Charles; Bernie, Aaron M.; Ramasamy, Ranjith

    2014-01-01

    Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction. PMID:24497673

  8. [Klinefelter syndrome in a boy with symptoms of precocious puberty].

    PubMed

    Bieniasz, Jolanta; Wikiera, Beata; Głąb, Ewa; Noczyńska, Anna

    2013-01-01

    Klinefelter syndrome is one of the most frequent sex chromosomal aberration. It is usually not recognized before puberty and many patients remain never diagnosed. Delayed puberty and hypergonadotropic hypogonadism are typical in this syndrome. Early diagnosis and therapy with androgens is important for patients. We present case of 8-year old boy with Klinefelter syndrome who was admitted to our department because of precocious puberty.

  9. 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

  10. 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.

  11. Relationship between sex hormones and cognitive performance in men with substance use*

    PubMed Central

    Zilbermint, Mihail F.; Wisniewski, Amy B.; Xu, Xiaoqiang; Selnes, Ola A.; Dobs, Adrian S.

    2012-01-01

    BACKGROUND Hypogonadism is common with opiate-like drug use and may contribute to cognitive abnormalities. With the increasing epidemic of HIV and substance use (SU) worldwide, it is important to understand the impact of these conditions on cognition, which may affect quality of life and possibly decrease adherence to treatment. We hypothesized that men with SU, by virtue of hypogonadism secondary to HIV and/or SU, may demonstrate impaired cognition. METHODS We recruited men aged 18-50 from a population of low income, innercity individuals. Details of HIV and SU status, serum blood levels of total testosterone (TT), free testosterone (FT) and estradiol (E2) were assessed. All subjects were administered ten neuropsychological tests. RESULTS Our sample consisted of 68 men (mean age: 43.2 years (SD 5.8), African Americans: 86.6%). The recruited population was primarily from low socioeconomic status and unemployed. The mean level of TT was 553.9 ng/dL (SD 262.0), the mean level of FT was 69.5 pg/mL (SD 34.8), mean E2 was 3.2 pg/mL (SD 4.4). We found that 30.9% were hypogonadal and it was associated with higher SU. RESULTS We observed some relationships between sex hormones and cognitive domains, however, after adjustment for age, drug use category, education, depression, HIV, there was no statistically significant correlation between cognitive performance and sex hormone levels. CONCLUSIONS In this cross-sectional study of men with a high prevalence of SU and hypogonadism, endogenous levels of TT, FT or E2 were not related to cognitive performance. Other factors need to be identified which may contribute to poor cognitive function in the setting of SU. PMID:23021515

  12. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential.

    PubMed

    Cadilla, Rodolfo; Turnbull, Philip

    2006-01-01

    Modulation of the androgen receptor has the potential to be an effective treatment for hypogonadism, andropause, and associated conditions such as sarcopenia, osteoporosis, benign prostatic hyperplasia, and sexual dysfunction. Side effects associated with classical anabolic steroid treatments have driven the quest for drugs that demonstrate improved therapeutic profiles. Novel, non-steroidal compounds that show tissue selective activity and improved pharmacokinetic properties have been developed. This review provides an overview of current advances in the development of selective androgen receptor modulators (SARMs).

  13. Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones.

    PubMed

    van Oeveren, Arjan; Motamedi, Mehrnoush; Martinborough, Esther; Zhao, Shuo; Shen, Yixing; West, Sarah; Chang, William; Kallel, Adam; Marschke, Keith B; López, Francisco J; Negro-Vilar, Andrés; Zhi, Lin

    2007-03-15

    A series of selective androgen receptor modulators (SARMs) with a wide spectrum of receptor modulating activities was developed based on optimization of the 4-substituted 6-bisalkylamino-2-quinolinones (3). Significance of the trifluoromethyl group on the side chains and its interactions with amino acid residues within the androgen receptor (AR) ligand binding domain are discussed. A representative analog (9) was tested orally in a rodent model of hypogonadism and demonstrated desirable tissue selectivity.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Does bone mineral density and knowledge influence health-related behaviors of elderly men at risk for osteoporosis?

    PubMed

    Patel, Avni; Coates, Penelope S; Nelson, Joel B; Trump, Donald L; Resnick, Neil M; Greenspan, Susan L

    2003-01-01

    To determine if bone mineral density (BMD) substantially influences health-related behaviors in men at risk for osteoporosis, we surveyed 102 men who were participating in a study of prostate cancer and bone loss. Subjects included 68 men with prostate cancer, 44 of whom were hypogonadal on androgen deprivation therapy, and 34 healthy age-matched controls without prostate cancer. At least 6 mo after an initial evaluation, assessment of BMD, and osteoporosis information session, men were administered a questionnaire regarding their healthrelated behaviors. We found that men with osteopenia were 4 times as likely (13%) and men with osteoporosis were more than 10 times as likely (41%) to start taking bisphosphonates compared to men with a normal bone mass (3%, p < 0.0001). Men with low bone mass were more likely to begin taking calcium (p < 0.05) and vitamin D supplements (p < 0.05). Hypogonadal men were 10 times as likely to begin using bisphosphonates (34%) compared to the control group (3%, p < 0.0001) and twice as likely to begin using calcium supplements (57% vs 24%, p < 0.05). Caffeine consumption, alcohol consumption, dietary calcium intake, exercise, and smoking habits were not different in men with osteoporosis or those who were hypogonadal compared to controls. We conclude that men with low bone mass and hypogonadism were more likely to start using bisphosphonates, calcium supplements, and vitamin D supplements after having a bone density test. However, they were not more likely to make significant health-related lifestyle changes after obtaining the results of their bone mass.

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

    PubMed Central

    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

    2015-01-01

    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

  20. Hypersensitivity of Primordial Germ Cells to Compromised Replication-Associated DNA Repair Involves ATM-p53-p21 Signaling

    PubMed Central

    Zeng, Ruizhu; Southard, Teresa L.; Shima, Naoko; Schimenti, John C.

    2014-01-01

    Genome maintenance in germ cells is critical for fertility and the stable propagation of species. While mechanisms of meiotic DNA repair and chromosome behavior are well-characterized, the same is not true for primordial germ cells (PGCs), which arise and propagate during very early stages of mammalian development. Fanconi anemia (FA), a genomic instability syndrome that includes hypogonadism and testicular failure phenotypes, is caused by mutations in genes encoding a complex of proteins involved in repair of DNA lesions associated with DNA replication. The signaling mechanisms underlying hypogonadism and testicular failure in FA patients or mouse models are unknown. We conducted genetic studies to show that hypogonadism of Fancm mutant mice is a result of reduced proliferation, but not apoptosis, of PGCs, resulting in reduced germ cells in neonates of both sexes. Progressive loss of germ cells in adult males also occurs, overlaid with an elevated level of meiotic DNA damage. Genetic studies indicated that ATM-p53-p21 signaling is partially responsible for the germ cell deficiency. PMID:25010009

  1. Testicular dysfunction in human immunodeficiency virus-infected men.

    PubMed

    Poretsky, L; Can, S; Zumoff, B

    1995-07-01

    This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

  2. Testicular function after renal transplantation.

    PubMed

    Handelsman, D J; Ralec, V L; Tiller, D J; Horvath, J S; Turtle, J R

    1981-05-01

    Gonadal function was assessed in seventeen adult male renal transplant recipients, with well established good homograft function, for a mean of 4.9 years. Patients were assessed clinically and by measurement of basal concentrations of FSH, LH, prolactin, testosterone and oestradiol, FSH and LH responses to bolus injections of LHRH and semen analysis. Retrospectively all had symptoms consistent with marked hypogonadism prior to transplantation but in nine out of sixteen this was reversed with transplantation. Residual hypogonadism was evident in seven of sixteen patients and correlated with duration of haemodialysis longer than 1 year (P less than 0.01). Even among patients with clinically normal gonadal function, defects in the hypothalamic--pituitary--testicular axis remained. Elevated basal serum FSH, excessive FSH responses to LHRH and lowered basal serum testosterone were found. In the group with residual hypogonadism more marked changes, including elevated basal LH and excessive LH responses to LHRH, were also found. Fertility was recorded in two men on three occasions since transplantation. Sperm counts were normal in five and abnormal in four patients. Testicular volume and sperm density were inversely correlated with basal and stimulated FSH and LH levels.

  3. Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

    PubMed

    De Rosa, Michele; Zarrilli, Stefano; Di Sarno, Antonella; Milano, Nicola; Gaccione, Maria; Boggia, Bartolomeo; Lombardi, Gaetano; Colao, Annamaria

    2003-01-01

    Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

  4. Genetic insights into human isolated gonadotropin deficiency.

    PubMed

    Trarbach, Ericka Barbosa; Silveira, Leticia Gontijo; Latronico, Ana Claudia

    2007-01-01

    The identification of naturally occurring genetic mutations has provided unique insight into the current knowledge of the human hypothalamic-pituitary-gonadal axis. In the past decade, several monogenic causes have been reported in patients with isolated gonadotropin deficiency. Kallmann Syndrome is a clinically and genetically heterogeneous disorder, characterized by isolated hypogonadotropic hypogonadism and anosmia or hyposmia. To date, loss-of-function mutations in the genes encoding anosmin-1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the X-linked and autosomal dominant forms of this syndrome, respectively. More recently, several heterozygous, homozygous or compound heterozygous mutations in the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2) were described in Kallmann syndrome. In addition, complex genetic transmission (digenic inheritance) was recently demonstrated in this condition. Regarding isolated hypogonadotropic hypogonadism without olfactory abnormalities, loss-of-function mutations in the Gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) or the G-protein coupled receptor 54 (GPR54) genes, both encoding transmembrane receptors, have been described, as well as FGFR1 mutations. Finally, mutations of the beta sub-units of LH and FSH have been described in patients with selective gonadotropin deficiency. We review the role of these distinct genetic factors in human isolated hypogonadotropic hypogonadism.

  5. Inducing puberty.

    PubMed

    Delemarre, Eveline M; Felius, Bram; Delemarre-van de Waal, Henriette A

    2008-12-01

    Puberty is the result of increasing pulsatile secretion of the hypothalamic gonadotropin releasing hormone (GnRH), which stimulates the release of gonadotropins and in turn gonadal activity. In general in females, development of secondary sex characteristics due to the activity of the gonadal axis, i.e., the growth of breasts, is the result of exposure to estrogens, while in boys testicular growth is dependent on gonadotropins and virilization on androgens. Hypogonadotropic hypogonadism is a rare disease. More common is the clinical picture of delayed puberty, often associated with a delay of growth and more often familial occurring. Especially, boys are referred because of the delay of growth and puberty. A short course (3-6 months) of androgens may help these boys to overcome the psychosocial repercussions, and during this period an increase in the velocity of height growth and some virilization will occur. Hypogonadotropic hypogonadism may present in a congenital form caused by developmental disorders, some of which are related to a genetic disorder, or secondary to hypothalamic-pituitary dysfunction due to, among others, a cerebral tumor. In hypogonadotropic hypogonadism puberty can be initiated by the use of pulsatile GnRH, gonadotropins, and sex steroids. Sex steroids will induce development of the secondary sex characteristics alone, while combined administration of gonadotropins and GnRH may induce gonadal development including fertility.

  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. 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

  8. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    PubMed Central

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  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. 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.

  11. 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

  12. The vulnerable man: impact of testosterone deficiency on the uraemic phenotype.

    PubMed

    Carrero, Juan Jesús; Stenvinkel, Peter

    2012-11-01

    Testosterone deficiency or hypogonadism is a common finding in men undergoing dialysis, to a great extent a consequence of the failing kidney per se. Testosterone restoration in hypogonadism is common practice among endocrinologists. However, there is currently little awareness of this condition among both uremic patients and nephrologists, and in many cases, testosterone deficiency remains unscreened and untreated. This review article summarizes our current understanding of the role of testosterone deficiency at the crossroad of cardiometabolic complications of patients with chronic kidney disease. Pathways discussed include, among others, the plausible role of testosterone deficiency in the development of anaemia and ESA hyporesponsiveness, muscle catabolism, endothelial dysfunction, cognitive dysfunction, decreased libido, cardiovascular disease and mortality. As there are limited sources to guide decision-making, we also review existing testosterone replacement therapy studies in the context of CKD as well as considerations for side and adverse effects. This review makes a case for consideration of screening and better management of hypogonadism in men undergoing dialysis.

  13. A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25-q26.

    PubMed

    Cilliers, Deirdre D; Parveen, Rahat; Clayton, Peter; Cairns, Stephen A; Clarke, Sheila; Shalet, Stephen M; Black, Graeme C M; Newman, William G; Clayton-Smith, Jill

    2007-01-01

    X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.

  14. Endocrine Aspects of 4H Leukodystrophy: A Case Report and Review of the Literature

    PubMed Central

    Billington, Emma; Bernard, Geneviève; Gibson, William; Corenblum, Bernard

    2015-01-01

    Introduction. 4H leukodystrophy is an autosomal recessive RNA polymerase III-related leukodystrophy, characterized by hypomyelination, with or without hypodontia (or other dental abnormalities) and hypogonadotropic hypogonadism. Case Presentation. We describe a 28-year-old female who presented with primary amenorrhea at the age of 19. She had a history of very mild neurological and dental abnormalities. She was found to have hypogonadotropic hypogonadism, and magnetic resonance imaging of the brain showed hypomyelination. The diagnosis of 4H leukodystrophy was made. She was subsequently found to have mutations in the POLR3B gene, which encodes the second largest subunit of RNA polymerase III. She wished to become pregnant and failed to respond to pulsatile GnRH but achieved normal follicular growth and ovulation with subcutaneous gonadotropin therapy. Discussion. Patients with 4H leukodystrophy may initially present with hypogonadotropic hypogonadism, particularly if neurological and dental manifestations are subtle. Making the diagnosis has important implications for prognosis and management. Progressive neurologic deterioration is expected, and progressive endocrine dysfunction may occur. Patients with 4H leukodystrophy should be counseled about disease progression and about this disease's autosomal recessive inheritance pattern. In those who wish to conceive, ovulation induction may be achieved with subcutaneous gonadotropin therapy, but pulsatile GnRH does not appear to be effective. PMID:26113998

  15. Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis.

    PubMed

    Aghazadeh, Yasaman; Zirkin, Barry R; Papadopoulos, Vassilios

    2015-01-01

    Reduced serum testosterone (T), or hypogonadism, is estimated to affect about 5 million American men, including both aging and young men. Low serum T has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass and bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Administering exogenous T, known as T-replacement therapy (TRT), reverses many of the symptoms of low T levels. However, this treatment can result in luteinizing hormone suppression which, in turn, can lead to reduced sperm numbers and infertility, making TRT inappropriate for men who wish to father children. Additionally, TRT may result in supraphysiologic T levels, skin irritation, and T transfer to others upon contact; and there may be increased risk of prostate cancer and cardiovascular disease, particularly in aging men. Therefore, the development of alternate therapies for treating hypogonadism would be highly desirable. To do so requires greater understanding of the series of steps leading to T formation and how they are regulated, and the identification of key steps that are amenable to pharmacological modulation so as to induce T production. We review herein our current understanding of mechanisms underlying the pharmacological induction of T formation in hypogonadal testis.

  16. 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

  17. A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

    PubMed Central

    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

  18. 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

  19. Acute stress masking the biochemical phenotype of partial androgen insensitivity syndrome in a patient with a novel mutation in the androgen receptor.

    PubMed

    Pitteloud, Nelly; Villegas, Jacob; Dwyer, Andrew A; Crowley, William F; McPhaul, Michael J; Hayes, Frances J

    2004-03-01

    Hypogonadism has traditionally been classified as either hypogonadotropic or hypergonadotropic based on serum gonadotropin levels. However, when hypothalamic suppression of GnRH secretion occurs, it can mask an underlying hypergonadotropic state. In this report we document the unusual case of a 61-yr-old man with androgen insensitivity and coincidental functional hypogonadotropic hypogonadism (HH). Although functional HH is not a well-recognized entity in the male, major stress has been reported to cause transient suppression of the hypothalamic-pituitary-gonadal axis in men. The patient in question was noted to have undervirilization, minimal pubertal development, hypogonadal testosterone, and low gonadotropin levels consistent with congenital HH during a hospital admission for myocardial infarction. However, the patient had also had surgery for hypospadias, a clinical feature not typically part of the phenotypic spectrum of congenital HH. We therefore hypothesized that the combination of acute stress and chronic glucocorticoid administration for temporal arteritis induced transient HH in a patient with a disorder of sexual differentiation in whom gonadotropin levels would have otherwise been elevated. Using clinical, molecular, and genetic studies, the patient was found to have partial androgen insensitivity syndrome (PAIS) caused by a novel mutation (Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient confirmed the characteristic gonadotropin and sex steroid abnormalities of PAIS. We describe for the first time a patient with PAIS presenting with a reversible hypogonadotropic biochemical profile triggered by an acute illness and corticosteroid therapy. This case highlights the necessity for caution when interpreting gonadotropin levels during acute stress.

  20. Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

    PubMed

    Berga, Sarah L; Loucks, Tammy L

    2006-12-01

    Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

  1. X-linked adrenal hypoplasia congenita: clinical and follow-up findings of two kindreds, one with a novel NR0B1 mutation.

    PubMed

    Pereira, Bernardo Dias; Pereira, Iris; Portugal, Jorge Ralha; Gonçalves, João; Raimundo, Luísa

    2015-04-01

    X-linked adrenal hypoplasia congenita typically manifests as primary adrenal insufficiency in the newborn age and hypogonadotropic hypogonadism in males, being caused by mutations in NR0B1 gene. We present the clinical and follow-up findings of two kindreds with NR0B1 mutations. The proband of kindred A had a diagnosis of primary adrenal insufficiency when he was a newborn. Family history was relevant for a maternal uncle death at the newborn age. Beyond 2 year-old steroid measurements rendered undetectable and delayed bone age was noticed. Molecular analysis of NR0B1 gene revealed a previously unreported mutation (c.1084A>T), leading to a premature stop codon, p.Lys362*, in exon 1. His mother and sister were asymptomatic carriers. At 14 year-old he had 3 mL of testicular volume and biochemical surveys (LH < 0.1 UI/L, total testosterone < 10 ng/dL) concordant with hypogonadotrophic hypogonadism. Kindred B had two males diagnosed with adrenal insufficiency at the newborn age. By 3 year-old both siblings had undetectable androgen levels and delayed bone age. NR0B1 molecular analysis identified a nonsense mutation in both cases, c.243C>G; p.Tyr81*, in exon 1. Their mother and sister were asymptomatic carriers. At 14 year-old (Tanner stage 1) hypothalamic-pituitary-gonadal axis evaluation in both males (LH < 0.1UI/L, total testosterone < 10 ng/dL) confirmed hypogonadotropic hypogonadism. In conclusion, biochemical profiles, bone age and an X-linked inheritance led to suspicion of NR0B1 mutations. Two nonsense mutations were detected in both kindreds, one previously unreported (c.1084A>T; p.Lys362*). Mutation identification allowed the timely institution of testosterone in patients at puberty and an appropriate genetic counselling for relatives.

  2. Treatment of anabolic-androgenic steroid dependence: Emerging evidence and its implications.

    PubMed

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

    2010-06-01

    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 pharmacological 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.

  3. New facets of androgen replacement therapy during childhood and adolescence.

    PubMed

    Rogol, Alan D

    2005-07-01

    The goals of androgen therapy for adolescents are to promote linear growth and secondary sexual characteristics, at the same time as permitting the normal accrual of muscle mass and bone mineral content. Secondary goals are mainly in the psychosocial sphere, in which pubertally delayed boys feel that they look too young, are not considered a 'peer' in their age group and have difficulty competing in athletic endeavours. These goals are irrespective of the causes of delayed pubertal development: constitutional delay of growth and puberty (CDGP), a transient but very common form of pubertal delay and, much less commonly, primary or secondary permanent hypogonadism. Not all boys with CDGP require testosterone therapy, but those that come to a referral practice are likely candidates, as the watchful waiting period has finished. Although a range of androgen preparations is available for adults (injectable, oral, implantable and cutaneous patches and gels), most are drug delivery devices that are appropriate for full adult androgen replacement. These doses are too large for the induction of puberty. Therefore, at present, the injectable form is the only one that is easily adaptable for the increasing amounts of androgen necessary for the various stages of pubertal development. All preparations deliver testosterone that is readily converted to dihydrotestosterone by 5-alpha reductase. The author's practice is to begin with injecting 50-75 mg of one of the long-acting esters (enanthate or cypionate) per month, and gradually escalate to 100-150 mg/month, before changing to twice monthly dosage. As most adolescents have delayed puberty, the therapy is needed for 6-18 months before the hypothalamic-pituitary-gonadal axis functions at the late adolescent/adult level in those with CDGP. Those with permanent hypogonadism will require lifelong therapy. Once adequate virilisation is induced, and virtually full adult height is reached, any of the therapies noted above can be used

  4. Predicting low testosterone in aging men: a systematic review

    PubMed Central

    Millar, Adam C.; Lau, Adrian N.C.; Tomlinson, George; Kraguljac, Alan; Simel, David L.; Detsky, Allan S.; Lipscombe, Lorraine L.

    2016-01-01

    Background: Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men. We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men. Methods: We searched the MEDLINE and Embase databases (January 1966 to July 2014) for studies that compared clinical features with a measurement of serum testosterone in men. Three of the authors independently reviewed articles for inclusion, assessed quality and extracted data. Results: Among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between 2% and 77%. Threshold testosterone levels used for reference standards also varied substantially. The summary likelihood ratio associated with decreased libido was 1.6 (95% confidence interval [CI] 1.3–1.9), and the likelihood ratio for absence of this finding was 0.72 (95% CI 0.58–0.85). The likelihood ratio associated with the presence of erectile dysfunction was 1.5 (95% CI 1.3–1.8) and with absence of erectile dysfunction was 0.83 (95% CI 0.76–0.91). Of the multiple-item instruments, the ANDROTEST showed both the most favourable positive likelihood ratio (range 1.9–2.2) and the most favourable negative likelihood ratio (range 0.37–0.49). Interpretation: We found weak correlation between signs, symptoms and testosterone levels, uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition. It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men. PMID:27325129

  5. Revisiting hyper- and hypo-androgenism by tandem mass spectrometry.

    PubMed

    Fanelli, Flaminia; Gambineri, Alessandra; Mezzullo, Marco; Vicennati, Valentina; Pelusi, Carla; Pasquali, Renato; Pagotto, Uberto

    2013-06-01

    Modern endocrinology is living a critical age of transition as far as laboratory testing and biochemical diagnosis are concerned. Novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for steroid measurement in biological fluids have abundantly demonstrated their analytical superiority over immunometric platforms that until now have dominated the world of steroid hormones determination in clinical laboratories. One of the most useful applications of LC-MS/MS is in the hypogonadism and hyperandrogenism field: LC-MS/MS has proved particularly suitable for the detection of low levels of testosterone typical of women and children, and in general more reliable in accurately determining hypogonadal male levels. This technique also offers increased informative power by allowing multi-analytical profiles that give a more comprehensive picture of the overall hormonal asset. Several LC-MS/MS methods for testosterone have been published in the last decade, some of them included other androgen or more comprehensive steroid profiles. LC-MS/MS offers the concrete possibility of achieving a definitive standardization of testosterone measurements and the generation of widely accepted reference intervals, that will set the basis for a consensus on the diagnostic value of biochemical testing. The present review is aimed at summarizing technological advancements in androgen measurements in serum and saliva. We also provide a picture of the state of advancement of standardization of testosterone assays, of the redefinition of androgen reference intervals by novel assays and of studies using LC-MS/MS for the characterization and diagnosis of female hyperandrogenism and male hypogonadism.

  6. 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

  7. 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

  8. 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

  9. The child with micropenis.

    PubMed

    Menon, P S; Khatwa, U A

    2000-06-01

    Micropenis refers to an extremely small penis with a stretched penile length of less than 2.5 SD below the mean for age or stage of sexual development. It should be differentiated from a buried or hidden penis and aphallia. It is important to use a standard technique of stretched penile measurement and nomograms for age to identify children with micropenis. All children above 1 year of age with a stretched penile length of less than 1.9 cm need evaluation. Based on etiology they can be classified as hypogonadotropic hypogonadism (hypothalamic or pituitary failure), hypergonadotropic hypogonadism (testicular failure), partial androgen insensitivity syndrome and idiopathic groups. The help of a pediatric endocrinologist, geneticist, pediatric surgeon and/or urologist is often necessary. Growth velocity is an important determinant of associated hypothalamic or pituitary pathology. GnRH and/or hCG stimulation tests are often helpful in evaluating the etiology. Similarly chromosomal studies are indicated in a few. Often the diagnosis is inferred by the presence of clinical features suggestive of a syndrome usually associated with hypogonadotropic hypogonadism. Irrespective of the underlying cause a short course of testosterone should be tried in patients with micropenis and an assessment of the penis to respond should be made. Transdermal DHT has also been reported to be effective in prepubertal children. Children with hypopituitarism and GH deficiency respond to appropriate hormonal therapy. Surgical correction is not indicated in the common endocrine types of micropenis. Many studies have shown that most testosterone treated children have satisfactory gain in length of penis and sexual function. Thus sexual reassignment is done very infrequently now.

  10. X-linked adrenal hypoplasia congenita: clinical and follow-up findings of two kindreds, one with a novel NR0B1 mutation.

    PubMed

    Pereira, Bernardo Dias; Pereira, Iris; Portugal, Jorge Ralha; Gonçalves, João; Raimundo, Luísa

    2015-04-01

    X-linked adrenal hypoplasia congenita typically manifests as primary adrenal insufficiency in the newborn age and hypogonadotropic hypogonadism in males, being caused by mutations in NR0B1 gene. We present the clinical and follow-up findings of two kindreds with NR0B1 mutations. The proband of kindred A had a diagnosis of primary adrenal insufficiency when he was a newborn. Family history was relevant for a maternal uncle death at the newborn age. Beyond 2 year-old steroid measurements rendered undetectable and delayed bone age was noticed. Molecular analysis of NR0B1 gene revealed a previously unreported mutation (c.1084A>T), leading to a premature stop codon, p.Lys362*, in exon 1. His mother and sister were asymptomatic carriers. At 14 year-old he had 3 mL of testicular volume and biochemical surveys (LH < 0.1 UI/L, total testosterone < 10 ng/dL) concordant with hypogonadotrophic hypogonadism. Kindred B had two males diagnosed with adrenal insufficiency at the newborn age. By 3 year-old both siblings had undetectable androgen levels and delayed bone age. NR0B1 molecular analysis identified a nonsense mutation in both cases, c.243C>G; p.Tyr81*, in exon 1. Their mother and sister were asymptomatic carriers. At 14 year-old (Tanner stage 1) hypothalamic-pituitary-gonadal axis evaluation in both males (LH < 0.1UI/L, total testosterone < 10 ng/dL) confirmed hypogonadotropic hypogonadism. In conclusion, biochemical profiles, bone age and an X-linked inheritance led to suspicion of NR0B1 mutations. Two nonsense mutations were detected in both kindreds, one previously unreported (c.1084A>T; p.Lys362*). Mutation identification allowed the timely institution of testosterone in patients at puberty and an appropriate genetic counselling for relatives. PMID:25993682

  11. Treatment of anabolic-androgenic steroid dependence: Emerging evidence and its implications.

    PubMed

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

    2010-06-01

    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 pharmacological 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

  12. Use of steroids for self-enhancement: an epidemiologic/societal perspective.

    PubMed

    Yesalis, C E

    2001-03-01

    Humans are basically competitive. For centuries, athletes have used various substances to enhance performance, increase strength, and prolong endurance. In the early 1940s, research indicating that testosterone improved a sense of well-being, appearance, and sexual performance led to the use of anabolic steroid hormones by a select few athletes. Today, even among high school students, the use of androgenic steroid hormones is prevalent, with 1% to 2% of adolescent girls and 4% to 6% of adolescent boys having used an anabolic steroid at least once. An estimated 1 million people in the United States are current of former users of anabolic-androgenic steroid hormones, with men having a higher prevalence of use than women. Androgenic steroid use has been associated with the use of other illicit drugs, cigarette smoking, and alcohol use. Nevertheless, anabolic-androgenic steroid hormones appear to have legitimate uses in certain patients. In HIV-infected, hypogonadal men, anabolic steroid hormones optimize muscle strength and muscle mass when combined with resistance exercise. Although a large number of people have used these drugs for many years, no studies of the long-term health effects have been done. However, when taken in supraphysiologic doses, these drugs are known to cause a wide range of acute adverse effects. When used in less then supraphysiologic doses in eugonadal or hypogonadal HIV-infected patients, these drugs reverse HIV-related hypogonadism, muscle wasting, and perhaps lipodystrophy. Provided that the oral preparations are not used and patients are closely monitored, anabolic-androgenic steroid hormones offer HIV-infected patients a better quality of life and an improved sense of well-being.

  13. 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.

  14. 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

  15. 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. PMID:27625843

  16. Kisspeptin: a critical regulator of puberty and reproductive function.

    PubMed

    Sam, Amir H; Dhillo, Waljit S

    2010-08-01

    Kisspeptin has emerged as a critical player in the initiation of puberty and reproductive function. In humans, inactivating mutations of the kisspeptin receptor result in hypogonadotrophic hypogonadism and kisspeptin receptor activating mutations cause precocious puberty. Kisspeptin potently stimulates the release of gonadotrophins predominantly through the release of gonadotrophin-releasing hormone (GnRH). Here we review the data from animal and human studies exploring the role of kisspeptin in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin signalling presents a novel target for therapeutic manipulation of the HPG axis.

  17. Mutations along the hypothalamic-pituitary-gonadal axis affecting male reproduction.

    PubMed

    Huhtaniemi, Ilpo; Alevizaki, Maria

    2007-12-01

    Disorders in male reproductive function are caused by mutations of key genes at all levels of the hypothalamic-pituitary- testicular axis. They may affect the ontogeny and function of the hypothalamic centres governing gonadotrophin synthesis and secretion, the development of the anterior pituitary gland, the production of gonadotrophins and the function of their receptor genes, and finally the genes responsible for testicular hormone production and gametogenesis. This review focuses on mutations that affect the synthesis and secretion of hypothalamic gonadotrophin-releasing hormone, pituitary follicle-stimulating hormone and luteinising hormone, as well as their testicular receptors, thus covering a selected group of genetic causes of hypo- and hypergonadotrophic male hypogonadism.

  18. 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.

  19. A reappraisal of the CHARGE association.

    PubMed Central

    Oley, C A; Baraitser, M; Grant, D B

    1988-01-01

    We describe 14 boys and six girls, including monozygotic twins, with the CHARGE association. All of the children had at least four of the seven major features included in the mnemonic CHARGE and all had ear anomalies or deafness or both and either coloboma or choanal atresia or both. All the boys had evidence of hypogonadism. A characteristic facial appearance (unusually shaped ears, unilateral facial palsy, square face, malar flattening, pinched nostrils) was observed in many of our cases. The aetiology remains unknown. All our cases are sporadic. Images PMID:3351900

  20. [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

  1. 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

  2. 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.

  3. [Mineral and bone disorders in renal transplantation].

    PubMed

    Bacchetta, Justine; Lafage-Proust, Marie-Hélène; Chapurlat, Roland

    2013-12-01

    The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. PMID:24176653

  4. Endocrine complications during and after adolescence in a patient with cystinosis

    PubMed Central

    Ahn, Moon Bae; Kim, Sung Eun; Cho, Won Kyoung; Suh, Byung Kyu

    2016-01-01

    Cystinosis is a rare disease characterized by abnormal lysosomal cystine accumulation of cystine due to impaired lysosomal transport. We previously reported the first case of cystinosis in Korea in a 12-year-old boy with short stature, general weakness, and photophobia. The diagnosis was confirmed based on ophthalmic findings and biochemical analyses (serum leukocyte cystine measurement). Major endocrine manifestations at diagnosis included hypothyroidism, growth retardation, and hypogonadism. Despite oral cysteamine administration and renal replacement therapy, multiple complications including both endocrine and nonendocrine disorders developed during and after adolescence. In this report, we review the presenting features and factors related to the long-term complications in a patient with cystinosis. PMID:27777912

  5. Etiology, biology, and epidemiology of ovarian cancer.

    PubMed

    Baker, T R; Piver, M S

    1994-01-01

    Epithelial ovarian cancer kills more women per year than all other gynecologic cancers combined. Pregnancy, oral contraceptive use, and tubal ligation decrease the risk of the disease, whereas risk is increased for women whose family history is consistent with one of the familial ovarian cancer syndromes. Several theories have been postulated concerning the etiology of ovarian cancer, including the incessant ovulation theory and that based on the model of hypergonadotropic hypogonadism. Chromosomal abnormalities and allele losses have been described in ovarian cancers. Involvement of oncogenes and tumor suppressor genes has been investigated as well. Genetic linkage studies are ongoing in families whose history is consistent with one of the familial ovarian cancer syndromes.

  6. Substituted 6-(1-pyrrolidine)quinolin-2(1H)-ones as novel selective androgen receptor modulators.

    PubMed

    Martinborough, Esther; Shen, Yixing; Oeveren, Arjan van; Long, Yun Oliver; Lau, Thomas L S; Marschke, Keith B; Chang, William Y; López, Francisco J; Vajda, Eric G; Rix, Peter J; Viveros, O Humberto; Negro-Vilar, Andrés; Zhi, Lin

    2007-10-18

    The androgen receptor is a ligand inducible transcription factor that is involved in a broad range of physiological functions. Here we describe the discovery of a new class of orally available selective androgen receptor modulators. The lead compound, 6-[(2R,5R)-2-methyl-5-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-4-trifluoromethylquinolin-2(1H)-one (6a), showed excellent anabolic activity in muscle with reduced effect on the prostate in a rat model of hypogonadism. The compound also improved bone strength in a rat model of post-menopausal osteoporosis.

  7. 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

  8. [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

  9. Bardet-Biedl syndrome presenting with steroid sensitive nephrotic syndrome

    PubMed Central

    Singh, K. K.; Kumar, R.; Prakash, J.; Krishna, A.

    2015-01-01

    Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by postaxial polydactyly, retinitis pigmentosa, central obesity, mental retardation, hypogonadism, and renal involvement. Renal involvement in various forms has been seen in BBS. Cases with nephrotic range proteinuria not responding to steroid have been described in this syndrome. Here we report a case of BBS who presented with nephrotic range proteinuria. The biopsy findings were suggestive of minimal change disease. The child responded well to steroid therapy and remains in remission. PMID:26628797

  10. 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

  11. Priapism in teenage boys following depot testosterone.

    PubMed

    Donaldson, James F; Davis, Nikki; Davies, Justin H; Rees, Roland W; Steinbrecher, Henrik A

    2012-01-01

    Priapism is rare in children and may result in erectile dysfunction and sexual aversion behaviours. Testosterone therapy is commonly regarded as safe in children and is widely used in constitutional delay of growth and puberty, hypogonadism, hypospadias and micropenis. We report two cases of priapism in teenage boys with constitutional delay of growth and puberty after a change in the formulation of depot testosterone. One case required surgical intervention and the other was preceded by stuttering priapism. These cases illustrate the importance of patient and/or parent counselling before testosterone administration and consideration of lower doses in at-risk patients.

  12. 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

  13. Are human male patients with DAX1/NR0B1 mutations infertile?

    PubMed

    Ravel, Célia; Hyon, Capucine; Siffroi, Jean-Pierre; Christin-Maitre, Sophie

    2014-05-01

    DAX-1 stands for Dosage sensitive sex-reversal, Adrenal hypoplasia congenital (AHC), on the X chromosome. DAX-1 mutations usually cause primary adrenal insufficiency or congenital adrenal hypoplasia in early childhood and hypogonadotropic hypogonadism (MIM # 300200). DAX-1 protein is necessary to maintain normal spermatogenesis. In humans, male fertility has been studied in few patients carrying DAX-1 mutations. Cases of azoospermia have been reported, as well as unsuccessful gonadotropin treatments. The clinician should be informed that TESE-ICSI technique carries a potential hope to father non-affected children, as shown in this review. PMID:24751136

  14. 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.

  15. 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

    2016-03-10

    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.

  16. Bone Loss in Obesity and Obstructive Sleep Apnea: A Review of Literature

    PubMed Central

    Chakhtoura, Marlene; Nasrallah, Mona; Chami, Hassan

    2015-01-01

    Introduction: Obstructive sleep apnea (OSA) is a common sleep-related respiratory disorder. It is associated with many endocrinopathies including hypogonadotropic hypogonadism, hypercortisolism, and glucose intolerance that may lead to bone loss with secondary osteoporosis. Methods: We report the case of a 41-year-old man who presented with bilateral 9th rib fractures and was found to have obstructive sleep apnea and osteoporosis. We also present a literature review on this topic. Results: OSA can lead to bone loss through various mechanisms. Some are shared with obesity, including hypogonadism, altered adrenergic tone, inflammation, oxidative stress, vitamin D deficiency and diabetes mellitus; others are specific to OSA, such as hypoxia and altered glucocorticoids regulation. Conclusion: There are no guidelines on screening for osteoporosis in OSA. Further research is needed to assess the incidence of bone loss and fractures in OSA. Citation: Chakhtoura M, Nasrallah M, Chami H. Bone loss in obesity and obstructive sleep apnea: a review of literature. J Clin Sleep Med 2015;11(5):575–580. PMID:25580607

  17. 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

  18. Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation.

    PubMed

    Annaloro, C; Usardi, P; Airaghi, L; Giunta, V; Forti, S; Orsatti, A; Baldini, M; Delle Volpe, A; Lambertenghi Deliliers, G

    2008-05-01

    Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.

  19. 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

  20. Testosterone in men with advanced liver disease: abnormalities and implications.

    PubMed

    Sinclair, Marie; Grossmann, Mathis; Gow, Paul J; Angus, Peter W

    2015-02-01

    Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials. PMID:25087838

  1. Hypothalamic-pituitary function (LH, FSH and prolactin) in males with chronic liver diseases.

    PubMed

    Geisthövel, W

    1979-07-01

    Because of the central importance of the liver for the metabolism of estrogens and androgens the chronically ill liver per se represents an essential disturbing factor within the hypothalamic-pituitary-gonadal axis caused by the altered hepatic metabolism of the steroid hormones as well as the abnormal synthesis of steroid-hormone-binding proteins with changed free fractions of sex hormones. The question has been differently answered whether a chronic hepatic disease can also be the reason for disturbance on hypothalamic-pituitary and/or testicular level. Recent plasma determination of LH/FSH before and after LHRH and clomiphene, of sex hormones before and after HCG as well as unbound sex hormones in males with chronic hepatic diseases lead to the following conclusion. 1. Chronic liver disease (without idopathic hemochromatosis). Even sever chronic hepatic diseases are not accompanied by primary hypopituitarism. With regard to the impaired Leydig cells stimulation by HCG and the abnormal seminal fluid and testicular histology one can suppose a primary gonadal hypogonadism. However, an additional hypothalamic disturbance has to be considered. 2. Idiopathic hemochromatosis. Presumably in hemochromatosis a primary insufficiency of pituitary and/or testes can take place related to the general metabolic disturbances of this illness. The classic hypothesis of an exclusively primary lesion with secondary hypogonadism does not appear to be correct.

  2. The role of mutations affecting gonadotrophin secretion and action in disorders of pubertal development.

    PubMed

    Huhtaniemi, Ilpo T

    2002-03-01

    A number of mutations that disturb the development and function of the hypothalamic-pituitary-gonadal (HPG) axis and cause disturbances in pubertal development are known today. These mutations have effects at all levels of the HPG axis, from the migration of gonadotrophin releasing hormone (GnRH) neurones from the nasal cavity to the hypothalamus, GnRH secretion, GnRH action, pituitary gonadotroph differentiation, gonadotrophin synthesis and secretion, right through to gonadotrophin action. Most of the mutations are inactivating, thus causing hypogonadism and arrest or delay of pubertal development. One exception is the activating mutations of the LH receptor, which causes the male-limited gonadotrophin-independent precocious puberty. The human mutations and animal models with disrupted function of orthologous genes have clarified the molecular pathogenesis of hypogonadism and disturbances of pubertal development. The correct diagnosis of these disorders using molecular biological techniques is now possible. This allows the selection of specific treatments and correct counselling of the patients and their families.

  3. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception.

    PubMed

    Oduwole, Olayiwola O; Vydra, Natalia; Wood, Nicholas E M; Samanta, Luna; Owen, Laura; Keevil, Brian; Donaldson, Mandy; Naresh, Kikkeri; Huhtaniemi, Ilpo T

    2014-06-01

    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.

  4. [Association between the serum level of testosterone and other comorbidities in obstructive sleep apnea].

    PubMed

    Bercea, Raluca; Bercea, Bogdan; Mihăescu, Traian

    2012-01-01

    Testosterone seems to play a role in the pathophysiology of OSAS but the mechanisms are not yet well defined. Research of this relationship has focused on two main assumptions: first case support the emergence of OSAS or augmentation of OSAS severity in men treated with testosterone for symptomatic hypogonadism; the second hypothesis suggest that serum testosterone deficiency is due to hypoxia and microarousals generated by OSAS with direct impact on hypothalamic-pituitary-gonadal axis. The correlation between sleep apnea and androgenic disorders should be considered in the light of the intervention of many other factors which can act as confounding factors: age, obesity and other associated pathologies (chronic lung disease, smoking status). Many studies conducted so far on this interrelation (sleep apnea, endocrine system) have ignored these factors. In most cases CPAP (continuous positive airway pressure) therapy revert low serum testosterone levels to normal levels. Depressive status and fatigue, as OSAS consequences associated with hypogonadism have been reported in the literature and may have clinically significant aspects due to summary effect, with notable improvement after CPAP therapy avoiding adverse effects of hormonal or antidepressant treatment. The clinical implications and major consequences of association between androgen dysfunction and sleep apnea syndrome require a correct management in the recognition and treatment of obstructive sleep apnea syndrome associated with comorbidities.

  5. The relationship between circulating kisspeptin and sexual hormones levels in healthy females.

    PubMed

    Katagiri, Fumihiko; Kotani, Masato; Hirai, Tsuyoshi; Kagawa, Jiro

    2015-03-13

    The kisspeptin (metastin) is an endogenous peptide, which regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin was detected in peripheral blood, although GnRH was not. Previously, we measured plasma kisspeptin levels in male healthy subjects and patients with hypogonadism using enzyme immunoassay (EIA) to elucidate a normal range in healthy males and clinical implications of kisspeptin in male hypogonadism. We suggested that the plasma kisspeptin levels were received feedback from testosterone. In this study, we focused female subjects and elucidated the relationship between menstrual cycle and plasma kisspeptin levels to understand kisspeptin-hypothalamic-pituitary-gonadal axis. We measured plasma kisspeptin levels in eight female volunteers. The plasma kisspeptin levels in female are significantly higher than those in male. There are no significant correlation between plasma kisspeptin levels and sexual hormones. We revealed that the kisspeptin might stimulate a start of menstruation as a trigger, and progress menstruation covered for weakened ovarian function. We suggest that kisspeptin may be closely related with menstrual cycle and that the measurement of plasma kisspeptin levels is useful for understanding of reproductive system.

  6. Gonadotropin-releasing hormone pulsatile administration restores luteinizing hormone pulsatility and normal testosterone levels in males with hyperprolactinemia.

    PubMed

    Bouchard, P; Lagoguey, M; Brailly, S; Schaison, G

    1985-02-01

    Hyperprolactinemia in men is frequently associated with hypogonadism. Normalization of serum PRL levels is generally associated with an increase in serum testosterone (T) to normal. To determine the mechanism of the inhibitory effect of hyperprolactinemia on the hypothalamic-pituitary-gonadal axis, we studied the effect of intermittent pulsatile GnRH administration on LH pulsatility and T levels in four men with prolactinomas. All patients had high PRL values (100-3000 ng/ml), low LH (mean +/- SEM, 2.2 +/- 0.1 mIU/ml), and low T values (2.3 +/- 0.3 ng/ml), with no other apparent abnormality of pituitary function. GnRH was administered iv using a pump delivering a bolus dose of 10 micrograms every 90 min for 12 days. No LH pulses were detected before treatment. Pulsatile GnRH administration resulted in a significant increase in basal LH levels (6.7 +/- 0.6 mIU/ml; P less than 0.001) and restored LH pulsatility. In addition, T levels increased significantly to normal values in all patients (7.8 +/- 0.4 ng/ml; P less than 0.001) and were normal or supranormal as long as the pump was in use, although PRL levels remained elevated. These data, therefore, suggest that hyperprolactinemia produces hypogonadism primarily by interfering with pulsatile GnRH release.

  7. The diagnosis and treatment of stress-induced anovulation.

    PubMed

    Berga, S L; Loucks, T L

    2005-02-01

    Behaviors that activate the hypothalamic-pituitary-adrenal (HPA) axis or suppress the hypothalamic-pituitary-thyroidal (HPT) axis can disrupt the hypothalamic-pituitary-gonadal (HPG) axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that serve as psychogenic stressors and present metabolic challenges. Complete recovery of gonadal function depends upon restoration of the HPA and HPT axes. Hormone replacement strategies have limited benefit because they do not promote recovery from these allostatic endocrine adjustments in the HPA and HPT axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only an alteration in the hypothalamic-pituitary-ovarian (HPO) axis. Further, use of sex hormones masks deficits that accrue from altered HPA and HPT function. Long-term deleterious consequences of stress-induced anovulation may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the HPA and HPT axes. Failure to reverse the hormonal milieu induced by stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes have the potential to permit resumption of ovarian function along with recovery of the HPT and HPA axes. Full endocrine recovery offers better individual, maternal, and child health.

  8. NELF knockout is associated with impaired pubertal development and subfertility.

    PubMed

    Quaynor, Samuel D; Ko, Eun Kyung; Chorich, Lynn P; Sullivan, Megan E; Demir, Durkadin; Waller, Jennifer L; Kim, Hyung-Goo; Cameron, Richard S; Layman, Lawrence C

    2015-05-15

    Puberty and reproduction require proper signaling of the hypothalamic-pituitary-gonadal axis controlled by gonadotropin-releasing hormone (GnRH) neurons, which arise in the olfactory placode region and migrate along olfactory axons to the hypothalamus. Factors adversely affecting GnRH neuron specification, migration, and function lead to delayed puberty and infertility. Nasal embryonic luteinizing hormone-releasing factor (NELF) is a predominantly nuclear protein. NELF mutations have been demonstrated in patients with hypogonadotropic hypogonadism, but biallelic mutations are rare and heterozygous NELF mutations typically co-exist with mutations in another gene. Our previous studies in immortalized GnRH neurons supported a role for NELF in GnRH neuron migration. To better understand the physiology of NELF, a homozygous Nelf knockout (KO) mouse model was generated. Our findings indicate that female Nelf KO mice have delayed vaginal opening but no delay in time to first estrus, decreased uterine weight, and reduced GnRH neuron number. In contrast, male mice were normal at puberty. Both sexes of mice had impaired fertility manifested as reduced mean litter size. These data support that NELF has important reproductive functions. The milder than expected phenotype of KO mice also recapitulates the human phenotype since heterozygous NELF mutations usually require an additional mutation in a second gene to result in hypogonadotropic hypogonadism.

  9. Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

    PubMed

    Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

    2005-07-01

    Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

  10. Age-related changes in male gonadal function. Implications for therapy.

    PubMed

    Maas, D; Jochen, A; Lalande, B

    1997-07-01

    In contrast with women, who experience a complete and abrupt cessation of ovarian function during the menopause, aging men largely maintain their testicular androgen production. Nevertheless, most cross-sectional studies indicate that there is a partial decrease in testosterone levels with aging, although this has not been confirmed by other studies. The disparity among studies stems from differences in study design, patient numbers, assay techniques and inclusion criteria. Proposed mechanisms for an age-associated decline in testosterone production include: (i) defects in the hypothalamic-pituitary-testicular axis; (ii) an increase in sex hormone binding globulin levels; (iii) environmental factors; (iv) medication use; and (v) chronic illness. The potential beneficial effects of testosterone replacement therapy in hypogonadal men include increased bone density, increased muscle strength, an improved feeling of well-being and an improved metabolic profile. These benefits need to be weighted against the potential risks of androgen therapy, such as erythrocytosis, sleep apnoea, and the stimulation of benign prostatic hypertrophy or an occult prostate malignancy. Consequently, androgen replacement should be used with caution in elderly men with hypogonadism until the results of well-controlled prospective studies are available.

  11. Clinical and molecular analysis of human reproductive disorders in Brazilian patients.

    PubMed

    Latronico, A C; Costa, E M F; Domenice, S; Correa, R V; Kohek, M B F; Arnhold, I J P; Mendonca, B B

    2004-01-01

    Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHbeta, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

  12. The expression of the RLF/INSL3 gene is reduced in Leydig cells of the aging rat testis.

    PubMed

    Paust, H J; Wessels, J; Ivell, R; Mukhopadhyay, A K

    2002-12-01

    The relaxin-like factor (RLF), which is the product of the INSL3 gene, is highly expressed in the fetal and adult-type Leydig cells of all species so far examined. In adult testes it is upregulated at puberty but appears subsequently to be expressed in a constitutive manner, independently of acute changes in the hypothalamic-pituitary-gonadal (HPG) axis. Functional hypogonadism with decreased testosterone is prevalent in the aging male. In order to test whether this is a property of the HPG axis, or of the Leydig cells themselves, RLF/INSL3 was used as an independent marker to assess rat Leydig cell differentiation status. Hybridization analysis showed that in the testes of old (2 years) rats, RLF/INSL3 mRNA expression was dramatically reduced, compared to young (3 months) animals. This was also evident at the protein level using immunohistochemistry. The results suggest that increasing functional hypogonadism in older male mammals is likely caused by a dedifferentiation of the Leydig cells themselves.

  13. Endocrinology of the hypothalamic-pituitary-testicular axis with particular reference to the hormonal control of spermatogenesis.

    PubMed

    Matsumoto, A M; Bremner, W J

    1987-02-01

    The normal physiology of the hypothalamic-pituitary-testicular axis in man is reviewed. According to current concepts, LH plays an important role in the initiation and maintenance of spermatogenesis by stimulating Leydig cell production of high concentrations of T within the testes. FSH is thought to be important in spermatid maturation (spermiogenesis) during the initiation of spermatogenesis by stimulation of Sertoli cells. Studies of selective gonadotrophin replacement in experimentally-induced hypogonadotrophic hypogonadal men demonstrate that qualitatively normal sperm production can be achieved by replacement of either LH or FSH alone, but both LH and FSH are necessary to maintain quantitatively normal spermatogenesis. Studies of gonadotrophin replacement in spontaneously-occurring hypogonadotrophic men suggest that the requirement for FSH activity to stimulate sperm production is greatest during the initiation of sperm production at the time of puberty. The initiation of spermatogenesis in postpubertal men with acquired hypogonadotrophic hypogonadism and the maintenance of spermatogenesis after its initiation can often be achieved with LH activity alone.

  14. 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.

  15. [Antipsychotics and hyperpolactinaemia: pathophysiology, clinical relevance, diagnosis and therapy].

    PubMed

    Riecher-Rössler, Anita; Schmid, Christoph; Bleuer, Stefan; Birkhäuser, Martin

    2009-01-01

    Hyperprolactinaemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics such as amisulpiride, risperidone or ziprasidone. Besides galactorrhoea, potential consequences are suppression of the hypothalamic-pituitary-gonadal axis with hypogonadism, sexual dysfunction, infertility and in women also irregularities of the menstrual cycle and amenorrhoea. Potential long term consequences are mainly osteopenia and osteoporosis with an enhanced risk of fractures. Hyperprolactinaemia, if not clearly caused by a prolactin inducing antipsychotic, should always be thoroughly investigated. Ideally, prolactin should be measured before starting a patient on a new antipsychotic. Furthermore, before neuroleptic treatment is begun, and also in regular intervals after that, patients should be asked about potential clinical signs of hyperprolactinaemia. Hyperprolactinaemia which is clearly due to antipsychotics but without clinical symptoms only requires regular controls of bone mineral density. However, if clinical symptoms occur, switching to a prolactin sparing antipsychotic may be necessary. In these cases fertility is often regained and the women concerned have to be informed about the enhanced risk of pregnancy and counselled regarding contraception. If switching is not possible, estradiol has to be substituted in women. Also in men with hypogonadism hormonesubstitution (with testosterone) is usually indicated. Generally hyperprolactinaemia in psychiatric patients should be taken more seriously in the future.

  16. Endocrinology of the aging male.

    PubMed

    Araujo, Andre B; Wittert, Gary A

    2011-04-01

    The endocrinology of the aging male is complex, with multiple hormones along the hypothalamic-pituitary-testicular (HPT) axis interacting with one another in feedback. As men age, there is a small and progressive (not precipitous, as in women) decline in several sex hormones, in particular testosterone and dehydroepiandrosterone, and related increases in luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin. The importance of these changes is wide-ranging because of the ubiquitous role of sex hormones in male physiology. This chapter discusses the endocrinology of the aging male. We provide an overview of the regulation of the HPT axis with an emphasis on the changes that occur with aging and the measurement of gonadal steroids, including hormone pulsatility, within-subject and circadian variations. The difficulties of assessing the symptoms of late-onset hypogonadism are highlighted. There is a comprehensive discussion of the epidemiology of sex hormone changes, including their age associations, prevalence of symptomatic hypogonadism, secular changes, risk factors, and the association of sex hormones with outcomes.

  17. 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.

  18. 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

  19. [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

  20. 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

  1. A new oral testosterone undecanoate formulation.

    PubMed

    Köhn, Frank-Michael; Schill, Wolf-Bernhard

    2003-11-01

    Testosterone undecanoate has been available on the market for more than 20 years. This testosterone ester is used worldwide for oral treatment of male hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid, leading to inconvenient storage conditions. It will now be available in a new formulation with castor oil and propylene glycol laurate instead of oleic acid, thus improving storage conditions markedly (stable at room temperature for approximately 3 years). Pharmacokinetic and pharmacodynamic studies have demonstrated bioequivalence of the old and the new formulation of testosterone undecanoate. Therefore, the results of studies that were performed with the old formulation can be transferred to the clinical use of the new formulation. Controlled studies have shown its efficacy in the treatment of symptoms associated with reduced serum testosterone levels. In these cases testosterone undecanoate improves bone mineral density, quality of life, muscle mass, libido and mood. Further studies will help evaluate the efficacy and safety of the new formulation in the treatment of elderly men with late-onset hypogonadism. PMID:14579074

  2. 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.

  3. Kallmann syndrome in women: from genes to diagnosis and treatment.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Smolarczyk, Roman; Katulski, Krzysztof; Genazzani, Andrea R

    2013-04-01

    Kallmann syndrome (KS) can be characterized as genetic disorder marked by hypogonadotropic hypogonadism and anosmia. Franz Jozef Kallmann was the first who described this disease in 1944. He suggested, that this disease has hereditary background. At present, six genes are regarded as causal genes of KS. These genes can be listed in chronological order: KAL1, FGFR1, FGF8, CHD7, PROKR2 and PROK2. The sensitivity of molecular testing of KS is only about 30%. Diagnosis based on clinical findings is therefore such important. Cardinal features of patients with KS include hypogonadotropic hypogonadism and anosmia or hyposmia. Some non-reproductive, non-olfactory symptoms can also be present, depending on the genetic form of disease. Some patients with KS present midline cranial anomalies (cleft lip, cleft palate and imperfect fusion). Sometimes patients can also suffer from missing teeth (dental agenesis). Optic problems, such as colour blindness or optic atrophy also can occur in KS patients. Very characteristic symptom in KS patients is mirror movements of the upper limbs (imitation synkinesis for contralateral limbs). The type of treatment in women with KS depends on the goal of therapy. After the diagnosis of syndrome, the main goal of the treatment is to induce and maintain secondary sex characteristic (estrogen-progestin therapy). The further goal in some patients can be related to enable fertility (gonadotropin, gonadotropin-releasing hormone therapy). PMID:23368665

  4. Compound heterozygous PNPLA6 mutations cause Boucher–Neuhäuser syndrome with late-onset ataxia

    PubMed Central

    Deik, A.; Johannes, B.; Rucker, J. C.; Sánchez, E.; Brodie, S. E.; Deegan, E.; Landy, K.; Kajiwara, Y.; Scelsa, S.; Saunders-Pullman, R.

    2014-01-01

    PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher–Neuhäuser syndrome. Boucher–Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher–Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher–Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient’s genomic DNA from coding exons 26–29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher–Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases. PMID:25267340

  5. Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.

    PubMed

    Deik, A; Johannes, B; Rucker, J C; Sánchez, E; Brodie, S E; Deegan, E; Landy, K; Kajiwara, Y; Scelsa, S; Saunders-Pullman, R; Paisán-Ruiz, C

    2014-12-01

    PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.

  6. Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Ravani, Pietro; Obici, Laura; Dallera, Nadia; Del Barba, Andrea; Negrinelli, Alessandro; Tardanico, Regina; Nardi, Matilde; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2015-06-01

    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.

  7. Changes in Testosterone Levels and Sex Hormone-Binding Globulin Levels in Extremely Obese Men after Bariatric Surgery

    PubMed Central

    Laichuthai, Nitchakarn; Suwannasrisuk, Preaw; Houngngam, Natnicha; Udomsawaengsup, Suthep; Snabboon, Thiti

    2016-01-01

    Objective. Obesity is a risk factor for hypogonadotropic hypogonadism in men. Weight loss has been shown to improve hypogonadism in obese men. This study evaluated the early changes in sex hormones profile after bariatric surgery. Methods. This is a prospective study including 29 morbidly obese men. Main outcomes were changes in serum levels of total testosterone (TT), free testosterone (cFT), SHBG, estradiol, adiponectin, and leptin at 1 and 6 months after surgery. Results. The mean age of patients was 31 ± 8 years and the mean BMI was 56.8 ± 11.7 kg/m2. Fifteen patients underwent Roux-en-Y gastric bypass and 14 patients underwent sleeve gastrectomy. At baseline, 22 patients (75.9%) had either low TT levels (<10.4 nmol/L) or low cFT levels (<225 pmol/L). Total testosterone and SHBG levels increased significantly at 1 month after surgery (p ≤ 0.001). At 6 months after surgery, TT and cFT increased significantly (p ≤ 0.001) and 22 patients (75.9%) had normalized TT and cFT levels. There were no changes in estradiol levels at either 1 month or 6 months after surgery. Conclusions. Increases in TT and SHBG levels occurred early at 1 month after bariatric surgery while improvements in cFT levels were observed at 6 months after bariatric surgery. PMID:27725831

  8. Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.

    PubMed

    Deik, A; Johannes, B; Rucker, J C; Sánchez, E; Brodie, S E; Deegan, E; Landy, K; Kajiwara, Y; Scelsa, S; Saunders-Pullman, R; Paisán-Ruiz, C

    2014-12-01

    PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases. PMID:25267340

  9. 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.

  10. 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

  11. 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

  12. Increased hGH production rate after low-dose estrogen therapy in prepubertal girls with Turner's syndrome.

    PubMed

    Mauras, N; Rogol, A D; Veldhuis, J D

    1990-12-01

    Low-dose estrogen therapy significantly increases radioimmunoassayable serum hGH concentrations in the prepubertal hypogonadal female. In this study, we have examined the effects of short- and long-term low-dose ethinyl estradiol therapy on the endogenous production rates and metabolic clearance rates of hGH. We used deconvolution mathematical modeling to provide quantitative estimates of individual secretory parameters and to calculate subject-specific hGH metabolic clearance rates, by using all serum hGH concentrations and their variances considered simultaneously. Nine girls with Turner's syndrome (mean age 7.7 +/- 0.5 y) were studied on three separate nights by drawing blood every 20 min from 2200 to 0800 h before (I), after 1 wk (II), and 5 wk (III) of 100 ng/kg/d ethinyl estradiol therapy orally. We found that the endogenous hGH production rate more than doubled in all patients studied after 5 wk of ethinyl estradiol therapy (194 +/- 22 (I), 290 +/- 43 (II), and 412 +/- 66 (III) micrograms/L/12 h; p less than 0.05 for I and III). The half-life of endogenous hGH was not altered in the estrogen treatment paradigm with a mean of 19 +/- 1.6 min in study I and 18 +/- 1.2 min in both studies II and III. Our results suggest that even prepubertal concentrations of gonadal steroids in the hypogonadal female may be physiologically relevant to the maintenance of normal somatotrope secretory function.

  13. 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

  14. Effect of penile size on nocturnal erections: evaluation with NPTR testing with men having micropenis.

    PubMed

    Yaman, O; Soygür, T; Akand, M; Tokatli, Z

    2005-01-01

    There has been conflicting opinions in the literature regarding sexual function in hypogonadal men with micropenis. In this study we aimed to evaluate erectile function in hypogonadal men with micropenis by nocturnal penile tumescence and rigidity testing (NPTR) and compared the results with young potent normal penile sized men. A total of 15 men (ages 17-30 y) defined having a micropenis with a stretched penile length of less than 9.3 cm were constituted the study group. Mean stretched penile length was 6.8+/-1.6 cm (range 3.6-7.8 cm). Karyotype analysis showed 46XY in all cases. Control group included 22 potent and normal penile sized men (23-29 y). All subjects completed three sessions of consecutive nights using the RigiScan Plus device. Comparison of the results of NPTR of control group with study group revealed that number and duration of erectile episodes (P < 0.001), duration of tip rigidity > 60% (P < 0.01), TAU tip and TAU base (P = 0.001), and RAU base (P = 0.01) were found to be significantly lower in men with micropenis. In conclusion, our study showed that men with micropenis are associated with decreased nocturnal erectile activity.

  15. Testosterone and obesity.

    PubMed

    Kelly, D M; Jones, T H

    2015-07-01

    Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism. PMID:25982085

  16. Organic causes of erectile dysfunction in men under 40.

    PubMed

    Ludwig, Wesley; Phillips, Michael

    2014-01-01

    There are a significant number of men under 40 who experience erectile dysfunction (ED). In the past, the vast majority of cases were thought to be psychogenic in nature. Studies have identified organic etiologies in 15-72% of men with ED under 40. Organic etiologies include vascular, neurogenic, Peyronie's disease (PD), medication side effects and endocrinologic sources. Vascular causes are commonly due to focal arterial occlusive disease. Young men with multiple sclerosis, epilepsy and trauma in close proximity to the spinal cord are at increased risk of ED. It is estimated that 8% of men with PD are under 40, with 21% of these individuals experiencing ED. Medications causing ED include antidepressants, NSAIDs and finasteride (Propecia), antiepileptics and neuroleptics. Hormonal sources are uncommon in the young population, however possible etiologies include Klinefelter's syndrome, congenital hypogonadotropic hypogonadism, and acquired hypogonadotropic hypogonadism. The workup of young men with ED should include a thorough history and physical examination. The significant prevalence of vascular etiologies of ED in young men should prompt consideration of nocturnal penile tumescence testing and penile Doppler ultrasound. Treatment options that may improve ED include exercise and oral PDE-5 inhibitors. PMID:24281298

  17. 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

  18. Directed Mouse Embryonic Stem Cells into Leydig-Like Cells Rescue Testosterone-Deficient Male Rats In Vivo

    PubMed Central

    Yang, Yan; Su, Zhijian; Xu, Wenting; Luo, Jiao; Liang, Rui; Xiang, Qi; Zhang, Qihao; Ge, Ren-shan

    2015-01-01

    The primary function of Leydig cells is to secrete testosterone, which is critical in the regulation of male reproduction and development. Low levels of testosterone will lead to male hypogonadism. Stem cell-derived Leydig cell transplantation may be a promising alternative therapy for male hypogonadism. Thus far, others have reported that Leydig-like cells can be derived from mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells. However, the efficiency of the differentiating Leydig cells remains low, and progress toward generating functional adult Leydig cells (ALCs) is limited. Herein, we describe a robust method of directing differentiation of mouse embryonic stem cells (mESCs) into Leydig-like cells in vitro by overexpression of the transcription factor steroidogenic factor-1 (SF-1) and treatment with a combination of 8-Bromoadenosine-3′,5′-cyclic monophosphate and forskolin. These differentiated cells express mRNA encoding the steroidogenic enzymes and produce progesterone and testosterone. Importantly, when transplanted into male rats that had their original Leydig cells selectively eliminated by ethylene dimethanesulfonate, these in vitro-derived Leydig-like cells further developed into functional ALCs that rescued serum testosterone levels. These data provide evidence that mESCs can be induced to differentiate into Leydig-like cells in vitro, which can develop in the in vivo microenvironment. PMID:25340537

  19. Abnormalities of sex differentiation.

    PubMed

    Nawata, H; Takayanagi, R; Yanase, T; Ikuyama, S; Okabe, T

    1996-01-01

    Sex differentiation is determined by a cascade of events proceeding from chromosomal sex to the completion of sexual maturation at puberty. Many factors involved in this cascade have been identified. Here we focus on DAX-1, androgen receptor and cytochrome P450c17, and discuss their functions in sex differentiation. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism using PCR amplification of genomic DNA and complete exonic sequencing, and established that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. Androgen insensitivity syndrome (AIS) is a good model to clarify the relationship between the structure and function of androgen receptor, the androgen receptor gene mutation and clinical phenotype. We analyzed 15 cases of AIS and demonstrate the structural and functional relationships of the androgen receptor. We have sequenced the CYP17 (P450c17) gene in DNA from several patients with 17 alpha-hydroxylase deficiency, reconstructed the mutations in a human P450c17 cDNA and expressed the mutant P450c17 in COSl cells to characterize the kinetic properties of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular bases of cases clinically reported as 17 alpha-hydroxylase deficiency have turned out to be complete or partial combined deficiencies of 17 alpha-hydroxylase/17,20-lyase. PMID:8864743

  20. MEN REGRET ANABOLIC STEROID USE DUE TO A LACK OF COMPREHENSION REGARDING THE CONSEQUENCES ON FUTURE FERTILITY

    PubMed Central

    Kovac, J.R.; Scovell, J.; Ramasamy, R.; Rajanahally, S.; Coward, RM.; Smith, R.P.; Lipshultz, L.I.

    2014-01-01

    Summary 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Testosterone for the aging male; current evidence and recommended practice

    PubMed Central

    Stanworth, Roger D; Jones, T Hugh

    2008-01-01

    An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defining the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specific nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefit. The traditional benefits of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible beneficial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations. PMID:18488876

  6. The impact of obesity on the male reproductive axis.

    PubMed

    Mihalca, R; Fica, S

    2014-06-15

    Obesity, defined as a body mass index (BMI) >30 kg/m2, has seen an important increase in prevalence in the last decades, not only in Europe and the United States, but also in developing countries. It is an established risk factor for numerous pathologic conditions like diabetes mellitus, cardiovascular diseases and cancer, but has also been linked to male hypogonadism. Several studies showed a negative impact of excessive BMI on testosterone levels, sexual function and sperm parameters. Possible mechanisms beyond this phenomenon are reduced hypothalamic and pituitary secretory function, excess estrogen production and reduced circulating sex-hormone binding globulin (SHBG). Peptides produced by the adipocyte may also trigger modifications of the reproductive function. Independently of the method used, non-surgical approach or bariatric techniques, weight reduction and a return to a normal BMI have been associated with improvement in the sexual function and levels of sexual hormones in obese males, showing that obesity related hypogonadism is preventable. Sexual and reproductive health might represent additional motivational factors for men in order to maintain a healthy life-style.

  7. Testosterone supplementation: what and how to give.

    PubMed

    Jockenhövel, F

    2003-09-01

    Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 alpha-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and sexual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel, a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful

  8. 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

  9. beta-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population.

    PubMed

    Papadimas, John; Goulis, Dimitrios G; Mandala, Eudokia; Georgiadis, George; Zournatzi, Vassiliki; Tarlatzis, Basil C; Bontis, John N

    2002-01-01

    beta-thalassemia (beta-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic- pituitary-gonadal axis in patients with beta-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with beta-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into beta-thal major (51 males and 62 females) and beta-thal intermedia phenotypes (16 males and 6 females). Male patients with beta-thal major were subdivided into three groups a) eugonadal (35%, Tanner's stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanner's stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanner's stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with beta-thal major were subdivided into: a) eugonadal (32%, Tanner's stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanner's stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanner's stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with beta-thal intermedia were subdivided into eugonadal (75% of males, 33% of females) and hypogonadal (25% of males, 67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, beta-thal patients could be eugonadal or develop early or late onset HH. trade mark-thal intermedia patients have a more favorable

  10. A comprehensive review of erectile dysfunction in men with diabetes.

    PubMed

    Kamenov, Z A

    2015-03-01

    Erectile dysfunction (ED) is more common in men with diabetes (DM). Dependent on the selected population, age, DM type and duration, the prevalence of diabetic ED (DED) varies from 32 to 90%. In 12-30% of men ED is the first sign of diabetes, diagnosed later. Today men with diabetes live longer than ever, and develop more late diabetic complications. Having in mind also the global ageing of the world population all this data suggests an increasing number of men with DED in the future. The main factors playing in the complex pathogenesis of DED are diabetic neuropathy (oxidative stress, polyol pathway, advanced glycation end-products, nerve growth factor deficiency, dysfunction of protein kinase C, tissue remodeling, etc.), macrovascular arterial disease (endothelial dysfunction, abnormal collagen deposition and smooth muscle degeneration, dyslipidemia, arterial hypertension, veno-occlusive dysfunction, etc.), hypogonadism, structural remodeling of the corporeal tissue, psychogenic components and adverse drug reactions. The diagnostic process is based on the results of questionnaires, neurological, vascular (Doppler) and other more rarely used investigations.Because of the complex pathogenesis of DED diabetic men represent a "difficult" treatment group. The difficulties are from the "beginning", because patients do not talk about their problem spontaneously, and doctors do not ask about it. The treatment of DED should be team work, preferably including also specialists in sexual medicine. Psychological support and counseling of the couple is necessary in most cases. The general measures include implementation of a healthier lifestyle, improved glycemic-, lipids-, and arterial pressure control, and careful re-evaluation of the concomitant medications. The specific treatment includes as first line therapy the inhibitors of phosphodiesterase type 5 (PDE-5) with lesser effectiveness compared to non-DM men. There are rare studies with selected diabetic populations and

  11. Pharmacologic management of human immunodeficiency virus wasting syndrome.

    PubMed

    Badowski, Melissa; Pandit, Neha Sheth

    2014-08-01

    Pharmacologic interventions for human immunodeficiency virus (HIV) wasting have been studied since the 1990s, but the results of these interventions have been difficult to compare because the studies used different HIV wasting definitions and assessed various patient outcomes. Thus, we performed a systematic review of the current literature to identify studies that evaluated pharmacologic management of HIV wasting and to compare and contrast treatment options. Further, we provide a comprehensive review of these treatment options and describe the definition of HIV wasting used in each study, the outcomes assessed, and whether antiretroviral therapy was used during the HIV wasting treatment. Literature searches of the PubMed/Medline (1946-2014) and Google Scholar databases were performed, and a review of the bibliographies of retrieved articles was performed to identify additional references. Only English-language articles pertaining to humans and HIV-infected individuals were evaluated. Thirty-six studies were identified that assessed pharmacologic interventions to treat HIV wasting. Appetite stimulants, such as megestrol acetate, have been shown to increase total body weight (TBW) and body mass index in HIV-infected patients with wasting. Studies evaluating dronabinol showed conflicting data on TBW increases, but the drug may have minimal benefit on body composition compared with other appetite stimulants. Testosterone has been shown to be effective in HIV wasting for those who suffer from hypogonadism. Recombinant human growth hormone has been evaluated for HIV wasting and has shown promising results for TBW and lean body mass increases. Thalidomide has been studied; however, its use is limited due to its toxicities. Although megestrol acetate and dronabinol are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting, it is important to recognize other comorbidities such as depression or hypogonadism that may contribute to the

  12. Kallmann syndrome and paranoid schizophrenia: a rare combination

    PubMed Central

    Verhoeven, Willem M A; Egger, Jos I M; Hovens, Johannes E; Hoefsloot, Lies

    2013-01-01

    Kallmann syndrome (KS) is a genetically heterogeneous and rare disorder characterised by the combination of hypothalamic hypogonadism and anosmia/hyposmia, a variable degree of intellectual disability and several somatic anomalies. In about one-third of the patients, mutations have been identified in at least seven different genes. Virtually no data are available about possible neuropsychiatric symptoms in KS. Here, a young adult male is described with a previous clinical diagnosis of KS and recent paranoid schizophrenia of which positive, but not negative symptoms, fully remitted upon treatment with antipsychotics. Neither genome-wide array analysis nor mutation analyses disclosed imbalances or mutations in any of presently known KS disease genes. This is the first report on a patient with KS and paranoid schizophrenia in whom extensive genetic analyses were performed. It is concluded that further studies are warranted in order to elucidate a possible increased risk for psychiatric symptoms in patients with KS. PMID:23329708

  13. The conventional management of male infertility.

    PubMed

    Nieschlag, Eberhard; Lenzi, Andrea

    2013-12-01

    Although the male reproductive function is impaired in about half of infertile couples, the evaluation of male infertility is underrated or neglected even today. In addition to a physical examination and imaging techniques, semen analysis as well as endocrine and genetic analyses should be part of the routine investigation. Few disorders have become subjects of rational treatment of the infertile male, even though, as examples, hypogonadotropic hypogonadism is treatable by gonadotropins and obstructive azoospermia by reconstructive surgery. Early treatment of maldescended testes and sexually transmitted diseases can prevent infertility. Similar pregnancy rates from patients with varicocele following surgery or counseling demonstrate the important role of the physician in the treatment of infertility. In the age of evidence-based medicine, most empirical treatments have been demonstrated to be ineffective. Instead, symptomatic treatment by assisted reproductive techniques has become a central tool to overcome otherwise untreatable male infertility.

  14. [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

  15. Pituitary stalk lesion in a 13-year-old female.

    PubMed

    Zilbermint, Mihail; Ramnitz, Mary S; Lodish, Maya B; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J; Quezado, Martha M; Stratakis, Constantine A

    2014-03-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.

  16. Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

    PubMed

    Numakura, Chikahiko; Kitanaka, Sachiko; Kato, Mitsuhiro; Ishikawa, Shigeo; Hamamoto, Yoshioki; Katsushima, Yuriko; Kimura, Toshiyuki; Hayasaka, Kiyoshi

    2010-09-01

    SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.

  17. 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

  18. Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome.

    PubMed

    Lower, Karen M; Turner, Gillian; Kerr, Bronwyn A; Mathews, Katherine D; Shaw, Marie A; Gedeon, Agi K; Schelley, Susan; Hoyme, H Eugene; White, Susan M; Delatycki, Martin B; Lampe, Anne K; Clayton-Smith, Jill; Stewart, Helen; van Ravenswaay, Conny M A; de Vries, Bert B A; Cox, Barbara; Grompe, Markus; Ross, Shelley; Thomas, Paul; Mulley, John C; Gécz, Jozef

    2002-12-01

    Börjeson-Forssman-Lehmann syndrome (BFLS; OMIM 301900) is characterized by moderate to severe mental retardation, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large but not deformed ears. Previously, the gene associated with BFLS was localized to 17 Mb in Xq26-q27 (refs 2-4). We have reduced this interval to roughly 9 Mb containing more than 62 genes. Among these, a novel, widely expressed zinc-finger (plant homeodomain (PHD)-like finger) gene (PHF6) had eight different missense and truncation mutations in seven familial and two sporadic cases of BFLS. Transient transfection studies with PHF6 tagged with green fluorescent protein (GFP) showed diffuse nuclear staining with prominent nucleolar accumulation. Such localization, and the presence of two PHD-like zinc fingers, is suggestive of a role for PHF6 in transcription.

  19. 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

  20. 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

  1. Microcephaly, short stature, and developmental delay associated with a chemotactic defect and transient hypogammaglobulinaemia in two brothers.

    PubMed Central

    Say, B; Barber, N; Miller, G C; Grogg, S E

    1986-01-01

    Two brothers presented with unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation. They both developed eczema in infancy and have had recurrent infections. Additional physical findings in both boys included hypogonadism, flexion contractures, hypoplastic patellae, and scoliosis. Their facial similarity was striking with sloping foreheads, beaked noses, large, protruding ears, and micrognathia. Low levels of serum gammaglobulins and defective chemotaxis were present in both boys in infancy. The hypogammaglobulinaemia was transient and improved, reaching normal levels by 3 1/2 years and 15 months, respectively. Defective chemotaxis and recurrent infections have persisted to the present. Both parents were normal. The mode of inheritance was not clear, as both X linked and autosomal recessive patterns were possible. Although patients with congenital malformations who also had immunodeficiency have previously been reported, immune system abnormalities, especially those of a transient nature, may frequently go unrecognised. Images PMID:3746838

  2. Ten-year follow-up of a giant prolactinoma.

    PubMed

    Fernandes, Vera; Santos, Maria Joana; Almeida, Rui; Marques, Olinda

    2015-11-20

    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.

  3. [DAX-1 abnormality].

    PubMed

    Kinoshita, Ei-ichi

    2002-02-01

    DAX-1 is an orphan nuclear receptor that plays a key role in the development and function of the adrenal gland and hypothalamic-pituitary-gonadal axis. Absence of DAX-1 results in X-linked adrenal hypoplasia congenita, a human inherited disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. The DAX-1 gene may be responsible for a male-to-female sex reversal syndrome, referred to as dosage sensitive sex reversal(DSS), due to the duplication of a small region of human chromosome Xp21. Dax-1 and Sry have been shown to act antagonistically in the mouse system, where over-expression of Dax-1 leads to female development and increasing activity of Sry to male development. Although these data strongly implicate Dax-1 in sex determination, there is no evidence that DAX-1 is equivalent to DSS in human.

  4. GPR54 and puberty.

    PubMed

    Colledge, William H

    2004-11-01

    At puberty, pulsatile secretion of hormones initiates sexual maturation of the gonads. The G-protein-coupled receptor GPR54 is crucially involved in the initiation of puberty, along with its ligand metastin. Mice lacking GPR54 fail to undergo puberty and have immature reproductive organs and low levels of sex steroids and gonadotrophic hormones, but have normal levels of gonadotrophin-releasing hormone in the hypothalamus. In humans, several cases of hypogonadism have been ascribed to mutations in GPR54. Production of metastin and, to a lesser extent, GPR54 are negatively regulated by testosterone and oestrogen, and injecting GPR54 ligands can increase hormone secretion in rodents. Thus, GPR54 is required for normal functioning of the hypothalamic-pituitary-gonadal axis, probably at the level of gonadotrophin-releasing-hormone secretion.

  5. Role of testosterone in the pathogenesis, progression, prognosis and comorbidity of men with chronic kidney disease.

    PubMed

    Dousdampanis, Periklis; Trigka, Konstantina; Fourtounas, Costas; Bargman, Joanne M

    2014-06-01

    Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin-angiotensin system (RAS), the production of endothelin and the regulation of anti- or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.

  6. The ageing male reproductive tract.

    PubMed

    Sampson, N; Untergasser, G; Plas, E; Berger, P

    2007-01-01

    Ageing of the male reproductive system is characterized by changes in the endocrine system, hypogonadism, erectile dysfunction and proliferative disorders of the prostate gland. Stochastic damage accumulating within ageing leads to progressive dysregulation at each level of the hypothalamic-pituitary-gonadal (HPG) axis and in local auto/paracrine interactions, thereby inducing morphological changes in reproductive target organs, such as the prostate, testis and penis. Despite age-related changes in the HPG axis, endocrine functions are generally sufficient to maintain fertility in elderly men. Ageing of the male reproductive system can give rise to clinically relevant manifestations, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile dysfunction (ED). In this review, we discuss morphological/histological changes occurring in these organs and current views and concepts of the underlying pathology. Moreover, we emphasize the molecular/cellular pathways leading to reduced testicular/penile function and proliferative disorders of the prostate gland.

  7. [Effect of chronic consumption of alcohol on the hypothalamo-pituitary-testicular axis in the rat].

    PubMed

    Mateos, A; Fermoso, J; Agrasal, C; Martín, I; Paz-Bouza, J; Tresguerres, J A; Esquifino, A I

    1987-03-01

    An experimental model of chronic alcohol abuse is developed, in order to study the hypothalamic-pituitary testicular axis in the rat. For this purpose basal plasma prolactin, gonadotropins, testosterone and estradiol have been measured. Also these hormones were studied after LHRH or hCG stimulation. This experimental model allows us to study the role of alcohol in hypogonadism induction. Chronic alcohol administration resulted in an inconstant decrease in plasma testosterone levels and very diminished response of it to hCG. Along with these modifications, there was an increase in basal plasma estrogen levels, as has been shown in the human. The decrease in plasma LH levels in alcoholic rats together with a normal response to LHRH suggest a toxic role of alcohol at higher levels than the pituitary. The existence of a hyperprolactinemic state under chronic alcohol ingestion is confirmed. The decrease in plasma prolactin levels after LHRH administration suggests that prolactin and gonadotropin secretion are very closely related.

  8. Preadolescent and adolescent endocrinology: physiology and physiopathology. II. Hormonal changes during abnormal pubertal development.

    PubMed

    Sizonenko, P C

    1978-08-01

    Based on the knowledge of the physiology of regulation of gonadotropins and gonadal steroids, basal levels of these hormones might be indicative of the etiologic factors of abnormal pubertal development. In addition, stimulatory tests may help in the diagnosis of such conditions. It is interesting that the pubertal maturation of the adrenal cortex is independent of the hypothalamic-pituitary-gonadal axis. The role of the adrenal cortex for the pubertal development remains questionable: adrenal androgens are low in isosexual precocious puberty, low in delayed adolescence, and normal in hyper- or hypogonadotropic hypogonadism. The importance of this role is doubled in congenital virilizing adrenal hyperplasia. When the disease is untreated, although adrenal androgens in excess advance bone age and hypothalamic maturation, girls remain prepubertal. When the therapeutic control is good, normal puberty occurs. The action of the adrenal androgens on growth and puberty remains to be determined.

  9. 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.

  10. Behaviorally induced reproductive compromise in women and men.

    PubMed

    Berga, S L

    1997-02-01

    Behaviors that activate the hypothalamic-pituitary-adrenal (HPA) axis or suppress the hypothalamic-pituitary-thyroidal (HPT) axis can disrupt the hypothalamic-pituitary-gonadal (HPG) axis in women and men. Individuals with functional hypothalamic hypogonadism typically display a combination of behaviors that serve as psychogenic stressors and metabolic challenges. Complete recovery of gonadal function depends upon restoration of the HPA and HPT axes. Hormone replacement strategies have limited benefit, because they do not achieve this objective and they mask deficits that accrue from altered HPA and HPT function. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile gonadoropin-releasing hormone (GnRH), fertility management alone will not permit the HPA and HPT axes to recover. Thus, for complete recovery to ensue, biopsychosocial interventions that address the individual's unique set of psychogenic factors and metabolic challenges must be devised.

  11. Kisspeptins: regulators of metastasis and the hypothalamic-pituitary-gonadal axis.

    PubMed

    Murphy, K G

    2005-08-01

    The kisspeptins are the peptide products of the KiSS-1 gene and the endogenous agonists for the GPR54 receptor. Although KiSS-1 was initially discovered as a metastasis suppressor gene, recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. Disrupted GPR54 signalling causes hypogonadotrophic hypogonadism in rodents and man. Central or peripheral administration of kisspeptin potently stimulates the hypothalamic-pituitary-gonadal axis, increasing circulating gonadotrophin concentrations in a number of animal models. These effects appear likely to be mediated via the hypothalamic gonadotrophin-releasing hormone system, although kisspeptins may have direct effects on the anterior pituitary gland. Hypothalamic KiSS-1 expression is regulated by circulating sex steroids. The precise physiological role of the kisspeptin system in the regulation of reproductive function remains to be elucidated.

  12. Infertility in spinal-cord injured male.

    PubMed

    Ver Voort, S M

    1987-02-01

    Sterility in spinal-cord injured (SCI) men is believed to be caused by ejaculatory dysfunction, genital ductal blockage secondary to infection, and/or impaired spermatogenesis. Semen from SCI men demonstrates diminished numbers of motile, morphologically normal sperm. Testicular biopsies demonstrate impaired spermatogenesis. Leydig and Sertoli cells appear to be normal. Endocrine evaluations reveal normal testosterone levels with an adequate Leydig cell reserve. Luteinizing hormone (LD) and follicle-stimulating hormone (FSH) levels are normal or high with normal or exaggerated stimulation responses. Acute depressions in testosterone, FSH, and LH levels can be seen following SCI, most markedly in quadriplegics. A normal hypothalamic-pituitary-testicular axis is implied by these findings, indicating a primary hypogonadism. Causes of impaired spermatogenesis may include local testicular temperature elevations, nondrainage of the reproductive tract, antisperm antibodies, and recurrent genitourinary infections. Treatment of infertility involves removal of these offending factors, and research is needed to correlate the impaired spermatogenesis with these factors.

  13. Time-dependent effects of alcohol on the hypothalamic-hypophyseal-testicular function in the rat.

    PubMed

    Esquifino, A I; Mateos, A; Agrasal, C; Martin, I; Canovas, J M; Fermoso, J

    1989-04-01

    Adult male rats were followed throughout ethanol administration, in order to examine the time-dependent effects of ethanol on the hypothalamic-pituitary-gonadal axis. The results indicate that there is an increase in plasma prolactin levels together with a reduction in basal plasma luteinizing hormone (LH) levels, which are evident from the beginning of the intoxication period. An exaggerated response of LH to luteinizing hormone-releasing hormone was also evident from 2nd week on, in ethanol-treated rats. Basal and human chorionic gonadotropin-stimulated plasma testosterone levels were decreased in alcohol-treated as compared to control rats, at all time points studied. In addition, plasma estradiol levels were increased in ethanol-fed rats. These data suggest a direct suppressive effect of ethanol on LH release in the beginning of the intoxication period. Subsequent elevations of plasma estradiol and prolactin levels may have contributed to the maintenance of hypogonadism at the end of the intoxication period.

  14. Cytokines and the hypothalamic-pituitary-adrenal axis.

    PubMed

    Hermus, A R; Sweep, C G

    1990-12-20

    After administration of the cytokines interleukin 1 (IL1), tumor necrosis factor (TNF), interleukin 2 and interleukin 6 to laboratory animals or humans, plasma levels of glucocorticoids are elevated. This effect is mediated by activation of the hypothalamic-pituitary unit. IL1 and TNF inhibit aldosterone production by rat adrenocortical cells in vitro and stimulate renin release by rat renal cortical cells. Administration of IL1 or TNF in rats suppresses hypothalamic-pituitary-thyroid function, whereas IL1 acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. During stimulation of the immune system (e.g. during infectious diseases), peculiar alterations in hormone secretion occur (hypercortisolism, hyperreninemic hypoaldosteronism, euthyroid sick syndrome, hypogonadism). The role of cytokines in these alterations remains to be established.

  15. Gonadotropic axis and Trypanosoma brucei gambiense infection.

    PubMed

    Boersma, A; Noireau, F; Hublart, M; Boutignon, F; Lemesre, J L; Racadot, A; Degand, P

    1989-06-01

    A gonad endocrine survey on 46 Congolese patients (15 women and 31 men) with parasitologically confirmed trypanosomiasis found amenorrhoea in 60% of the women and impotence in 70% of the men. The basic gonad endocrine examination showed a decrease in oestradiol levels in about 65% of the women. Both amenorrhoea and low oestrogen levels were observed in the second phase (P2) of the disease, but low oestrogen levels were sometimes noted in the first phase of the disease (P1). In the men, about 50% of the cases (P2) showed a decrease in testosterone. However, as in the women, the variation of testosterone was also observed in the first phase (P1). A static and dynamic examination of the hypothalamic-pituitary-gonadal axis was undertaken in order to investigate the origin of these hypogonadisms. A supra - or extra-hypophyseal origin is discussed.

  16. Secondary partial empty sella syndrome in an elite bodybuilder.

    PubMed

    Dickerman, R D; Jaikumar, S

    2001-06-01

    The pituitary gland is a hormone-responsive gland and is known to vary in size depending on the hormonal status of the patient and the multifaceted positive and negative feedback hypothalamic-pituitary-gonadal axis. Partial empty sella syndrome with an atrophied pituitary gland is seen in primary neuroendocrinopathies such as growth hormone deficiency, primary hypothyroidism, central diabetes insipidus and hypogonadism. Partial empty sella has also been shown to occur in patients with elevations in intracranial pressure. Secondary partial empty sella syndrome with significant pituitary gland atrophy from negative feedback inhibition of long-term exogenous hormonal use has not been previously reported. We are reporting on a case of partial empty sella syndrome occurring in an elite bodybuilder with a long history of exogenous abuse of growth hormone, testosterone and thyroid hormone. The pathophysiological mechanisms of secondary partial empty sella syndrome from exogenous hormone use and the possibility for elevations in intracranial pressure contributing to this syndrome will be discussed.

  17. Psychological stress and the function of male gonads.

    PubMed

    Jóźków, Paweł; Mędraś, Marek

    2012-01-01

    Stress is generally a natural phenomenon that affects behaviour, physiological processes, and neuroendocrine, neurochemical, neurological and immune responses. Many somatic and mental disorders are thought to result from chronic stress. Stress-induced gonadal dysfunction is not restricted to humans, but is observed in all higher animals. Stress-induced gonadal dysfunction comprises disturbances of the hypothalamic-pituitary-gonadal axis and of spermatogenesis. Various stressors induce changes in the secretion of neurotransmitters and hormones, such as CRH, ADH, beta-endorphins, somatostatin, VIP, PRL, GH, TSH, dopamine, serotonin, neuropeptide Y, melatonin, ACTH, glucocorticosteroids, catecholamines and androgens. In acute stress, testicular function is principally modified by cytokines and fluctuating concentrations of gonadotropins, while in chronic stress, hypogonadotropic hypogonadism and disruption of spermatogenesis of varying severity, including spermatogenetic arrest, are observed. In spite of the decades-long interest in the relationships between psychological stress and the function of male gonads, many questions in this area remain unanswered.

  18. The role of kisspeptin signalling in the regulation of the GnRH-gonadotrophin ovarian axis in mice.

    PubMed

    Colledge, W H; d'Anglemont de Tassigny, X

    2010-05-01

    Kisspeptins are a series of overlapping peptides encoded by the Kiss1 gene that are required for central activation of the hypothalamic-pituitary-ovarian axis at puberty. Mutations that interfere with kisspeptin signalling prevent normal pubertal development in humans and mice. Mutations in the kisspeptin receptor GPR54, cause infertility and hypogonadotrophic hypogonadism in humans. The failure of the Gpr54 and Kiss1 mutant mice to ovulate has led to the suggestion that kisspeptin signalling may be required for the preovulatory luteinizing hormone (LH) surge. Although kisspeptin signalling has been shown to have an important central role in regulating the physiology of the ovary, the expression profile of Kiss1 and Gpr54 suggests that they may also have direct functions in the ovary and the placenta.

  19. The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy.

    PubMed

    Hamed, Sherifa A

    2016-06-01

    Epilepsy is a common chronic medical illness. Hyposexuality is the most frequent abnormality in men and women with epilepsy. In men with epilepsy, hypoandrogenimia, hypogonadism and sperm abnormalities are common. Testicular atrophy was also infrequently reported. In women with epilepsy, hyperandrogenism, polycystic ovaries (PCOs) and PCO syndrome are frequent. Decreased serum free testosterone, dehydroepiandrosterone levels, free androgen index and free testosterone/leutinizing hormone (LH) ratio and increased sex hormone binding globulin, estradiol, prolactin, LH, follicle stimulating hormone (FSH) levels and LH/FSH ratio are common with epilepsy. Disturbance of central and/or peripheral control of hypothalamic-pituitary-gonadal axis and alteration of central neurotrasmitters (GABA, glutamate and serotonin) by epileptic discharges or antiepileptic drugs (AEDs), direct gonadal toxicity by AEDs and pcyshicatric/psychosocial factors are all incriminated in sexual, reproductive and gonadal abnormalities associated with epilepsy. Patients may benefit from multidisplinary evaluation, tight seizure control, change the AED, androgen therapy, genital vasodilators, L-carnitine supplementation and psychotherapy.

  20. Clomiphene citrate therapy for male infertility.

    PubMed

    Allag, I S; Alexander, N J

    1979-11-01

    We have summarized 697 reported cases of the use of clomiphene citrate for the improvement of semen quality. Basal levels of gonadotropins are useful criteria for the differential diagnosis of hypo- and hypergonadotropic hypogonadism. Patients with an intact hypothalamic-pituitary-gonadal axis are most likely to respond to clomiphene citrate. Twenty-five mg. per day, administered in a cyclic fashion for a period of six to nine months, caused the greatest improvement. A higher dose (50 mg. per day) may be effective in men who do not respond to 25 mg. During the course of therapy gonadotropin levels and semen samples should be analyzed periodically. This drug is not currently approved for use in men; the incidence of side effects, particularly with long-term treatment, is unknown.

  1. 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.

  2. Aging with HIV: a cross-sectional study of comorbidity prevalence and clinical characteristics across decades of life.

    PubMed

    Vance, David E; Mugavero, Michael; Willig, James; Raper, James L; Saag, Michael S

    2011-01-01

    Nurses and nurse practitioners require information on the health problems faced by aging HIV-infected adults. In this descriptive, cross-sectional study, we reviewed the electronic medical records of 1,478 adult patients seen in an HIV clinic between May 2006 and August 2007 to examine patterns of comorbidities, and immunological and clinical characteristics across each decade of life. With increasing age, patients were found to have lower HIV viral loads, more prescribed medications, and a higher prevalence of comorbid conditions, including coronary artery disease, hypertension, hypercholesterolemia, hypogonadism, erectile dysfunction, diabetes, peripheral neuropathy, hepatitis C, esophageal gastric reflux disease, and renal disease. Fortunately, with increasing age, patients were also more likely to have public or private health insurance and tended to be more compliant to medical appointments. With growing interest in aging with HIV, this study highlights the vastly different comorbidity profiles across decades of life, calling into question what constitutes "older" with HIV. PMID:20471864

  3. 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

  4. [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

  5. 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

  6. [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

  7. Male osteoporosis and androgenic therapy: from testosterone to SARMs

    PubMed Central

    Cilotti, Antonio; Falchetti, Alberto

    2009-01-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance. Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials. PMID:22461251

  8. [Gonadotrophic axis dysfunction in men with HIV-infection/aids].

    PubMed

    Ponte, Clarisse Mourão Melo; Gurgel, Maria Helane Costa; Montenegro, Renan Magalhães

    2009-11-01

    Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

  9. Androgen deficiency and metabolic syndrome in men

    PubMed Central

    Winter, Ashley G.; Zhao, Fujun

    2014-01-01

    Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of androgen deficiency in MetS is multifactorial, and consists of inflammatory, enzymatic, and endocrine derangements. Many options for the concomitant treatment of both disorders exist. Direct treatment of MetS, whether by diet, exercise, or surgery, may improve T levels. Conversely, testosterone replacement therapy (TRT) has been shown to improve MetS parameters in multiple randomized controlled trials (RTCs). PMID:26816752

  10. Molecular cytogenetic characterization of a case of primary amenorrhea with intrachromosomal triplication of the X chromosome q arm.

    PubMed

    Ocak, Z; Surucu, R

    2012-01-01

    This is a unique case of intrachromosomal triplication of the X chromosome q arm detected with cytogenetic and spectral karyotyping in a 21-year-old woman with primary amenorrhea, who had been referred because of primary hypergonadotropic hypogonadism and Mullerian hypoplasia. Intrachromosomal triplications are rare rearrangements resulting in partial tetrasomy. Since 1993, at least 34 cases of intrachromosomal triplications involving 9 different chromosomes have been reported. The vast majority of the reported triplications are on the 15th chromosome, arised de novo and had middle inverted repetitions. In this report the genotype-fenotype correlation in a case of primary amenorrhea associated with triplication of the X chromosome q arm and the possible mechanisms of this rearrangement are discussed. Further the clinical usability of SKY analysis as a molecular cytogenetic tool in searching for genomic instability arising from cytogenetic rearrangements is highlighted. PMID:22876590

  11. Perrault syndrome - a rare case report.

    PubMed

    Sampathkumar, Geethalakshmi; Veerasigamani, Narendrakumar

    2015-03-01

    Perrault syndrome is a rare disease comprising pure gonadal dysgenesis (46 XX) and sensorineural hearing loss in females and deafness alone in affected males. It is an autosomal recessive disorder. Over the years many additional features like marfanoid habitus and central nervous system findings have also been reported. Herein we report a case of sporadic Perrault syndrome in 18-year-old female who presented to our hospital with deaf mutism and primary amenorrhoea. On evaluation, the patient had hypergonadotropic hypogonadism, streak gonads and a normal karyotype (46 XX). Audiologic evaluation showed sensorineural deafness. The patient was started on hormone replacement therapy. She is on regular follow up. We present this case for its infrequent incidence and also to add to the ever expanding clinical spectrum of this disease. PMID:25954653

  12. Perrault Syndrome – A Rare Case Report

    PubMed Central

    Narendrakumar, Veerasigamani

    2015-01-01

    Perrault syndrome is a rare disease comprising pure gonadal dysgenesis (46 XX) and sensorineural hearing loss in females and deafness alone in affected males. It is an autosomal recessive disorder. Over the years many additional features like marfanoid habitus and central nervous system findings have also been reported. Herein we report a case of sporadic Perrault syndrome in 18-year-old female who presented to our hospital with deaf mutism and primary amenorrhoea. On evaluation, the patient had hypergonadotropic hypogonadism, streak gonads and a normal karyotype (46 XX). Audiologic evaluation showed sensorineural deafness. The patient was started on hormone replacement therapy. She is on regular follow up. We present this case for its infrequent incidence and also to add to the ever expanding clinical spectrum of this disease. PMID:25954653

  13. Pituitary stalk lesion in a 13-year-old female

    PubMed Central

    Zilbermint, Mihail; Ramnitz, Mary S.; Lodish, Maya B.; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J.; Quezado, Martha M.

    2016-01-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI. PMID:24129100

  14. 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

  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

    Zhang, Zhe; Feng, Ye; Ye, Dan; Li, Cheng-jiang; Dong, Feng-qin; Tong, Ying

    2015-11-01

    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. 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

  17. Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

    PubMed

    Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

    1998-12-01

    A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia. PMID:9932637

  18. Testosterone deficiency syndrome: benefits, risks, and realities associated with testosterone replacement therapy.

    PubMed

    Hassan, Jacob; Barkin, Jack

    2016-02-01

    Testosterone deficiency syndrome, which has sometimes been termed age-related or late-onset hypogonadism, is a syndrome characterized by both clinical manifestations as well as a biochemical deficiency of testosterone. This condition is associated with considerable morbidity and mortality, accounting for billions of dollars in health care costs. There is some evidence that suggests that restoring testosterone levels in these individuals may help to manage or delay progression of the associated morbidities. Furthermore, despite controversies in the literature and media, testosterone replacement has proven to be quite safe in most men with minimal if any adverse effects when dosing to achieve the eugonadal range. It is nevertheless very important for clinicians to be aware of the possible risks and contraindications of treatment to ensure proper patient selection and appropriate monitoring. PMID:26924592

  19. Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

    PubMed

    Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

    2013-01-01

    We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

  20. Differential Gene Expression Reveals Mitochondrial Dysfunction in an Imprinting Center Deletion Mouse Model of Prader-Willi Syndrome

    PubMed Central

    Fan, Weiwei; Coskun, Pinar E.; Nalbandian, Angèle; Knoblach, Susan; Resnick, James L.; Hoffman, Eric; Wallace, Douglas C.; Kimonis, Virginia E.

    2013-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder caused by deficiency of imprinted gene expression from the paternal chromosome 15q11-15q13 and clinically characterized by neonatal hypotonia, short stature, cognitive impairment, hypogonadism, hyperphagia, morbid obesity and diabetes. Previous clinical studies suggest that a defect in energy metabolism may be involved in the pathogenesis of PWS. We focused our attention on the genes associated with energy metabolism and found that there were 95 and 66 mitochondrial genes differentially expressed in PWS muscle and brain, respectively. Assessment of enzyme activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the brain, heart, liver and muscle were assessed. We found the enzyme activities of the cardiac mitochondrial complexes II+III were upregulated in the imprinting center deletion (PWS-IC) mice compared to the wild type littermates. These studies suggest that differential gene expression, especially of the mitochondrial genes may contribute to the pathophysiology of PWS. PMID:24127921

  1. Mini puberty and its interpretation

    PubMed Central

    Kurtoğlu, Selim; Baştuğ, Osman

    2014-01-01

    Gonadotropins which are high in the middle of the fetal life are measured to be considerably low in the cord blood and estrogen is found to be high in the cord blood. Gonodotropins are supressed by estrogen. After delivery, the hypothalamo-pituitary-gonadal axis is activated when estrogen is eliminated and a hormone profile which reaches pubertal levels is established. These changes are called mini puberty. In boys, long-term testicular functions and sperm production are regulated with mini puberty and mini puberty contributes to masculinization of the brain. The role of mini puberty in female newborns is not known. Central hypogonadism, Turner syndrome and ovarian hyperstimulation in preterm babies may be diagnosed with evaluation of mini puberty. In this article, mini puberty and related problems were reviewed and the importance of this issue was emphasized. PMID:26078661

  2. Short-term use of gonadotropin-releasing hormone agonist (leuprolide) for in vitro fertilization.

    PubMed

    Katayama, K P; Roesler, M; Gunnarson, C; Stehlik, E; Jagusch, S

    1988-12-01

    A common problem encountered by in vitro fertilization (IVF) programs is the premature occurrence of the spontaneous luteinizing hormone (LH) surge during ovarian stimulation cycles. Administration of gonadotropin-releasing hormone agonists (GnRH-a) for 2 to 3 weeks produces a state of hypogonadotropic hypogonadism, thus allowing ovarian stimulation to proceed uncomplicated by a spontaneous LH surge. We have elected to treat seven patients with GnRH-a in a "short-term" protocol, with GnRH-a initiated on cycle day 3 along with exogenous gonadotropins. In this series, we found that the spontaneous LH surge was abolished, while ovarian responsiveness seemed to be improved. These results suggest that the initial surge of gonadotropins elicited by GnRH-a administration may enhance ovarian stimulation and that spontaneous LH surge is blocked when GnRH-a and exogenous gonadotropins are initiated concomitantly.

  3. Selective androgen receptor modulators: in pursuit of tissue-selective androgens.

    PubMed

    Omwancha, Josephat; Brown, Terry R

    2006-10-01

    The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2.

    PubMed

    Aslanger, Ayca D; Altunoglu, Umut; Aslanger, Emre; Satkın, Bilge N; Uyguner, Zehra Oya; Kayserili, Hülya

    2014-02-01

    The disorder comprising Macrocephaly, Alopecia, Cutis laxa, and Scoliosis has been designated MACS syndrome. It is a rare condition, inherited in an autosomal recessive pattern. Three families from different ethnic origins have so far been reported and were all linked to homozygous mutations in RIN2, a gene encoding the Ras and Rab interactor 2 protein involved in cell trafficking. We describe herein the fourth family with MACS syndrome in two siblings carrying a novel homozygous mutation, c.1878_1879insC in exon 8 of the RIN2 gene, which predicts p.Ile627Hisfs*7. We also report on additional findings not previously described in MACS syndrome, including bronchiectasis and hypergonadotropic hypogonadism. Finally, our overall data support the argument that RIN2 syndrome is a more appropriate name for the disorder.

  9. Isolated adrenocorticotropin deficiency presenting as primary infertility.

    PubMed

    Atkin, S L; Masson, E A; White, M C

    1995-06-01

    A 31 year old female presented with primary infertility and gave a two year history of amenorrhea without symptoms or signs of endocrine dysfunction. Examination was normal and investigation showed low oestradiol and progesterone levels with decreased LH pulsatility. The cortisol responses were impaired following hypoglycaemic stress and a short synacthen test, but the cortisol response to a prolonged synacthen test was normal. An inadequate ACTH response to CRF testing confirmed the diagnosis of isolated ACTH deficiency. Hydrocortisone therapy was followed by an ovulatory menstrual cycle. Amenorrhea again ensued following the reduction of the steroid dose and normal menses resumed on normal steroid replacement therapy. Six hourly gonadotrophin pulsatility showed a significant increase in both pulse amplitude and mean LH and FSH levels following steroid treatment. Isolated ACTH deficiency is a rare but treatable cause of hypogonadism and infertility, and this case gives further insight on the role of cortisol on the hypothalamo-pituitary gonadal axis.

  10. GnRH Pulsatility, the Pituitary Response and Reproductive Dysfunction

    PubMed Central

    Tsutsumi, Rie; Webster, Nicholas J.G.

    2015-01-01

    GnRH plays an essential role in neuroendocrine control of reproductive function. In mammals, the pattern of gonadotropin secretion includes both pulse and surge phases, which are regulated independently. The pulsatile release of GnRH and LH plays an important role in the development of sexual function and in the normal regulation of the menstrual cycle. The importance of GnRH pulsatility was established in a series of classic studies. Fertility is impaired when GnRH pulsatility is inhibited by chronic malnutrition, excessive caloric expenditure, or aging. A number of reproductive disorders in women with including hypogonadotropic hypogonadism, hypothlamic amenorrhea, hyperprolactinemia and polycystic ovary syndrome (PCOS) are also associated with disruption of the normal pulsatile GnRH secretion. Despite these findings, the molecular mechanisms of this pulsatile GnRH regulation are not well understood. Here, we review recent studies about GnRH pulsatility, signaling and transcriptional response, and its implications for disease. PMID:19609045

  11. LEP — EDRN Public Portal

    Cancer.gov

    Leptin (LEP) is secreted by white adipocytes and plays a major role in the regulation of body weight. This protein, which acts through the leptin receptor, functions as part of a signaling pathway that can inhibit food intake and/or regulate energy expenditure to maintain constancy of the adipose mass. Leptin has also been implicated in the regulation of reproduction, glucose homeostasis, bone formation, wound healing and the immune system. Leptin has several endocrine functions and is also involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis and wound healing. Mutations in the leptin gene and/or its regulatory regions cause severe obesity and morbid obesity with hypogonadism. The leptin gene has also been linked to type 2 diabetes mellitus development.

  12. Fertility and fragrance: another cause of Kallmann syndrome

    PubMed Central

    Melmed, Shlomo

    2015-01-01

    Kallmann syndrome is an inherited deficiency of gonadotropin-releasing hormone (GnRH) that is characterized by hypogonadism with delayed or absent puberty and dysfunctional olfaction. While Kallmann syndrome–associated mutations have been identified in some sets of patients, for many of these individuals, the underlying cause remains unknown. In this issue of the JCI, Cariboni and colleagues identify mutations in semaphorin 3E (SEMA3E) in two brothers with Kallmann syndrome. In animal models, loss of SEMA3E signaling recapitulated phenotypes of the probands and resulted in enhanced GnRH neuron death during development. The results of this study offer important insight into the development of Kallmann syndrome and provide tools for elucidating mutations that underlie complex hormonal phenotypes. PMID:25985271

  13. Rathke's cleft cyst as a cause of growth hormone deficiency and micropenis.

    PubMed

    Setian, N; Aguiar, C H; Galvão, J A; Crivellaro, C E; Dichtchekenian, V; Damiani, D

    1999-05-01

    Rathke's cleft cyst has rarely been reported in pediatric patients, and such cysts are usually found by chance, in 2-33% of routine necropsies, as they have not interfered with pituitary function. In general, they are intrasellar with a single layer of ciliated cuboidal or columnar epithelium containing mucoid material. The age range in which symptomatic Rathke's cleft cysts occur is between 30 and 60 years. This paper reports an 8.1-year-old boy presenting with growth hormone deficiency and micropenis attributable to hypogonadotropic hypogonadism (HH), implying altered pituitary function since intrauterine life. At this age (before puberty) the diagnosis of HH can be made by means of the LHRH agonist stimulation test, since conventional LHRH is not able to discriminate HH from a normal prepubertal child. To our knowledge, this is the first case of micropenis caused by Rathke's cleft cyst interfering with gonadotropin and growth hormone secretion since intrauterine life.

  14. [Insufficiency of penis development (micropenis). Etiological data in a series of 25 cases].

    PubMed

    Vanelli, M; Chaussain, J L; Vassal, J; Job, J C

    1979-05-01

    The diagnosis of micropenis was made in 25 boys aged 1 month to 16 years. This abnormality was associated with hypothalamic-pituitary deficiency in 12 boys (hypogonadotrophic hypogonadism, hypopituitary growth failure, Prader-Willi syndrome), with testicular disorders in 5 boys (anorchia, testicular dysgenesis). In the other 8 the micropenis was an isolated finding but the testicular response to HCG and the LH response to LHRH was significantly reduced (p less than 0.005). The results suggest there may be isolated gonadotrophia deficiency. The variety of conditions that are responsible for micropenis suggest that testosterone deficiency is an important causative factor. HGH may also be important as the penis may be small in HGH deficiency and growth occurs with treatment.

  15. Response of micropenis to topical testosterone and gonadotropin.

    PubMed

    Klugo, R C; Cerny, J C

    1978-05-01

    Five patients were treated with gonadotropin and topical testosterone for micropenis associated with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonadotropin weekly for 3 weeks, with a 6-week interval followed by 10% topical testosterone cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent for both modes of therapy. Average penile growth response with gonadotropin was 14.3% increase in length and 5.0% increase of girth. Topical testosterone produced an average increase of 60% in penile length and 52.9% in girth. The greatest growth response occurred in prepubertal male subjects with a minimal response in postpubertal male subjects. This study suggests that 10% topical testosterone cream twice daily will produce effective penile growth. The response appears to be greater in younger children, which is consistent with previously published studies of age-related 5 reductase activity.

  16. Micropenis: does early treatment with testosterone do more harm than good?

    PubMed

    McMahon, D R; Kramer, S A; Husmann, D A

    1995-08-01

    Micropenis secondary to hypogonadotropic hypogonadism was induced in the Sprague-Dawley rat using long acting microspheres of the gonadotropic agonist leuprolide acetate. Following the induction of micropenis treatment was initiated with testosterone at day 7, 28, 56 or 84 of life. All treatment protocols resulted in improved phallic growth compared to the untreated animals with micropenis (p < 0.01). Treatment of animals with testosterone beginning on day 7 of life resulted in premature growth of the penis and the redevelopment of micropenis in adulthood. In contrast, delaying testosterone therapy until day 56 (pubertal) or 84 (early postpubertal) resulted in complete penile development. These findings suggest that early exposure of the penis to androgens in childhood may eventually result in a significant reduction of phallic size in adulthood.

  17. 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

  18. Male osteoporosis and androgenic therapy: from testosterone to SARMs.

    PubMed

    Cilotti, Antonio; Falchetti, Alberto

    2009-09-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance.Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials.

  19. [Metabolic syndrome: jumble syndrome of obesity or specific entity? Which treatment: diet or polypill?].

    PubMed

    Martin-Du Pan, Rémy C; Ruiz, Juan

    2008-02-01

    The reality of metabolic syndrome (MS) as a specific entity is debatable. However, the simple measure of waist circumference (>94 cm in men and >80 cm in women) is useful: (1) to check for insulin resistance by measuring serum levels of fasted glucose and insuline, cholesterol, triglycerides; (2) to look for diseases associated with MS such as hypertension, non alcohoolic steatohepatitis, sleep apnea, polycystic ovary disease, hypogonadism and to measure serum levels of ferritine, ALAT, ASAT, urate acid, CRP hs, testosterone and (3) to make obese people aware of their risk of becoming diabetic and to motivate them to change their life style. The utility of exercise and of various diets is discussed as well as the efficiency of drugs acting on different components of MS such as rimonabant, orlistat, metformin, glitazones, telmisartan and testosterone. The importance of political measures to fight the obesity epidemic is underlined. PMID:18386674

  20. Testosterone replacement therapy: should it be performed in erectile dysfunction?

    PubMed

    Celik, Orcun; Yücel, Selcuk

    2013-09-01

    The classical etiology of erectile dysfunction (ED) comprises aging and vascular, neurogenic, psychological and hormonal components. Recent studies have shown that ED can be the forerunner of serious cardiovascular disturbances. It has also been reported that peripheral neuropathy and microvascular injuries caused by pathophysiological changes in patients with diabetes and obesity lead to ED in a significant number of such cases. These patients develop clinically significant ED and comprise a significant portion of the patient group which do not respond to PDE-5 inhibitors. Testosterone has been shown to increase the expression of PDE-5. This function of testosterone supports its effect on the regulation of erection and increasing the sexual libido. In view of the complexity of ED, as well as the effect of testosterone on erection, it is concluded that PDE-5 inhibitors in combination with testosterone replacement would be a better therapy alternative in the management of erectile dysfunction in hypogonadal patients. PMID:24350081

  1. [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

  2. 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

  3. Use of a clinicoradiological score to determine the presurgical diagnosis of autoimmune hypophysitis in a teenage girl.

    PubMed

    Bose, Vivek; Caturegli, Patrizio; Conrad, Jens; Omran, Wael; Boor, Stephan; Giese, Alf; Gutenberg, Angelika

    2013-03-01

    The distinction between autoimmune hypophysitis and other non-hormone secreting pituitary masses is often difficult to determine with certainty without pituitary biopsy and pathological examination. To aid in this distinction, the authors recently published a clinicoradiological scoring system, which they used in the case of a 15-year-old girl presented here. The patient presented with headache, visual field defects, polydipsia, and polyuria, and she was found to have secondary hypogonadism and hypoadrenalism. Magnetic resonance imaging showed a pituitary mass of approximately 2 cm in diameter. Application of the clinicoradiological parameters gave a score of -6, which favored a diagnosis of hypophysitis over that of adenoma. The presence of pituitary autoantibodies substantiated the diagnosis of hypophysitis. The patient was treated conservatively with high-dose prednisolone, and her symptoms improved markedly. This case illustrates the utility of using a clinicoradiological score when autoimmune hypophysitis is suspected since it can identify patients who can be treated without the need for pituitary surgery.

  4. Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome

    PubMed Central

    Takagi, Masaki; Miyoshi, Tatsuya; Nagashima, Yuka; Shibata, Nao; Yagi, Hiroko; Fukuzawa, Ryuji; Hasegawa, Tomonobu

    2016-01-01

    Heterozygous kinase domain mutations or homozygous extracellular domain mutations in FGFR1 have been reported to cause Hartsfield syndrome (HS), which is characterized by the triad of holoprosencephaly, ectrodactyly and cleft lip/palate. To date, more than 200 mutations in FGFR1 have been described; however, only 10 HS-associated mutations have been reported thus far. We describe a case of typical HS with hypogonadotropic hypogonadism (HH) harboring a novel heterozygous mutation, p.His253Pro, in the extracellular domain of FGFR1. This is the first report of an HS-associated heterozygous mutation located in the extracellular domain of FGFR1, thus expanding our understanding of the phenotypic features and further developmental course associated with FGFR1 mutations. PMID:27790375

  5. 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

  6. 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

  7. 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

  8. DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation.

    PubMed

    Lalli, Enzo; Sassone-Corsi, Paolo

    2003-08-01

    The unusual orphan member of the nuclear hormone receptor superfamily DAX-1 (NR0B1) owes its name to its double role in human pathology. On one side, duplications in Xp21, containing the DAX-1 gene, cause phenotypic sex reversal in XY individuals. On the other side, DAX-1 gene mutations are responsible for adrenal hypoplasia congenita, invariably associated with hypogonadotropic hypogonadism. DAX-1 functions as a global negative regulator of steroid hormone production by repressing the expression of multiple genes involved in the steroidogenic pathway. Here we review the mechanism of DAX-1 function in adrenal and gonadal differentiation, with special emphasis on recent results showing the critical role of DAX-1 protein misfolding in the pathogenesis of adrenal hypoplasia congenita. PMID:12775766

  9. New Genes Controlling Human Reproduction and How You Find Them

    PubMed Central

    Crowley, William F.; Pitteloud, Nelly; Seminara, Stephanie

    2008-01-01

    The neuroendocrine control of reproduction in all mammals is governed by a hypothalamic neural network of approximately 1,500 gonadotropin releasing hormone (GnRH) secreting neurons that control activity of the reproductive axis across life. Recently, the syndrome of human GnRH deficiency, either with anosmia, termed Kallmann Syndrome (KS), or with a normal sense of smell, termed normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH), have proven important disease models that have revealed much about the abnormalities that can befall the GnRH neurons as they differentiate, migrate, form networks, mature and senesce. Mutations in several genes responsible for these highly coordinated developmental processes have thus been unearthed by the study of this prismatic disease model. This paper discusses several of the more important discoveries in this rapidly evolving field and puts them into a developmental and physiologic context. PMID:18596868

  10. [Testosterone replacement therapy and prostate cancer: the downfall of a paradigm?].

    PubMed

    Castillo, Octavio A; López-Fontana, Gastón; Vidal-Mora, Ivar; López Laur, José Daniel

    2015-04-06

    For six decades, it has been a part of the conventional medical wisdom that higher levels of testosterone increase the risk of prostate cancer. This belief is mostly derived from the well-documented regression of prostate cancer after surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Moreover, men with hypogonadism have substantial rates of prostate cancer in prostatic biopsies, suggesting that low testosterone has no protective effect against the development of prostate cancer. Moreover, prostate cancer rate is higher in elderly patients when hormonal levels are low. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

  11. An update on testosterone, HDL and cardiovascular risk in men

    PubMed Central

    Thirumalai, Arthi; Rubinow, Katya B; Page, Stephanie T

    2015-01-01

    Testosterone prescriptions have risen steadily and sharply in the USA despite a lack of clear understanding of the relationship between androgens and cardiovascular disease. In men with increasing age, testosterone levels decline and cardiovascular disease risk goes up. Ties between hypogonadism and cardiovascular disease are suggested by observational data, yet therapy with testosterone replacement has not been shown to mitigate that risk. To the contrary, recent literature has raised concern for increased cardiovascular disease in certain groups of men receiving testosterone therapy. In this article, we review current literature in an attempt to better understand what it suggests is the true relationship between testosterone and cardiovascular disease. We also take a closer look at effects of testosterone on lipids and HDL in particular, to see if this explains the cardiovascular effects seen in clinical studies. PMID:26257830

  12. Diabetes insipidus from neurosarcoidosis: long-term follow-up for more than eight years.

    PubMed

    Tabuena, Rollin P; Nagai, Sonoko; Handa, Tomohiro; Shigematsu, Michio; Hamada, Kunio; Ito, Isao; Izumi, Takateru; Mishima, Michiaki; Sharma, Om P

    2004-10-01

    Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium enhancement and attenuation in the intensity of the posterior lobe of the pituitary was detected without enhancement. Corticosteroid therapy resulted in the initial improvement of symptoms and gradual decrease in the tumor size but failed to cure polyuria due to DI. The use of desmopressin was necessary for a long period. None of these patients died from DI or central neurosarcoidosis.

  13. Is there a potential immune dysfunction with anabolic androgenic steroid use?: A review.

    PubMed

    Brenu, E W; McNaughton, L; Marshall-Gradisnik, S M

    2011-05-01

    Anabolic androgenic steroids (AAS) are artificial substances, acting through androgen receptors and were primarily developed for the treatment of hypogonadism, tumors, hypercalcemia, hypercalcuria and other chronic diseases. The discovery, in the early 1930s that these substances may have other benefits related to improvement in physique and athletic performance, has encouraged extensive use of these substances by amateur and professional athletes and members of the general public. The range of AAS used can be classified as either endogenous or exogenous. When used for ergogenic or recreational purposes the dosage is more often higher than the recommended dosage, and at supraphysiological levels, AAS can cause a number of serious side effects including liver dysfunction, myocardial infarction and potentially stroke, due to its ability to increase platelet and platelet aggregation. Furthermore, these high dosages may or can affect other physiological systems including the immune system. Hence, this paper reviews the current research on the effects of a number of specific AAS in the immune system.

  14. Obesity in the ageing man.

    PubMed

    Michalakis, K; Goulis, D G; Vazaiou, A; Mintziori, G; Polymeris, A; Abrahamian-Michalakis, A

    2013-10-01

    As the population is ageing globally, both ageing and obesity are recognized as major public health challenges. The aim of this narrative review is to present and discuss the current evidence on the changes in body composition, energy balance and endocrine environment that occur in the ageing man. Obesity in the ageing man is related to changes in both body weight and composition due to alterations in energy intake and total energy expenditure. In addition, somatopenia (decreased GH secretion), late-onset hypogonadism (LOH), changes in thyroid and adrenal function, as well as changes in appetite-related peptides (leptin, ghrelin) and, most importantly, insulin action are related to obesity, abnormal energy balance, redistribution of the adipose tissue and sarcopenia (decreased muscle mass). A better understanding of the complex relationship of ageing-related endocrine changes and obesity could lead to more effective interventions for elderly men.

  15. 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

  16. [Stimulation of spermatogenesis: For whom? Why? How?].

    PubMed

    Bertrand-Delepine, J; Leroy, C; Rigot, J-M; Catteau-Jonard, S; Dewailly, D; Robin, G

    2016-09-01

    The stimulation of spermatogenesis is the best treatment of infertility for male hypogonadotropic-hypogonadism. The results are very pleasing because a real improvement of semen is sometimes obtained with spontaneous pregnants describing in the literature but after a long duration of treatment, often many months. Sometimes, the treatment improves the technical conditions of ICSI for the embryologists. Stimulation of spermatogenesis by gonadotrophins rFSH and/or hCG is the most used but others treatments, like pulsatile GnRH therapy or clomifene citrate can be used. The purpose of this review is to described the different protocols of stimulation of spermatogenesis and explain their results and finally to see if others indications of stimulation of spermatogenesis are existing. PMID:27475410

  17. 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

  18. Testosterone and the metabolic syndrome

    PubMed Central

    Muraleedharan, Vakkat; Jones, T. Hugh

    2010-01-01

    Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life. However, there are no Long-term interventional studies to assess the effect of testosterone replacement on mortality in men with Low testosterone Levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome. PMID:23148165

  19. Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome.

    PubMed

    Braun, J-J; Noblet, V; Durand, M; Scheidecker, S; Zinetti-Bertschy, A; Foucher, J; Marion, V; Muller, J; Riehm, S; Dollfus, H; Kremer, S

    2014-12-01

    Bardet-Biedl syndrome (BBS) is a well-recognized ciliopathy characterized by cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity, hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction (anosmia, hyposmia) have been also described in BBS patients. Moreover, morphological brain anomalies have been reported and prompt for further investigations to determine whether they are primary or secondary to peripheral organ involvement (i.e. visual or olfactory neuronal tissue). The objective of this article is to evaluate olfactory disorders in BBS patients and to investigate putative correlation with morphological cerebral anomalies. To this end, 20 BBS patients were recruited and evaluated for olfaction using the University of Pennsylvania Smell Identification Test (UPSIT). All of them underwent a structural magnetic resonance imaging (MRI) scan. We first investigated brain morphological differences between BBS subjects and 14 healthy volunteers. Then, we showed objective olfaction disorders in BBS patients and highlight correlation between gray matter volume reduction and olfaction dysfunction in several brain areas.

  20. 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.