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Sample records for combined hormone replacement

  1. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  2. [Hormone replacement therapy].

    PubMed

    Nozue, E

    1994-03-01

    Hormone replacement therapy after menopause has shown so many advantages, such as reduction in risk of coronary artery disease and osteoporotic fracture besides treatment for climacteric symptoms, yet disadvantage such as a probability of an increase in the risk of breast cancer with long-term use still remains. In Japan HRT is now at the starting point. We must try to make more effort to accumulate data on the safety of HRT during-and-after menopause. It is our hope that doctors, not only gynecologists, but also doctors of other specialties will join our program for the health and happiness of women after menopause.

  3. Hormone replacement therapy.

    PubMed

    Scharbo-Dehaan, M

    1996-12-01

    More than 40 million women in the United States are now going through or are past menopause. Another 3.5 million or more will reach midlife in the next decade. As their life expectancy increases (mean life expectancy of women is now approximately 84 years), so does the need for therapeutic regimens related to reproductive function and aging in woman. Few medical treatments available to menopausal and postmenopausal women have as much potential benefit as well as possible health risks as hormone replacement therapy (HRT). Despite the increasing amount of scientific data available regarding the benefits of HRT, a degree of uncertainty still remains, both in the minds of some women, and with some health professionals, regarding the risks associated with long-term therapy. Even though the literature is voluminous, contradictory, and unclear, health providers must be able to keep abreast of current knowledge about the benefits, risks, and unknowns of these drugs. The purpose of this article is to provide a review and an update on the types of hormones available for HRT, their pharmacology and pharmacokinetics, and their risks, benefits, and contraindications. Newer products, specially compounded formulas, new regimens, and new modes of delivery that offer women alternatives and allow care to be individualized are described. In addition, some of the ongoing management dilemmas that practitioners face with the woman who chooses HRT are presented with practical solutions and suggestions.

  4. Hormone replacement therapy and longevity.

    PubMed

    Comhaire, F

    2016-02-01

    To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post-menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.

  5. Perspectives in hormone replacement therapy.

    PubMed

    Kenemans, P; van Unnik, G A; Mijatovic, V; van der Mooren, M J

    2001-06-15

    Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.

  6. Pharmacogenetic modulation of combined hormone replacement therapy by progesterone-metabolism genotypes in postmenopausal breast cancer risk.

    PubMed

    Rebbeck, T R; Troxel, A B; Norman, S; Bunin, G; DeMichele, A; Schinnar, R; Berlin, J A; Strom, B L

    2007-12-15

    Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided p(interaction) = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism.

  7. Hormone replacement after thyroid and parathyroid surgery.

    PubMed

    Schäffler, Andreas

    2010-11-01

    Hypothyroidism and hypocalcemia are common after thyroid and parathyroid surgery. In this article, the authors provide clinically-oriented recommendations to help surgeons, general practitioners, internists, and endocrinologists give their affected patients adequate hormone replacement therapy. Selective evaluation of original articles and reviews that were retrieved by a PubMed search over the years 1980 to 2010, as well as of the recommendations of medical societies including the Endocrine Society (USA), the German Society for Endocrinology (Deutsche Gesellschaft für Endokrinologie), and the American and European Thyroid Associations. Important issues in L-thyroxine replacement therapy include: the selection of the hormone preparation (T4 or T4/T3), combination with iodine (yes/no), the definition of therapeutic TSH ranges (particularly after surgery for thyroid cancer), the extent of remaining thyroid tissue after goiter surgery and its significance, underlying diseases, and drug interactions. The major issues in the treatment of postoperative hypoparathyroidism are: the selection of suitable calcium and vitamin D preparations, the definition of therapeutic goals, the treatment of hypercalciuria and hyperphosphatemia, and the option of recombinant parathormone therapy. Effective treatment requires an appropriate choice of medication and an understanding of its pharmacokinetics as well as of the possible effects of the patient's underlying disease, comorbidities, and other medications on its absorption and metabolism.

  8. [Hormone replacement therapy: curse or blessing?].

    PubMed

    Schmidt, M; Fink, D; Lang, U; Kimmig, R

    2006-01-01

    There is a controversial discussion on the risks and benefits of hormonal replacement therapy (HRT), and many women and doctors have revised their opinions of HRT over the last few years. Complementary and alternative therapies can be considered an option to treat menopausal symptoms. The following issue summarizes the actual knowledge of treatment options of menopausal symptoms.

  9. Growth hormone replacement therapy in Costello syndrome.

    PubMed

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  10. Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17beta-estradiol and norethindrone acetate.

    PubMed

    Odmark, I S; Jonsson, B; Bäckström, T

    2001-05-01

    We studied bleeding patterns in postmenopausal women who were using 2 types of continuous combination regimens. A prospective, double-blind, randomized study of 208 postmenopausal women treated with conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 5 mg, or with 17beta-estradiol, 2 mg, and norethindrone acetate, 1 mg. The mean number of bleeding days decreased during the first 4 months of treatment (P <.002) but not thereafter. The number of bleeding days was fewer (P <.002) and the time until amenorrhea was shorter (P <.02) in patients receiving conjugated estrogen and medroxyprogesterone acetate than in patients receiving 17beta-estradiol and norethindrone acetate. The odds ratio for progression to amenorrhea with the use of conjugated estrogen and medroxyprogesterone acetate was 1.58, in comparison with the use of 17beta-estradiol and norethindrone acetate. A thick endometrium at the start of treatment resulted in more bleeding days than were found for a thin endometrium (P <.03). Body mass index, age, and blood pressure had no predictive value for bleeding problems. Treatment with continuous combined conjugated estrogen and medroxyprogesterone acetate resulted in fewer bleeding problems than did treatment with 17beta-estradiol and norethindrone acetate. Endometrial thickness may help to predict the chance of achieving amenorrhea during early hormone replacement therapy.

  11. Hormone Replacement Therapy, Iron, and Breast Cancer

    DTIC Science & Technology

    2005-10-01

    culture models with different status of estrogen and progesterone receptors as well as an iron loaded transgenic mouse model. Our results have shown that...Hormone replacement therapy, iron, estrogen, cell proliferation, progesterone , breast cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...release an egg every month. Estrogen and progesterone together help regulate this event. As a woman matures, the ovaries have fewer eggs to stimulate

  12. [How to stop hormone replacement therapy?].

    PubMed

    Polo, Päivi

    2015-01-01

    Hormone replacement therapy is indicated for the treatment of menopausal and urogenital symptoms. The therapy is recommended to be started at the lowest effective dose for a minimum period of time. Discontinuation of the therapy or at least reduction of the dose should be considered yearly. The treatment can be stopped immediately or gradually. The risk of recurrence of menopausal symptoms is equal for both techniques of cessation. Furthermore, the number of those having restarted the therapy does not differ between cessation techniques. A woman is thus able to choose her own cessation technique. Immediate cessation is often successful, whereby complicated instructions for drug reduction are avoided.

  13. Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: a direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens.

    PubMed

    Simon, J A; Symons, J P

    2001-01-01

    To determine whether there are differences between continuous combined hormone replacement therapies on bleeding control. Nine hundred and forty-five postmenopausal women were randomized to one of seven double-blind treatment groups (placebo, 0.25 mg norethindrone acetate (NA)/5 microg ethinyl estradiol (EE), 1 mg NA/5 microg EE, 0.5 mg NA/10 microg EE, 1 mg NA/10 microg EE, 5 microg EE, and 10 micro EE) or unmasked 0.625 mg conjugated equine estrogens (CEE)/2.5 mg medroxyprogesterone acetate (MPA). Treatment was for 12 months; subjects kept daily diaries recording whether they had bleeding and/or spotting. The results focused on currently commercially available hormone replacement therapy products (femhrt [1 mg NA/5 microg EE] and Prempro [0.625 mg CEE/2.5 mg MPA]) as well as a high-dose NA/EE dose combination (1/10) over the first 6 months of use, the most critical period in establishing treatment adherence. At the end of month 6 there was a greater incidence of amenorrhea with both NA/EE dose combinations compared with CEE/MPA (p = 0.009 for 1 mg NA/5 microg EE and p = 0.006 for 1 mg NA/10 microg EE). Statistically significantly more women were amenorrheic at every month based on cumulative amenorrhea for 1 mg NA/5 microg (p < 0.05) compared with CEE/MPA; at months 3 and 6 more women were amenorrheic on 1 mg NA/10 microg EE compared with CEE/MPA using the cumulative amenorrhea parameter. The results indicate that statistically significantly more women attained amenorrhea based on various parameters when administered continuous combined NA/EE compared with CEE/MPA. The potential for long-term treatment compliance based on better bleeding control may optimize the opportunity to prevent osteoporosis as well as other associated health benefits.

  14. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    PubMed

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  15. [Historical perspective of hormone replacement therapy].

    PubMed

    Chanson, Philippe

    2005-02-28

    Clinical manifestations of menopause are partly related to estrogen deficiency. Estrogen replacement was long believed to reverse not only climacteric symptoms but also other chronic conditions associated with menopause such as osteoporosis, cognitive disorders or cardiovascular risk. However, it rapidly became obvious that hormone replacement therapy (HRT) was also associated with an increased risk of breast cancer and venous thrombo-embolic events. Until the end of the 1990's, based on cohort studies, HRT was thought to prevent cardiovascular complications of atherosclerosis. Risk/benefit ratio was thus considered as in favor of HRT, explaining its very wide prescription, after specific contra-indications have been ruled out. In 1998, the publication of HERS, the first randomized controlled study evaluating the effects of HRT in secondary cardiovascular prevention, allowed the scientific community to be conscious of the fact that HRT, not only did not prevent cardiovascular risk but also, probably, aggravated it. In 2002, the premature interruption of WHI study, by confirming that this was also true for primary prevention, has profoundly altered the common beliefs about HRT. Indeed, if HRT was associated with an increased cardiovascular risk, the benefits/risks ratio became unfavorable. Since that time, less women are treated and some of them have stopped their HRT. Recent recommendations have been published about indications of HRT, mainly based on the presence of climacteric symptoms. The potential interest of transdermic route for administration of estrogens needs to be confirmed. The potential deleterious effect of progestins needs to be explored. The difficult story of HRT had, at least, the merit to show, one more time, that in medicine, scientific evidence is always better than beliefs.

  16. Hormone Replacement Therapy and Your Heart

    MedlinePlus

    ... and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand potential risks to your heart and whether hormone therapy is right for you. By Mayo Clinic Staff ...

  17. Sex hormones, vascular function and the outcome of hormone replacement therapy in cardiovascular disease.

    PubMed

    Khalil, Raouf A

    2007-05-01

    Cardiovascular disease is more common in men and post-menopausal women than premenopausal women, suggesting that female sex hormones have vascular benefits. Cytosolic/nuclear estrogen and progesterone receptors mediate genomic transcriptional effects that stimulate endothelial cell growth and inhibit smooth muscle proliferation. Sex hormone receptors on the plasma membrane trigger nongenomic stimulation of endothelium-dependent nitric oxide-cyclic (c)GMP, prostacyclin-cAMP and hyperpolarizing vascular relaxation pathways, as well as inhibition of [Ca2+](i), protein kinase C and Rho-kinase-dependent mechanisms of smooth muscle contraction. Despite the vasodilator effects of sex hormones, the Heart and Estrogen/progestin Replacement Study (HERS), HERS-II and Women's Health Initiative clinical trials have shown minimal benefits of hormone replacement therapy (HRT) in post-menopausal cardiovascular disease. The prospect of HRT relies on further mechanistic analysis of the vascular effects of natural sex hormones and phytoestrogens, and the identification of specific estrogen receptor modulators. Androgens have vascular effects, and modulators of the estrogen/testosterone ratio could provide better HRT combinations. The timing/duration and the type, dose and route of administration of HRT should be customized according to the subject's age and pre-existing cardiovascular condition, thereby enhancing the outcome of HRT in cardiovascular disease.

  18. The replacement of serum by hormones in cell culture media.

    PubMed

    Sato, G; Hayashi, I

    1976-12-01

    The replacement of serum by hormones in cell culture media. (Reemplazo del suero por hormonas en el medio de cultivo de células). Arch. Biol. Med. Exper. 10: 120-121, 1976. The serum used in cell culture media can be replaced by a mixture of hormones and some accesory blood factors. The pituitary cell line GH3 can be grown in a medium in which serum is replaced by triiodothyronine, transferrin, parathormone, tyrotrophin releasing hormone and somatomedins. Hela and BHK cell strains can also be grown in serum free medium supplemented with hormones. Each cell type appears to have different hormonal requirements yet it may found that some hormones are required for most cell types.

  19. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    PubMed

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  20. Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

    PubMed Central

    Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

    2012-01-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

  1. Informing women about hormone replacement therapy: the consensus conference statement

    PubMed Central

    Mosconi, Paola; Donati, Serena; Colombo, Cinzia; Mele, Alfonso; Liberati, Alessandro; Satolli, Roberto

    2009-01-01

    Background The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/benefits. Methods We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: a literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone

  2. Hormone replacement therapy: the need for reconsideration.

    PubMed

    Rosenberg, L

    1993-12-01

    Millions of menopausal women are taking hormone supplements. Observational studies suggest that unopposed estrogens reduce the risk of cardiovascular disease and fractures and increase the risk of endometrial cancer and, possibly, breast cancer. In the absence of information from randomized trials, how much of the apparent beneficial effect on heart disease is due to the tendency of healthier women to use these drugs is unknown. The effect on the cardiovascular system of estrogen taken with a progestin is unknown, and this regimen may increase the risk of breast cancer. An approach to health and illness that focuses on a single cause or preventive and on single organ systems is severely limited. Alternative ways to improve cardiovascular and skeletal health that do not increase the risk of cancer are available. A reconsideration of the appropriate use of hormone supplements is needed.

  3. Postmenopausal hormone replacement and cardiovascular disease: incorporating research into practice.

    PubMed

    Chase, Susan K; Youngkin, Ellis Quinn

    2004-01-01

    The long-standing practice of prescribing hormones to postmenopausal women was based in part on the observation that following menopause, women's incidence of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cerebral vascular accident increased. Recent large-scale research has shown an increase in cardiovascular events for postmenopausal women receiving estrogen replacement in oral form. This article examines research on positive effects of hormone replacement therapy, discusses what is known about the development of cardiovascular disease in women, and evaluates recent research that has shown increased cardiovascular risk in women receiving hormone replacement. It concludes with recommendations for preventing cardiovascular disease in women. This is essential information for nurses, who need to be informed of ways to maintain their own health while serving as sources of health information for the public at large.

  4. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    PubMed Central

    Comasco, Erika; Frokjaer, Vibe G.; Sundström-Poromaa, Inger

    2014-01-01

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women's brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the left inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in several cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

  5. [Effects of growth hormone replacement therapy on bone metabolism].

    PubMed

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  6. The Language of Journalism in Treatments of Hormone Replacement News

    ERIC Educational Resources Information Center

    MacDonald, Susan Peck

    2005-01-01

    Researchers studying science communication have criticized the sensationalism that often appears in journalistic accounts of science news. This article looks at the linguistic sources of that sensationalism by analyzing the journalistic coverage of the Women's Health Initiative (WHI) study of hormone replacement research, which was abruptly…

  7. Hormone replacement therapy and the prevention of postmenopausal osteoporosis.

    PubMed

    Gambacciani, Marco; Levancini, Marco

    2014-09-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  8. Benefits and risks of sex hormone replacement in postmenopausal women.

    PubMed

    Seelig, Mildred S; Altura, Burton M; Altura, Bella T

    2004-10-01

    Because cardiovascular disease (CVD), which is far less common in young women than in men, but increases in prevalence in the postmenopausal years to that of men, estrogen repletion therapy (ERT) or combined hormone replacement therapy (HRT), has been widely used to protect against development of both CVD and osteoporosis, and possibly to delay or prevent cognitive loss or Alzheimer's disease (AD). To test the validity of favorable findings in many small-scale studies, and in clinical practice, a large-scale trial: the Women's Health Initiative (WHI) was undertaken by the National Institutes of Health (NIH), a trial that was prematurely ended because of increased CVD complications, despite some lessening of hip fractures. This paper suggests that the customary high intake of calcium (Ca)-advised to protect against osteoporosis, and the marginal magnesium (Mg) intake in the USA, might well be contributory to the adverse CV effects, that were all thromboembolic in nature. The procoagulant effect of estrogen is intensified by Ca; Mg-which counteracts many steps in the coagulation cascade and inhibits platelet aggregation and adhesion-is commonly consumed in sub-optimal amounts. The high American dietary Ca/Mg ratio might also be contributory to the WHI failure to confirm ERT's favorable mental effects. Discussed are mechanisms by which Mg enhances estrogen's central nervous system protective effects. Mg's improvement of cerebral blood flow, which improves brain metabolism, can also enhance removal of the beta amyloid peptide, accumulation of which is implicated in AD.

  9. Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer

    PubMed Central

    Hannoush, Zeina C.; Weiss, Roy E.

    2016-01-01

    Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body’s response to TH, and individualized therapy may be necessary in such patients. PMID:26886951

  10. Hormone replacement therapy and risk of epithelial ovarian cancer

    PubMed Central

    Purdie, D M; Bain, C J; Siskind, V; Russell, P; Hacker, N F; Ward, B G; Quinn, M A; Green, A C

    1999-01-01

    It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaign PMID:10507786

  11. Hormone replacement therapy and risk of epithelial ovarian cancer.

    PubMed

    Purdie, D M; Bain, C J; Siskind, V; Russell, P; Hacker, N F; Ward, B G; Quinn, M A; Green, A C

    1999-10-01

    It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.

  12. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study.

    PubMed

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Fechine, Pierre; Umbelino, Sonia; Lyra, Arão; Borges, Boniek; Freitas, Allan; Queiroz, Danilo Caldas de; Ruela, Ronaldo; Almeida, Jackson Guedes; Quintans, Lucindo

    2014-02-01

    To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  13. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    PubMed Central

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Fechine, Pierre; Umbelino, Sonia; Lyra, Arão; Borges, Boniek; Freitas, Allan; de Queiroz, Danilo Caldas; Ruela, Ronaldo; Almeida, Jackson Guedes; Quintans, Lucindo

    2014-01-01

    OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. PMID:24519196

  14. Alzheimer's disease, apolipoprotein E and hormone replacement therapy.

    PubMed

    Depypere, H; Vierin, A; Weyers, S; Sieben, A

    2016-12-01

    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  15. Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults.

    PubMed

    Beshyah, S A; Freemantle, C; Shahi, M; Anyaoku, V; Merson, S; Lynch, S; Skinner, E; Sharp, P; Foale, R; Johnston, D G

    1995-01-01

    The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months

  16. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    PubMed Central

    Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

    2013-01-01

    Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

  17. Stroke in women - oral contraception, pregnancy, and hormone replacement therapy.

    PubMed

    Rantanen, Kirsi; Tatlisumak, Turgut

    2013-01-01

    Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.

  18. Hormone signaling pathways under stress combinations.

    PubMed

    Suzuki, Nobuhiro

    2016-11-01

    As sessile organisms, plants are continuously exposed to various environmental stresses. In contrast to the controlled conditions employed in many researches, more than one or more abiotic and/or biotic stresses simultaneously occur and highly impact growth of plants and crops in the field environments. Therefore, an urgent need to generate crops with enhanced tolerance to stress combinations exists. Researchers, however, focused on the mechanisms underlying acclimation of plants to combined stresses only in recent studies. Plant hormones might be a key regulator of the tailored responses of plants to different stress combinations. Co-ordination between different hormone signaling, or hormone signaling and other pathways such as ROS regulatory mechanisms could be flexible, being altered by timing and types of stresses, and could be different depending on plant species under the stress combinations. In this review, update on recent studies focusing on complex-mode of hormone signaling under stress combinations will be provided.

  19. [What's new in hormone replacement therapy of postmenopausal women? II. Risks of hormone replacement therapy (HRT)].

    PubMed

    Martin-Du Pan, R C; Luzuy, F

    2000-06-01

    A 50 year old woman has a 10% lifetime risk of developing a breast cancer. Depending on the duration of the treatment, HRT can increase this risk by 30 to 45%. The risk of endometrial cancer, which affects 2.3% of women, is increased even if sequential progestogens are given together with estrogens. The risk of venous thrombosis is increased 3 times. The occurrence of ictus is not modified by HRT. On the other hand estrogens may prevent the abdominal deposit of fat. The cancer risks associated with HRT must be balanced against their protective effects on cardio-vascular (C-V)diseases. In untreated women, mortality due to C-V disease is 39% whereas mortality due to breast cancer is 3% and only 0.3% for endometrial cancer. This article discusses also the possibility of HRT and of non hormonal treatments in patients with previous breast cancer.

  20. Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.

    PubMed

    Newcomb, P A; Longnecker, M P; Storer, B E; Mittendorf, R; Baron, J; Clapp, R W; Bogdan, G; Willett, W C

    1995-10-15

    Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.

  1. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

    PubMed

    Stanická, Sona; Vondra, Karel; Pelikánová, Terezie; Vlcek, Petr; Hill, Martin; Zamrazil, Václav

    2005-01-01

    We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

  2. Genetics Home Reference: combined pituitary hormone deficiency

    MedlinePlus

    ... People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and ...

  3. Managing the menopause - British Menopause Society Council consensus statement on hormone replacement therapy.

    PubMed

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Stevenson, John; Williamson, Jennifer

    2003-09-01

    The British Menopause Society Council aims to aid health professionals to inform and advise women about the menopause. The oestrogen plus progestogen arm of the Women's Health Initiative was stopped in July 2002. This guidance regarding hormone replacement therapy (HRT) use responds to the results and analysis that have been published since then. Because there are few effective alternatives to HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have a major role. HRT is also most effective for prevention of osteoporosis. Unopposed oestrogens are contraindicated in women with an intact uterus, and hence a range of oestrogen and progestogen combinations, with differing routes of delivery, now exists under the title of "HRT". Treatment choice should be based on up to date information and targeted to individual women's needs. Hormone replacement still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  4. Combined Hormonal Birth Control: Pill, Patch, and Ring

    MedlinePlus

    ... AQ FREQUENTLY ASKED QUESTIONS FAQ185 CONTRACEPTION Combined Hormonal Birth Control: Pill, Patch, and Ring • What are combined hormonal birth control methods? • How do combined hormonal methods prevent ...

  5. Combined Hormonal Birth Control: Pill, Patch, and Ring

    MedlinePlus

    ... AQ FREQUENTLY ASKED QUESTIONS FAQ185 CONTRACEPTION Combined Hormonal Birth Control: Pill, Patch, and Ring • What are combined hormonal birth control methods? • How do combined hormonal methods prevent pregnancy? • ...

  6. Hormone replacement therapy benefits meibomian gland dysfunction in perimenopausal women

    PubMed Central

    Jin, Xiuming; Lin, Zhenyun; Liu, Yufang; Lin, Lin; Zhu, Binbin

    2016-01-01

    Abstract Meibomian gland dysfunction (MGD) is believed to be the leading cause of dry eye (DE) disease worldwide. The connection between aging and MGD has long been recognized. However, few studies have addressed the relationship between MGD and hormone replacement therapy (HRT) in perimenopausal women, and not have examined the prevalence of MGD in perimenopausal women. The purpose of this study was to address and evaluate the possible relationship between MGD and HRT in perimenopausal women. The results suggest that perimenopausal women have a high prevalence of DE related to perimenopausal symptoms. The study also shows that perimenopausal women who use HRT can gain benefits for DE as well as for perimenopausal symptoms. Physicians caring for women who are experiencing DE related to perimenopausal symptoms should consider HRT. PMID:27495030

  7. Periodontal aspects in menopausal women undergoing hormone replacement therapy.

    PubMed

    López-Marcos, Joaquín Francisco; García-Valle, Silvia; García-Iglesias, Angel Agustín

    2005-01-01

    Currently, an important number of women use HRT to control their hormonal problems during menopause. A large percentage of these have problems at periodontal level. The present study aims at examining the effects that menopause, due to a decline in the synthesis of hormones, mainly of estrogens, can cause on the oral dental health of such women; in particular on the characteristics of the gingiva and periodontium, checking whether characteristics such as gingival recession, pain, tooth mobility and periodontal pocket formation might permit physicians to evaluate the degree of bone loss in menopausal woman. Menopausal women aged 40 to 58 years of age undergoing hormone replacement therapy that had gingival periodontal disturbances. The total population of the study comprised 210 patients, divided into two groups. One group received HRT administered in patches and the other group did not receive this therapy. Gynecologic and odonto-stomatologic protocols were established for data collection. In order to assess the efficacy of the treatment a descriptive statistical study for sociodemographic variables, analysis of variance, McNemar's test and the Stuart-Maxwell test were performed. The mean age of the patients studied was 49.6 years. HRT acts as a protective factor in dental pain and improves tooth mobility and depth of the probing of periodontal pockets. With respect to the variable gingival recession, no significant results were found either for the group not receiving HRT or for the group being treated with patches. The response to the HR therapy in periodontal disease is probably due to the existence of estrogen receptors localized in the gingiva and in the periodontal ligament.

  8. Changes in magnetic resonance mammography due to hormone replacement therapy

    PubMed Central

    Pfleiderer, Stefan OR; Sachse, Steffen; Sauner, Dieter; Marx, Christiane; Malich, Ansgar; Wurdinger, Susanne; Kaiser, Werner A

    2004-01-01

    Background The aim of the present article is to investigate effects of hormone replacement therapy (HRT) on contrast medium enhancement patterns in postmenopausal patients during magnetic resonance mammography (MRM). Materials and methods Two hundred and fifteen patients receiving hormonal medication were divided into four groups: 150 patients with 1 MRM during HRT (group A), 13 patients with 2 MRMs under HRT (group B), 30 patients with 1 MRM during HRT and 1 MRM after HRT withdrawal (group C), and 22 women with 1 MRM after HRT withdrawal (group D). Dynamic MRM was performed at 1.5 Tesla. Signal intensity changes were characterized by five time curves: minimal enhancement (type I), weak continuous enhancement (type II), strong continuous enhancement (type III), and a steep initial slope followed by a plateau phenomenon (type IV) or a washout effect (type V). Results Of all 193 patients under HRT (group A + group B + group C), 60 patients (31.1%) showed curve type I, 88 patients (45.6%) showed type II and 45 patients (23.3%) showed type III. There were significant differences to 52 patients after HRT withdrawal (group C + group D) (P < 0.0001), with 42 patients (80.8%) for curve type I, 8 patients (15.4%) for type II, and 2 patients (3.8%) for type III. In both MRM sessions in group B, 69% of the patients showed identical curve types without significant differences (P = 0.375). In group C, 28 of 30 patients (93%) dropped to lower curve types with significant differences in curve types during and after HRT (P < 0.0001). Conclusion The majority of patients receiving postmenopausal HRT showed bilateral symmetrical, continuous enhancement without evidence of a plateau phenomenon or a washout effect due to HRT in MRM. Hormonal effects could be proven and were reproducible and reversible. PMID:15084246

  9. Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

    PubMed Central

    Rubin, Mishaela R.; Bilezikian, John P.

    2013-01-01

    Objective Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. Subjects and methods Standard histomorphometric and μCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. Results Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. Conclusion Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D. PMID:20485912

  10. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    MedlinePlus

    ... Can it cause vaginal bleeding? I'm taking hormone therapy for menopause symptoms, and my monthly menstrual periods ... Laughlin-Tommaso, M.D. Some forms of menopause hormone therapy may cause monthly bleeding. This includes cyclic hormone ...

  11. Menopausal Women's Access Path to Bioidentical Hormone Replacement Therapy: An Exploratory.

    PubMed

    Moro, Doris; Young, Wendy; Stein, Richard; Isaac, Winston; Goodman, Deborah

    2010-01-01

    The objective of this exploratory qualitative study was to describe (1) the key factors affecting women's initial decision to explore the use of bioidentical hormone, (2) where women gather their information on bioidentical hormones, (3) the enablers and barriers to obtaining bioidentical hormones, and (4) how to improve the bioidentical hormone replacement therapy access path. The study was conducted in a compounding pharmacy located in a large urban area in southern Ontario, Canada. The participants included four postmenopausal women between the ages of 46 and 72 who self-identified as users of bioidentical hormone replacement therapy and with comprehensive provincial healthcare coverage. Participants were recruited at a compounding pharmacy with the use of tri-fold brochures, tear-sheets, and posters. The women participated in an audio-taped mini focus group. Discussion was guided by six open-ended questions. Verbatim quotes were analyzed using an affinity diagram. Participants identified three key factors related to their initial decision: (1) symptoms unalleviated by synthetic hormone replacement therapy, (2) side effects from synthetic hormone replacement therapy, and (3) personal preference. They obtained information and support from many sources, including: family/friends, publications, and specialists in menopausal health. Once participants had made a decision, they obtained a prescription and accessed bioidentical hormone replacement therapy at a compounding pharmacy. Knowledgeable primary care physicians and compounding pharmacists were seen as enablers. Lack of support/Information and costs were identifies as barriers. Improvements to bioidentical hormone replacement therapy access path were suggested. The results of this study suggest that there may be value in implementing strategies to further encourage family physicians and other specialists in menopausal health to discuss options regarding hormone replacement therapy with patients. For example, the

  12. Improving adherence to hormone replacement therapy with effective patient-physician communication.

    PubMed

    Sarrel, P M

    1999-03-01

    Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

  13. Hormone Replacement Therapy and Risk for Neurodegenerative Diseases

    PubMed Central

    Dye, Richelin V.; Miller, Karen J.; Singer, Elyse J.; Levine, Andrew J.

    2012-01-01

    Over the past two decades, there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy (HRT) with regards to neurodegenerative disease. Here, we review basic science studies, randomized clinical trials, and epidemiological studies, and discuss the putative neuroprotective effects of HRT in the context of Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and HIV-associated neurocognitive disorder. Findings to date suggest a reduced risk of Alzheimer's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol. With regards to Parkinson's disease, there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol; however, results of clinical and epidemiological studies are inconclusive at this time, and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment. Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder. Limits to the existing research are discussed, along with proposed future directions for the investigation of HRT and neurodegenerative diseases. PMID:22548198

  14. Manufacturing heterosexuality: hormone replacement therapy and menopause in urban Oaxaca.

    PubMed

    Ramirez, Michelle

    2006-01-01

    For several decades, hormone replacement therapies have been prescribed to women, not only to prevent disease but to improve the sexual functioning of menopausal women. The medical promotion of continued sexual activity in a woman's post-reproductive years is exported to locations outside of North America and Europe, which provides an opportunity to critically examine the cultural roots that have informed expert biomedical representations. This ethnographic study examined menopause and social class in Oaxaca de Juarez, Mexico using interviews, questionnaires, and textual analysis. The research found that biomedicine in conjunction with the pharmaceutical industry promoted culturally constructed gender hierarchies under the guise of optimal menopausal health. However, women's actual experience of gender and sexuality in mid-life diverged significantly from these expert representations. Themes that emerged in interviews and questionnaires included the importance of motherhood in old age, diminished sexual desire as not problematic, and greater sexual freedom at a post-reproductive age. Ultimately, biomedical discourse was not the sole arbiter of appropriate menopausal womanhood and femininity.

  15. Social and behavioural influences on the uptake of hormone replacement therapy among younger women.

    PubMed

    Kuh, D; Hardy, R; Wadsworth, M

    2000-06-01

    To describe the social and behavioural influences on the uptake of hormone replacement therapy before the age of 50. Nationally representative birth cohort study with detailed hormone replacement therapy histories and prospective data on health, social and behavioural factors collected throughout life. England, Scotland and Wales. General population sample of 1,572 women followed to the age of 50 years. Age at first hormone replacement therapy use By the age of 50 years, 45% of women had tried hormone replacement therapy and one third were current users. Over two-fifths of users had tried more than one preparation and over one quarter had episodic use. For the vast majority, prescribing conformed to current guidelines. More educated women took hormone replacement therapy for long term prevention compared with their less educated peers. Hysterectomy increased the chances of taking hormone replacement therapy, particularly where an oophorectomy had also been performed, and was associated with longer and more continuous use. Results of a Cox's proportional hazards model showed that the age at which first hormone replacement therapy is used by women who have not had a hysterectomy was influenced by previous contact with health services for menstrual disorders, previous use of oral contraception and cigarettes, past reporting of health problems and low social class. The relation between smoking and low social class with early use of hormone replacement therapy may be due to their association with early menopause. The trend over the last two decades towards greater use of hormone replacement therapy has continued unabated for younger women. So far, hormone replacement therapy users in this generation have had less healthy lifestyles and social advantages than nonusers, in contrast to many older mainly American studies based on earlier generations. This may have long term implications for health and health care as the postwar baby boom generation ages.

  16. Managing the menopause: British Menopause Society Council consensus statement on hormone replacement therapy.

    PubMed

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Marsden, Jo; Stevenson, John; Williamson, Jennifer

    2005-12-01

    The British Menopause Society Council aims to help health professionals inform and advise women about the menopause. This guidance regarding estrogen-based hormone replacement therapy (HRT), including tibolone, which is classified in the British National Formulary as HRT, responds to the results and analysis of the randomized Women's Health Initiative studies and the observational Million Women Study. Treatment choice should be based on up-to-date information and targeted to individual women's needs. HRT still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  17. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    PubMed

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  18. [Postmenopausal hormone replacement therapy and the cardiovascular system].

    PubMed

    Yildirir, Aylin

    2010-03-01

    Women suffer from cardiovascular diseases 10 years later than men, therefore female sex has been considered to be a 'protective factor'. However, the risk in women increases rapidly after menopause and the declining levels of endogenous estrogen is thought to be responsible. Postmenopausal hormone replacement therapy (HRT) decreases the severity and intensity of menopausal symptoms and improves women's quality of life. Until the last 10 years, based on the results of observational studies, postmenopausal HRT was thought to protect women against cardiovascular events and decrease the risk of coronary artery disease by 35-50%. However, recent randomized primary and secondary prevention trials did not support the cardioprotective effect of HRT. The different results of observational and randomized controlled trials are discussed to be related to the differences in the study population. The study population in observational and prospective cohort studies included relatively young women at the earlier stages of menopause, whereas studies showing neutral or negative effects of HRT included women older than 50 years old at least 10 years in menopause. Furthermore, the effects of estrogen depend on the state of vascular pathology. In relatively healthy vessels with no or early signs of atherosclerosis, estrogen prevent the development or progression of atherosclerotic lesions, whereas in the presence of established atherosclerotic lesions, estrogen promotes atherosclerosis or may even trigger acute events. Therefore, it is critically important to predict which women can safely receive HRT and which are at increased risk from HRT. Under the light of current knowledge, HRT should not be used for prevention from cardiovascular disease in postmenopausal women and the many other preventive strategies, (diet, exercise, blood pressure or cholesterol control) that are proven to be effective but underused, should be kept in mind.

  19. Experience of hormone replacement therapy among women of Sarawak, Malaysia.

    PubMed

    Alwi, S A R Syed; Rubiah, Z Siti; Lee, P Y; Mallika, P S; Haizal, M N Md

    2010-12-01

    To determine the usage of hormone replacement therapy (HRT) and knowledge about HRT among women of Sarawak in Malaysia. A prospective study using a face-to-face interview was conducted on 356 randomly selected Sarawakian women aged between 40 and 65 years. The mean age of respondents was 50.83 ± 6.30 years and the mean age of menopause was 51.28 ± 2.28 years. Twenty-three percent of women were premenopausal, 39.6% perimenopausal and 37.4% postmenopausal. Only 36% of the respondents were aware of the existence of HRT; this is especially among those who were younger women, better educated and working. The main sources of information on HRT were friends and relatives (92.2%), newspapers/magazines (89.1%) and television/radio (64.1%). HRT usage among respondents was low (8.1%), mainly for relief of menopausal symptoms such as night sweats (100%), mood swings (93.1%), irritability (93.1%), and hot flushes (86.2%); only 24.1% used it for the prevention of osteoporosis. All women on HRT had taken HRT for less than 3 years. The main reason given for not being on HRT was that it was not recommended by their doctors (56.6%); only 8.3% worried about the side-effects and 4.3% were on other forms of treatment. The use of and knowledge about HRT among women of Sarawak were found to be low in our study. The main sources of information about HRT are from friends/relatives and the mass media. Health-care providers should play an important role in promoting, counseling and health education regarding HRT needs to rectify these problems.

  20. Adult Growth Hormone Deficiency – Benefits, Side Effects, and Risks of Growth Hormone Replacement

    PubMed Central

    Reed, Mary L.; Merriam, George R.; Kargi, Atil Y.

    2013-01-01

    Deficiency of growth hormone (GH) in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality. When dosed appropriately, GH replacement therapy (GHRT) is well tolerated, with a low incidence of side effects, and improves most of the alterations observed in GH deficiency (GHD); beneficial effects on mortality, cardiovascular events, and fracture rates, however, remain to be conclusively demonstrated. The potential of GH to act as a mitogen has resulted in concern over the possibility of increased de novo tumors or recurrence of pre-existing malignancies in individuals treated with GH. Though studies of adults who received GHRT in childhood have produced conflicting reports in this regard, long-term surveillance of adult GHRT has not demonstrated increased cancer risk or mortality. PMID:23761782

  1. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism.

    PubMed

    Muderris, Iptisam Ipek; Boztosun, Abdullah; Oner, Gokalp; Bayram, Fahri

    2011-01-01

    Primary hypothyroidism may be associated with ovarian enlargement and/ or cyst formation. We evaluated the effect of thyroid hormone replacement therapy on hormonal changes, ovarian volume and sonographic appearance. Open, prospective study of women admitted to university gynecology clinic. The study included 26 patients with untreated hypothyroidism who had polycystic (n=10) or normal-appearing (n=16) ovaries and 20 euthyroidic controls. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandosterone-sulfate, prolactin, estradiol, luteinizing hormone, follicle-stimulating hormone, free T3, free T4 and thyroid-stimulating horone, together with ovarian volumes, were determined and repeated after euthyroidism was achieved. Ovarian volumes of patients with hypothyroidism were significantly greater compared with controls, and their magnitudes diminished significantly during thyroid hormone replacement therapy. Hypothyroidic patients with polycystic ovaries had significantly higher serum free testosterone and dehydroepiandosterone-sulfate, but lower androstenodione levels compared with those who had normal-appearing ovaries. Serum total testosterone concentrations were significantly higher in hypothyroidic patients without polycystic ovaries, and thyroid hormone replacement therapy achieved a significant reduction in total as well as free testosterone. Severe longstanding hypothyroidism leads to increased ovarian volume and/or cyst formation. A decrease in ovarian volume, resolution of ovarian cysts and reversal of the polycystic ovary syndrome-like appearance, together with improvement in serum hormone levels, occurred after euthyroidism was achieved.

  2. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.

    PubMed

    Ruiz, Andres D; Daniels, Kelly R

    2014-01-01

    Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P < 0.01), irritability (36%, P = 0

  3. [Hormonal deficiencies in the elderly: is there a role for replacement therapy?].

    PubMed

    Racaru-Honciuc, Valentina; Betea, Daniela; Scheen, André J

    2014-08-27

    Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed.

  4. Hormone replacement in disorders of sex development: Current thinking.

    PubMed

    Hewitt, Jacqueline; Zacharin, Margaret

    2015-06-01

    Congenital disruptions of sex hormone production lead to wide-ranging developmental and physiological effects in individuals who have atypical chromosomal, gonadal or anatomic sex. Aberrant developmental sex hormone exposure causes disorders of genital anatomy, attainment of secondary sexual characteristics and has long-term effects on metabolism, fertility and psychological functioning. Principles in the management of disorders of sex development (DSD) aim to improve physiological health and long-term outcome, as well as development of male or female sexual anatomy. Concerns raised by DSD patient advocacy groups about beneficence and autonomy with respect to prescribed hormone treatments and avoidance of unnecessary genital and gonadal surgery have demanded greater informed consent and attention to long-term outcome. Hormone treatment is influenced by underlying clinical diagnosis and by factors such as sex of rearing and gender identity of the affected individual. We describe diagnostic criteria for different DSDs, clinical considerations in management protocols, together with current concepts and detailed practical hormone treatments for male and female individuals with DSD. Gender identity issues requiring multidisciplinary consensus, ethical consideration and informed consent or assent from the young person are also addressed.

  5. Replacement therapy: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine, testosterone and estrogen.

    PubMed

    Mitchell, D H; Owens, B

    1996-06-01

    Replacement therapy is routinely used to treat hormone deficiencies of patients who have had surgery or radiation therapy that damages the hypothalamus or pituitary gland. Hormones commonly replaced include: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine (T4), testosterone and estrogen. AVP, synthesized in the hypothalamus, is stored in and released by the posterior lobe of the pituitary gland. GH is synthesized and released by the anterior pituitary gland. The other hormones are produced and released by target glands each of which is stimulated by a specific anterior pituitary hormone, which in turn is controlled by release of a specific hypothalamic hormone. Feedback control by a high circulating concentration of the target gland's hormone regulates hypothalamic hormone release. Deficiency of AVP, important for water balance in the body, is restored with the synthetic analogue, 1-desamino-8-D-arginine vasopressin (DDAVP); it is given as a nasal spray or by injection. GH is required for normal growth in the developing child; recombinant GH, produced in bacteria, is injected subcutaneously. Adrenocorticotropic hormone (ACTH) controls release of cortisol which is produced by the adrenal cortex and enables the body to cope with stress; cortisol is replaced with prednisolone given orally. Thyroid stimulating hormone (TSH) controls release of the thyroid hormones, T4 and triiodothyronine (T3), which promote growth and development, and regulate energy metabolism; for replacement of T4, oral synthetic L-thyroxine is given. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control release of testosterone, which promotes maturation of sperm and development of male sexual characteristics; replacement testosterone is administered intramuscularly. In females, FSH and LH control release of estrogens and progesterone which prepare the reproductive tract for release of the ovum, fertilization, implantation and development of the embryo

  6. [Decrease of labor absenteeism associated with hormone replacement therapy in postmenopausal women].

    PubMed

    Blümel, J E; Sáez, L; Roncagliolo, M E; Tacla, X; Brandt, A

    1995-08-01

    Absenteeism affects efficiency and costs of health care. Most of health workers are middle age women, whose climacteric symptoms may reduce their work capacity working at a public hospital in Santiago during 1992. Fifty-eight percent were postmenopausal and 34.8% of these were receiving hormone replacement therapy. Global absenteeism rate was 17.1 days/year. These figures were 14.8 days/year for premenopausal and 17.8 days/year for postmenopausal women (NS). Among the latter, those women receiving hormone replacement therapy had a significantly lower absenteeism rate (9.4 days/year compared to 20.4 days/year among those not receiving hormones). Osteoarticular diseases were responsible for 44.3% and psychiatric diseases for 18.1% of sick leaves. No differences in absenteeism were observed between different professional levels. We conclude that hormone replacement therapy is associated with a better working capacity in postmenopausal women.

  7. Variations on hormone replacement therapy: an answer to the 'one dose fits all' Women's Health Initiative study.

    PubMed

    Studd, John

    2007-11-01

    The Women's Health Initiative study worked on the assumption that one dose would fit all asymptomatic postmenopausal women. The investigators therefore often used the wrong dose, of the wrong hormones, on the wrong patients and therefore came to many wrong conclusions. Different combinations of different hormones are necessary for different symptoms and different age groups. Hormone replacement therapy may be commenced in the perimenopausal phase, the early postmenopause, the late postmenopause or after hysterectomy and bilateral salpingo-oophorectomy or a premature menopause. These all require different treatments. Similarly, various indications such as vasomotor symptoms, sexual problems, depression or the treatment/prevention of osteoporosis all need different combinations of estradiol and possibly progestogen and testosterone, according to the specific requirements of the patient.

  8. [Oral or trandsdermanl hormone replacement therapy reduces interleukine-6 levels].

    PubMed

    Saucedo García, Renata; Basurto Acevedo, Lourdes; Rico Rosillo, Guadalupe; Galván, Rosa E; Zárate Treviño, Arturo

    2006-03-01

    To compare the effect of oral and transdermal estrogen replacement therapy (ET) on circulating interleukin-6 (IL-6) in post-menopausal women. Prospective open trial study in 55 healthy hysterectomized postmenopausal women with a mean age of 52 years. Twenty-seven women received oral conjugated equine estrogens (0.625 mg daily) and the remaining 28 received transdermal estrogen replacement therapy (50 microg/day) during 6 months. At baseline both groups were similar as to age, body weight, and body mass index as well as serum levels of LH, FSH, 17-beta estradiol (E2) and IL-6. Baseline elevated IL-6 levels decreased significantly (p<0.05) after both oral and transdermal estrogen replacement therapy; this decrement showed no difference between the two groups. After the follow-up there were no differences in body weight and body mass index between groups; however, in the oral group there was a trend to increment this parameters. Serum levels of E2 and IL-6 were negatively correlated in the two groups and IL-6 was positively correlated with body mass index in untreated women and this correlation was the same in women with estrogen replacement therapy. The decrement of IL-6 after estrogen replacement therapy was similar for both routes of administration; in addition IL-6 had a negative correlation with E2 and a positive correlation with body mass index.

  9. Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis

    PubMed Central

    Li, Zhanzhan; Zhou, Qin; Li, Yanyan; Fu, Jun; Huang, Xinqiong; Shen, Liangfang

    2016-01-01

    The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency. PMID:27835910

  10. Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy.

    PubMed

    Going, Scott; Lohman, Timothy; Houtkooper, Linda; Metcalfe, Lauve; Flint-Wagner, Hilary; Blew, Robert; Stanford, Vanessa; Cussler, Ellen; Martin, Jane; Teixeira, Pedro; Harris, Margaret; Milliken, Laura; Figueroa-Galvez, Arturo; Weber, Judith

    2003-08-01

    Osteoporosis is a major public health concern. The combination of exercise, hormone replacement therapy, and calcium supplementation may have added benefits for improving bone mineral density compared to a single intervention. To test this notion, 320 healthy, non-smoking postmenopausal women, who did or did not use hormone replacement therapy (HRT), were randomized within groups to exercise or no exercise and followed for 12 months. All women received 800 mg calcium citrate supplements daily. Women who exercised performed supervised aerobic, weight-bearing and weight-lifting exercise, three times per week in community-based exercise facilities. Regional bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. Women who used HRT, calcium, and exercised increased femoral neck, trochanteric and lumbar spine bone mineral density by approximately 1-2%. Trochanteric BMD was also significantly increased by approximately 1.0% in women who exercised and used calcium without HRT compared to a negligible change in women who used HRT and did not exercise. The results demonstrate that regional BMD can be improved with aerobic, weight-bearing activity combined with weight lifting at clinically relevant sites in postmenopausal women. The response was significant at more sites in women who used HRT, suggesting a greater benefit with hormone replacement and exercise compared to HRT alone.

  11. [Role of hormone-replacement therapy for prevention of coronary artery disease in women].

    PubMed

    Gohlke-Bärwolf, C; von Schacky, C

    2005-01-01

    The postmenopausal increase in the incidence of coronary artery disease implied a protective effect of estrogens. Nonrandomized, clinical and experimental studies have supported this notion. In the first randomized study (HERS 1998) no protective effect on prognosis of postmenopausal women with coronary artery disease was demonstrated. Also, in healthy postmenopausal women no beneficial effect of a hormone-replacement therapy on coronary events was shown (WHI-Study 2002, 2004). Therefore, hormone-replacement therapy is not recommended for prophylaxis of cardiovascular disease in healthy women or in women with documented coronary artery disease (Recommendation class I, evidence-level A). The continuation or the start of a hormone- replacement therapy is only justified for therapy of severe menopausal symptoms. Women should be informed that changes in lifestyle including not smoking, a heart healthy diet, and regular exercise are the most important measures to prevent cardiovascular diseases.

  12. Postmenopausal hormone replacement therapy and risk of acute pancreatitis: a prospective cohort study

    PubMed Central

    Oskarsson, Viktor; Orsini, Nicola; Sadr-Azodi, Omid; Wolk, Alicja

    2014-01-01

    Background: Several case reports have suggested that women’s use of exogenous sex hormones is associated with acute pancreatitis; however, relevant epidemiologic data are sparse. We examined the association between postmenopausal hormone replacement therapy and risk of acute pancreatitis. Methods: We conducted a prospective study involving 31 494 postmenopausal women (aged 48–83 yr) from the population-based Swedish Mammography Cohort. Participants completed a baseline questionnaire in 1997 assessing their use of hormone replacement therapy. We linked the cohort to the hospital-based Swedish National Patient Register to determine hospital admissions for acute pancreatitis through 2010. Relative risks (RRs) were calculated using Cox proportional hazard models. Results: Over a total follow-up of 389 456 person-years, we identified 237 cases of incident acute pancreatitis. The age-standardized incidence rates per 100 000 person-years were 71 cases among women who had ever used hormone replacement therapy and 52 cases among women who had never used such hormones. Among ever users of hormone replacement therapy, the multivariable-adjusted RR of acute pancreatitis was 1.57 (95% confidence interval [CI] 1.20–2.05) compared with never users. The risk did not differ by current or past use, but it seemed to be higher among women who used systemic therapy (RR 1.92, 95% CI 1.38–2.66) and among those with duration of therapy of more than 10 years (RR 1.87, 95% CI 1.11–3.17). Interpretation: Use of postmenopausal hormone replacement therapy was associated with increased risk of acute pancreatitis. Physicians should consider this potential increase in risk when prescribing such therapy. PMID:24468693

  13. Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer

    PubMed Central

    Rennert, Gad; Rennert, Hedy S.; Pinchev, Mila; Lavie, Ofer; Gruber, Stephen B.

    2009-01-01

    Purpose Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency–related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. Patients and Methods The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. Results Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. Conclusion The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation. PMID:19704062

  14. Effects of recombinant growth hormone replacement and physical rehabilitation in recovery of gross motor function in children with cerebral palsy

    PubMed Central

    Reimunde, Pedro; Rodicio, Cristina; López, Natalia; Alonso, Alba; Devesa, Pablo; Devesa, Jesús

    2010-01-01

    Cerebral palsy is an important health issue that has a strong socioeconomic impact. There is no cure for cerebral palsy, and therapeutic approaches only report small benefits for affected people. In this study we assessed the effects of growth hormone treatment (0.3 μg/kg/day) combined with physical rehabilitation in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy (four males and six females, mean age 5.63 ± 2.32 years) as compared with that observed in a similar population of cerebral palsy children (five males, five females, mean age 5.9 ± 2.18 years) without growth hormone deficiency treated only with physical rehabilitation for two months. The Gross Motor Function Measure (GMFM-88) and Modified Ashworth Scale were performed before commencing the treatment and after completion thereof. In children with cerebral palsy and growth hormone deficiency, Dimension A (P < 0.02), dimension B (P < 0.02), and dimension C (P < 0.02) of the GMFM-88, and the total score of the test (P < 0.01) significantly improved after the treatment; dimension D and dimension E did not increase, and four of five spastic patients showed a reduction in spasticity. However, in children with cerebral palsy and without growth hormone deficiency, only the total score of the test improved significantly after the treatment period. This indicates that growth hormone replacement therapy was responsible for the large differences observed between both groups in response to physical rehabilitation. We propose that the combined therapy involving growth hormone administration and physical rehabilitation may be a useful therapeutic approach in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy. PMID:21151628

  15. Effects of recombinant growth hormone replacement and physical rehabilitation in recovery of gross motor function in children with cerebral palsy.

    PubMed

    Reimunde, Pedro; Rodicio, Cristina; López, Natalia; Alonso, Alba; Devesa, Pablo; Devesa, Jesús

    2010-11-30

    Cerebral palsy is an important health issue that has a strong socioeconomic impact. There is no cure for cerebral palsy, and therapeutic approaches only report small benefits for affected people. In this study we assessed the effects of growth hormone treatment (0.3 μg/kg/day) combined with physical rehabilitation in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy (four males and six females, mean age 5.63 ± 2.32 years) as compared with that observed in a similar population of cerebral palsy children (five males, five females, mean age 5.9 ± 2.18 years) without growth hormone deficiency treated only with physical rehabilitation for two months. The Gross Motor Function Measure (GMFM-88) and Modified Ashworth Scale were performed before commencing the treatment and after completion thereof. In children with cerebral palsy and growth hormone deficiency, Dimension A (P < 0.02), dimension B (P < 0.02), and dimension C (P < 0.02) of the GMFM-88, and the total score of the test (P < 0.01) significantly improved after the treatment; dimension D and dimension E did not increase, and four of five spastic patients showed a reduction in spasticity. However, in children with cerebral palsy and without growth hormone deficiency, only the total score of the test improved significantly after the treatment period. This indicates that growth hormone replacement therapy was responsible for the large differences observed between both groups in response to physical rehabilitation. We propose that the combined therapy involving growth hormone administration and physical rehabilitation may be a useful therapeutic approach in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy.

  16. Osteoporosis and cardiovascular disease: benefit-risk of hormone replacement therapy.

    PubMed

    Sammartino, A; Cirillo, D; Mandato, V D; Di Carlo, C; Nappi, C

    2005-01-01

    Post-menopausal osteoporosis represents a major public health problem. Osteoporotic fractures in older women constitute a major cause of disability, mortality and economic burden. Cardiovascular disease (CVD) is the primary cause of death in women in westernized countries, with more than one in two women dying from CVD. In literature it is well established that an early menopause increases the risk of CVD and that a later menopause is associated with longer overall survival. Until a few years ago, in the management guidelines, a combination of lifestyle and use of hormonal replacement therapy (HRT) was suggested to reduce the CVD risk in post-menopausal women. However, recent studies such as the Women's Health Initiative (WHI) trial and the Heart and Estrogen/Progestin Replacement Study (HERS) I and II has forced practitioners to reconsider their options for prevention of CVD in post-menopausal women. The increased risk of CVD and stroke which were not counterbalanced by the smaller reduction in numbers of hip fractures in the WHI and in the HERS I-II suggest new characteristics of women in which HRT could possibly exert a favourable risk/benefit ratio. The use of HRT in post-menopausal women might be considered in symptomatic women and it might be individualized for each patients. Therefore, for cardiovascular and osteoporosis risk, regular prevention programmes should serve the needs of middle-aged women.

  17. Impact of hormone therapy for women aged 35 to 65 years, from contraception to hormone replacement.

    PubMed

    Kase, Nathan G

    2009-01-01

    Midlife women (aged 35-65 years) present a complex combination of clinical challenges and health care opportunities. To meet these issues effectively, recognition of the various phases of the entire menopausal transition is necessary, because each possesses unique biological properties underlying phase-specific clinical presentations. The aim of this article is to inform health care decisions by defining the endocrine, metabolic, and clinical consequences of therapeutic inaction or intervention at each stage of the midlife experience. Using PubMed, MEDLINE was searched for age- and phase-specific publications about ovarian function and corresponding clinical manifestations in women aged 35 to 65 years. Large, long-term longitudinal prospective, case-control, and observational studies were selected for inclusion. Results of the Framingham Heart Study, Study of Women's Health Across the Nation, Nurses' Health Study (NHS), and Women's Health Initiative (WHI), as well as materials from the World Health Organization and American College of Obstetricians and Gynecologists, were obtained from the relevant groups' Web sites in 2008. Synthesis of the data acquired, particularly the confirmatory and contrasting elements displayed in the WHI and NHS publications, leads to a set of guiding principles whereby individualized phase-specific management strategies may be safely employed. These include the value of weight control and exercise; use of specific nonhormonal therapies for defined indications; definition of strict inclusion/exclusion criteria; and individualization of timing, regimen, dosage, and portal of entry for possible hormone therapy. An evidence-based, restrictive inclusion/exclusion strategy can be used to maximize benefits and minimize risks for this large, growing, and health-conscious but increasingly vulnerable population.

  18. Hormone replacement therapy and breast cancer mortality in Swedish women: results after adjustment for 'healthy drug-user' effect.

    PubMed

    Yuen, J; Persson, I; Bergkvist, L; Hoover, R; Schairer, C; Adami, H O

    1993-07-01

    No change of breast cancer mortality has been reported previously after long-term hormone replacement therapy. A conceivable explanation for the apparent discrepancy between incidence and mortality may be selection bias due to lower prevalence of breast cancer in women who receive replacement hormones, compared with nonexposed women. We used a new approach to correct for bias due to this 'healthy drug-user effect,' by adjusting the external, population-based, mortality rates for such cases prevalent during the recruitment period of our cohort. In this cohort of some 23,000 Swedish women, who were prescribed various hormone replacement regimens, breast cancer mortality was analyzed after follow-up to 12 years. External analyses revealed overall standardized mortality ratios for breast cancer rising from 0.71 to 0.81, but not significantly different from unity, after adjustment procedures. In multivariate regression models, excluding prevalent cases in the cohort, women prescribed estradiol, conjugated estrogens, or an estrogen-progestin combination were not at a higher risk relative to those given other and weak estrogens, relative risks being 0.81 and 0.68, respectively. On the basis of the present analytical approach, we conclude that breast cancer mortality does not appear to be changed overall or in subgroups, despite increased incidence.

  19. Functional Changes after Recombinant Human Growth Hormone Replacement in Patients with Chronic Traumatic Brain Injury and Abnormal Growth Hormone Secretion.

    PubMed

    Mossberg, Kurt A; Durham, William J; Zgaljardic, Dennis J; Gilkison, Charles R; Danesi, Christopher P; Sheffield-Moore, Melinda; Masel, Brent E; Urban, Randall J

    2017-02-15

    We explored the effects of recombinant human growth hormone (rhGH) replacement on physical and cognitive functioning in subjects with a moderate-to-severe traumatic brain injury (TBI) with abnormal growth hormone (GH) secretion. Fifteen individuals who sustained a TBI at least 12 months prior to study enrollment were identified as having abnormal GH secretion by glucagon stimulation testing (maximum GH response less than 8 ng/mL). Peak cardiorespiratory capacity, body composition, and muscle force testing were assessed at baseline and one year after rhGH replacement. Additionally, standardized neuropsychological tests that assess memory, processing speed, and cognitive flexibility, as well as self-report inventories related to depression and fatigue, were administered at baseline and 1 year after rhGH replacement. Comparison tests were performed with proper post hoc analyses. All analyses were carried out at α < 0.05. Peak O2 consumption, peak oxygen pulse (estimate of cardiac stroke volume), and peak ventilation all significantly increased (p < 0.05). Maximal isometric and isokinetic force production were not altered. Skeletal muscle fatigue did not change but the perceptual rating of fatigue was reduced by ∼25% (p = 0.06). Cognitive performance did not change significantly over time, whereas self-reported symptoms related to depression and fatigue significantly improved. The observed changes suggest that rhGH replacement has a positive impact on cardiorespiratory fitness and a positive impact on perceptual fatigue in survivors of TBI with altered GH secretion.

  20. Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer.

    PubMed

    Colditz, G A

    1998-06-03

    We sought to determine the strength of the evidence suggesting that estrogen and postmenopausal replacement hormones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE on hormones and breast cancer, including reports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link between environmental factors and disease were used to review the evidence for a causal relationship between female hormones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose-response pattern, biologic plausibility, temporality, strength of association, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The positive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hormones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relationship between use of estrogens and progestins, levels of endogenous estrogens, and breast cancer incidence in postmenopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal

  1. [Hormone replacement and selective estrogen receptor modulators (SERMS) in the prevention and treatment of postmenopausal osteoporosis].

    PubMed

    Pfeilschifter, J

    2001-07-01

    For many years, hormone replacement therapy (HRT) has been regarded as one of the most reliable means of prophylaxis and treatment for postmenopausal osteoporosis. As HRT ameliorates menopausal symptoms, it is widely prescribed among early postmenopausal women. A variety of different modes of replacement that suit each individual requirement are available in terms of schedule (cyclic or combined application of gestagens) and route of application (oral or transdermal). HRT effectively prevents spinal bone loss and delays bone loss at the hip up to a very old age. With continued use after menopause, HRT might theoretically halve the incidence of vertebral and hip fractures. However, long-term use or use of HRT in old age is rarely practiced, and the actual benefit of a transient use for future fracture prevention remains unclear. Raloxifene is the first member of the novel class of selective estrogen receptor modulators (SERMs) that has been approved for the prophylaxis and treatment of postmenopausal osteoporosis. It combines the positive effects of estrogen on the skeleton with estrogen-antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and decreases the incidence of vertebral fractures in osteoporotic women, but avoids many of the side effects that are responsible for the poor long-term compliance to HRT such as resumption or continuation of regular menses, breast tenderness, or breast cancer. It even markedly reduces the risk of breast cancer. Both estrogen and raloxifene are characterized by a large number of extraskeletal effects that have to be taken into account when counseling postmenopausal women on the use of these agents for the prevention or treatment of osteoporosis.

  2. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer

    PubMed Central

    Campagnoli, Carlo; Clavel-Chapelon, Françoise; Kaaks, Rudolf; Peris, Clementina; Berrino, Franco

    2005-01-01

    Controlled studies and most observational studies published over the last 5 years suggest that the addition of synthetic progestins to estrogen in hormone replacement therapy (HRT), particularly in continuous-combined regimen, increases the breast cancer (BC) risk compared to estrogen alone. By contrast, a recent study suggests that the addition of natural progesterone in cyclic regimens does not affect BC risk. This finding is consistent with in vivo data suggesting that progesterone does not have a detrimental effect on breast tissue. The increased BC risk found with the addition of synthetic progestins to estrogen could be due to the regimen and/or the kind of progestin used. Continuous-combined regimen inhibits the sloughing of mammary epithelium that occurs after progesterone withdrawal in a cyclic regimen. More importantly, the progestins used (medroxyprogesterone acetate and 19-Nortestosterone-derivatives) are endowed with some non-progesterone-like effects, which can potentiate the proliferative action of estrogens. Particularly relevant seem to be the metabolic and hepatocellular effects (decreased insulin sensitivity, increased levels and activity of insulin-like growth factor-I, and decreased levels of SHBG), which contrast the opposite effects induced by oral estrogen. PMID:15908197

  3. Endometrial safety of hormone replacement therapy: review of literature.

    PubMed

    Van Gorp, Toon; Neven, Patrick

    2002-06-25

    Unopposed estrogens for treating menopausal symptoms were extensively used when epidemiological findings associated them with an increased endometrial cancer risk. Adding progestogens reverse this side effect efficiently but patient, dose, type and especially time during which the progestogen is administered are important. Long-term uterine safety of the long cycle HRT with administration of the progestogen every 3 months remains unclear. Because regular bleeding lowers compliance, continuous combined estrogen-progestogen treatment has become popular. Many different regimens are now available using oral, transdermal, subcutaneous, intravaginal or intra-uterine application of the estrogen and/or progestogen. Available but inadequate studies seem to point towards a slightly decreased endometrial cancer risk with continuous combined preparations compared with non-HRT-users and an increased risk with long-term oral but not vaginal treatment with low-potency estrogen formulations such as estriol. Newer compounds for menopausal health such as tibolone and raloxifene seem to be safe. As for any women with abnormal vaginal bleeding, those on HRT must have an intra-uterine evaluation. Transvaginal ultrasound (TVU) is very accurate in predicting a normal uterine cavity but inaccurate in predicting endometrial pathology because of a low specificity and positive predictive value of a thick echogenic endometrium. In all such cases a three-dimensional visualisation of intra-uterine lesions is more accurate. Periodic examination with TVU and/or endometrial biopsy of HRT exposed endometrium in asymptomatic women is not cost-effective. The available limited data on the use of HRT in hysterectomised women for early stage endometrial cancer show little evidence in terms of recurrence.

  4. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 2.

    PubMed

    Deleruyelle, Laura J

    2016-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provides a brief discussion

  5. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.

    PubMed

    Deleruyelle, Laura J

    2017-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion

  6. Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation

    SciTech Connect

    Webber, C.E.; Beaumont, L.F.; Gordon, C.L.

    1995-12-01

    Hormone replacement therapy (HRT) in postmenopausal women suppress the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty-six women who at recruitment were on average 3.5 years postmenopausal were placed on calcium supplementations. Six months later, 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p=0.007). Tibia lead content (mean {plus_minus} SD) for women on calcium only was 11.13 {plus_minus}6.22 {mu}g/g bone mineral. For women on HRT, tibia bone lead was 19.37 {plus_minus}8.62 {mu}g/g bone mineral on low-dose HRT and 16.87 {plus_minus} 11.68 {mu}g/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum, or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone. 27 refs., 1 fig., 1 tab.

  7. Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review).

    PubMed

    Laway, Bashir Ahmad; Bhat, Javid Rasool; Mir, Shahnaz Ahmad; Khan, Raja Sultan Zaman; Lone, Mohd Iqbal; Zargar, Abdul Hamid

    2010-03-01

    Reports of pancytopenia in patients with Sheehan's syndrome are rare, because the disorder is not commonly seen in western countries. A case series of pancytopenia in three patients of Sheehan's syndrome is presented. Three women aged 22, 30, and 34 years developed Sheehan's syndrome preceded by post partum hemorrhage. During investigations, they were found to have pancytopenia with hypocellular marrow. Treatment with thyroxine and glucocorticoids resulted in complete recovery after attaining euthyroid and eucortisolemic state. Review of literature revealed the rarity of the disorder, with only four cases reported so far. Multiple anterior pituitary hormone deficiencies in Sheehan's syndrome are responsible for pancytopenia; replacement of thyroid and cortisol hormones results in complete recovery.

  8. Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone.

    PubMed

    Mueck, A O

    2012-04-01

    Most available postmenopausal hormone replacement therapies (HRT) offer similar efficacy, but differ with respect to the cardiovascular risks associated with their use. There is a wealth of evidence to suggest that, unlike oral estrogens, transdermal estradiol does not increase the risk of venous thromboembolism, probably due to its lack of effect on the coagulation cascade, including thrombin generation and resistance to activated protein C, and does not increase the risk of stroke. It is cardioprotective, significantly reducing the incidence of myocardial infarction compared with non-users; it significantly reduces the incidence of new-onset diabetes, a risk factor for myocardial infarction. Micronized progesterone has also been shown not to increase the risk of venous thromboembolism and further reduced the incidence of new-onset diabetes when combined with transdermal estrogen. Micronized progesterone has a neutral effect on the vasculature, including a neutral or beneficial effect on blood pressure. Therefore, experimental and clinical data indicate that transdermal estradiol and micronized progesterone could represent the optimal HRT, particularly in women at risk of adverse events.

  9. Insulin resistance in postmenopausal women: concurrent effects of hormone replacement therapy and coffee.

    PubMed

    Catalano, D; Trovato, G M; Spadaro, D; Martines, G F; Garufi, G; Tonzuso, A; Grasso, D; Sciacchitano, S G

    2008-10-01

    In postmenopausal women, an increase in insulin resistance is associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Hormone replacement therapy (HRT) can reduce insulin resistance and coffee use is reported to decrease the incidence of diabetes. The aim of our study was to assess possible concurrent effects of HRT and espresso coffee intake on insulin resistance and on interdependent nutritional and clinical features. A total of 478 healthy postmenopausal, non-diabetic women (aged 54.5 +/- 4.2 years) were studied: 360 had been on HRT for at least 2 years and 118 were not treated. Insulin resistance was assessed by a conventional homeostasis model (HOMA-IR). Insulin resistance is directly related to body mass index (p < 0.0001), and not with age and blood pressure; hypertensive menopausal women have a slightly higher body mass index but the same degree of insulin resistance as normotensive women. Women on HRT show lower insulin resistance, but not lower prevalence of arterial hypertension. Coffee use is associated with a decrease in insulin resistance in non-obese women receiving HRT, but not in other subsets. The combination of coffee consumption and HRT could lower insulin resistance in postmenopausal women. In overweight women, greater insulin sensitivity is associated with intake of espresso coffee and not with HRT; in normal weight women, only HRT is associated with lower insulin resistance.

  10. Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

    PubMed Central

    Sare, Gillian M.; Gray, Laura J.; Bath, Philip M.W.

    2008-01-01

    Aims Randomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear. Methods and results RCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14–1.53) and VTE (OR 2.05, 95% CI 1.44–2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90–1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12–1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE. Conclusion HRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy. PMID:18599555

  11. Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults.

    PubMed

    Feldt-Rasmussen, Ulla; Wilton, Patrick; Jonsson, Peter

    2004-06-01

    Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were

  12. Angiogenic and tissue remodeling factors in the prostate of elderly rats submitted to hormonal replacement.

    PubMed

    Montico, Fábio; Hetzl, Amanda Cia; Cândido, Eduardo Marcelo; Cagnon, Valéria Helena Alves

    2013-11-01

    The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague-Dawley rats were separated into one Young group (4-months old), treated with peanut oil (5 mL kg(-1) , s.c.), and six Senile groups. The senile rats (10-months old) were subdivided into: Senile group (SEN) (5 mL kg(-1) peanut oil, s.c.); Testosterone group (TEST) (5 mg kg(-1) testosterone cipionate, s.c.); Estrogen group (EST) (25 µg kg(-1) 17β-estradiol, s.c.); castrated group (CAS) (surgical castration); castrated-testosterone group (CT) (same treatment as CAS and TEST groups); and castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin-like growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders.

  13. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?

    PubMed

    Holtorf, Kent

    2009-01-01

    The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease. Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected. Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized

  14. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy.

    PubMed

    Beck, V; Unterrieder, E; Krenn, L; Kubelka, W; Jungbauer, A

    2003-02-01

    Extracts from red clover (Trifolium pratense), soybean (Glycine max.) and black cohosh (Cimicifuga racemosa) are frequently used as alternative compounds for hormone replacement therapy (HRT) to treat menopausal disorders. Fifteen commercially available products made either from red clover, soybean or black cohosh were tested in in vitro assays in this study. The main polycyclic phenolic compounds of soy and red clover products were biochanin A, genistein, daidzein, formononetin, and glycitein. In red clover products glycitein was not abundant. All the compounds showed clear estrogenic activity through estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) and affinity to progesterone receptor (PR) and androgen receptor (AR), whereas the compounds from black cohosh did not. This was corroborated by synthetic isoflavones such as biochanin A, daidzein, genistein and formononetin. They exerted affinity to PR and AR in the range of 0.39-110 mM. Statistical analysis applying principal component analysis (PCA) revealed that all red clover and soy products are grouped in different clusters. Red clover products showed a higher affinity to AR and PR than soy products, which is explained by the higher amount of isoflavones present. In vitro assays and chemical analysis showed that theoretical estrogenic activity expressed as equivalent E2 concentration is in the same range as recommended for synthetic estrogens. Broader spectrum of action and hypothesized lower side effects by action through ERbeta make them suitable for alternative hormone replacement therapy.

  15. Blood pressure, arterial function, structure, and aging: the role of hormonal replacement therapy in postmenopausal women.

    PubMed

    Scuteri, Angelo; Ferrucci, Luigi

    2003-01-01

    The occurrence of natural menopause may indicate that a woman is entering a period of increased risk for cardiovascular disease, due to both chronologic aging and lower levels of estrogen. This brief review aims to demonstrate the relevance of changes in blood pressure and large artery structure and function occurring after menopause. These changes, i.e., thickening and stiffening of large arteries (which, in turn would also result in increased systolic and pulse pressures), were found to predict subsequent cardiovascular events, independently of other known cardiovascular risk. The benefits of early hormone replacement therapy on the life expectancy of women have dramatically lost consensus since publication of the Womens Health Initiative study results. However, the authors believe that those results should increase the attention paid by clinicians and public health researchers to the individualization of hormone replacement therapy prescription for postmenopausal women, and to a better characterization of those vascular parameters and profiles identifying postmenopausal women who are most likely to benefit from specific hormone replacement therapy in terms of cardiovascular protection.

  16. Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes.

    PubMed

    Pérez-Torres, Israel; Guarner-Lans, Verónica; Zúñiga-Muñoz, Alejandra; Velázquez Espejel, Rodrigo; Cabrera-Orefice, Alfredo; Uribe-Carvajal, Salvador; Pavón, Natalia

    2016-01-01

    We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2 exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2 deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes.

  17. Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes

    PubMed Central

    Velázquez Espejel, Rodrigo; Cabrera-Orefice, Alfredo; Uribe-Carvajal, Salvador; Pavón, Natalia

    2016-01-01

    We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2 exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2 deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes. PMID:27630756

  18. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

    PubMed

    Losa, Marco; Scavini, Marina; Gatti, Elisa; Rossini, Alessandro; Madaschi, Sara; Formenti, Ilaria; Caumo, Andrea; Stidley, Christine A; Lanzi, Roberto

    2008-12-01

    Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

  19. Does Hormone Replacement Normalize Bone Geometry in Adolescents with Anorexia Nervosa?

    PubMed Central

    DiVasta, Amy D.; Feldman, Henry A.; Beck, Thomas J.; LeBoff, Meryl S.; Gordon, Catherine M.

    2013-01-01

    Young women with anorexia nervosa (AN) have reduced secretion of dehydroepiandrosterone (DHEA) and estrogen contributing to skeletal deficits. In this randomized, placebo-controlled trial, we investigated the effects of oral DHEA+ combined oral contraceptive (COC) vs. placebo on changes in bone geometry in young women with AN. Eighty women with AN, aged 13-27 yr, received a random, double-blinded assignment to micronized DHEA (50 mg/d) + COC (20μg ethinyl estradiol/0.1mg levonorgestrel) or placebo for 18 mo. Measurements of aBMD at the total hip were obtained by dual-energy X-ray absorptiometry at 0, 6, 12, and 18 mo. We used the Hip Structural Analysis (HSA) Program to determine BMD, cross-sectional area (CSA), and section modulus at the femoral neck and shaft. Each measurement was expressed as a percentage of the age-, height-, and lean mass-specific mean from an independent sample of healthy adolescent females. Over the 18 months, DHEA+COC led to stabilization in femoral shaft BMD (0.0 ± 0.5 % of normal mean for age, height, and lean mass/year) compared with decreases in the placebo group (−1.1 ± 0.5% per year, p=0.03). Similarly, CSA, section modulus, and cortical thickness improved with treatment. In young women with AN, adrenal and gonadal hormone replacement improved bone health and increased cross sectional geometry. Our results indicate that this combination treatment has a beneficial impact on surrogate measures of bone strength, and not only bone density, in young women with AN. PMID:23744513

  20. Anti-ischemic effect of chronic oestrogen replacement therapy alone or in combination with medroxyprogesterone acetate in different replacement schemes.

    PubMed

    Cerquetani, E; Leonardo, F; Pagnotta, P; Galetta, P; Onorati, D; Fini, M; Rosano, G M

    2001-09-28

    Oestrogen replacement therapy in postmenopausal women has a protective effect upon the cardiovascular system and improves exercise-induced myocardial ischemia. Although in hormone replacement schemes progestins are required to reduce the likelihood of uterine malignancies, little is known on the cardiovascular effect of progestins. The purpose of this study was to evaluate the effect of oestrogen replacement alone and two different estrogen-progestin replacement therapy schemes upon exercise induced myocardial ischemia. The study population included 18 female menopausal patients with coronary artery disease. After a baseline exercise test patients received conjugated equine estrogens (CEE) 0.625 mg alone for 30 days when they underwent a second exercise test and were randomized to receive in a cross-over design medroxyprogesterone acetate (MPA) either in continuous combined therapy (2.5 mg/daily) for 28 days or in cyclical therapy (10 mg o.d. from day 16 to day 28). After CEE alone two patients with a previously positive exercise test showed a negative exercise test. CEE increased time to 1 mm ST compared to baseline (352+/-185 vs 265+/-133 s, P<0.01). In the 2 pts in whom the exercise test was negative after CEE the test remained negative during continuous combined MPA therapy while become positive during cyclical MPA. CEE+continuous combined MPA increased both time to 1 mm ST and exercise time compared to baseline (386+/-165 vs 265+/-133 s, P<0.01 and 545+/-198 vs 465+/-186 s, P<0.05, respectively). No difference was found between baseline and CEE+cyclical MPA in either time to 1 mm ST or exercise time (268+/-164 vs 265+/-133 s, P=NS and 455+/-223 vs 465+/-186 s, P=NS, respectively). Continuous combined therapy with CEE+MPA improves exercise-induced myocardial ischemia in female patients with coronary artery disease while the beneficial effect of CEE is reduced by cyclical therapy.

  1. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.

    PubMed

    Woo, Jean; Lau, Edith; Ho, Suzanne C; Cheng, Francis; Chan, Cynthia; Chan, Agnes S Y; Haines, Christopher J; Chan, Thomas Y K; Li, Martin; Sham, Aprille

    2003-01-01

    Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.

  2. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

    PubMed Central

    Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

    2014-01-01

    Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the

  3. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors.

    PubMed

    Holmberg, Lars; Iversen, Ole-Erik; Rudenstam, Carl Magnus; Hammar, Mats; Kumpulainen, Eero; Jaskiewicz, Janusz; Jassem, Jacek; Dobaczewska, Daria; Fjosne, Hans E; Peralta, Octavio; Arriagada, Rodrigo; Holmqvist, Marit; Maenpaa, Johanna; Maenpa, Johanna

    2008-04-02

    Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test). After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

  4. Endometrial effects during hormone replacement therapy with a sequential oestradiol valerate/cyproterone acetate preparation.

    PubMed

    Koninckx, P R; Lauweryns, J M; Cornillie, F J

    1993-03-01

    Three sequential oestradiol valerate (E2V) and cyproterone acetate (CPA) combinations based on 11 days of oestrogen and 10 days of oestrogen-progestogen administration were investigated during hormone replacement therapy in two prospective, double-blind randomized trials. Treatment A comprised 2 mg E2V and 1 mg CPA, treatment B, 1 mg and 0.5 mg and treatment C, 2 mg and 2 mg, respectively. During treatment A hot flushes (P < 0.0001), night sweating (P < 0.0001), depression (P = 0.0001), dizziness (P = 0.0001) and insomnia (P = 0.003) decreased significantly. The only side effect was breast tenderness, which was experienced by 18% of the women. Weight and blood pressure, thyroid, adrenal, liver and kidney functions, parathyroid hormone and vitamin D, platelets and blood cell counts did not change during the 12 months of therapy. In the women who received treatment A the menstrual flow became less abundant during the early months of treatment (P < 0.0001), the menses being scanty in around 30% of the women, while some 10% had amenorrhoea. Spotting occurred in 10-20% of the subjects. Endometrial biopsies were atrophic in 10% of the women, whereas a normal secretory phase was observed in 45% and irregular secretion in 45%. After careful analysis using visual analog scales, these findings were interpreted as indicating a high-normal progestational effect. In comparison with the pattern observed in normal menstrual cycles the women who received treatment A had a more heterogenic glandular epithelium, with more papillae, larger stromal cells, a more pronounced decidual reaction and more fibrinoid material. No cases of hyperplasia were seen. Treatment B was less effective than treatment A in relieving climacteric complaints. Irregular bleeding was troublesome in over 20% of cases and amenorrhoea occurred in 50%. Endometrial biopsies were atrophic in 57% of the women. The effectiveness of treatment C in alleviating flushes, sweating, dizziness and depression was the same as

  5. [Climateric symptoms and hormone replacement treatment among 50 years old Icelandic women.].

    PubMed

    Benediktsdóttir, B; Tómasson, K; Gíslason, T

    2000-01-01

    The objective of the research was to estimate the prevalence and treatment of climacteric symptoms among 50 years old women, including which doctors are prescribing the hormone replacement treatment (HRT) and what information is given about the risk and benefit of HRT. All (n=956) 50 years old women living in Reykjavík and neighbouring towns were included. A detailed questionnaire was posted to the women with two follow-up reminders. A non-response survey was conducted by phone among those not responding. The response rate was 72.2% (n=690). Sleep disturbances were the most common climacteric complaint occurring every day, mainly difficulty in maintaining sleep (14.8%). Hot flushes occuring every day (3.6%) and every night (2.2%) were more common than palpitations occuring every day (0.5%) and every night (0.2%). One fourth of the women had been to a doctor because of anxiety and 17% because of depression. Women who had been oophorectomised, were suffering from insomnia, hypertension, had high body mass index (BMI) or were not on HRT were more likely to suffer from hot flushes and palpitations. More than every other woman was on HRT (54%). Combination of oestrogen and progesterone were most commonly used. Hot flushes were less common in women on HRT and one third reported better sleep after starting HRT. Women on HRT more frequently visited doctors, were more often suffering from anxiety, chronic tiredness, fibromyalgia and pain. They more often were heavy smokers and had chronic bronchitis. Most often the HRT was started by gynaecologists (67%) but continued by family doctors (56%). About one fifth claimed that they had not received information about the risk and benefit of HRT. More than every other 50 years old woman is on HRT. These women differ in various ways from women not receiving HRT, which underlines the importance of accurate diagnosis and treatment of climacteric symptoms. Better patient information is needed.

  6. Transdermal hormone replacement therapy and Doppler findings in normal and overweight postmenopausal patients.

    PubMed

    Persico, N; Mancini, F; Artini, P G; Regnani, G; Volpe, A; de Aloysio, D; Battaglia, C

    2004-11-01

    The aim of this study was to evaluate the effects of transdermal hormone replacement therapy on some biological cardiovascular risk factors, specifically the thromboxane B2 levels, plasma viscosity and the lipid profile. Furthermore, we investigated the Doppler flow modifications at the level of the uterine artery, the internal carotid, the ophthalmic and the bladder wall arteries, and we finally evaluated whether there were significant differences in the examined parameters between normal and overweight postmenopausal women. Forty-five postmenopausal women (mean age+/-standard deviation, 53.5+/-3.8 years) participated in the study and were divided into two groups (27 with a body mass index of < 25 kg/m2 and 18 with a body mass index of > 25 kg/m2). Patients were treated with a continous estradiol transdermal supplement and a 12-day course of medroxyprogesterone acetate every 2 months, and were studied at baseline and after 6 months (in the estrogen-only phase of the second cycle). Our results showed a beneficial effect of hormone substitution on plasma viscosity, thromboxane B2 levels and lipid profile after 6 months of therapy and significant improvements of Doppler flow parameters in the examined vessels. Furthermore, we observed a lower impact of the treatment in overweight women. In conclusion, obesity represents an additional cardiovascular risk condition and it can only partially be modified by the administration of hormone replacement therapy.

  7. Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

    PubMed Central

    Sonnenschein, Carlos

    2008-01-01

    "The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

  8. Persisting cyclical uterine bleeding in patients treated with radical radiation therapy and hormonal replacement for carcinoma of the cervix

    SciTech Connect

    McKay, M.J.; Bull, C.A.; Houghton, C.R.; Langlands, A.O. )

    1990-04-01

    Radical radiation therapy used for carcinoma of the cervix will ablate ovarian function. Since January 1986, our policy has been to administer oral combination oestrogen-progesterone replacement hormonal therapy to all premenopausal patients undergoing radical radiation with or without synchronous chemotherapy, for invasive cervix cancer. Five out of 22 (23%) such patients unexpectedly experienced between one and four episodes of cyclical per vaginal bleeding after the completion of radiation therapy. Bleeding episodes occurred in the absence of persistent tumor or radiation reaction, and suggest persisting endometrial response to exogenous hormonal stimulation. Uterine activity was temporarily retained in these five patients despite a minimal endometrial surface dose of between 4800 and 6490 cGy. The limited number of cycles before bleeding spontaneously ceased may represent the slow death of endometrial cells subsequent to radiation or radiochemotherapy treatment, and has not previously been described. In view of the paucity of data on the radiosensitivity of normal endometrium, we have carefully examined these patients who appear to have retained endometrial sensitivity to hormonal stimuli after radical radiation-chemotherapy for uterine cervix cancer.

  9. An audit of growth hormone replacement for GH-deficient adults in Scotland.

    PubMed

    Philip, Sam; Howat, Isobel; Carson, Maggie; Booth, Anne; Campbell, Karen; Grant, Donna; Patterson, Catherine; Schofield, Christopher; Bevan, John; Patrick, Alan; Leese, Graham; Connell, John

    2013-04-01

    Guidelines on the clinical use of growth hormone therapy in adults were issued by the UK National Institute for Clinical Excellence (NICE) in August 2003. We conducted a retrospective clinical audit on the use of growth hormone (GH) in Scotland to evaluate the use of these guidelines and their impact on clinical practice. The audit had two phases. In phase I, the impact of NICE criteria on specialist endocrine practice in starting and continuing GH replacement was assessed. In phase II, the reasons why some adults in Scotland with growth hormone deficiency were not on replacement therapy were evaluated. A retrospective cross-sectional case note review was carried out of all adult patients being followed up for growth hormone deficiency during the study period (1 March 2005 to 31 March 2008). Phase I of the audit included 208 patients and phase II 108 patients. Sellar tumours were the main cause of GH deficiency in both phases of the audit. In phase I, 53 patients (77%) had an AGHDA-QoL score >11 documented before commencing GH post-NICE guidance, compared with 35 (25%) pre-NICE guidance. Overall, only 39 patients (18%) met the full NICE criteria for starting and continuing GH (pre-NICE, 11%; post-NICE, 35%). Phase II indicated that the main reasons for not starting GH included perceived satisfactory quality of life (n = 47, 43%), patient reluctance (16, 15%) or a medical contraindication (16, 15%). Although the use of quality of life assessments has increased following publication of the NICE guidelines, most adults on GH in Scotland did not fulfil the complete set of NICE criteria. The main reason for not starting GH therapy in adult GH-deficient patients was perceived satisfactory quality of life. © 2012 Blackwell Publishing Ltd.

  10. Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

    PubMed Central

    LaClair, Matthew

    2016-01-01

    This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296–309, 2014. doi:10.1111/jne. 12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life. PMID:26909674

  11. Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

    PubMed

    LaClair, Matthew; Lacreuse, Agnès

    2016-05-01

    This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296-309, 2014. doi: 10.1111/jne.12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life.

  12. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

    PubMed Central

    2012-01-01

    Introduction Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. Methods Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. Results For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. Conclusions An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women

  13. The role of hormone replacement therapy in the intensive care management of deceased organ donors: a primer for nurses.

    PubMed

    Smetana, Keaton S; Kimmons, Lauren A; Jones, G Morgan

    2015-01-01

    Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

  14. Novel mutations associated with combined pituitary hormone deficiency.

    PubMed

    Romero, Christopher J; Pine-Twaddell, Elyse; Radovick, Sally

    2011-06-01

    The pituitary gland produces hormones that play important roles in both the development and the homeostasis of the body. A deficiency of two or several of these pituitary hormones, known as combined pituitary hormone deficiency, may present in infants or children due to an unknown etiology and is considered congenital or idiopathic. Advancements in our understanding of pituitary development have provided a genetic basis to explain the pathophysiological basis of pituitary hormone disease. Nevertheless, there are several challenges to the precise characterization of abnormal genotypes; these exist secondary to the complexities of several of the hypothalamic/pituitary developmental factors and signals, which ultimately integrate in a temporal and spatial dependent manner to produce a mature gland. Furthermore, the clinical presentation of pituitary hormone disease may be dynamic as subsequent hormone deficiencies may develop over time. The characterization of patients with mutations in genes responsible for pituitary development provides an opportunity to discover potential novel mechanisms responsible for pituitary pathophysiology. The focus of this review is to report the most recent mutations in genes responsible for pituitary development in patients with hypopituitarism and emphasize the importance to physicians and researchers for characterizing these patients. Continuing efforts toward understanding the molecular basis of pituitary development as well as genetic screening of patients with pituitary disease will offer new insights into both diagnostic and potential therapeutic options that will decrease the morbidity and mortality in patients with hypopituitarism.

  15. Alternative hormone replacement regimens: is there a need for further clinical trials?

    PubMed

    Welty, Francine K

    2003-12-01

    To review the randomized trials of hormone replacement therapy. Studies have shown that conjugated equine estrogen 0.625 mg a day plus medroxyprogesterone acetate 2.5 mg a day increased the risk of cardiovascular events during the first year of treatment in women both with and without coronary heart disease. Conjugated equine estrogen plus medroxyprogesterone acetate also increased the overall risk of myocardial infarction and stroke in women without coronary heart disease, and myocardial infarction or death in women with coronary heart disease, and also increased the risk of breast cancer, cognitive decline and dementia. Unopposed, oral 17B-estradiol increased the risk of stroke during the first 6 months of treatment in women with a previous stroke. Oral 17B-estradiol with or without cyclic progestin had no effect on the progression of atherosclerosis or reinfarction. Transdermal 17B-estradiol plus cyclic progestin was associated with a non-significant increase in coronary heart disease events in women with coronary heart disease. Compared with placebo, cardiovascular events increased in the ongoing estrogen-only arm of the Women's Health Initiative, indicating that unopposed conjugated equine estrogen is unlikely to be cardioprotective. However, oral 17B-estradiol retarded the progression of subclinical atherosclerosis in younger women without coronary heart disease. Hormone replacement therapy should not be initiated for the primary or secondary prevention of coronary heart disease in women. A trial of 17B-estradiol started at menopause in women without coronary heart disease should be considered.

  16. Continuation rates for oral contraceptives and hormone replacement therapy. The ESHRE Capri Workshop Group.

    PubMed

    2000-08-01

    Despite the safety and effectiveness of low oestrogen-dose oral contraceptives (OC) and postmenopausal hormone replacement there is poor continuity of use of these agents by women. Patterns of use and the reasons affecting different frequencies of use in different countries are presented. Continuity and discontinuation rates are difficult to assess accurately but it is believed that the main reasons why women discontinue use of these agents are concerns about their perceived health risks and the presence of, or fear of, adverse clinical effects, particularly unscheduled uterine bleeding and weight gain. More information is needed about OC continuation rates in order to improve the acceptability of these safe, effective agents. Most women discontinue use of postmenopausal hormonal replacement within 2 years of initiating the therapy. Reasons include disappearance of symptoms of oestrogen deficiency, lack of awareness of health benefits of oestrogen, presence of side-effects (such as breast tenderness and weight gain), presence of uterine bleeding and increasing age. Suggestions to increase continuation of OC include extensive individual pretreatment counselling with a different emphasis in different age groups, education at the time of follow-up visits and telephone calls, and extensive use of educational aids such as brochures, pamphlets and audio tapes, and improvement of pharmaceutical packaging information. In conclusion there is an urgent need to assess the value of these strategies by long-term large controlled studies.

  17. Hormone replacement therapy, cancer, controversies, and women's health: historical, epidemiological, biological, clinical, and advocacy perspectives

    PubMed Central

    Krieger, N.; Lowy, I.; Aronowitz, R.; Bigby, J.; Dickersin, K.; Garner, E.; Gaudilliere, J.; Hinestrosa, C.; Hubbard, R.; Johnson, P.; Missmer, S.; Norsigian, J.; Pearson, C.; Rosenberg, C.; Rosenberg, L.; Rosenkrantz, B.; Seaman, B.; Sonnenschein, C.; Soto, A.; Thornton, J.; Weisz, G.

    2005-01-01

    Routine acceptance of use of hormone replacement therapy (HRT) was shattered in 2002 when results of the largest HRT randomised clinical trial, the women's health initiative, indicated that long term use of oestrogen plus progestin HRT not only was associated with increased risk of cancer but, contrary to expectations, did not decrease, and may have increased, risk of cardiovascular disease. In June 2004 a group of historians, epidemiologists, biologists, clinicians, and women's health advocates met to discuss the scientific and social context of and response to these findings. It was found that understanding the evolving and contending knowledge on hormones and health requires: (1) considering its societal context, including the impact of the pharmaceutical industry, the biomedical emphasis on individualised risk and preventive medicine, and the gendering of hormones; and (2) asking why, for four decades, since the mid-1960s, were millions of women prescribed powerful pharmacological agents already demonstrated, three decades earlier, to be carcinogenic? Answering this question requires engaging with core issues of accountability, complexity, fear of mortality, and the conduct of socially responsible science. PMID:16100311

  18. TOMOGRAFIC AND TENSIOMETRIC ASSESSMENT ON FEMURS FROM OOPHORECTOMIZED RATS SUBJECTED TO HORMONE REPLACEMENT THERAPY

    PubMed Central

    Martynetz, Fábio Alexandre; Pessole Biondo-Simões, Maria de Lourdes; Martynetz, Juliano Rodrigo; Martynetz, Tatiana Daher; Zimerman, Elise; Neto, Heraldo Mello

    2015-01-01

    Objective: To analyze the biomechanical and tomographic effects of hormone replacement therapy (HRT) on femurs from rats subjected to induced menopause. Methods: Forty-five adult Wistar rats were divided equally into three groups. The first and second groups consisted of rats subjected to oophorectomy, and the third was the control group, consisting of nonoophorectomized rates. After verifying that hormone failure had occurred (exfoliative cytological test), only the first group received HRT, over a two-month period. After this period, the femurs were disarticulated and subjected to biomechanical tests in a universal testing machine to evaluate their strength, and were subjected to tomographic evaluation to determine the bone mineral density. Results: The exfoliative cytological test showed that hormone failure was induced in all the oophorectomized animals. A significant difference (p = 0.030) in maximum strength measurements was observed between the groups (higher in the group with HRT). Greater bone fragility was observed in the oophorectomized animals without HRT than in those with HRT (p = 0.010), in relation to the control group (p = 0.0107). There was greater bone strength in the oophorectomized rats with HRT than in those without HRT, and these values were similar to those of the control group (p = 0.179). In the tomographic evaluation, no significant differences were found between the groups (p = 0.625). Conclusion: A significant increase in bone strength was observed with the use of HRT. However, treatment with HRT did not show any significant change in bone mineral density. PMID:27019837

  19. Hormone replacement therapy, cancer, controversies, and women's health: historical, epidemiological, biological, clinical, and advocacy perspectives.

    PubMed

    Krieger, Nancy; Löwy, Ilana; Aronowitz, Robert; Bigby, Judyann; Dickersin, Kay; Garner, Elizabeth; Gaudillière, Jean-Paul; Hinestrosa, Carolina; Hubbard, Ruth; Johnson, Paula A; Missmer, Stacey A; Norsigian, Judy; Pearson, Cynthia; Rosenberg, Charles E; Rosenberg, Lynn; Rosenkrantz, Barbara G; Seaman, Barbara; Sonnenschein, Carlos; Soto, Ana M; Thornton, Joe; Weisz, George

    2005-09-01

    Routine acceptance of use of hormone replacement therapy (HRT) was shattered in 2002 when results of the largest HRT randomised clinical trial, the women's health initiative, indicated that long term use of oestrogen plus progestin HRT not only was associated with increased risk of cancer but, contrary to expectations, did not decrease, and may have increased, risk of cardiovascular disease. In June 2004 a group of historians, epidemiologists, biologists, clinicians, and women's health advocates met to discuss the scientific and social context of and response to these findings. It was found that understanding the evolving and contending knowledge on hormones and health requires: (1) considering its societal context, including the impact of the pharmaceutical industry, the biomedical emphasis on individualised risk and preventive medicine, and the gendering of hormones; and (2) asking why, for four decades, since the mid-1960s, were millions of women prescribed powerful pharmacological agents already demonstrated, three decades earlier, to be carcinogenic? Answering this question requires engaging with core issues of accountability, complexity, fear of mortality, and the conduct of socially responsible science.

  20. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women

    PubMed Central

    Vickers, Madge R; Lawton, Beverley; Ford, Deborah; Martin, Jeannett; Meredith, Sarah K; DeStavola, Bianca L; Rose, Sally; Dowell, Anthony; Wilkes, Helen C; Darbyshire, Janet H; Meade, Tom W

    2007-01-01

    Objective To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy). Design Multicentre, randomised, placebo controlled, double blind trial. Setting General practices in UK (384), Australia (91), and New Zealand (24). Participants Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56 583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22 300) started treatment. Interventions Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned. Main outcome measures Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life. Results The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences

  1. Case-control study of increased mammographic breast density response to hormone replacement therapy.

    PubMed

    Vachon, Celine M; Sellers, Thomas A; Vierkant, Robert A; Wu, Fang-Fang; Brandt, Kathleen R

    2002-11-01

    Previous studies have demonstrated an association between current hormone replacement therapy (HRT) use and increased mammographic breast density. Many of these studies have also shown that only 20-35% of women initiating HRT respond in this manner. This subgroup of HRT responders may be at an increased risk of breast cancer. We performed a case-control study to investigate how women who experience increased density in response to HRT (cases) differ from women who do not experience an increase in density with HRT use (controls) with regard to breast cancer risk factors, type of HRT, weight change, and baseline breast density. Participants were female residents of Olmsted County, Minnesota who received routine screening mammograms at the Mayo Clinic. Cases included 172 women identified between the years 1998 and 1999 by Mayo radiologists as having a HRT response. Controls were women who did not experience an increase in mammographic density with HRT use and were matched to cases on age (+/-3 years), menopausal status, duration of HRT, month of initiation of HRT, and months between baseline and follow-up mammograms. Mammograms were obtained from cases and controls before and during HRT therapy. Breast density was read as a four-category Bi-Rads density grade measure and as a quantitative percentage estimate, using a computer-assisted method. Risk factor information was obtained from both chart review and a mammography database of patient-provided information. There was no association between HRT response and first-degree family history of breast cancer [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.4-1.5], parity (OR, 0.8; 95% CI, 0.4-1.7), later age at first birth (OR, 0.8 for age >25 years versus nulliparous women; 95% CI, 0.4-1.8), or history of biopsy (OR, 0.9; 95% CI, 0.6-1.5). There was also no association with baseline weight or change in weight between a woman's baseline and follow-up mammograms. However, there was evidence of an association between

  2. Tetrac can replace thyroid hormone during brain development in mouse mutants deficient in the thyroid hormone transporter mct8.

    PubMed

    Horn, Sigrun; Kersseboom, Simone; Mayerl, Steffen; Müller, Julia; Groba, Claudia; Trajkovic-Arsic, Marija; Ackermann, Tobias; Visser, Theo J; Heuer, Heike

    2013-02-01

    The monocarboxylate transporter 8 (MCT8) plays a critical role in mediating the uptake of thyroid hormones (THs) into the brain. In patients, inactivating mutations in the MCT8 gene are associated with a severe form of psychomotor retardation and abnormal serum TH levels. Here, we evaluate the therapeutic potential of the TH analog 3,5,3',5'-tetraiodothyroacetic acid (tetrac) as a replacement for T(4) in brain development. Using COS1 cells transfected with TH transporter and deiodinase constructs, we could show that tetrac, albeit not being transported by MCT8, can be metabolized to the TH receptor active compound 3,3',5-triiodothyroacetic acid (triac) by type 2 deiodinase and inactivated by type 3 deiodinase. Triac in turn is capable of replacing T(3) in primary murine cerebellar cultures where it potently stimulates Purkinje cell development. In vivo effects of tetrac were assessed in congenital hypothyroid Pax8-knockout (KO) and Mct8/Pax8 double-KO mice as well as in Mct8-KO and wild-type animals after daily injection of tetrac (400 ng/g body weight) during the first postnatal weeks. This treatment was sufficient to promote TH-dependent neuronal differentiation in the cerebellum, cerebral cortex, and striatum but was ineffective in suppressing hypothalamic TRH expression. In contrast, TSH transcript levels in the pituitary were strongly down-regulated in response to tetrac. Based on our findings we propose that tetrac administration offers the opportunity to provide neurons during the postnatal stage with a potent TH receptor agonist, thereby eventually reducing the neurological damage in patients with MCT8 mutations without deteriorating the thyrotoxic situation in peripheral tissues.

  3. Impact of growth hormone replacement therapy on sleep in adult patients with growth hormone deficiency of pituitary origin

    PubMed Central

    Morselli, Lisa L.; Nedeltcheva, Arlet; Leproult, Rachel; Spiegel, Karine; Martino, Enio; Legros, Jean-Jacques; Weiss, Roy E.; Mockel, Jean; Van Cauter, Eve; Copinschi, Georges

    2013-01-01

    Objectives We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, as compared to healthy controls individually matched for age, gender and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here we examined the impact of recombinant human GH (rhGH) therapy, compared to placebo, on objective sleep quality in a subset of patients from the same cohort. Design Single-blind randomized cross-over design study. Methods Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22–74 yr, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo. Results Valid data were obtained in 13 patients. At the end of rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479±11 vs 431±19 min respectively; p=0.005), primarily due to an earlier wake up time, and a decrease in the intensity of SWS (delta activity) (559±125 vs 794±219 μV2, respectively; p=0.048). Conclusions Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH. PMID:23447518

  4. Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl-¹¹C]WAY-100635.

    PubMed

    Kranz, Georg S; Rami-Mark, Christina; Kaufmann, Ulrike; Baldinger, Pia; Hahn, Andreas; Höflich, Anna; Savli, Markus; Stein, Patrycja; Wadsak, Wolfgang; Mitterhauser, Markus; Winkler, Dietmar; Lanzenberger, Rupert; Kasper, Siegfried

    2014-07-01

    Preclinical research points to a strong modulatory influence of gonadal hormones on the serotonin system. However, human data corroborating this association remains scarce. The aim of this study was to examine the effects of hormone replacement therapy on 5-HT₁A receptor binding in postmenopausal women using positron emission tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635. In this randomized, double-blind, longitudinal study, 30 postmenopausal women underwent treatment with either a combination of oral 17β-estradiol valerate and micronized progesterone (group 1, n=10), oral 17β-estradiol valerate (group 2, n=10), or placebo (group 3, n=10). Two PET measurements were performed, one the day before treatment start and the second after at least eight weeks of treatment. Plasma levels of estradiol (E₂), progesterone (P₄), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were collected prior to PET measurements. As expected, hormone replacement therapy led to a significant increase in E₂ and P4 plasma levels in group 1 and to a significant increase in E₂ levels in group 2. The 5-HT₁A receptor binding did not change significantly after estrogen, combined estrogen/progesterone treatment or placebo in any of the investigated brain regions. There were no significant correlations between changes in E₂ or P4 values and changes in 5-HT₁A receptor binding. Although we were not able to confirm effects of gonadal hormone treatment on 5-HT₁A receptor binding, our data do not preclude associations between sex steroid levels and serotonin, the neurotransmitter implicated most strongly in the pathogenesis of affective and anxiety disorders. ClinicalTrials.gov Identifier: NCT00755963.

  5. Hormone replacement therapy and prevention of osteoporosis: risk assessment and practical advice.

    PubMed

    Balogh, A; Bettembuk, P

    1997-02-01

    A review of the Debrecen Regional Osteoporosis Program (DROP) in Hungary is given, with special reference to the detection of postmenopausal osteoporosis (PMOP) and its treatment by hormone replacement therapy (HRT). The new definition of osteoporosis by focusing on bone mineral density (BMD) measurements has the major advantage of practical usefulness. The algorithm of managing osteoporotic patients can be easily constructed from the result of bone densitometry as the primary diagnostic tool. The DROP serves a total population of 550,000, is equipped with a DXA bone densitometer, a bone metabolism laboratory and backed by a multidisciplinary team of clinicians from gynecology, radiology, rheumatology, internal medicine, and orthopedic surgery. In 1995 the total number of patients undergoing densitometry was 3170. In 2045 patients T scores of -1 or below were found. From this total number, 348 patients received HRT for 1 year or longer. The results of the treatment showed a positive response (i.e. no bone loss, or net gain) in 65%, while half of the 'non responders' proved in fact non compliant. The contradiction between risk assessment and early diagnosis is explained and replacing 'risk assessment' by 'selection criteria for bone densitometry' is proposed. 'Prevention of osteoporosis' is also to be replaced by 'prevention of complications', i.e. osteoporotic fractures. One of these measures is HRT. Its rational use in the prevention and treatment of osteoporosis and its relation to other treatment methods in the authors' own experience is discussed.

  6. Hormone replacement therapy and cardiovascular disease: lessons from a monkey model of postmenopausal women.

    PubMed

    Williams, J Koudy; Suparto, Irma

    2004-01-01

    Concerns exist about the cardiovascular effects of hormone replacement therapy (HRT) in postmenopausal women because results from the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) are contradictory. In both of these studies, postmenopausal conjugated equine estrogens + medroxyprogesterone acetate did not reduce risk, and somewhat increased the risk of myocardial infarction in both primary (WHI) and secondary (HERS) prevention. These results appear to contradict numerous observational clinical trials and animal studies, which reported profound beneficial effects of HRT on cardiovascular disease risk. Results of both human and monkey studies indicate that estrogen replacement therapy (ERT)/HRT is effective in inhibiting progression of early stage (fatty streak) atherosclerosis but that ERT/HRT is much less effective in inhibiting progression of more advanced (established plaque) atherosclerosis. Results of these monkey studies are consistent with those of studies in women wherein ERT/HRT was initiated in postmenopausal women with different initial amounts of atherosclerosis. Based on these findings, it is speculated that ERT/HRT may be more cardioprotective in younger postmenopausal women with less coronary artery disease, and less effective in women with established coronary artery disease. Researchers are challenged to define the relative cardiovascular risk/benefit in different populations of postmenopausal women based on differences in age, amounts of pre-existing atherosclerosis, and risk factors.

  7. Plasma total homocysteine concentrations in adults with growth hormone (GH) deficiency: effects of GH replacement.

    PubMed

    Lewandowski, Krzysztof C; Murray, Robert D; Drzewoski, J; O'Callaghan, Chris J; Czupryniak, L; Hillhouse, Edward W; Shalet, Stephen M; Randeva, Harpal S

    2003-11-01

    Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an independent cardiovascular risk factor, thus potentially contributing to benefits of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8 male), mean age 39-years, with GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. After an overnight fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4), creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2) and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical statistical models, univariate and multivariate correlation. GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068, p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/-0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once individuals had achieved 'adequate' GH replacement, was no longer significantly different (p=0.090). When separated by gender, at 6 months (V3) there was a small, but significant increase in Hcy in men (p=0.028), but not in women (p=0.58). There was no significant change in B12, folate, free T4 or creatinine levels. Univariate analysis revealed that only B12 and folate showed significant negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate: parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple variable model, both B12 and folate remained significantly negatively associated with plasma total homocysteine (p=0.018; p<0.001, respectively). In this observational study

  8. What is this thing called hormone replacement therapy? Discursive construction of medication in situated practice.

    PubMed

    Stephens, Christine; Budge, R Claire; Carryer, Jenny

    2002-03-01

    The use of hormone replacement therapy (HRT) involves complex decisions for mid-aged women owing to controversy about the meaning of menopause and uncertainty regarding risks and benefits. Qualitative studies show that women can hold apparently contradictory beliefs, for example, both resisting and relying on medicalization. Focus group data (48 participants) and discourse analysis theorizing were used to investigate the complex discursive field available to women to construct HRTand to explain apparent contradictions. Interpretative repertoires identified in this study (threatening change, natural, biomedical, and drug) support previous findings. It is not contradictory to use different repertoires to achieve different discursive acts. The application of these findings to the development of decision tools that help women to arrive at individually appropriate decisions is discussed.

  9. Hormone replacement therapy and age-related brain shrinkage: regional effects.

    PubMed

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2004-11-15

    Neuroprotective properties of estrogen have been established in animal models, but clinical trials of hormone replacement therapy (HRT) produced contradictory results. We examined the impact of HRT on age-related regional changes in human brain volume. Six brain regions were measured twice, five years apart, in 12 healthy women who took HRT and in matched controls who did not. The controls showed a typical pattern of differential brain shrinkage in the association cortices and the hippocampus with no change in the primary visual cortex. In contrast, women who took HRT showed comparable shrinkage of the hippocampus but no significant shrinkage of the neocortex. Future large scale studies may benefit from applying regional rather than global measures in assessment of brain integrity.

  10. Hormone Replacement Therapy: An Increased Risk of Recurrence and Mortality for Breast Cancer Patients?

    PubMed Central

    Lupo, Molly; Dains, Joyce E.; Madsen, Lydia T.

    2015-01-01

    Historically, randomized controlled trials (RCTs) have shown an increased risk of recurrence and mortality among women who have used primarily oral HRT after breast cancer. However, many of these studies have had design flaws that may impact the findings. Numerous investigators have concluded that additional RCTs should be performed, but because of ethical issues and logistic challenges, large-scale RCTs are unlikely. Thus, the authors conducted an integrative review investigating recurrence and mortality data among breast cancer survivors who have used hormone replacement therapy (HRT). They recommend a stepwise algorithm for treating vaginal symptoms in breast cancer survivors: (1) start with nonhormonal treatments; (2) progress to a detailed discussion among patients and health-care professionals about the current known risks and benefits of vaginal estrogen; and (3) conclude with mutual decision-making between health-care providers and patients regarding the use of vaginal estrogen treatment. PMID:26705493

  11. Sex hormone replacement therapy and modulation of vascular function in cardiovascular disease.

    PubMed

    Koledova, Vera V; Khalil, Raouf A

    2007-07-01

    Epidemiological and experimental studies suggest vascular protective effects of estrogen. Cardiovascular disease (CVD) is less common in premenopausal women than in men and postmenopausal women. Cytosolic/nuclear estrogen receptors (ERs) have been shown to mediate genomic effects that stimulate endothelial cell growth but inhibit vascular smooth muscle proliferation. However, the Heart and Estrogen/Progestin Replacement Study (HERS), HERS-II and Women's Health Initiative clinical trials demonstrated that hormone replacement therapy (HRT) may not provide vascular benefits in postmenopausal women and may instead trigger adverse cardiovascular events. HRT may not provide vascular benefits because of the type of hormone used. Oral estrogens are biologically transformed by first-pass metabolism in the liver. By contrast, transdermal preparations avoid first pass metabolism. Also, natural estrogens and phytoestrogens may provide alternatives to synthetic estrogens. Furthermore, specific ER modulators could minimize the adverse effects of HRT, including breast cancer. HRT failure in CVD could also be related to changes in vascular ERs. Genetic polymorphism and postmenopausal decrease in vascular ERs or the downstream signaling mechanisms may reduce the effects of HRT. HRT in the late postmenopausal period may not be as effective as during menopausal transition. Additionally, while HRT may aggravate pre-existing CVD, it may thwart its development if used in a timely fashion. Lastly, the vascular effects of progesterone and testosterone, as well as modulators of their receptors, may modify the effects of estrogen and thereby provide alternative HRT strategies. Thus, the beneficial effects of HRT in postmenopausal CVD can be enhanced by customizing the HRT type, dose, route of administration and timing depending on the subject's age and cardiovascular condition.

  12. Hormone replacement therapy and risk of meningioma in women: a meta-analysis.

    PubMed

    Fan, Zuo-Xu; Shen, Jian; Wu, Yao-Yao; Yu, Hai; Zhu, Yu; Zhan, Ren-Ya

    2013-08-01

    The relationship between hormone replacement therapy (HRT) and the incidence of meningioma in women has been investigated in several epidemiologic studies, but their results were not entirely consistent. Here, we performed a meta-analysis of case-control and cohort studies to analyze this association. The PubMed database was searched from inception to 30 September 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from the retrieved articles. Two researchers evaluated study eligibility and extracted the data independently. Odds ratios (ORs) or relative risks and 95 % confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models. A total of 11 studies (six case-control and five cohort studies) were included in this meta-analysis, involving 1,820,954 participants, of whom 3,249 had meningioma. When compared to never users of HRT, the pooled OR with ever users for meningioma was 1.29 (95 % CI 1.03-1.60). Sensitivity analyses restricted to postmenopausal women yielded similar results (OR: 1.22; 95 % CI 1.02-1.46). Subgroup analyses showed that the pooled ORs were 1.27 (95 % CI 1.08-1.49, p < 0.05) and 1.12 (95 % CI 0.95-1.32) for current and past users of HRT, respectively. Hormone replacement therapy use is associated with an increased risk of meningioma in women, as well as in postmenopausal women. Besides, the significant risk elevation is present in current users but not in past users. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

  13. [Hormone replacement therapy and cancer of the breast. 1. Does replacement therapy increase the risk of cancer of the breast?].

    PubMed

    Ayres de Campos, D; Barros, H; Martinez de Oliveira, J

    1997-10-01

    It has been extensively demonstrated that hormonal replacement therapy (HRT) constitutes an effective treatment of menopausal symptoms. There is also substantial epidemiological evidence suggesting that this treatment protects women against cardiovascular disease and osteoporosis. The possible increase in breast cancer risk appears as its principal disadvantage and is often invoked as the reason why both doctors and patients decline this therapy. In this paper we review the current knowledge on HRT and breast cancer risk. A computerised bibliographical search (MEDLINE) of literature in the English language published in the last 15 years was conducted, followed by a manual search of references. We focused our attention on four main questions: 1) Does HRT increase the risk of breast cancer? 2) Are different doses and drugs associated with different risks? 3) What effect on risk have the association of a progestin does? 4) Does HRT increase the risk of breast cancer in women with major risk factors for the disease? Overall, epidemiological studies suggest that women who have used HRT before have a slightly higher risk of breast cancer than those who have never used it, in most studies not exceeding 10%. The use of HRT for less than 5 years does not seem to be associated with increased risk, while some studies have shown relative risks in the order of 1.20-1.30 with therapies exceeding 10-15 years in duration. Different doses of conjugated equine estrogens do not seem to be associated with different risks of breast cancer. Data on the risk of other estrogen preparations is scarce and far from conclusive, but the majority of studies suggest a similar risk to that of conjugated estrogens. Evidence on opposed HRT is also scarce and contradictory. A substantial body of evidence exists to suggest that HRT in women with benign breast disease does not increase the risk of breast cancer. Data on HRT in women with a family history of breast cancer is inconclusive; some studies

  14. Age at menopause and hormone replacement therapy as risk factors for head and neck and oesophageal cancer (Review).

    PubMed

    McCarthy, Caroline E; Field, John K; Marcus, Michael W

    2017-10-01

    There were ~986,000 cases of head and neck cancer (HNC) and oesophageal cancer diagnosed worldwide in 2012. The incidence of these types of cancer is much higher in males than females, although this disparity decreases in the elderly population, suggesting a role for hormones as a risk factor. This systematic review investigates the potential role of female hormones [age at menopause and use of hormone replacement therapy (HRT)] as risk factors for HNC/oesophageal squamous cell carcinoma (SCC). The electronic databases MEDLINE, Web of Science, EMBASE and Cochrane were searched. Only studies with at least 50 cases of HNC/oesophageal SCC, with data on age at menopause, smoking, alcohol, age and socioeconomic status or educational attainment, were included. The Newcastle Ottawa Scale was used for assessing risk of bias. Eight studies met the inclusion criteria (5 oesophageal SCC, 2 HNC and 1 combined oesophageal SCC and HNC). HRT was shown to reduce the risk of HNC (HR, 0.78; 95% CI, 0.61-0.99) in one study. Our results showed that earlier age at menopause is a risk factor for oesophageal SCC, with women entering menopause at <45 years having double the risk of those entering menopause at age >50 years. Similar, but less striking, results were observed for HNC. HRT was found to reduce the risk of HNC/oesophageal SCC, but the evidence is inconclusive. We, therefore, recommend that consideration should be given to collecting data on reproductive factors and exposure to HRT, as routine practice, in future epidemiological and clinical studies of these cancers. The concept of oestrogen deficiency as a risk for HNC/oesophageal SCC deserves further exploration in future laboratory and clinical studies.

  15. Women's stories: ethnic variations in women's attitudes and experiences of menopause, hysterectomy, and hormone replacement therapy.

    PubMed

    Mingo, C; Herman, C J; Jasperse, M

    2000-01-01

    To increase understanding of women's midlife changes, 23 focus groups were held to investigate the possible ethnic variations in attitude toward and experience with menopause, hysterectomy, and hormone replacement therapy (HRT) in non-Hispanic white, Hispanic, and Navajo women in New Mexico. The medical definition of menopause, no menstrual bleeding for 12 months, did not coincide with the women's definition of menopause as the hormonal fluctuations they experienced before, during, and after any change in their menstrual cycle. More women reported having to fight to have a hysterectomy than having one unnecessarily. Women complained about the lack of information and preparation prior to having a hysterectomy and expressed dissatisfaction with doctor-patient communication, but they were satisfied with their hysterectomy because they felt better after the surgery. Although women in the study reported that menopause and hysterectomy are seldom discussed openly, they all participated freely in the storytelling focus groups. The most traditional women, primarily rural Navajo and newly immigrated Latina, related few or no menopausal symptoms with natural menopause or after hysterectomy. Many of these women had not even heard of HRT. Many women who had been prescribed HRT expressed dissatisfaction with the side effects and dosage. Unsupervised tinkering with the dosage was the rule rather than the exception. The study revealed that women are much more alike than they are different. Traditional women in all ethnic groups had more in common with each other than they did with the least traditional women in their own ethnic group.

  16. Hormone replacement therapy and heart disease: the remains of the oestrogen hypothesis

    PubMed Central

    Maas, A.H.E.M.; van der Schouw, Y.T.; Grobbee, D.E.; van der Graaf, Y.

    2003-01-01

    Background While observational data for postmenopausal women using hormone replacement therapy (HRT) have shown a protective effect against cardiovascular disease, prospective, randomised trials have demonstrated a harmful effect on the vascular system. Design and results The effects of HRT on lipids, haemostatic parameters, inflammation, and the vascular wall are described. Reasons for the different results of observational and experimental studies of HRT are postulated. The timing of hormonal supplementation seems crucial. Used chronically, HRT has no harmful effects; however, first-time use of HRT after a recent cardiovascular event results in an early increase in adverse cardiovascular events. In most observational studies, women started HRT for postmenopausal symptoms, whereas in experimental studies women started HRT 10 to 20 years or longer after the menopause. Conclusion HRT has more effect in maintaining vascular health than in alleviating endothelial dysfunction. HRT is not beneficial but harmful in women at risk of a cardiovascular event. The interval between the menopause and starting HRT plays a crucial role in the effectiveness of HRT on the vascular system. PMID:25696160

  17. Acute and chronic effects of hormone replacement therapy on the cardiovascular system in healthy postmenopausal women.

    PubMed

    Kirwan, Lori D; MacLusky, Neil J; Shapiro, Heather M; Abramson, Beth L; Thomas, Scott G; Goodman, Jack M

    2004-04-01

    Previous studies have shown that conjugated estrogens and continuous medroxyprogesterone increases heart disease risk in healthy women. Little is known about the effects of the natural ovarian hormones estradiol and progesterone on cardiovascular function at rest and exercise. The purpose of this study was to investigate the short- and longer-term effects of a cyclic format of hormone replacement therapy (HRT) (1 mg estradiol daily with cyclic micronized progesterone, 200 mg for 10 d/month) on cardiovascular function at rest and during exercise in healthy, postmenopausal women. A double-blind, cross-over study was conducted in 31 patients. Peak oxygen uptake and ventilatory threshold in addition to submaximal cardiac output were determined. Peripheral measures of resting and peak ischemic blood flows were also determined. Measurements were made at baseline, after 4 h of estrogen/placebo exposure, and subsequently after 1, 2, and 3 months. The sequence of data collection was repeated after 6-wk washout. Oral estradiol with cyclic micronized progesterone increases peak ischemic peripheral blood flow chronically but fails to improve exercise tolerance and peak oxygen uptake. Similarly, submaximal central cardiovascular function is unaffected by HRT. This suggests that estradiol has a beneficial effect on peripheral blood flow, but this benefit offers little advantage in terms of peak exercise performance after 3 months of HRT.

  18. Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

    PubMed

    Baumgärtner, A K; Häusler, A; Seifert-Klauss, V; Schuster, T; Schwarz-Boeger, U; Kiechle, M

    2011-10-01

    Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p<0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55-1.19, p=0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45-1.02, p=0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57-6.91, p=0.28 and HR 4.59, 95%CI 0.91-23.25, p=0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

  19. 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

  20. Elimination of Two Hormones by Ultrasonic and Ozone Combined Processes

    NASA Astrophysics Data System (ADS)

    Mingcan Cui,; Younggyu Son,; Myunghee Lim,; Seungmin Na,; Jeehyeong Khim,

    2010-07-01

    A direct ultrasonic (US) and ozone (O3) combination (US/O3) process for the removal of two hormones, estrone (E1) and estriol (E3), in aqueous solutions was investigated. These two hormones were detected in a wastewater treatment plant effluent in Korea. It was found that the ultrasonic/ozone process showed a higher removal performance than the US and O3 process even though the O3 process also showed approximately the same removal efficiency after 60 min. Chemical oxygen demand/total organic carbon (CODcr/TOC) ratios for E1 and E3 decreased, indicating that biodegradability could be increased significantly in the US/O3 process. The optimal pH condition was determined above the neutral pH condition.

  1. Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy

    PubMed Central

    Kangas, Reeta; Törmäkangas, Timo; Fey, Vidal; Pursiheimo, Juha; Miinalainen, Ilkka; Alen, Markku; Kaprio, Jaakko; Sipilä, Sarianna; Säämänen, Anna-Marja; Kovanen, Vuokko; Laakkonen, Eija K.

    2017-01-01

    Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein- and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age +HRT -related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17β-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17β-estradiol, fat-, glucose- and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature. PMID:28195143

  2. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage

    PubMed Central

    Wu, Xianwei

    2017-01-01

    Objective Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). Methods We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002–2003, 2008–2009 and 2012–14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians’ HT recommendations from 2002 to 2009, and 2012 to 2014. Results Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Conclusion Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap. PMID:28158240

  3. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy.

    PubMed

    Petri Nahas, Eliana; Nahás Neto, Jorge; De Luca, Laurival; Traiman, Paulo; Pontes, Anaglória; Dalben, Ivete

    2004-08-20

    To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy (HRT). This prospective, double-blind and placebo-controlled study included 50 postmenopausal women randomly divided into two groups: 25 women on soy germ isoflavones (60 mg per day, capsules) and 25 women on placebo. Inclusion criteria included: non-vegetarian, non-asian women whose last menstruation dated at least 12 months prior to the beginning of the study, with FSH > 40 mIU/ml, hot flushes and contraindication for HRT, not using tamoxifen or antibiotic and no disease of the gastrointestinal tract. For 6 months, the Kupperman menopausal index (KMI), the vaginal cytological maturation value (MV) and both hormonal and lipid profiles were assessed. The t-test and analysis of variance (ANOVA) were employed to compare the two groups. In both groups, a decreased KI rate was observed. However, isoflavone was significantly superior to placebo in reducing hot flushes (44% versus 10%, respectively) (P < 0.05). After 6 months, the isoflavone group showed increased estradiol levels with unchanged FSH, LH, and vaginal cytology, and a reduction of 11.8% in LDL and an increase of 27.3% in HDL (P < 0.05 ). In the placebo group, just a reduction in MV was observed after 6 months (P < 0.05 ). Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile, showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT.

  4. Hormonal replacement therapy in women with Turner's syndrome in Poland: Analysis of 176 cases.

    PubMed

    Wacław, Jez; Irzyniec, Tomasz Jerzy

    2009-08-01

    Turner syndrome (TS) is one of the forms of gonadal malfunction. The study aims at the analysis of hypophysis-gonad axis (HGA) of women with TS who use and do not use hormonal replacement therapy (HRT). One hundred and seventy-six Poles with TS were investigated in the years 1995-2004. The information about the application of HRT was given during the interview. The HGA was examined by the estimation of gonadotropin (FSH, LH) and 17beta-estradiol (E(2)) levels. HRT was administered to 89% of women with TS at some point of their life. However, at the time of writing this report only 54% of them have been taking this drug. The variety of hormonal preparations used by the patients was great. In women with TS using the HRT, in contradiction to women with TS who do not use it, lower concentrations of FSH (32.1 +/- 22.1 vs. 44.2 +/- 23.3 IU/l) and LH (20.8 +/- 17.5 vs. 26.6 +/- 18.1 IU/l) as well as higher level of E(2) (135.5 +/- 147.9 vs. 89.9 +/- 100.6 pmol/l) were observed. The negative correlation between E(2) and FSH levels was not observed in women with TS using HRT, despite the elevation of 17beta-estradiol levels and the reduction of gonadotropin concentration. (1) Large percentage of women with TS does not use HRT. (2) Women with TS, who receive HRT, use this method of treatment insufficiently.

  5. Partisan perspectives in the medical literature: a study of high frequency editorialists favoring hormone replacement therapy.

    PubMed

    Tatsioni, Athina; Siontis, George C M; Ioannidis, John P A

    2010-09-01

    Unfavorable results of major studies have led to a large shrinkage of the market for hormone replacement therapy (HRT) in the last 6 years. Some scientists continue to strongly support the use of HRT. We analyzed a sample of partisan editorializing articles on HRT to examine their arguments, the reporting of competing interests, the journal venues and their sponsoring societies. Through Thomson ISI database, we selected articles without primary data written by the five most prolific editorialists that addressed clinical topics pertaining to HRT and that were published in regular journal issues in 2002-2008. We recorded the number of articles with a partisan stance and their arguments, the number of partisan articles that reported conflicting interests, and the journal venues and their sponsoring societies publishing the partisan editorials. We analyzed 114 eligible articles (58 editorials, 16 guidelines, 37 reviews, 3 letters), of which 110 (96%) had a partisan stance favoring HRT. Typical arguments were benefits for menopausal and related symptoms (64.9%), criticism of unfavorable studies (78.9%), preclinical data that showed favorable effects of HRT (50%), and benefits for major outcomes such as osteoporosis and fractures (49.1%), cardiovascular disease (31.6%), dementia (24.6%) or colorectal cancer (20.2%), but also even breast cancer (4.4%). All 5 prolific editorialists had financial relationships with hormone manufacturers, but these were reported in only 6 of the 110 partisan articles. Four journals published 15-37 partisan articles each. The medical societies of these journals reported on their websites that several pharmaceutical companies sponsored them or their conferences. There is a considerable body of editorializing articles favoring HRT use and very few of these articles report conflicts of interest. Full disclosure of conflicts of interest is needed, especially for articles without primary data.

  6. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage.

    PubMed

    Chew, Fiona; Wu, Xianwei

    2017-01-01

    Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002-2003, 2008-2009 and 2012-14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians' HT recommendations from 2002 to 2009, and 2012 to 2014. Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap.

  7. Hormone replacement therapy and incidence of central nervous system tumours in the Million Women Study.

    PubMed

    Benson, Victoria S; Pirie, Kirstin; Green, Jane; Bull, Diana; Casabonne, Delphine; Reeves, Gillian K; Beral, Valerie

    2010-10-01

    We examined the relation between the use of hormone replacement therapy (HRT) and the incidence of central nervous system (CNS) tumours in a large prospective study of 1,147,894 postmenopausal women. Women were aged 56.6 years on average at entry, and HRT use was recorded at recruitment and updated, where possible, about 3 years later. During a mean follow-up of 5.3 years per woman, 1,266 CNS tumours were diagnosed, including 557 gliomas, 311 meningiomas and 117 acoustic neuromas. Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). In past users of HRT the relative risk was 1.07 (95% CI: 0.93-1.24) for all CNS tumours. Among current users of HRT, there was significant heterogeneity by the type of HRT with the users of oestrogen-only HRT at higher risk of all CNS tumours than users of oestrogen-progestagen HRT (RR = 1.42, 95% CI: 1.21-1.67 versus RR = 0.97, 95% CI: 0.82-1.16) (heterogeneity p < 0.001). Among current users of oestrogen-only and oestrogen-progestagen HRT, there was no significant heterogeneity by duration of use, hormonal constituent or mode of administration of HRT.

  8. Pulmonary thrombosis associated with antidiuretic hormone replacement therapy due to secondary diabetes insipidus after traumatic brain injury: A case report

    PubMed Central

    Naito, Kiyohito; Watari, Taiji; Yasunari, Eisuke; Yamano, Miki; Mogami, Atsuhiko; Obayashi, Osamu; Kaneko, Kazuo

    2012-01-01

    INTRODUCTION Diabetes insipidus is a well-recognized complication of traumatic brain injury. The majority of patients with post-traumatic diabetes insipidus will require antidiuretic hormone (ADH) replacement therapy and tend to show dehydration. On the other hand, some negative effects of ADH on blood coagulation, such as increased platelet cohesion and the promotion of von Willebrand factor release, have also been reported. However, the incidence of thrombosis during antidiuretic hormone replacement therapy is disputed. PRESENTATION OF CASE A case of pulmonary thrombosis associated with ADH replacement therapy due to secondary diabetes insipidus after traumatic brain injury is presented here. DISCUSSION In our case, there were three factors that may have contributed to the observed thrombosis (dehydration, bed rest for a long period and ADH replacement therapy). CONCLUSION We believe that controlling urinary output and monitoring urinary and serum osmotic pressure are necessary for the management for diabetes insipidus patients after traumatic brain injury. In particular, we must carefully monitor the management of such patients during antidiuretic hormone replacement therapy. PMID:23131855

  9. Pulmonary thrombosis associated with antidiuretic hormone replacement therapy due to secondary diabetes insipidus after traumatic brain injury: A case report.

    PubMed

    Naito, Kiyohito; Watari, Taiji; Yasunari, Eisuke; Yamano, Miki; Mogami, Atsuhiko; Obayashi, Osamu; Kaneko, Kazuo

    2013-01-01

    Diabetes insipidus is a well-recognized complication of traumatic brain injury. The majority of patients with post-traumatic diabetes insipidus will require antidiuretic hormone (ADH) replacement therapy and tend to show dehydration. On the other hand, some negative effects of ADH on blood coagulation, such as increased platelet cohesion and the promotion of von Willebrand factor release, have also been reported. However, the incidence of thrombosis during antidiuretic hormone replacement therapy is disputed. A case of pulmonary thrombosis associated with ADH replacement therapy due to secondary diabetes insipidus after traumatic brain injury is presented here. In our case, there were three factors that may have contributed to the observed thrombosis (dehydration, bed rest for a long period and ADH replacement therapy). We believe that controlling urinary output and monitoring urinary and serum osmotic pressure are necessary for the management for diabetes insipidus patients after traumatic brain injury. In particular, we must carefully monitor the management of such patients during antidiuretic hormone replacement therapy. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Effect of hormone replacement on exercise cardiopulmonary reserve and recovery performance in subclinical hypothyroidism.

    PubMed

    Mainenti, M R M; Teixeira, P F S; Oliveira, F P; Vaisman, M

    2010-11-01

    Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and muscle dysfunction, but there is no consensus about the benefits of levothyroxine (L-T₄) intervention on cardiopulmonary performance during exercise. The aim of the present study was to investigate the effects of L-T₄ on cardiopulmonary exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50) years old, were submitted to two ergospirometry tests, with an interval of 6 months of normalization of thyroid-stimulating hormone (TSH) levels (L-T₄ replacement group) or simple observation (TSH = 6.90 μIU/mL; L-T₄ = 1.02 ng/dL). Patients with TSH >10 μIU/mL were excluded from the study to assure that they would receive treatment in this later stage of SH. Twenty 30- to 57-year-old women with no thyroid dysfunction (TSH = 1.38 μIU/mL; L-T₄ = 1.18 ng/dL) were also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs 0.30; P < 0.05) were found for SH patients. The treated group presented greater variation than the untreated group for pulmonary ventilation reserve (20.45 to 21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = -4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There were no relevant differences in cardiopulmonary recovery for either group at baseline or after follow-up. In the sample studied, L-T₄ replacement improved exercise cardiopulmonary reserve, but no modification was found in recovery performance after exercise during this period of analysis.

  11. Beneficial Effects on Pregnancy Outcomes of Thyroid Hormone Replacement for Subclinical Hypothyroidism.

    PubMed

    Blumenthal, Norman J; Eastman, Creswell J

    2017-01-01

    Background. Hypothyroidism and raised thyroid antibody levels have been associated with adverse obstetrical outcomes. Several studies have investigated causal associations, but results have been inconsistent and few studies have reported the effects of thyroxine replacement therapy on pregnancy outcomes in hypothyroid patients. Objective. The primary study objective was to determine the outcome of pregnancies in women diagnosed with overt and subclinical hypothyroidism (SCH) (serum TSH > 2.5 mIU/L) and those with elevated circulating thyroid autoantibody levels in the first trimester of pregnancy and after the institution of appropriate thyroxine replacement therapy to maintain the serum TSH ≤ 2.5 mIU/L. Study Design. This prospective observational study was undertaken between 2013 and 2016. Blood samples were taken from 1025 women at presentation for thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TGAb), and thyroid peroxidase antibodies (TPOAb). Those with a TSH > 2.5 mIU/L were treated with thyroxine and managed appropriately to ensure that the TSH was maintained ≤2.5 mIU/L. Outcomes in these patients were compared to those in euthyroid patients. Maternal antenatal complications and perinatal outcomes were recorded. Results. There were a total of 1025 patients of whom 382 (37.5%) were nulliparous. 10.1% had a TSH level > 2.5 mIU/L and 18.2% had at least one raised thyroid antibody level. No differences in adverse outcomes of pregnancy were evident in women treated for SCH or overt hypothyroidism compared to the euthyroid group. There was also no association between raised thyroid antibodies and adverse pregnancy outcomes in either group. Conclusion. There were no adverse outcomes of pregnancy found in pregnant women who had been diagnosed and treated with thyroxine for SCH at the time of presentation when compared to euthyroid patients. There was also no relationship with thyroid antibodies and adverse pregnancy outcomes in the

  12. Beneficial Effects on Pregnancy Outcomes of Thyroid Hormone Replacement for Subclinical Hypothyroidism

    PubMed Central

    Eastman, Creswell J.

    2017-01-01

    Background. Hypothyroidism and raised thyroid antibody levels have been associated with adverse obstetrical outcomes. Several studies have investigated causal associations, but results have been inconsistent and few studies have reported the effects of thyroxine replacement therapy on pregnancy outcomes in hypothyroid patients. Objective. The primary study objective was to determine the outcome of pregnancies in women diagnosed with overt and subclinical hypothyroidism (SCH) (serum TSH > 2.5 mIU/L) and those with elevated circulating thyroid autoantibody levels in the first trimester of pregnancy and after the institution of appropriate thyroxine replacement therapy to maintain the serum TSH ≤ 2.5 mIU/L. Study Design. This prospective observational study was undertaken between 2013 and 2016. Blood samples were taken from 1025 women at presentation for thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TGAb), and thyroid peroxidase antibodies (TPOAb). Those with a TSH > 2.5 mIU/L were treated with thyroxine and managed appropriately to ensure that the TSH was maintained ≤2.5 mIU/L. Outcomes in these patients were compared to those in euthyroid patients. Maternal antenatal complications and perinatal outcomes were recorded. Results. There were a total of 1025 patients of whom 382 (37.5%) were nulliparous. 10.1% had a TSH level > 2.5 mIU/L and 18.2% had at least one raised thyroid antibody level. No differences in adverse outcomes of pregnancy were evident in women treated for SCH or overt hypothyroidism compared to the euthyroid group. There was also no association between raised thyroid antibodies and adverse pregnancy outcomes in either group. Conclusion. There were no adverse outcomes of pregnancy found in pregnant women who had been diagnosed and treated with thyroxine for SCH at the time of presentation when compared to euthyroid patients. There was also no relationship with thyroid antibodies and adverse pregnancy outcomes in the

  13. Comparison of Piascledine (Avocado and Soybean Oil) and Hormone Replacement Therapy in Menopausal-Induced Hot Flashing

    PubMed Central

    Panahi, Yunes; Beiraghdar, Fatemeh; Kashani, Nafise; Baharie Javan, Nika; dadjo, yahya

    2011-01-01

    Different symptoms in Climacteric period, includes hot flash. Hormone replacement therapy (HRT) is common therapy for relief of menopausal symptoms but has possible contraindications and side effects. Recently Piascledine (combination of Avocado oil with Soybean oil) showed effects in reducing hot flash severity. Present study designed to compare the effects of HRT with Piascledine in treatment of hot flash. The cases of this study were sixty-six women at the age range of 40 to 70 years and complaints of menopause-induced hot flashing, whose last menstruation dated at least 6 months prior to the beginning of the study. The patients in this open label clinical trial, randomized to receive Piascledine capsule 1 mg or HRT (0.625 mg oral daily Conjugated Estrogen tablets, plus 2.5 mg continuous oral daily Medroxyprogesterone Acetate tablets) for 2 month. Hot flash property and severity was assessed via a daily check list and Visual analog scale. Climacteric symptom was measured before and after intervention using Greene Climacteric Scale (GCS) and Blatt-kupperman Menopausal Index (BKMI). Thirty-three eligible patients were allocated in each group. From the Piascledine group, one patient and from the HRT group, 16 patients weren›t willing to attend the study; therefore, 32 and 17 woman received treatment in Piascledine and HRT groups. 4 patients were withdrawn for vaginal bleeding and one for breast tenderness from HTR group. Hot flash severity in both groups decreased during the time similarly. With regard to GCS (p = 0.571) and BMKI (p = 0.891), the outcome was similar among the two groups. Due to low HRT compliance and its possible risks in long period of time and considering the same activity of soybean supplement and HRT in relieving the hot flash as menopausal symptoms in women, it seems that soybean supplements can be an alternative therapy to hormone. PMID:24250433

  14. Analysis of menstrual calendars and serum alpha 2-PEG in women on hormone replacement therapy for 12 months.

    PubMed

    Habiba, M; al-Azzawi, F

    1994-10-01

    This study was conducted to assess endometrial protection in women on a cyclical combined hormone replacement regimen with 1 mg norethisterone BP, and to evaluate the use of the bleeding pattern and serum alpha 2-PEG in monitoring the endometrial response to exogenous hormone therapy. Fifty-one postmenopausal women attending the Menopause Research Unit at Leicester Royal Infirmary, UK, completed the study. All patients were at least 1 year after the menopause, with an average of 26 months since the last menstrual period. All women were prescribed a regimen of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg, and oestradiol 0.6 mg) continuously, with 1 mg of norethisterone added for 12 days out of each 28-day treatment cycle. Menstrual diaries were collected and analysed. The secretory changes were assessed by histology, menstrual bleeding pattern and a biological marker of secretory activity (alpha 2-PEG). Withdrawal bleeding occurred on average on days 11, 12, 11, 12 and 13 on months 2, 3, 6, 9 and 12, respectively. There was a poor degree of consistency in the bleeding pattern. The level of alpha 2-PEG increased from the average baseline measurement of 2.7 ng/ml (S.D., 4.12) to 8.5 ng/ml (S.D., 4.16) after progestogen treatment. This rise, although significant, did not correlate with the uterine bleeding pattern. There was no statistically significant correlation between the level of alpha 2-PEG and endometrial histology. The findings highlight the fact that cycle predictability on HRT, as exemplified in this regimen, is poor. The level of alpha 2-PEG is a poor predictor of the endometrial histology and has a poor correlation with the day of onset of bleeding.

  15. An update on menopausal hormone replacement therapy in women and cardiovascular disease.

    PubMed

    Valdiviezo, Carolina; Lawson, Shari; Ouyang, Pamela

    2013-04-01

    This review presents the available evidence for effects of menopausal hormone replacement therapy (MHT), more specifically estrogen, and selective estrogen receptor modulators on the cardiovascular system with a focus on randomized controlled trials (RCTs) published since 2010. In contrast to early observational studies, the Women's Health Initiative, the largest randomized controlled trial of MHT in generally healthy women, suggested harmful cardiovascular effects. Subsequent subanalyses of the Women's Health Initiative and other studies suggest the cardiovascular effects of MHT may vary by age and time since menopause, giving rise to a 'timing hypothesis'. Recent trials have looked at this issue by evaluating surrogate markers of cardiovascular disease (CVD) or CVD events adjudicated as secondary outcomes in RCTs and show a reduction in events with MHT. Athough the data overall do not support the use of MHT or selective estrogen receptor modulator for primary prevention of CVD, evidence is accumulating that careful use of MHT for perimenopausal symptoms may not carry CVD harm. This review highlights some of the strengths and weaknesses of these recent reports. Ongoing studies of MHT will shed more light on the interaction between age or time after menopause and the vascular effects of MHT.

  16. Should a doctor prescribe hormone replacement therapy which has been manufactured from mare's urine?

    PubMed

    Cox, D

    1996-08-01

    Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease.

  17. Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis

    PubMed Central

    Wang, Siqi; Wang, Yuqiong; Xu, Jinming; Chen, Yuxin

    2017-01-01

    Abstract Background: Association between exogenous estrogen intake and cholelithiasis risk has been reported in several epidemiological studies, including oral contraceptive (OC) and hormone replacement therapy (HRT), while the results were controversial. This study aimed to perform a comprehensive meta-analysis of this issue. Methods: PUBMED, EMBASE, and Cochrane library database were searched up to October 2016. Two reviewers independently extracted data from eligible studies, relative risks (RRs), and/or odds ratios (ORs) with 95% confidence intervals (95% CIs) for the highest versus lowest categories of intake were adopted. Either a fixed- or a random-effects model was adopted to estimate overall RRs or ORs. Besides, subgroup and publication bias analyses were applied to explain the heterogeneity. An original study was also conducted to verify our conclusion. Results: A total of 19 studies with approximately 556,620 participants were included in this meta-analysis. The pooled RR of cholelithiasis for the highest versus the lowest categories was 1.59 (95% CI: 1.44–1.75), indicating that exogenous estrogen was positive associated with the intake of exogenous estrogen. However, the pooled RR of OC intake and cholelithiasis risk was 1.19 (95% CI: 0.97–1.45), and the RR for HRT was 1.79 (95% CI: 1.61–2.00). Conclusion: The HRT was positively associated with the cholelithiasis risk, and the OC will not increase the risk of cholelithiasis. PMID:28383429

  18. Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A Quantitative Systematic Review

    PubMed Central

    Bae, Jong-Myon; Kim, Eun Hee

    2015-01-01

    Objectives: The epidemiological characteristics of breast cancer incidence by age group in Korean women are unique. This systematic review aimed to investigate the association between hormone replacement therapy (HRT) and breast cancer risk in Korean women. Methods: We searched electronic databases such as KoreaMed, KMbase, KISS, and RISS4U as well as PubMed for publications on Korean breast cancer patients. We also conducted manual searching based on references and citations in potential papers. All of the analytically epidemiologic studies that obtained individual data on HRT exposure and breast cancer occurrence in Korean women were selected. We restricted the inclusion of case-control studies to those that included age-matched controls. Estimates of summary odds ratio (SOR) with 95% confidence intervals (CIs) were calculated using random effect models. Results: One cohort and five case-control studies were finally selected. Based on the heterogeneity that existed among the six studies (I-squared=70.2%), a random effect model was applied. The summary effect size of HRT history from the six articles indicated no statistical significance in breast cancer risk (SOR, 0.983; 95% CI, 0.620 to 1.556). Conclusions: These facts support no significant effect of HRT history in the risk of breast cancer in Korean women. It is necessary to conduct a pooled analysis. PMID:26429288

  19. Should a doctor prescribe hormone replacement therapy which has been manufactured from mare's urine?

    PubMed Central

    Cox, D

    1996-01-01

    Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease. PMID:8863143

  20. Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population.

    PubMed

    Gavaler, Judith S

    2002-02-01

    The assumption that estradiol (E2) concentrations are reliably increased to therapeutic levels in postmenopausal women receiving hormone replacement therapy (HRT) has not been explicitly tested. Nor have factors that may modulate the E2 levels achieved been evaluated. The author examined E2 concentrations in a multiracial study population of 309 postmenopausal women treated with oral HRT and observed that 51.1% had achieved estradiol levels of at least 45 pg/ml (achievers). The odds of being an achiever were significantly elevated among non-Caucasian women by a HRT dose greater than 0.625 mg, current moderate drinking, and increasing duration of HRT use. The odds were significantly decreased by having a high school education or less and increasing time since last HRT dose. White postmenopausal women had significantly reduced odds of being an achiever, and both a dose of less than 0.625 mg and a dose equal to 0.625 mg significantly reduced the odds of being an achiever. Increasing body mass index and menopause duration were both associated with lower odds. This report demonstrates not only that women treated with HRTdo not all achieve therapeutic levels of estradiol but also that factors can be identified that modulate the E2 concentration achieved in response to HRT administration.

  1. Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy.

    PubMed

    Hampson, Elizabeth; Duff-Canning, Sarah J

    2016-02-01

    Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n=39), or taking estrogens in combination with a progestin (n=25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Effect of missed combined hormonal contraceptives on contraceptive effectiveness: a systematic review☆

    PubMed Central

    Zapata, Lauren B.; Steenland, Maria W.; Brahmi, Dalia; Marchbanks, Polly A.; Curtis, Kathryn M.

    2015-01-01

    Background Combined hormonal contraceptives (CHCs) are popular methods of reversible contraception in the United States, but adherence remains an issue as reflected in their lower rates of typical use effectiveness. The objective of this systematic review was to evaluate evidence on the effect of missed CHCs on pregnancy rates as well as surrogate measures of contraceptive effectiveness (e.g., ovulation, follicular development, changes in hormone levels, cervical mucus quality). Study Design We searched the PubMed database for peer-reviewed articles published in any language from database inception through April 2012. We included studies that examined measures of contraceptive effectiveness during cycles with extended hormone-free intervals or nonadherence (e.g., omission of pills, delayed patch replacement) on days not adjacent to the hormone-free interval. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. Results The search strategy identified 1387 articles, of which 26 met our study selection criteria. There is wide variability in the amount of follicular development and risk of ovulation among women who extended the pill-free interval to 8–14 days; in general, the risk of ovulation was low, and among women who did ovulate, cycles were usually abnormal (i.e., low progesterone levels, small follicles and/or poor cervical mucus) (Level I, good, indirect to Level II-3, fair, indirect). Studies of women who missed one to four consecutive pills or 1–3 consecutive days of delay before patch replacement at times other than adjacent to the hormone-free interval reported little follicular activity and low risk of ovulation (Level I, fair, indirect to Level II-3, poor, indirect). Studies comparing 30 mcg versus 20 mcg mc ethinyl estradiol pills showed more follicular activity when 20 mcg ethinyl estradiol pills were missed (Level I, good, indirect). Conclusion Most of the studies in this evidence base relied on

  3. [Hormonal replacement therapy and breast cancer. A case-control study].

    PubMed

    Basavilvazo Rodríguez, María Antonia; Díaz Quiroz, Alfonso; Lemus Rocha, Roberto; Angeles Victoria, Leobardo; Zárate, Arturo; Hernández-Valencia, Marcelino

    2004-01-01

    Breast cancer is the second more frequently neoplasia in the woman and the first cause of mortality after 35 years old. It is considered a multifactorial illness, since is influenced for genetic, dietary and endocrine factors. Among these, hormonal replacement therapy (HRT) have been assigned benefits effect, as well as risks to increase the breast cancer incidence, because presence of estrogens receptor in the neoplasia cells makes think that the estrogens and other sexual hormones constitute a factor promoter of this cancer. The objective of this study was to determine the association of HRT as risk factor in the incidence of breast cancer, in women from oncology-gynecological service. Was carried out this descriptive study in patients that used HRT, considering as cases patients with breast cancer confirmed by hystophatological study and controls the patients without breast cancer. To statistical analysis took mean occurrence using the momios reason (MM), with confidence interval of 95% (CI), and chi2 test of Mantel-Haenszel, for a significant value of p < 0.05. Were included successively 250 patients, in 100 of these were confirmed diagnosis of breast cancer, 60 patients (37.5%) used HRT with mean of 3 years and 40 patients (44.4%) did not use HRT (Cases), the other 150 patients did not have breast cancer, 100 of these used HRT and 50 patients did not use HRT (Control). The statistical analysis showed that the HRT had a MM 0.75 (IC 95% 0.62-1.15) p=0.28, the maternal nursing with MM 0.68 (IC 95% 0.59-1.08) p=0.05, the multiparity with MM 0.42 (IC 95% 0.16-1.87) p=0.26, obesity MM 1.67 (IC 95% 0.99-1.54) p=0.05, familial history with MM 1.23 (IC 95% 0.83-1.54) p=0.05. These results show that does not exist a direct association between HRT and breast cancer. Therefore, whenever takes the decision to use the HRT should be considered the possible risks and benefits individualizing the patient, also the mammography should be present in mind, same that frequent

  4. Partisan Perspectives in the Medical Literature: A Study of High Frequency Editorialists Favoring Hormone Replacement Therapy

    PubMed Central

    Tatsioni, Athina; Siontis, George C. M.

    2010-01-01

    ABSTRACT Background Unfavorable results of major studies have led to a large shrinkage of the market for hormone replacement therapy (HRT) in the last 6 years. Some scientists continue to strongly support the use of HRT. Objectives We analyzed a sample of partisan editorializing articles on HRT to examine their arguments, the reporting of competing interests, the journal venues and their sponsoring societies. Data Sources Through Thomson ISI database, we selected articles without primary data written by the five most prolific editorialists that addressed clinical topics pertaining to HRT and that were published in regular journal issues in 2002–2008. Main Measures We recorded the number of articles with a partisan stance and their arguments, the number of partisan articles that reported conflicting interests, and the journal venues and their sponsoring societies publishing the partisan editorials. Key Results We analyzed 114 eligible articles (58 editorials, 16 guidelines, 37 reviews, 3 letters), of which 110 (96%) had a partisan stance favoring HRT. Typical arguments were benefits for menopausal and related symptoms (64.9%), criticism of unfavorable studies (78.9%), preclinical data that showed favorable effects of HRT (50%), and benefits for major outcomes such as osteoporosis and fractures (49.1%), cardiovascular disease (31.6%), dementia (24.6%) or colorectal cancer (20.2%), but also even breast cancer (4.4%). All 5 prolific editorialists had financial relationships with hormone manufacturers, but these were reported in only 6 of the 110 partisan articles. Four journals published 15–37 partisan articles each. The medical societies of these journals reported on their websites that several pharmaceutical companies sponsored them or their conferences. Conclusions There is a considerable body of editorializing articles favoring HRT use and very few of these articles report conflicts of interest. Full disclosure of conflicts of interest is needed, especially

  5. Treatable Bedridden Elderly―Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency

    PubMed Central

    Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

    2016-01-01

    Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency. PMID:27746435

  6. Treatable Bedridden Elderly -Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency.

    PubMed

    Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

    Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency.

  7. A survey of physicians' attitude and approach to hormone replacement therapy during menopuase.

    PubMed

    Kaplan, B; Rabinerson, D; Yogev, Y; Bar-Hava, I; Bar, J; Orvieto, R

    2002-01-01

    A major problem with postmenopausal hormone replacement therapy (HRT) is its relatively low long-term continuation rate. The aim of the present study was to assess the contribution of physicians to the low long-term continuation rate by surveying their attitude and approach to the use of HRT in postmenopausal women. A questionnaire was sent to registered members of the North American Menopause Society. Data were collected on demographics, medical education and affiliation, attitude to the use of HRT and its contraindications, and follow-up, strategies. The response rate was 21% (n = 218). Sixty-six percent of the physicians recommended HRT for every postmenopausal woman with no contraindications. and 11% also took age and/or time since menopause into consideration. Eighty-six percent claimed they would try to persuade symptom-free women not interested in HRT into changing their minds. There was no correlation between the time since completion of residency or affiliation with a medical school and physicians' attitude to prescribing HRT or contraindication to HRT, or management strategy. However, type of specialty was significantly correlated with physicians' tendency to recommend HRT. Specialists in menopause showed a lower tendency to unconditionally recommend HRT (in the absence of contraindications) (67%) than specialists in reproductive endocrinology (90%), infertility (90%). gynecology (83%), and perinatology (84%) (p < 0.006, C-measure = 0.25). The attitude toward HRT and the management strategies of members of the North American Menopause Society correlate with contemporary recommendations in the literature, indicating good training of young physicians and adequate updating of older ones. Thus, to increase the continuation rate of HRT, educational efforts should be directed primarily to the public rather than to medical professionals.

  8. Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy

    PubMed Central

    Gilligan, Lorna C.; Gondal, Ali; Tang, Vivien; Hussain, Maryam T.; Arvaniti, Anastasia; Hewitt, Anne-Marie; Foster, Paul A.

    2017-01-01

    Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability. As E1S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E1S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E1S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E2) and G1, a GPER agonist, significantly (p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E1S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes. PMID:28326039

  9. Substrate utilization during exercise in postmenopausal women on hormone replacement therapy.

    PubMed

    Johnson, Lisa G; Kraemer, Robert R; Kraemer, Ginger R; Haltom, Ron W; Cordill, Alison E; Welsch, Michael A; Durand, Robert J; Castracane, V Daniel

    2002-12-01

    It has been suggested that due to the slight direct or indirect effect of estrogen on lipolytic activity, the age-related decrease in production associated with the menopause may heighten the risk of cardiovascular and metabolic disease in women. While hormone replacement therapy (HRT) alone may have little or no effect on body mass in postmenopausal women, data suggest it can alter the shift toward abdominal adiposity. Furthermore, estrogen may have a synergistic effect on exercise-induced reduction in fat mass. Accordingly, the purpose of this investigation was to examine the potential influence of HRT on substrate utilization during 30 min of treadmill exercise at approximately 80% maximal oxygen uptake (VO(2max)) in postmenopausal women. Eight women were receiving HRT and nine women were not (NHRT). No significant differences between the HRT and NHRT groups were noted for age, body mass, body fat, VO(2max) or the percentage of VO(2max) maintained during exercise. Expired gas samples were analyzed every 30 s to determine respiratory exchange ratio (R) and % VO(2max). The R, total energy expended and percentage contributions from fats and carbohydrate were averaged over three periods during the exercise (min 1-10, 11-20, and 21-30). There was no effect of HRT on R, total energy expended or substrate contribution. Thus, treatment of postmenopausal women using HRT (primarily conjugated equine estrogens in doses of 0.625-1.25 mg x day(-1)) did not appear to affect the percentages of fat and carbohydrate utilized during 30 min of treadmill exercise at 80% of VO(2max). However, the exercise responses in this group of menopausal women were consistent with a duration-dependent increased reliance on fat as an energy source during exercise of moderate to vigorous intensity as has been demonstrated in younger populations.

  10. Hormone replacement therapy and breast cancer: heterogeneous risks by race, weight, and breast density.

    PubMed

    Hou, Ningqi; Hong, Susan; Wang, Wenli; Olopade, Olufunmilayo I; Dignam, James J; Huo, Dezheng

    2013-09-18

    Although studies have demonstrated a positive association between hormone replacement therapy (HRT) and breast cancer risk, this association may vary by patient factors. We analyzed 1642824 screening mammograms with 9300 breast cancer cases in postmenopausal women aged 45 years or older derived from the Breast Cancer Surveillance Consortium, a longitudinal registry of mammography screening in the United States. Multiple imputation methods were used to accommodate missing data for HRT use (14%) and other covariables. We performed logistic regression to estimate odds ratios (ORs) for breast cancer associated with HRT use within strata of race/ethnicity, age, body mass index (BMI), and breast density, with two-way interaction terms between HRT use and each key covariable of interest. P values for assessing possible interactions were computed from Wald z statistics. All statistical tests were two-sided. HRT use was associated with greater than 20% increased risk in white (OR = 1.21; 95% CI = 1.14 to 1.28), Asian (OR = 1.58; 95% CI = 1.18 to 2.11), and Hispanic women (OR = 1.35; 95% CI = 1.09 to 1.67) but not black women (OR = 0.91; 95% CI = 0.72 to 1.14; P interaction = .04). In women with low/normal BMI and extremely dense breasts, HRT use was associated with the highest breast cancer risk (OR = 1.49; 95% CI = 1.21 to 1.83), compared with nonusers. In overweight/obese women with less-dense breasts, no excess risk was associated with HRT use (adjusted ORs = 0.96 to 1.03). The impact of HRT use on breast cancer risk varies according to race/ethnicity, BMI, and breast density. This risk stratification could help in advising HRT use for the relief of menopausal symptoms.

  11. Dietary boron and hormone replacement therapy as risk factors for lung cancer in women.

    PubMed

    Mahabir, S; Spitz, M R; Barrera, S L; Dong, Y Q; Eastham, C; Forman, M R

    2008-05-01

    Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (p(trend) < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds.

  12. Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women

    PubMed Central

    Mahabir, S.; Spitz, M. R.; Barrera, S. L.; Dong, Y. Q.; Eastham, C.; Forman, M. R.

    2012-01-01

    Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (ptrend < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds. PMID:18343880

  13. A case-control study on the effect of hormone replacement therapy on ischaemic heart disease.

    PubMed

    Hippisley-Cox, Julia; Pringle, Mike; Crown, Nicola; Coupland, Carol

    2003-03-01

    Many clinicians believe that hormone replacement therapy (HRT) protects against coronary heart disease (CHD) in women. However, recent reports have cast some doubt on this because of lack of dose-response or duration-response effects. Since CHD is common in women--about half of all postmenopausal women will get it and about a third of these will die from it--the effect of HRT on CHD is of great public health importance. To determine the degree of cardioprotection conferred by HRT, including the effect of duration, time since last issue, the addition of progestogens, route of administration, and dose. Population-based case-control study. Nine general practices recruited from the Trent Focus Collaborative Research Network. A total of 417 female cases with CHD matched by age and practice to 2435 controls with a case-control ratio of 1:5.8 were studied. The main outcome measure was the odds ratio for CHD calculated by conditional logistic regression adjusted for diabetes, hypertension, body mass index, and smoking. No evidence was found, either from univariate analysis or multivariate analysis, that use of HRT was associated with reduced risk of CHD (odds ratio = 1.32; 95% confidence interval = 0.93 to 1.87). Indeed, the trend was in the opposite direction. There was no association for different types of HRT (opposed or unopposed) or routes of administration. Similarly, there was no association for current or past use and no effect for dose or duration. This study adds to growing evidence that HRT does not confer cardioprotection. Until there is robust evidence to the contrary, general physicians need to assess risks and benefits of HRT independently of any possible reduction in risk of CHD.

  14. Efficacy of Postoperative Hormone Replacement Therapy on Prognosis of Patients with Serous Ovarian Carcinoma

    PubMed Central

    Zhang, Yong-Li; Chen, Jin-Hong; Lu, Wen; Li, Bi-Lan; Zhu, Qin-Yi; Wan, Xiao-Ping

    2016-01-01

    Background: Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in young female cancer survivors. We evaluated whether postoperative hormone replacement therapy (HRT) had a negative influence on the progression-free survival (PFS) of patients with papillary serous ovarian cancer (SOC). Methods: We retrospectively reviewed the medical records of patients with papillary SOC, treated from January 1980 to December 2009, who suffered from menopause with or without HRT. Clinical characteristics of patients were compared between the two groups (HRT and non-HRT). Blood samples were collected from all the participants to detect serum cancer antigen (CA) 125. Hazard ratios with 95% confidential intervals for each variable were calculated by univariable and multivariable conditional Logistic regression analyses. Results: Among 112 identified patients, 31 were HRT users and 81 were not. The two groups did not significantly differ in median age at diagnosis (t = 0.652, P = 0.513), International Federation of Gynecology and Obstetrics (FIGO) stage (χ2 = 0.565, P = 0.754), differentiation (χ2 = 1.728, P = 0.422), resection status (χ2 = 0.070, P = 0.791), relapse (χ2 = 0.109, P = 0.741), chemotherapy course (t = −1.079, P = 0.282), follow-up interval (t = 0.878, P = 0.382), or PFS (t = 0.580, P = 0.562). Median Kupperman score at the onset of HRT was 30.81 and 12.19 after the therapy (t = 3.302, P = 0.001). According to the analysis, the strongest independent variables in predicting PFS were FIGO stage and disease that was not optimally debulked. Conclusions: Postoperative HRT is not a prognostic factor for PFS of patients with papillary SOC. However, multicenter studies are needed to verify and extend our findings. PMID:27231169

  15. Enhancement of cholesteryl ester transfer in plasma by hormone-replacement therapy.

    PubMed

    Ritsch, Andreas; Kaser, Susanne; Volgger, Birgit; Abfalter, Elisabeth; Sturm, Wolfgang; Gänzer, Hannes; Föger, Bernhard; Kirchmair, Rudolf; Ebenbichler, Christoph; Patsch, Josef R

    2002-05-01

    To study possible mechanisms for the suggested protective effect of hormone-replacement therapy (HRT) with respect to cardiovascular disease we investigated lipoprotein parameters, mass and activity of lipoprotein-metabolizing enzymes, magnitude of postprandial lipemia, and vascular endothelial function in 13 postmenopausal women. All patients were examined before and 3 months after implementation of HRT with estrogen alone (group A, n = 6) or estrogen plus gestagen (group B, n = 7). HRT (groups A and B) resulted in enhanced total transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins (56% +/- 11.45% v 50.82% +/- 13.68%, P <.05) and increased apoA-I plasma concentration (171 +/- 30 v 147 +/- 22 mg/dL, P <.05). Fasting triglycerides (TG) were increased (134 +/- 40 v 115 +/- 39 mg/dL, P <.05). In group A patients the magnitude of postprandial lipemia increased significantly (1,737 +/- 756 v 1,475 +/- 930 mg TG/dL plasma/8 h, P <.05) without any change in lipoprotein lipase (LPL) activity, but with a concomitant decrease in low-density lipoprotein (LDL) size. In both groups flow-mediated dilation (FMD) reflecting vascular endothelial function was not influenced, suggesting that HRT may not directly affect vascular function but rather alters lipoprotein metabolism. The increase of apoA-I was not accompanied by an equivalent rise of HDL cholesterol. Based on the present data this finding can be readily explained by an increase in CE transfer from HDL to TG-rich lipoproteins, which is not due to increased cholesteryl ester transfer protein (CETP) plasma levels, but rather reflects an increase in fasting and postprandial TG. In conclusion, the net effect of accelerated CE transfer due to HRT depends on the balance of proatherogenic aspects, like the generation of small dense LDL, and antiatherogenic aspects, like the stimulation of reverse cholesterol transport.

  16. The role of sex hormone replacement therapy on self-perceived competence in adolescents with delayed puberty.

    PubMed

    Schwab, J; Kulin, H E; Susman, E J; Finkelstein, J W; Chinchilli, V M; Kunselman, S J; Liben, L S; D'Arcangelo, M R; Demers, L M

    2001-01-01

    The objective of the present study was to determine the role of sex steroids in the development of self-perceived competence during adolescence. The Harter Self-Perception Scale was administered to 56 adolescents with delayed puberty who were receiving depo-testosterone (males) or conjugated estrogens (females) administered in 3-month blocks alternating with placebo. Treatment was given at three dose levels approximating early, middle, and late pubertal replacement levels. Hormone treatments had a significant positive effect for both males and females in one subscale domain--perceived job competence. Significant positive hormone effects were also obtained for perceptions of romantic appeal and close friendship in females and perception of athletic abilities in males. It can be inferred from the results of this study that the hormonal changes associated with sexual maturation have targeted influences on specific domains of self-perceived competence and that there are clear gender differences.

  17. Prevalence of hypothyroidism in diabetic kidney disease and effect of thyroid hormone replacement on estimate glomerular filtration rate

    PubMed Central

    Bajaj, Sarita; Purwar, Naincy; Gupta, Arvind; Gupta, Poonam; Srivastava, Anubha

    2016-01-01

    Aims: To determine the prevalence of subclinical and overt hypothyroidism in diabetic kidney disease (DKD) and effect of thyroid hormone replacement on progression of DKD. Materials and Methods: A prospective cohort study on 41 adult DKD patients who were screened for hypothyroidism. Hypothyroid DKD patients were started on levothyroxine replacement and were reviewed after 3 and 6 months. Results: Of the total population, 14 (34.1%) cases were hypothyroid, among whom 12 (29.3%) cases were subclinical, and 2 (4.8%) were overt hypothyroidism. Prevalence of hypothyroidism and mean thyroid stimulating hormone levels increased with increasing severity of DKD. There were 2 (14.3%) hypothyroid cases in stage 3b, 4 (28.5%) cases in stage 4, and 8 (57.2%) in stage 5 DKD. The mean estimate glomerular filtration rate (ml/min/1.73 m2) at baseline was 13.6 ± 13.3 which increased to 16.4 ± 14.5 and 21.2 ± 15.3 after 3 and 6 months of thyroid hormone replacement therapy (THRT), respectively (P < 0.001). Conclusions: Hypothyroidism is commonly associated with DKD. Prevalence of hypothyroidism increased with declining renal function. THRT significantly improved renal function in DKD patients with hypothyroidism after 3 and 6 months of therapy. PMID:27867882

  18. Hormone replacement therapy use and plasma levels of sex hormones in the Norwegian Women and Cancer postgenome cohort - a cross-sectional analysis.

    PubMed

    Waaseth, Marit; Bakken, Kjersti; Dumeaux, Vanessa; Olsen, Karina S; Rylander, Charlotta; Figenschau, Yngve; Lund, Eiliv

    2008-01-14

    Hormone replacement therapy use (HRT) is associated with increased breast cancer risk. Our primary objective was to explore hormone levels in plasma according to HRT use, body mass index (BMI) and menopausal status. A secondary objective was to validate self-reported questionnaire information on menstruation and HRT use in the Norwegian Women and Cancer postgenome cohort (NOWAC). We conducted a cross-sectional study of sex hormone levels among 445 women aged 48-62 who answered an eight-page questionnaire in 2004 and agreed to donate a blood sample. The samples were drawn at the women's local general physician's offices in the spring of 2005 and sent by mail to NOWAC, Tromsø, together with a two-page questionnaire. Plasma levels of sex hormones and Sex Hormone Binding Globulin (SHBG) were measured by immunometry. 20 samples were excluded, leaving 425 hormone measurements. 20% of postmenopausal women were HRT users. The plasma levels of estradiol (E2) increased with an increased E2 dose, and use of systemic E2-containing HRT suppressed the level of Follicle Stimulating Hormone (FSH). SHBG levels increased mainly among users of oral E2 preparations. Vaginal E2 application did not influence hormone levels. There was no difference in BMI between HRT users and non-users. Increased BMI was associated with increased E2 and decreased FSH and SHBG levels among non-users. Menopausal status defined by the two-page questionnaire showed 92% sensitivity (95% CI 89-96%) and 73% specificity (95% CI 64-82%), while the eight-page questionnaire showed 88% sensitivity (95% CI 84-92%) and 87% specificity (95% CI 80-94%). Current HRT use showed 100% specificity and 88% of the HRT-users had plasma E2 levels above the 95% CI of non-users. Users of systemic E2-containing HRT preparations have plasma E2 and FSH levels comparable to premenopausal women. BMI has an influence on hormone levels among non-users. NOWAC questionnaires provide valid information on current HRT use and menopausal

  19. Does structured counselling influence combined hormonal contraceptive choice?

    PubMed Central

    Merckx, Mireille; Donders, Gilbert G; Grandjean, Pascale; Van de Sande, Tine; Weyers, Steven

    2011-01-01

    Objective To assess the effect of structured counselling on women's contraceptive decisions and to evaluate gynaecologists’ perceptions of comprehensive contraceptive counselling. Methods Belgian women (18–40 years old) who were considering using a combined hormonal contraceptive (CHC) were counselled by their gynaecologists about available CHCs (combined oral contraceptive [COC], transdermal patch, vaginal ring), using a comprehensive leaflet. Patients and gynaecologists completed questionnaires that gathered information on the woman's pre- and post-counselling contraceptive choice, her perceptions, and the reasons behind her post-counselling decision. Results The gynaecologists (N = 121) enrolled 1801 eligible women. Nearly all women (94%) were able to choose a method after counselling (53%, 5%, and 27% chose the COC, the patch, and the ring, respectively). Counselling made many women (39%) select a different method: patch use increased from 3% to 5% (p < 0.0001); ring use tripled (from 9% to 27%, p < 0.0001). Women who were undecided before counselling most often opted for the method their gynaecologist recommended, irrespective of counselling. Conclusion Counselling allows most women to select a contraceptive method; a sizeable proportion of them decide on a method different from the one they initially had in mind. Gynaecologists’ preferences influenced the contraceptive choices of women who were initially undecided regarding the method to use. PMID:22066890

  20. Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey

    PubMed Central

    Real, F Gómez; Svanes, C; Björnsson, E H; Franklin, K; Gislason, D; Gislason, T; Gulsvik, A; Janson, C; Jögi, R; Kiserud, T; Norbäck, D; Nyström, L; Torén, K; Wentzel‐Larsen, T; Omenaas, E

    2006-01-01

    Background Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). Methods A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999–2001, and 8588 women aged 25–54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46–54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. Results HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: pinteraction = 0.030; wheeze: pinteraction = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (pinteraction = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. Conclusions In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways. PMID:16244093

  1. Evolution of glycated haemoglobin in adults on growth hormone replacement therapy.

    PubMed

    Andrea Parra R, Paola; Barquiel A, Beatriz; Fernández M, Alberto; Pérez F, Laura; Lecumberri S, Beatriz; Gaby Llaro C, Mary; Álvarez-Escolá, Cristina

    2015-05-01

    To evaluate the effects of GH replacement therapy (GHR) for 3 years on glycated haemoglobin (HbA1c) and on the presence of dysglycaemia at any time during follow-up in Spanish adult patients with growth hormone deficiency (GHD). A retrospective study of 41 patients with GHD was conducted using baseline and long-term data. Changes in HbA1c values during the first 3 years of GHR were studied in both the overall population and patients with or without dysglycaemia during follow-up. Dysglycaemia was defined as FPG ≥ 100 mg/dl and/or HbA1c ≥ 5.7%. Mean HbA1c value (5.4 ± 0.4% at baseline) increased during the first and second years of GHR (HbA1c 5.5 ± 0.4%, p=0.05, and 5.5 ± 0.4%, p=0.006 respectively). This increase was not maintained during the third year (HbA1c 5.4 ± 0.3%, p=0.107) of GHR. Twenty-eight patients (68.2%) had dysglycaemia during follow-up, 9 of them since baseline. In the 19 patients without baseline dysglycaemia, HbA1c increased during the first year and remained stable in the next 2 years (mean HbA1c 5.2 ± 0.4% at baseline; 5.5 ± 0.4% at 1 year, p<0.050; 5.4 ± 0.4% at 2 years, p=0.004, and 5.4 ± 0.4% at 3 years, p=0.016). In the 9 patients with baseline dysglycaemia, HbA1c did not significantly change during the 3 years of GHR therapy. HbA1c values increased during the first 2 years of GHR therapy. In patients with no dysglycaemia before treatment, HbA1c steadily increased over the 3 years. However, it did not change in patients with baseline dysglycaemia. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  2. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women

    PubMed Central

    Sanchez, Rafael Gabriel; Sanchez Gomez, Luis Maria; Carmona, Loreto; Figuls, Marta Roqué i; Cosp, Xavier Bonfill

    2014-01-01

    Background There is apparently compelling evidence, from observational studies, that hormone replacement therapy (HRT) may have benefits in reducing cardiovascular events in post-menopausal women. However, these observational data are subject to biases and confounding and require support from formally designed randomised controlled trials of the effects of HRT on cardiovascular disease risk. Objectives To assess the effects of HRT for the primary and secondary prevention of cardiovascular diseases in post-menopausal women. Search methods We searched MEDLINE (1998 to December 2002)), EMBASE (1998 to December 2002), the Cochrane Controlled Trials Register (CCTR) (Issue 4 2002), the National Research Register (1998 to present), ClinicalTrials.gov (1998 to present), and the database of Spanish Clinical Trials (1998 to present) and reference lists of articles. Selection criteria Randomised controlled trials comparing HRT with controls (placebo or no treatment) with a minimum follow up of 6 months for treating or preventing cardiovascular disease in postmenopausal women with or without cardiovascular disease. Data collection and analysis Three independent reviewers extracted information from the articles, solving discrepancies by consensus. All outcomes studied were dichotomous. Risk ratios and 95% confidence intervals (CI) were calculated for each study and plotted. Random effects meta-analysis was used in efficacy outcomes (cardiovascular events) and fixed-effects meta-analysis in variables regarding side effects (deep venous thrombosis). Main results No protective effect of HRT was seen for any of the cardiovascular outcomes assessed: all cause mortality, cardiovascular death, non-fatal MI, venous thromboemboli or stroke. Higher risks of venous thromboembolic events (Relative risk (RR) 2.15, 95% CI 1.61 to 2.86), pulmonary embolus (RR 2.15, 95% CI 1.41 to 3.28), and stroke (RR 1.44, 95% CI 1.10 to 1.89) was found in those randomised to HRT compared with placebo. No

  3. EFFECT OF GROWTH HORMONE REPLACEMENT THERAPY ON THE QUALITY OF LIFE IN WOMEN WITH GROWTH HORMONE DEFICIENCY WHO HAVE A HISTORY OF ACROMEGALY VERSUS OTHER DISORDERS

    PubMed Central

    Valassi, Elena; Brick, Danielle J.; Johnson, Jessica C.; Biller, Beverly M. K.; Klibanski, Anne; Miller, Karen K.

    2013-01-01

    Objective To compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes. Methods Fifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GH therapy in women with hypopituitarism conducted with use of the same design—one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36). Results The 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 ± 0.30 versus 0.67 ± 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 subscales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH. Conclusion In this study, GH replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly. PMID:22440981

  4. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks

    PubMed Central

    2014-01-01

    Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the ‘real-life’ efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy. PMID:25360241

  5. Growth Hormone Deficiency after Treatment of Acromegaly: A Randomized, Placebo-Controlled Study of Growth Hormone Replacement

    PubMed Central

    Miller, Karen K.; Wexler, Tamara; Fazeli, Pouneh; Gunnell, Lindsay; Graham, Gwenda J.; Beauregard, Catherine; Hemphill, Linda; Nachtigall, Lisa; Loeffler, Jay; Swearingen, Brooke; Biller, Beverly M. K.; Klibanski, Anne

    2010-01-01

    Context: The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study. Objective: The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly. Design: This was a 6-month, randomized, placebo-controlled study. Setting: The study was conducted at a clinical translational science center. Study Participants: Participants included 30 subjects with prior acromegaly and current GHD. Intervention: Interventions included GH or placebo. Main Outcome Measures: Body composition (dual-energy x-ray absorptiometry and cross-sectional computed tomography at L4), cardiovascular risk markers (high-sensitivity C-reactive protein (hsCRP), total, high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and carotid intimal-medial thickness), and quality of life were measured. Results: The mean GH dose at 6 months was 0.58 ± 0.26 mg/d. Total fat mass, visceral adipose tissue (−15.3 ± 18.6 vs. 1.3 ± 12.5%, P = 0.01), and total abdominal fat decreased, and fat-free mass increased, in the GH vs. placebo group. Mean hsCRP levels decreased, but there was no GH effect on other cardiovascular risk markers. There was no change in glycosylated hemoglobin or homeostasis model assessment insulin resistance index. Quality of life improved with GH. Side effects were minimal. Conclusions: This is the first randomized, placebo-controlled study of the effects of GH replacement therapy on body composition and cardiovascular end points in patients who have developed GH deficiency after treatment for acromegaly, a disease complicated by metabolic and body composition alterations and increased cardiovascular risk. GH replacement decreased visceral adipose tissue, increased fat-free mass, decreased hsCRP, and improved quality of life in patients with GHD after

  6. Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

    PubMed

    Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

    2006-06-01

    Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

  7. Primary Combined Replacements for Treatment of Distal Radius Physeal Arrest

    PubMed Central

    Schmidt, Ingo

    2014-01-01

    This is a case report of a 59-year-old female patient with a posttraumatic growth arrest of the distal radius, leading to radioscaphoid osteoarthritis, carpal instability, and a symptomatic ulnocarpal impaction syndrome that was successfully treated with combined total wrist arthroplasty and ulnar head implant. One year postoperatively, there was no change in position without any signs of loosening of both implants. Both subjectively and functionally, all clinical parameters—Disabilities of the Arm, Shoulder, and Hand (DASH), visual analog scale (VAS), grip strength—had improved. Level of Evidence: IV PMID:25097815

  8. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate

    PubMed Central

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-01-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes. PMID:21039986

  9. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate.

    PubMed

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-12-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin-testosterone-oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin-testosterone-oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.

  10. Hypopituitarism due to sports related head trauma and the effects of growth hormone replacement in retired amateur boxers.

    PubMed

    Tanriverdi, F; Unluhizarci, K; Karaca, Z; Casanueva, F F; Kelestimur, F

    2010-06-01

    Traumatic brain injury (TBI) has been recently recognized as a leading cause of pituitary dysfunction. Current data clearly demonstrated that sports related head trauma due to boxing, kickboxing, and soccer might results in pituitary hormone deficiencies, isolated growth hormone (GH) deficiency in particular. In the present report physiologic dose GH replacement therapy (GHRT) was performed in two GH deficient retired amateur boxers for the first time. The boxers received recombinant GH for 6 months. After 6 months of GHRT there were substantial improvements, but not complete normalization, in the body composition parameters, lipid profiles and quality of life scores in both boxers. These preliminary results suggest that GHRT may have beneficial effects in retired boxers with severe isolated GH deficiency due to sports related head trauma. But more data with higher number of boxers and longer GHRT duration are warranted.

  11. Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia.

    PubMed

    Stanosz, Staniaław; Zochowska, Ewa; Safranow, Krzysztof; Sieja, Krzysztof; Stanosz, Małgorzta

    2009-01-01

    The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 +/- 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17beta-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E(1)) was increased about 11-fold in the group of women receiving orally given HST (P < .0001

  12. Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

    PubMed

    Arsenault, Frédéric; Turcotte, Éric

    2016-03-01

    Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

  13. Seven years of growth hormone (GH) replacement improves quality of life in hypopituitary patients with adult-onset GH deficiency.

    PubMed

    Elbornsson, Mariam; Horvath, Alexandra; Götherström, Galina; Bengtsson, Bengt-Åke; Johannsson, Gudmundur; Svensson, Johan

    2017-02-01

    Few studies have determined the effects of long-term growth hormone (GH) replacement on quality of life (QoL). This study investigated the effects of 7 years of GH replacement on QoL. A prospective, single-center, open-label study of 95 adults (mean age 52.8 years; 46 men) with adult-onset GH deficiency (GHD). QoL was measured using Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) and Psychological General Well-Being (PGWB) scores. The GH dose was gradually increased from 0.13 mg/day to 0.42 mg/day. IGF-I SD score increased from -1.49 at baseline to 0.35 at study end. The GH replacement induced sustained improvements in total QoL-AGHDA and PGWB scores. GHD women had a more marked improvement in total QoL-AGHDA score than GHD men after 5 and 7 years. Most of the improvement in QoL was seen during the first year, but there was a small further improvement also after one year as measured using QoL-AGHDA. All QoL-AGHDA dimensions improved, but the improvement in memory and concentration as well as tenseness occurred later than that of other dimensions. Correlation analysis demonstrated that the patients with the lowest baseline QoL had the greatest improvement in QoL. Seven years of GH replacement improved QoL with the most marked improvements in GHD women and in patients with low baseline QoL. Most, but not all, of the improvement in QoL was seen during the first year. Some QoL-AGHDA dimensions (memory and concentration, tenseness) responded at a slower rate than other dimensions. © 2017 European Society of Endocrinology.

  14. Patterns of hormone replacement therapy in a population-based cohort of postmenopausal German women. Changes after HERS II and WHI.

    PubMed

    Clanget, C; Hinke, V; Lange, S; Fricke, R; Botko, R; Pfeilschifter, J

    2005-10-01

    In July 2002, data from the Women's Health Initiative (WHI) trial provided strong evidence for an increased risk of cardiovascular disease with use of combined estrogen plus progestogen in postmenopausal women. These unexpected results triggered a large and ongoing discussion about the role of hormone replacement therapy (HRT). We investigated the frequency of HRT before and after the publications of the WHI trial and the Heart and Estrogen/Progestin Replacement Study II (HERS II) in a population-based random sample of German women aged 45 - 65 years. A total of 8380 women completed a questionnaire on menopausal status, hysterectomy and HRT. 75 % were postmenopausal. Mean age was 56.1 years; mean age of natural menopause 49.9 years; mean duration of postmenopause was 11 years; 27 % of the women had undergone hysterectomy. The percentage of current HRT users dropped by 16 % (35.4 % to 29.8 %, p = 0.004), past users increased from 19.8 % to 23.5 % (p = 0.03). Among current HRT users, the share of combined conjugated estrogen/progestogen decreased by 41 % (p = 0.008). We observed a decreased prevalence of HRT among German women 7 months after publication of the HERS II and WHI results. The decline was, however less pronounced than reported from other countries. The use of conjugated estrogen/gestagen combinations declined disproportionately compared to other formulations.

  15. Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation.

    PubMed

    Elbornsson, Mariam; Götherström, Galina; Bengtsson, Bengt-Åke; Johannsson, Gudmundur; Svensson, Johan

    2013-12-01

    Little is known of the importance of previous irradiation therapy for baseline characteristics and responsiveness to GH replacement in GH deficient (GHD) adults. In this prospective, single-centre, open-label study, the effects of 10-year GH replacement were determined in 18 GHD adults that had previously received conventional external fractionated pituitary irradiation therapy (IRR group) and 18 non-irradiated GHD patients (non-IRR group). All patients had adult onset disease and complete deficiency of anterior pituitary hormones and both groups were comparable in terms of age, gender, body mass index (BMI), and waist:hip ratio. At baseline, IRR patients had higher serum triglyceride (TG) and insulin levels and lower high density lipoprotein (HDL)-cholesterol (HDL-C) level than non-IRR patients (all p<0.05). The 10-year GH replacement improved body composition, bone mass and serum lipid profile without any between-group differences, except for a marginally more beneficial response in serum TG level in the IRR patients. After 10 years, there was no between-group difference in any variable after correction for a higher replacement dose of glucocorticoids in the IRR patients at study end using an analysis of covariance. During the 10-year GH replacement, 5 IRR patients suffered from vascular events (2 fatal) whereas only one non-fatal vascular event occurred in the non-IRR patients. IRR patients with GHD display a more severely impaired cardiovascular risk profile at baseline, which was reversed by the 10-year GH replacement after correction for the higher glucocorticoid dose at study end. However, vascular events occurred more frequently in the IRR patients. © 2013.

  16. Efficacy and safety of growth hormone replacement therapy in Japanese adults with growth hormone deficiency: a post-marketing observational study.

    PubMed

    Shimatsu, Akira; Tai, Shigeru; Imori, Makoto; Ihara, Katsuichiro; Taketsuna, Masanori; Funai, Jumpei; Tanaka, Toshiaki; Teramoto, Akira; Irie, Minoru; Chihara, Kazuo

    2013-01-01

    This large-scale observational study examined the long-term effectiveness and safety of growth hormone (GH) replacement therapy for adult GH deficiency (GHD) in Japanese clinical practice using the Hypopituitary Control and Complications Study database. The study included 402 GHD patients for safety analyses and a subset of 209 patients (149 adult-onset and 60 childhood-onset GHD patients) who had not previously received GH replacement therapy for the efficacy analyses. Data on clinical, metabolic, quality of life (QoL) characteristics, and all adverse events (AEs) were collected at baseline (start of GH treatment), 6 months, 1 year and 2 years. Over the observation period, there were improvements from baseline in insulin-like growth factor-I standard deviation scores (P<0.001), although the changes in metabolic parameters were minimal. QoL (Short Form-36) Z-scores significantly increased from baseline in both onset-type groups for several subscale domains (P<0.05). A total of 145 (36.1%) patients experienced ≥1 AE. Common AEs were hyperlipidaemia (2.7%) and hyperinsulinaemia (2.2%). Some patients experienced recurrent hypothalamic/pituitary tumour (events per 1000 patient-years: 2.78), new benign (0.93), malignant tumour (10.28) or other new tumour (0.93), new diabetes mellitus (7.45), and new stroke (3.71). Seven patients died during the observation period. Our safety findings are inconclusive about the associations between GH replacement and AEs, although the incidence of diabetes mellitus and cardiovascular events are similar to those reported in the Japanese general population. In conclusion, the key beneficial effects of GH replacement therapy for GHD are observed in routine clinical practice in Japan.

  17. Long-term survival with growth hormone replacement after liver transplantation of pediatric nonalcoholic steatohepatitis complicating acquired hypopituitarism.

    PubMed

    Fujio, Atsushi; Kawagishi, Naoki; Echizenya, Taketora; Tokodai, Kazuaki; Nakanishi, Chikashi; Miyagi, Shigehito; Sato, Kazushige; Fujimori, Keisei; Ohuchi, Noriaki

    2015-01-01

    Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD). In adult patients, liver transplantation (LT) is the treatment of choice for end-stage liver disease secondary to NASH. However, little information is available regarding outcomes of LT in pediatric patients with NASH. We describe here a pediatric patient with NASH associated with hypopituitarism who underwent living donor liver transplantation (LDLT). An 11-year-old boy was diagnosed with a pituitary tumor, which was removed by trans-interhemispheric approach following bifrontal craniotomy. Histopathological examination revealed a mature teratoma. Eighteen months later, magnetic resonance imaging showed recurrence of the pituitary tumor, which was found to be a germinoma. He underwent 3 months of chemoradiotherapy, with a complete response. He gradually became obese, with elevated transaminase levels. At age 15 years, he developed fatigue and dyspnea and was found to have liver cirrhosis secondary to NASH with severe hepatopulmonary syndrome. He underwent LDLT using a right liver graft from his mother. Twelve months later, abdominal computed tomography showed recurrence of NAFLD. Five years after the LDLT, transaminases were slightly elevated. Growth hormone replacement therapy was started, reducing transaminase levels to their normal ranges. Ten years after LDLT, fatty liver remains stable, although his body mass index has not been reduced. Growth hormone replacement therapy may be effective in graft maintenance. This is the first case report of a patient with maintained stable liver function 10 years after LDLT for pediatric NASH.

  18. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  19. Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

    PubMed

    Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

    2014-11-01

    Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Role of chemotherapy in combination with hormonal therapy in first-line treatment of metastatic hormone-sensitive prostate cancer.

    PubMed

    Ceresoli, G L; De Vincenzo, F; Sauta, M G; Bonomi, M; Zucali, P A

    2015-12-01

    Prostate cancer (PC) is a heterogeneous disease, whose growth is driven by androgens and androgen receptors. Androgen deprivation therapy (ADT) is the standard treatment of hormone-naïve metastatic disease. The majority of patients are treated with medical castration with GnRH agonists or antagonists, which usually determines a profound PSA decline and a radiological and clinical benefit. However, essentially all patients experience progression to castration-resistant prostate cancer (CRPC), and overall prognosis remains disappointing. Early targeting of cells that survive hormonal therapy may potentially prevent the development of CRPC. Several trials have explored the use of combination therapy with ADT and chemotherapy, targeting both the androgen dependent and independent cells simultaneously. Docetaxel was administered in combination with ADT to men with hormone-naïve metastatic prostate cancer, in the attempt to improve the duration and quality of patient survival. Three large randomized trials (the GETUG-15, CHAARTED and more recently the STAMPEDE study) have assessed these endpoints, with partially conflicting results. Overall, the results from these trials seem to support the use of early docetaxel combined with ADT in selected hormone-naïve metastatic PC patients. Full publication of the results of all studies, with longer follow-up, and the results of other ongoing trials in this setting will hopefully further define the role and the indications of this therapeutic strategy.

  1. [Hormone replacement therapy in the management of postmenopausal osteoporosis and prevention of fracture risk].

    PubMed

    Ribot, Claude; Trémollières, Florence

    2006-10-01

    The consequences to the bone of estrogen deficiency are early and irreversible. Effective prevention of postmenopausal osteoporosis at the individual level requires early screening of women at risk of fractures and their early treatment. Hormone treatment prevents bone loss and has been proven effective in preventing fractures, even in situations of low risk. The benefit/risk ratio of hormone treatment can be optimized by the choice of the 'right moment' and the 'right treatment'. HRT, administered early and for a limited period, must be integrated into a strategy of long-term osteoporosis prevention that includes using the (drug and nondrug) means most appropriate to the patient's age and clinical condition and choosing the 'right moment' and 'right treatment.'

  2. Growth hormone replacement therapy prevents sarcopenia by a dual mechanism: improvement of protein balance and of antioxidant defenses.

    PubMed

    Brioche, T; Kireev, R A; Cuesta, S; Gratas-Delamarche, A; Tresguerres, J A; Gomez-Cabrera, M C; Viña, J

    2014-10-01

    The aim of our study was to elucidate the role of growth hormone (GH) replacement therapy in three of the main mechanisms involved in sarcopenia: alterations in mitochondrial biogenesis, increase in oxidative stress, and alterations in protein balance. We used young and old Wistar rats that received either placebo or low doses of GH to reach normal insulin-like growth factor-1 values observed in the young group. We found an increase in lean body mass and plasma and hepatic insulin-like growth factor-1 levels in the old animals treated with GH. We also found a lowering of age-associated oxidative damage and an induction of antioxidant enzymes in the skeletal muscle of the treated animals. GH replacement therapy resulted in an increase in the skeletal muscle protein synthesis and mitochondrial biogenesis pathways. This was paralleled by a lowering of inhibitory factors in skeletal muscle regeneration and in protein degradation. GH replacement therapy prevents sarcopenia by acting as a double-edged sword, antioxidant and hypertrophic. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Deciding about hormone therapy

    MedlinePlus

    HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding

  4. Hormone replacement therapy and risk for coronary heart disease. Data from the CORA-study--a case-control study on women with incident coronary heart disease.

    PubMed

    Windler, Eberhard; Zyriax, Birgit-Christiane; Eidenmüller, Britta; Boeing, Heiner

    2007-07-20

    Hormone replacement therapy (HRT) has been suggested to prevent cardiovascular disease, while some intervention studies have shed doubt on this concept. Thus, uncertainty remains whether current HRT use is beneficial as to cardiovascular disease or may even be harmful. This research investigates the association of hormone replacement therapy, risk factors and lifestyle characteristics with the manifestation of coronary heart disease in current HRT users versus never users. The coronary risk factors for atherosclerosis in women study (CORA-study) provide clinical and biochemical parameters and data on lifestyle in 200 consecutive pre- and postmenopausal women with incident coronary heart disease compared to 255 age-matched population-based controls, of which 87.9% were postmenopausal. Significantly more controls than cases used currently HRT for a median of 9.5 years (32.9% versus 20.2%), while 50.0% of cases and 42.5% of controls had never used HRT (p<0.02). Compared to women who never used HRT, current users ate less meat and sausage, had a significantly lower BMI and waist-to-hip ratio and a lower prevalence of hypertension, insulin resistance and diabetes. However, current users among cases were often smokers and smoked significantly more cigarettes than never users. In a multivariate analysis the risk of current HRT users for coronary artery disease was 57% lower than the risk of never users (odds ratio 0.428, CI 0.206-0.860, p<0.02). Adjustment for conventional and dietary risk factors revealed neither current HRT use, nor HRT use combined with smoking as independent risk factors. These data from the CORA-study are not compatible with an adverse impact of hormone replacement therapy on cardiovascular disease, rather support the notion of beneficial effects of HRT on weight, central adiposity, insulin sensitivity and blood pressure. Yet, the data do not support the presumption of a general healthy user effect in women on HRT either. Rather, in some women

  5. Night sleep EEG and daytime sleep propensity in adult hypopituitary patients with growth hormone deficiency before and after six months of growth hormone replacement.

    PubMed

    Schneider, Harald Jörn; Oertel, Heide; Murck, Harald; Pollmächer, Thomas; Stalla, Günter Karl; Steiger, Axel

    2005-01-01

    Hypopituitary patients with growth hormone deficiency (GHD) complain of reduced vitality, general fatigue, lack of concentration, irritability and reduced alertness during daytime. It is unclear whether these symptoms are primarily due to GH-deficiency and/or secondary to GHD related sleep impairments. Bi-directional interactions between the somatotropic system and human sleep patterns are well established. However, data on the effect of GH either in subjects without GHD or in patients with GHD under GH replacement therapy on the sleep electroencephalogram (EEG) are controversial. No reports exist about objective measures of daytime sleepiness in GH deficient patients before and during GH-therapy. To assess the effects of GH on nocturnal and daytime sleep in adult patients with GHD before and during recombinant human GH (rhGH, Somatropin) replacement therapy. Eighteen adult patients with GHD (4 women and 14 men) participated in the study. Mean age at the beginning of the study was 48.5 years (range 27-64 years). Ten patients were recruited from a double-blind, randomized placebo controlled trial over 6 months, followed by an open treatment period of 6 additional months (Group I). In all patients from this group, only the effects of the first 6 months of GH treatment were assessed. Eight additional patients were treated in an open study design for 6 months (Group II). Nocturnal sleep recordings and daytime sleep EEGs with a multiple sleep latency test were performed at baseline and after 6 months of additional GH replacement therapy. One patient dropped out due to side effects and was not included in sleep analysis. IGF-1 levels were increased in all patients, partially in a supraphysiologic range. Side effects were mainly mild but in one patient (from group II), general muscle pain led to interruption of the study. Therefore sleep analysis was only done in 17 patients. Sleep parameters were comparable to healthy control groups from the literature. GH substitution

  6. Resistance of pelvic arteries and plasma lipids in postmenopausal women: comparative study of tibolone and continuous combined estradiol and norethindrone acetate replacement therapy.

    PubMed

    Dören, M; Rübig, A; Coelingh Bennink, H J; Holzgreve, W

    2000-09-01

    We sought to compare vascular resistance and plasma lipids in postmenopausal women assigned to tibolone (a synthetic estrogen replacement steroid) therapy or continuous combined hormone replacement therapy. Pulsatility and resistance indexes in pelvic arteries (color Doppler transvaginal ultrasonography) and lipids were monitored in this double-blind 1-year trial of 100 women randomized to either 2.5 mg tibolone or 2 mg 17beta-estradiol plus 1 mg norethindrone acetate daily. Both indexes of the arcuate arteries (uterine arteries) were significantly reduced beyond 3 and 6 months (12 months) from baseline, respectively, by the combined regimen compared with tibolone alone. Tibolone increased the resistance index of arcuate arteries but did not affect uterine arteries. There was no effect of either regimen on the internal iliac arteries. The medians of the percentage changes from baseline of high-density lipoprotein cholesterol (triglycerides) were significant between groups after 1 year, as follows: -17% (-16%) in the tibolone group and -4% (+15%) in the combined group, respectively. Both regimens similarly reduced total and low-density lipoprotein cholesterol and lipoprotein Lp(a). Hormone replacement therapy may induce different or opposite changes of both vascular resistance and lipids. It is unknown whether these findings may modify cardiovascular risk.

  7. Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement.

    PubMed

    Yoshizawa, Miyako; Ieki, Yasuhiko; Takazakura, Eisuke; Fukuta, Kaori; Hidaka, Takao; Wakasugi, Takanobu; Shimatsu, Akira

    2017-01-01

    We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications.

  8. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement.

    PubMed

    Yovich, John L; Conceicao, Jason L; Stanger, James D; Hinchliffe, Peter M; Keane, Kevin N

    2015-08-01

    This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.

  9. Hormonal Replacement Therapy and the Risk of Lung Cancer in Women: An Adaptive Meta-analysis of Cohort Studies

    PubMed Central

    Bae, Jong-Myon; Kim, Eun Hee

    2015-01-01

    Objectives: Approximately 10% to 15% of lung cancer cases occur in never-smokers. Hormonal factors have been suggested to lead to an elevated risk of lung cancer in women. This systematic review (SR) aimed to investigate the association between hormonal replacement therapy (HRT) and the risk of lung cancer in women using cohort studies. Methods: We first obtained previous SR articles on this topic. Based on these studies we made a list of refereed, cited, and related articles using the PubMed and Scopus databases. All cohort studies that evaluated the relative risk of HRT exposure on lung cancer occurrence in women were selected. Estimate of summary effect size (sES) with 95% confidence intervals (CIs) were calculated. Results: A total of 14 cohort studies were finally selected. A random effect model was applied due to heterogeneity (I-squared, 64.3%). The sES of the 14 articles evaluating the impact of HRT exposure on lung cancer occurrence in women indicated no statistically significant increase in lung cancer risk (sES, 0.99; 95% CI, 0.90 to 1.09). Conclusions: These results showed that HRT history had no effect on the risk of lung cancer in women, even though the sES of case-control studies described in previous SR articles indicated that HRT had a protective effect against lung cancer. It is necessary to conduct a pooled analysis of cohort studies. PMID:26639742

  10. Hormonal Replacement Therapy and the Risk of Lung Cancer in Women: An Adaptive Meta-analysis of Cohort Studies.

    PubMed

    Bae, Jong-Myon; Kim, Eun Hee

    2015-11-01

    Approximately 10% to 15% of lung cancer cases occur in never-smokers. Hormonal factors have been suggested to lead to an elevated risk of lung cancer in women. This systematic review (SR) aimed to investigate the association between hormonal replacement therapy (HRT) and the risk of lung cancer in women using cohort studies. We first obtained previous SR articles on this topic. Based on these studies we made a list of refereed, cited, and related articles using the PubMed and Scopus databases. All cohort studies that evaluated the relative risk of HRT exposure on lung cancer occurrence in women were selected. Estimate of summary effect size (sES) with 95% confidence intervals (CIs) were calculated. A total of 14 cohort studies were finally selected. A random effect model was applied due to heterogeneity (I-squared, 64.3%). The sES of the 14 articles evaluating the impact of HRT exposure on lung cancer occurrence in women indicated no statistically significant increase in lung cancer risk (sES, 0.99; 95% CI, 0.90 to 1.09). These results showed that HRT history had no effect on the risk of lung cancer in women, even though the sES of case-control studies described in previous SR articles indicated that HRT had a protective effect against lung cancer. It is necessary to conduct a pooled analysis of cohort studies.

  11. Increased serum levels of growth hormone and insulin-like growth factor-I associated with simultaneous decrease of circulating insulin in postmenopausal women receiving hormone replacement therapy.

    PubMed

    Fonseca, E; Ochoa, R; Galván, R; Hernández, M; Mercado, M; Zárate, A

    1999-01-01

    Decreases in circulating growth hormone (GH) and its main biological messenger insulin-like growth factor-I (IGF-I) have been interpreted as part of the aging process. Because estrogens participate in modulating GH synthesis and secretion, hypoestrogenism in menopausal women may lead to GH deficiency. The aim of the present study was to determine the effect of hormone replacement therapy (HRT) on both GH and IGF-I levels as well as insulin concentrations in 50 menopausal women. Patients were assigned randomly into two treatment groups of 25 each; one group received three cycles of conjugated equine estrogen (CEE) 0.625 mg/day for 21 days, and the other, 1.25 mg/day during 21 days. Each also received chlormadinone acetate for 5 days. There was a control group consisting of regularly menstruating women. In the menopausal women, HRT increased significantly (p < 0.001) the low levels of GH and IGF-I; on the contrary the baseline insulin levels declined (p < 0.001) with HRT. A significant linear correlation (r = 0.90) was found between GH and IGF-I as well as with estradiol levels (r = 0.74) in the group of menopausal women receiving CEE 0.625 mg/day. This group of patients had a significant correlation (r = -0.63) between insulin and estradiol levels. No correlation was observed in the group receiving CEE 1.25 mg/day. HRT restored GH, IGF-I, and insulin levels to normal values in all women. Further research needs to be done to establish the beneficial effect of HRT regarding the prevention of the metabolic effects presumably caused by derangement in the somatotropic axis associated with aging.

  12. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein.

    PubMed

    Balaž, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Vlcek, Miroslav; Surova, Martina; Krumpolec, Patrik; Vanuga, Peter; Gašperíková, Daniela; Klimeš, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-01-01

    Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-α2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-α2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-α2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-α2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-α2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro.

  13. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein

    PubMed Central

    Balaž, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Vlcek, Miroslav; Surova, Martina; Krumpolec, Patrik; Vanuga, Peter; Gašperíková, Daniela; Klimeš, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2014-01-01

    Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-α2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-α2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-α2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-α2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-α2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro

  14. Issues to debate on the Women's Health Initiative (WHI) study. Hormone replacement therapy: an epidemiological dilemma?

    PubMed

    Machens, K; Schmidt-Gollwitzer, K

    2003-10-01

    In July 2002 the data of the prematurely stopped Estrogen plus Progestin study of the Women's Health Initiative (WHI) were presented in the Journal of the American Medical Association. The results of the Heart and Estrogen/Progestin Replacement Study (HERS/HERS II) were published in the same issue. The results of WHI for healthy postmenopausal women often are interpreted to be in analogy with the HERS/HERS II results for postmenopausal women with established coronary heart disease. As a result of HERS/HERS II and WHI, use of HRT in general became questionable. This is an unjustified judgement of HRT in general. This synoptic review and criticism of both studies will show the methodological weaknesses and their consequences and the reasons for limited generalizability of the study results from WHI and HERS/HERS II on normal HRT users.

  15. Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study.

    PubMed

    Devesa, Jesús; Alonso, Begoña; Casteleiro, Nerea; Couto, Paula; Castañón, Beatriz; Zas, Eva; Reimunde, Pedro

    2011-01-01

    Cerebral palsy (CP) is the main cause of physical disability in childhood and is an important health issue that has a strong socioeconomic impact. There is no effective treatment for CP and therapeutic approaches report only partial benefits for affected people. In this study we assessed the effects of growth hormone (GH) treatment combined with psychomotor and cognitive stimulation in the neurodevelopment of children with CP and GH deficiency (GHD). The study was carried out in 11 patients (7 boys and 4 girls; 4.12 ± 1.31 years) with GHD and CP who were treated with recombinant GH (rGH) and psychomotor and cognitive stimulation during 2 months. Battelle Developmental Inventory Screening Test (BDIST) was performed 2 months before commencing GH treatment, just before commencing GH administration, and after 2 months of combined treatment involving GH and cognitive stimulation. Psychomotor and cognitive status did not change during the period in which only cognitive stimulation was performed; however, significant improvements in personal and social skills, adaptive behavior, gross motor skills and total psychomotor abilities, receptive and total communication, cognitive skills and in the total score of the test (P < 0.01), and in fine motor skills and expressive communication (P < 0.02) were observed after the combined treatment period. Therefore, GH replacement together with psychomotor and cognitive stimulation seem to be useful for the appropriate neurodevelopment of children with GHD and CP.

  16. Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study

    PubMed Central

    Devesa, Jesús; Alonso, Begoña; Casteleiro, Nerea; Couto, Paula; Castañón, Beatriz; Zas, Eva; Reimunde, Pedro

    2011-01-01

    Cerebral palsy (CP) is the main cause of physical disability in childhood and is an important health issue that has a strong socioeconomic impact. There is no effective treatment for CP and therapeutic approaches report only partial benefits for affected people. In this study we assessed the effects of growth hormone (GH) treatment combined with psychomotor and cognitive stimulation in the neurodevelopment of children with CP and GH deficiency (GHD). The study was carried out in 11 patients (7 boys and 4 girls; 4.12 ± 1.31 years) with GHD and CP who were treated with recombinant GH (rGH) and psychomotor and cognitive stimulation during 2 months. Battelle Developmental Inventory Screening Test (BDIST) was performed 2 months before commencing GH treatment, just before commencing GH administration, and after 2 months of combined treatment involving GH and cognitive stimulation. Psychomotor and cognitive status did not change during the period in which only cognitive stimulation was performed; however, significant improvements in personal and social skills, adaptive behavior, gross motor skills and total psychomotor abilities, receptive and total communication, cognitive skills and in the total score of the test (P < 0.01), and in fine motor skills and expressive communication (P < 0.02) were observed after the combined treatment period. Therefore, GH replacement together with psychomotor and cognitive stimulation seem to be useful for the appropriate neurodevelopment of children with GHD and CP. PMID:21691590

  17. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    PubMed

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  18. New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

    PubMed

    Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

    1992-10-01

    The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

  19. Effects of 7 years of growth hormone replacement therapy in hypopituitary adults.

    PubMed

    Chrisoulidou, A; Beshyah, S A; Rutherford, O; Spinks, T J; Mayet, J; Kyd, P; Anyaoku, V; Haida, A; Ariff, B; Murphy, M; Thomas, E; Robinson, S; Foale, R; Johnston, D G

    2000-10-01

    Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids, with neutral or occasionally adverse effects on glucose tolerance. Fasting hyperinsulinemia has been reported. GH effects on cardiac function have been variable. The effects of long-term GH therapy, taking into account the consequences of increasing age, are not fully known. Thirty-three hypopituitary, initially middle-aged adults were studied over a 7-yr period; 12 patients took GH therapy (mean, 0.7 mg daily) continuously (group A); 11 took GH for only 6-18 months, a minimum of 5 yr previously (group B); and 10 patients never received GH therapy (group C). Other pituitary replacement was maintained. Effects on anthropometry, body composition (by bioimpedance analysis, total body potassium, and dual energy x-ray absorptiometry), circulating lipids, glucose and insulin concentrations, cardiac 2-dimensional and Doppler echocardiography, and exercise tolerance were assessed before and after the treatment period. Continuous GH therapy had no significant effect on body weight, but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution (waist to hip ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P < 0.005 for GH effect). A GH-induced decrease in subscapular skinfold thickness was also observed. By bioimpedance analysis, GH therapy caused an increase in total body water and fat-free mass, and a decrease in the percent body fat. Although changes occurred with time in all groups, no significant additional GH therapy effects were observed on glucose tolerance, insulin concentrations, lipid levels, cardiac dimensions, echocardiographic diastolic function, or exercise tolerance. In conclusion, prolonged GH

  20. Physiological growth hormone replacement and rate of recurrence of craniopharyngioma: the Genentech National Cooperative Growth Study.

    PubMed

    Smith, Timothy R; Cote, David J; Jane, John A; Laws, Edward R

    2016-10-01

    OBJECTIVE The object of this study was to establish recurrence rates in patients with craniopharyngioma postoperatively treated with recombinant human growth hormone (rhGH) as a basis for determining the risk of rhGH therapy in the development of recurrent tumor. METHODS The study included 739 pediatric patients with craniopharyngioma who were naïve to GH upon entering the Genentech National Cooperative Growth Study (NCGS) for treatment. Reoperation for tumor recurrence was documented as an adverse event. Cox proportional-hazards regression models were developed for time to recurrence, using age as the outcome and enrollment date as the predictor. Patients without recurrence were treated as censored. Multivariate logistic regression was used to examine the incidence of recurrence with adjustment for the amount of time at risk. RESULTS Fifty recurrences in these 739 surgically treated patients were recorded. The overall craniopharyngioma recurrence rate in the NCGS was 6.8%, with a median follow-up time of 4.3 years (range 0.7-6.4 years.). Age at the time of study enrollment was statistically significant according to both Cox (p = 0.0032) and logistic (p < 0.001) models, with patients under 9 years of age more likely to suffer recurrence (30 patients [11.8%], 0.025 recurrences/yr of observation, p = 0.0097) than those ages 9-13 years (17 patients [6.0%], 0.17 recurrences/yr of observation) and children older than 13 years (3 patients [1.5%], 0.005 recurrences/yr of observation). CONCLUSIONS Physiological doses of GH do not appear to increase the recurrence rate of craniopharyngioma after surgery in children, but long-term follow-up of GH-treated patients is required to establish a true natural history in the GH treatment era.

  1. Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype.

    PubMed

    McCullough, Marjorie L; Patel, Alpa V; Patel, Roshni; Rodriguez, Carmen; Feigelson, Heather Spencer; Bandera, Elisa V; Gansler, Ted; Thun, Michael J; Calle, Eugenia E

    2008-01-01

    Epidemiologic studies unequivocally show that greater body mass increases the risk of endometrial cancer, but whether risk varies by use of postmenopausal hormone therapy (HT), location of fat deposition, or cancer subtype is still unclear. We examined these associations among 33,436 postmenopausal women in the Cancer Prevention Study II Nutrition Cohort, who completed questionnaires on diet, lifestyle, and medical history at baseline in 1992. A total of 318 cases were eligible through June 2003. Cox-proportional hazards analyses were used to estimate multivariate-adjusted rate ratios (RR). As expected, adult body mass index (BMI) was a strong predictor of risk [RR, 4.70; 95% confidence interval (CI), 3.12-7.07 for BMI 35+ versus 22.5-25.0, P trend < 0.0001]. Use of estrogen plus progestin postmenopausal HT modified the association. Among never-users, risk was significantly linear across the entire range of BMI examined (RR, 0.51; 95% CI, 0.29-0.92 for <22.5 versus 22.5-25.0; RR, 4.41; 95% CI, 2.70-7.20 for > or =35 versus 22.5-25.0, P trend < 0.0001), but among ever estrogen plus progestin users, the association was not significant (P trend = 1.0; P interaction < 0.0001). We observed no difference in risk according to tendency for central versus peripheral fat deposition. Greater BMI (> or =30 versus <25.0) increased risk of both "type I" (classic estrogen pathway, RR, 4.22; 95% CI, 3.07-5.81) and "type II" (serous, clear cell, and all other high grade) cancers (RR, 2.87; 95% CI, 1.59-5.16). The increased risk of endometrial cancer across the range of BMI in women who never used postmenopausal HT stresses the need to prevent both overweight and obesity in women.

  2. Effects of oral chlortetracycline and dietary protein level on plasma concentrations of growth hormone and thyroid hormones in beef steers before and after challenge with a combination of thyrotropin-releasing hormone and growth hormone-releasing hormone.

    PubMed

    Rumsey, T S; McLeod, K; Elsasser, T H; Kahl, S; Baldwin, R L

    1999-08-01

    The objective of this study was to determine the effect of a subtherapeutic level of chlortetracycline (CTC) fed to growing beef steers under conditions of limited and adequate dietary protein on plasma concentrations of GH, thyroid-stimulating hormone (TSH), and thyroid hormones before and after an injection of thyrotropin-releasing hormone (TRH) + GHRH. Young beef steers (n = 32; average BW = 285 kg) were assigned to a 2x2 factorial arrangement of treatments of either a 10 or 13% crude protein diet (70% concentrate, 15% wheat straw, and 15% cottonseed hulls) and either a corn meal carrier or carrier + 350 mg of CTC daily top dressed on the diet. Steers were fed ad libitum amounts of diet for 56 d, and a jugular catheter was then placed in each steer in four groups (two steers from each treatment combination per group) during four consecutive days (one group per day). Each steer was injected via the jugular catheter with 1.0 microg/kg BW TRH + .1 microg/kg BW GHRH in 10 mL of saline at 0800. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 120, 240, and 360 min after releasing hormone injection. Plasma samples were analyzed for GH, TSH, thyroxine (T4), and triiodothyronine (T3). After 84 d on trial, the steers were slaughtered and the pituitary and samples of liver were collected and analyzed for 5'-deiodinase activity. Feeding CTC attenuated the GH response to releasing hormone challenge by 26% for both area under the response curve (P<.03) and peak response (P<.10). Likewise, CTC attenuated the TSH response to releasing hormone challenge for area under the response curve by 16% (P<.10) and peak response by 33% (P<.02), and attenuated the T4 response for area under the curve by 12% (P<.08) and peak response by 14% (P<.04). Type II deiodinase activity in the pituitary was 36% less (P<.02) in CTC-fed steers than in steers not fed CTC. The results of this study are interpreted to suggest that feeding subtherapeutic levels of CTC to young

  3. Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

    PubMed

    Cerne, Jasmina Ziva; Novakovic, Srdjan; Frkovic-Grazio, Snjezana; Pohar-Perme, Maja; Stegel, Vida; Gersak, Ksenija

    2011-08-01

    Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

  4. Molecular modulation of estrogen-induced apoptosis by synthetic progestins in hormone replacement therapy: An insight into the Women’s Health Initiative study

    PubMed Central

    Sweeney, Elizabeth; Fan, Ping; Jordan, Virgil Craig

    2014-01-01

    Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women, and can comprise an estrogen alone or an estrogen combined with a progestin. The Women’s Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in post-menopausal women, while combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the post-menopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone (Dex) increases GR transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, up-regulating ER-target genes and generating apoptosis in MCF-7:5C cells. The data suggests that women taking HRT comprising an estrogen plus MPA may have an increased the risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g. NETA) should be considered as alternatives to MPA. PMID:25304262

  5. Decline in breast cancer incidence in the Flemish region of Belgium after a decline in hormonal replacement therapy.

    PubMed

    Renard, F; Vankrunkelsven, P; Van Eycken, L; Henau, K; Boniol, M; Autier, P

    2010-12-01

    Breast cancer incidence rate in Belgian women was as high as 152.7 for 100 000 in 2003 (adjusted on European population). We made an estimation of the contribution of hormone replacement therapy (HRT) on breast cancer incidence from 1999 to 2005 in women aged 50-69 years in Flanders. Breast cancer data were extracted from the Belgium Cancer Registry. Drug consumption was computed from drug sales data. The fraction of breast cancers attributable to HRT was calculated by year, using the relative risks of the Million Women Study in the UK. The proportion of women aged 50-69 years using HRT in Flanders increased since 1992, peaked at 20% in 2001, then decreased to 8% in 2008. The incidence of breast cancer in 100 000 women aged 50-69 years in Flanders increased from 332.8 in 1999 to 407.9 in 2003, then decreased to 366.1 in 2005; the variations were mostly noticeable for tumors <20 mm in size. The fraction of breast cancers attributed to HRT peaked at 11% in 2001 and decreased afterward. The high level of breast cancer observed in the years 2001-2003 in Flanders can be partly attributed to the use of HRT. Since participation to mammography screening of Flemish women aged 50-69 years was still on the rise in 2003 and never exceeds 62%, the decrease in breast cancer incidence was likely to be due to the decrease in HRT use and not to screening saturation.

  6. Cessation of hormone replacement therapy after reports of adverse findings from randomized controlled trials: evidence from a British Birth Cohort.

    PubMed

    Mishra, Gita; Kok, Helen; Ecob, Russell; Cooper, Rachel; Hardy, Rebecca; Kuh, Diana

    2006-07-01

    We examined the cessation of hormone replacement therapy (HRT) among British women, by educational level, social class, and cardiovascular risk factors, at the time of publicity about 2 clinical trials of HRT that were halted after adverse findings. A total of 1387 women aged 57 years reported their monthly HRT use between January 2002 and February 2003. A succession of regression-based time-series models were fitted to detect changes in the proportion of HRT users stratified by education level, social class, hypertension, and obesity. The overall percentage of HRT users declined from 31% in January 2002 to less than 26% by February 2003. Changes in trends of HRT use were first detected in June 2002 (for women with advanced secondary educational qualification or higher) and in July 2002 (for all other groups). The rate of decline was greatest for women with no formal educational qualifications, from the manual social class, or who were hypertensive or obese. These decreases coincided with the announced cessation of a large US clinical trial of HRT. This publicity may have had a differential influence on the immediate decline in HRT use by various groups of British women.

  7. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study.

    PubMed

    Kotsopoulos, Joanne; Huzarski, Tomasz; Gronwald, Jacek; Moller, Pal; Lynch, Henry T; Neuhausen, Susan L; Senter, Leigha; Demsky, Rochelle; Foulkes, William D; Eng, Charis; Karlan, Beth; Tung, Nadine; Singer, Christian F; Sun, Ping; Lubinski, Jan; Narod, Steven A

    2016-01-01

    Many BRCA1 mutation carriers undergo elective surgical oophorectomy (often before menopause) to manage their elevated risk of developing ovarian cancer. It is important to clarify whether or not the use of hormone replacement therapy (HRT) to mitigate the symptoms associated with surgical or natural menopause is safe in women with an inherited BRCA1 mutation and no personal history of breast or ovarian cancer. We conducted a case-control analysis of 432 matched pairs of women with a BRCA1 mutation. Detailed information on HRT use after menopause (duration, type, age at first/last use, formulation) was obtained from a research questionnaire administered at the time of study enrollment. Conditional logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI) associated with HRT use. The mean duration of HRT use after menopause was 4.3 years among the cases and 4.4 years among the controls (P = 0.83). The adjusted OR for breast cancer comparing all women who ever used HRT to those who never used HRT was 0.80 (95 % CI 0.55-1.16; P = 0.24). Findings did not differ by type of menopause (natural vs. surgical), by recency of use, by duration of use, and by formulation type. These findings suggest that a short course of HRT should not be contra-indicated for BRCA1 mutation carriers who have undergone menopause and who have no personal history of cancer.

  8. Differential dietary nutrient intake according to hormone replacement therapy use: an underestimated confounding factor in epidemiologic studies?

    PubMed

    Vercambre, Marie-Noël; Fournier, Agnès; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Ringa, Virginie; Berr, Claudine

    2007-12-15

    Observational studies and randomized controlled trials have produced divergent results concerning the effect of hormone replacement therapy (HRT) on cardiovascular disease and, to a lesser extent, dementia. Residual confounding (confounding that remains even after adjustment for various socioeconomic and lifestyle factors) is one explanation that has been offered for these divergent results. The authors used data collected between 1990 and 1995 from 6,697 French women aged 61-72 years participating in a prospective cohort study to explore the hypothesis that nutritional intake varies according to HRT use and thus may be a source of residual confounding. After the authors adjusted for health and lifestyle factors, HRT users, compared with never users, had significantly higher intakes of alcohol; omega3 fatty acids; vitamins B6, B12, and D; and phosphorus and a lower intake of starch. These differential nutrient intakes were related to differences in eating habits. In particular, HRT users in the studied sample, compared with nonusers, ate significantly more fish. Most of the dietary differences were seen in both early users and delayers of HRT. To limit residual confounding in observational studies, dietary factors may be important parameters to be taken into account in analyses of HRT use and health outcomes.

  9. Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries.

    PubMed

    Zbuk, Kevin; Anand, Sonia S

    2012-01-01

    Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.

  10. Recurrent symptomatic hypoglycaemia with pancytopenia as a delayed presentation of Sheehan's syndrome with complete recovery after hormone replacement.

    PubMed

    Dharmshaktu, Pramila; Bhowmick, Jayeeta; Manglani, Danny; Dhanwal, Dinesh Kumar

    2013-11-21

    A 38-year-old woman presented to our hospital emergency section in altered sensorium and with blood pressure of 80/60 mm Hg. She gave a history of recurrent episodes of loss of consciousness for 15-20 days, generalised body swelling and generalised weakness for the past 5-6 years. On further evaluation she was found to have severe hypoglycaemic episodes. In view of history of pregnancy and significant blood loss during surgery and long history of lethargy, asthaenia and generalised anasarca, the patient was evaluated for Sheehan's syndrome. Her serum cortisol levels were very low and she was found to have central hypothyroidism. MRI of the brain also revealed small sella turcica and small pituitary gland suggestive of hypopituitarism. The patient was started on high-concentration dextrose drips, steroids and thyroid hormone replacement. The patient showed a marked improvement within 1 week of treatment. And she was discharged with an advice to follow-up at our outpatient department.

  11. Recurrent symptomatic hypoglycaemia with pancytopenia as a delayed presentation of Sheehan's syndrome with complete recovery after hormone replacement

    PubMed Central

    Dharmshaktu, Pramila; Bhowmick, Jayeeta; Manglani, Danny; Dhanwal, Dinesh Kumar

    2013-01-01

    A 38-year-old woman presented to our hospital emergency section in altered sensorium and with blood pressure of 80/60 mm Hg. She gave a history of recurrent episodes of loss of consciousness for 15–20 days, generalised body swelling and generalised weakness for the past 5–6 years. On further evaluation she was found to have severe hypoglycaemic episodes. In view of history of pregnancy and significant blood loss during surgery and long history of lethargy, asthaenia and generalised anasarca, the patient was evaluated for Sheehan's syndrome. Her serum cortisol levels were very low and she was found to have central hypothyroidism. MRI of the brain also revealed small sella turcica and small pituitary gland suggestive of hypopituitarism. The patient was started on high-concentration dextrose drips, steroids and thyroid hormone replacement. The patient showed a marked improvement within 1 week of treatment. And she was discharged with an advice to follow-up at our outpatient department. PMID:24265336

  12. Characteristics of scheduled bleeding manipulation with combined hormonal contraception in university students

    PubMed Central

    Lakehomer, Hannah; Kaplan, Paul F.; Wozniak, David G.; Minson, Christopher T.

    2013-01-01

    BACKGROUND There is a lack of information concerning the decision factors and sources of information influencing women who purposefully deviate from the prescribed use of their combined hormone contraceptives to exert elective control of their scheduled bleeding. STUDY DESIGN A self-administered email survey of scheduled bleeding practices and beliefs was distributed to 11,900 female students at the University of Oregon. Assessment of survey participant characteristics, scheduled bleeding manipulation features, and attitudes and knowledge toward hormonal contraception was analyzed. RESULTS Of 1719 respondents to the survey, 1374, 79.9% reported using combined hormonal contraception currently or recently. Approximately 17% of these women altered their scheduled bleeding pattern by deviating from package instructions. Of these, 50% indicated they delayed or skipped their scheduled bleeding for convenience or personal choice. Within this group, 47% of women indicated they learned to modify their scheduled bleeding from health care professionals, while 30% indicated such knowledge was obtained from family or friends. Characteristics that decreased the likelihood of this practice included being of Asian race, use of hormonal contraceptive for bleeding cycle regulation, following a regular exercise program, and personal preference for a monthly cycle. CONCLUSIONS The majority of university females who choose to modify their scheduled bleeding cycle with combined hormonal contraceptives do so for convenience rather than to avoid menstrual symptoms, and many learn from nonmedical sources. There is some disparity between the preferences of menstruation frequency and actual scheduled bleeding pattern behaviors, suggesting potential for improvement in patient education. PMID:23477500

  13. Predicting the effects of amino acid replacements in peptide hormones on their binding affinities for class B GPCRs and application to the design of secretin receptor antagonists

    NASA Astrophysics Data System (ADS)

    Te, Jerez A.; Dong, Maoqing; Miller, Laurence J.; Bordner, Andrew J.

    2012-07-01

    Computational prediction of the effects of residue changes on peptide-protein binding affinities, followed by experimental testing of the top predicted binders, is an efficient strategy for the rational structure-based design of peptide inhibitors. In this study we apply this approach to the discovery of competitive antagonists for the secretin receptor, the prototypical member of class B G protein-coupled receptors (GPCRs). Proteins in this family are involved in peptide hormone-stimulated signaling and are implicated in several human diseases, making them potential therapeutic targets. We first validated our computational method by predicting changes in the binding affinities of several peptides to their cognate class B GPCRs due to alanine replacement and compared the results with previously published experimental values. Overall, the results showed a significant correlation between the predicted and experimental ΔΔG values. Next, we identified candidate inhibitors by applying this method to a homology model of the secretin receptor bound to an N-terminal truncated secretin peptide. Predictions were made for single residue replacements to each of the other nineteen naturally occurring amino acids at peptide residues within the segment binding the receptor N-terminal domain. Amino acid replacements predicted to most enhance receptor binding were then experimentally tested by competition-binding assays. We found two residue changes that improved binding affinities by almost one log unit. Furthermore, a peptide combining both of these favorable modifications resulted in an almost two log unit improvement in binding affinity, demonstrating the approximately additive effect of these changes on binding. In order to further investigate possible physical effects of these residue changes on receptor binding affinity, molecular dynamics simulations were performed on representatives of the successful peptide analogues (namely A17I, G25R, and A17I/G25R) in bound and

  14. Types of hormone therapy

    MedlinePlus

    ... types of hormone therapy; Hormone replacement therapy - types; Menopause - types of hormone therapy; HT - types; Menopausal hormone ... Menopause symptoms include: Hot flashes Night sweats Sleep problems Vaginal dryness Anxiety Moodiness Less interest in sex ...

  15. Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 2. The Women's Health Initiative: estrogen plus progestogen.

    PubMed

    Shapiro, Samuel; Farmer, Richard D T; Mueck, Alfred O; Seaman, Helen; Stevenson, John C

    2011-07-01

    Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study (MWS), it is claimed that combined hormone replacement therapy (HRT) with estrogen plus progestogen is now an established cause of breast cancer. For unopposed estrogen therapy the evidence in the three studies is conflicting: the CR and MWS have reported increased risks in estrogen users, while the WHI has not. The authors have previously reviewed the findings in the CR (Part 1). To evaluate the evidence for causality in the WHI studies. Using generally accepted causal criteria, in this paper (Part 2) the authors evaluate the findings in the WHI for estrogen plus progestogen; in a related paper (Part 3) the authors evaluate the findings for unopposed estrogen. An evaluation of the MWS (Part 4), and of trends in breast cancer incidence following publication of the WHI findings in 2002 (Part 5) will follow. For estrogen plus progestogen the findings did not adequately satisfy the criteria of bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency or biological plausibility. HRT with estrogen plus progestogen may or may not increase the risk of breast cancer, but the WHI did not establish that it does.

  16. The effect of food on the bioavailability of norethindrone and ethinyl estradiol from norethindrone acetate/ethinyl estradiol tablets intended for continuous hormone replacement therapy.

    PubMed

    Boyd, Rebecca A; Zegarac, Elizabeth A; Eldon, Michael A

    2003-01-01

    As part of the development of a combination product containing norethindrone acetate and low-dose ethinyl estradiol for continuous hormone replacement therapy in postmenopausal women, a study was conducted to determine the effect of a high-fat meal on the bioavailability of norethindrone and ethinyl estradiol from tablets containing 1 mg norethindrone acetate/10 micrograms ethinyl estradiol. Eighteen healthy postmenopausal women participated in an open-label, single-dose, randomized, three-way crossover study in which 2 x 1/10 norethindrone acetate/ethinyl estradiol tablets were administered fasting and with a high-fat breakfast, and the same dose was administered in solution. Following each treatment, serial blood samples were collected for 48 hours, and plasma ethinyl estradiol and norethindrone concentrations were determined by a validated gas chromatography/mass spectrometry (GC/MS) method. Individual plasma ethinyl estradiol and norethindrone pharmacokinetic parameters were calculated by noncompartmental methods for each treatment and analyzed by ANOVA to obtain differences between least squares treatment mean values and associated 90% confidence intervals. Rates of ethinyl estradiol and norethindrone availability from tablets administered with food were slower than availability rates from tablets administered while fasting. Systemic exposure to ethinyl estradiol was unaffected by administration of tablets with food, whereas exposure to norethindrone increased by 27%. Because administration of norethindrone acetate/ethinyl estradiol 1/10 tablets with a high-fat meal did not decrease systemic exposure to norethindrone and ethinyl estradiol, this formulation can be taken without regard to meals.

  17. Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacement.

    PubMed

    Esposito, Valentina; Di Biase, Sebastiano; Lettiero, Teresa; Labella, Donato; Simeone, Rossella; Salerno, Mariacarolina

    2004-11-01

    This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. Seventeen prepubertal children with GHD (11 boys and six girls) aged 8.6 +/- 1.9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 microg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0.0001 and P < 0.007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8.4 +/- 2.9 vs. 6.0 +/- 2.9 micromol/l; P < 0.03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0.0001); serum Hcy levels decreased significantly (6.0 +/- 3.3 micromol/l; P < 0.002) compared to baseline values, becoming similar to control values. Total cholesterol (3.5 +/- 0.6 mmol/l) and the AI (2.5 +/- 0.8) decreased significantly with respect to both pretreatment (4.2 +/- 1.0 mmol/l; P < 0.0002 and 3.4 +/- 0.8; < 0.002, respectively) and control values (4.2 +/- 0.4 mmol/l; P < 0.0005 and 3

  18. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

    PubMed Central

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

  19. Serum free insulin-like growth factor-I in growth hormone-deficient adults before and after growth hormone replacement.

    PubMed

    Skjaerbaek, C; Vahl, N; Frystyk, J; Hansen, T B; Jørgensen, J O; Hagen, C; Christiansen, J S; Orskov, H

    1997-08-01

    The objective of the present study was to compare fasting levels of free IGF-I in serum from patients with adult onset growth hormone deficiency (GHD) and from healthy volunteers, and to examine the effect of GH replacement therapy in GHD on serum free IGF-I. Free IGF-I was measured using separation of free IGF-I by ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with GHD, in the latter before and after 1 year of treatment with GH (2 IU/m2) (n = 13) or placebo (n = 14). Free IGF-I was significantly decreased in patients with GHD (700 +/- 100 ng/l (mean +/- S.E.M.), range 55-2618 ng/l) compared with controls (1010 +/- 70 ng/l, range 231-2431 ng/l; P = 0.0016). Total IGF-I was 85 +/- 10 micrograms/l (GHD) and 160 +/- 10 micrograms/l (controls) (P < 0.0001). The ratio of free over total IGF-I was increased in GHD to 0.85 +/- 0.08% compared with 0.66 +/- 0.05% in controls (P = 0.04). In both GHD and controls, free IGF-I correlated significantly (P < 0.05) with total IGF-I (GHD r = 0.78; controls r = 0.42), IGFBP-1 (GHD r = -0.67; controls r = -0.46) and the molar ratio of total IGF-I over IGFBP-3 (GHD r = 0.58; controls r = 0.62). After 1 year of GH treatment, free IGF-I was increased to 2780 +/- 320 ng/l (P = 0.003) and total IGF-I was increased to 270 +/- 30 micrograms/l (P = 0.006) both of which values were greater than those in healthy volunteers. There were no changes in free or total IGF-I in the placebo-treated group. In conclusion, levels of free IGF-I are decreased in GHD, but measurements of free IGF-I in a single, fasting serum sample do not offer a better separation of patients with GHD from individuals with normal GH status than can be achieved by measurement of total IGF-I. One year of treatment with 2IU/m2 GH caused an increase of serum free IGF-I to supraphysiological levels.

  20. Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy.

    PubMed

    Stauffer, Brian L; Hoetzer, Greta L; Smith, Derek T; DeSouza, Christopher A

    2004-01-01

    We tested the hypothesis that hormone replacement therapy (HRT)-related increases in C-reactive protein (CRP) would either be blunted or absent in postmenopausal women who regularly perform endurance exercise. Plasma CRP is an independent predictor of future cardiovascular events in healthy men and women. Oral HRT increases plasma CRP concentrations in postmenopausal women. Regular aerobic exercise reduces the risk of cardiovascular events and is associated with lower CRP concentrations in adults. To date, no study has evaluated the influence of habitual physical activity on the elevation of CRP associated with HRT. Plasma CRP concentrations were measured in 114 postmenopausal women: 39 physically active (endurance trained) and 75 sedentary postmenopausal subjects. Sixty-five women were users of HRT (22 physically active and 43 sedentary), and 49 were nonusers (17 physically active and 32 sedentary). CRP levels were approximately 75% higher (P < 0.01) in the sedentary users vs. nonusers of HRT (1.9 +/- 1.8 vs. 1.1 +/- 1.0 mg/l). In contrast, there was no difference in CRP levels between the physically active users and nonusers of HRT (0.6 +/- 0.4 vs. 0.4 +/- 0.2 mg/l; P = 0.61). Regardless of HRT status, CRP concentrations were approximately 65% lower in the physically active compared with sedentary women. In conclusion, physically active postmenopausal women exhibit lower plasma CRP concentrations compared with sedentary controls. Importantly, the HRT-related elevation in plasma CRP levels observed in sedentary women is absent in women who engage in regular endurance exercise. These data suggest that habitual physical activity may prevent the elevation in CRP concentrations due to HRT.

  1. Three-year experience with access to nationally funded growth hormone (GH) replacement for GH-deficient adults.

    PubMed

    Holdaway, I M; Hunt, P; Manning, P; Cutfield, W; Gamble, G; Ninow, N; Staples-Moon, D; Moodie, P; Metcalfe, S

    2015-07-01

    Treatment of growth hormone (GH)-deficient adults with GH has been shown to improve a range of metabolic abnormalities and enhance quality of life. However, the results of access to nationally funded treatment have not been reported. Retrospective case series auditing nationally funded treatment of defined GH-deficient adults in New Zealand, with carefully designed entry and exit criteria overseen by a panel of endocrinologists. Applications for 201 patients were assessed and 191 approved for funded treatment over the initial 3 years since inception. The majority had GH deficiency following treatment of pituitary adenomas or tumours adjacent to the pituitary. After an initial 9-month treatment period using serum IGF-I measurements to adjust GH dosing, all patients reported a significant improvement in quality of life (QoL) score on the QoL-AGHDA(®) instrument (baseline (95%CI) 19 (18-21), 9 months 6 (5-7.5)), and mean serum IGF-I SD scores rose from -3 to zero. Mean waist circumference decreased significantly by 2.8 ± 0.6 cm. The mean maintenance GH dose after 9 months of treatment was 0.39 mg/day. After 3 years, 17% of patients had stopped treatment, and all of the remaining patients maintained the improvements seen at 9 months of treatment. Carefully designed access to nationally funded GH replacement in GH-deficient adults was associated with a significant improvement in quality of life over a 3-year period with mean daily GH doses lower than in the majority of previously reported studies. © 2014 John Wiley & Sons Ltd.

  2. The incidence of breast cancer and changes in the use of hormone replacement therapy: a review of the evidence.

    PubMed

    Verkooijen, Helena M; Bouchardy, Christine; Vinh-Hung, Vincent; Rapiti, Elisabetta; Hartman, Mikael

    2009-10-20

    Even though a link between hormone replacement therapy (HRT) and breast cancer has been well documented in the epidemiological literature since the 1980s, it was not until publication of the results of the Women's Health Initiative (WHI) study in 2002 and the Million Women Study in 2003 that women and doctors started reconsidering the use of HRT and sales of HRT started to drop. This paper evaluates the impact of the publication of these two landmark studies on the expected and observed changes in the incidence of breast cancer. Between 2001-2002 and 2005-2006, sharp and significant reductions in the incidence of breast cancer of up to 22% were reported in many US and European populations, temporally consistent with the drop in usage of HRT. Declines in the rates of breast cancer were strongest for 50-60-year-old women (those most likely to be current users of HRT), affected mainly ER+ and PR+ cancers (those most strongly associated with HRT use), and were largest among women with the highest pre-decline prevalence of HRT use and the sharpest decline in its use. A considerable amount of scientific evidence supports the hypothesis that the decline in the incidence of breast cancer is in large part attributable to the sudden drop in HRT use following publication of the WHI and Million Women studies. Nevertheless, the problem of how to advise women contemplating HRT use today remains. Medical relief will remain necessary for many women with menopausal complaints, and so new therapeutic options need to be explored.

  3. OGT and OGA expression in postmenopausal skeletal muscle associates with hormone replacement therapy and muscle cross-sectional area.

    PubMed

    Toivonen, Minna H M; Pöllänen, Eija; Ahtiainen, Maarit; Suominen, Harri; Taaffe, Dennis R; Cheng, Sulin; Takala, Timo; Kujala, Urho M; Tammi, Markku I; Sipilä, Sarianna; Kovanen, Vuokko

    2013-12-01

    Protein glycosylation via O-linked N-acetylglucosaminylation (O-GlcNAcylation) is an important post-translational regulatory mechanism mediated by O-GlcNAc transferase (OGT) and responsive to nutrients and stress. OGT attaches an O-GlcNAc moiety to proteins, while O-GlcNAcase (OGA) catalyzes O-GlcNAc removal. In skeletal muscle of experimental animals, prolonged increase in O-GlcNAcylation associates with age and muscle atrophy. Here we examined the effects of hormone replacement therapy (HRT) and power training (PT) on muscle OGT and OGA gene expression in postmenopausal women generally prone to age-related muscle weakness. In addition, the associations of OGT and OGA gene expressions with muscle phenotype were analyzed. Twenty-seven 50-57-year-old women participated in a yearlong randomized placebo-controlled trial: HRT (n=10), PT (n=8) and control (n=9). OGT and OGA mRNA levels were measured from muscle samples obtained at baseline and after one year. Knee extensor muscle cross-sectional area (CSA), knee extension force, running speed and vertical jumping height were measured. During the yearlong intervention, HRT suppressed the aging-associated upregulation of OGT mRNA that occurred in the controls. The effects of PT were similar but weaker. HRT also tended to increase the OGA mRNA level compared to the controls. The change in the ratio of OGT to OGA gene expressions correlated negatively with the change in muscle CSA. Our results suggest that OGT and OGA gene expressions are associated with muscle size during the critical postmenopausal period. HRT and PT influence muscle OGT and OGA gene expression, which may be one of the mechanisms by which HRT and PT prevent aging-related loss of muscle mass.

  4. Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study.

    PubMed

    Feigelson, Heather Spencer; Jonas, Carolyn R; Teras, Lauren R; Thun, Michael J; Calle, Eugenia E

    2004-02-01

    Excess adiposity and hormone replacement therapy (HRT) are important contributors to postmenopausal breast cancer risk. HRT has been shown to modify the association between body weight and breast cancer risk, although few studies are sufficiently large to examine the risk of breast cancer associated with body mass index (BMI) and weight gain separately among current HRT users and nonusers. This study includes 1,934 incident breast cancer cases occurring among 62,756 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort. Age-adjusted incidence rates were calculated, and Cox proportional hazards models were used to examine the association of BMI and adult weight gain (since age 18 years) with breast cancer risk stratified by HRT use. Total adult weight gain strongly predicted breast cancer risk among former and never HRT users (P for trend < 0.0001). Weight gain of 21-30 pounds was associated with a rate ratio of 1.4 (95% confidence interval 1.1-1.8); rates doubled among women gaining >70 pounds compared with women who maintained their weight within 5 pounds of their weight at age 18. After accounting for weight gain, neither recent BMI nor BMI at age 18 were independent predictors of risk. Among current HRT users, no association was seen between breast cancer and either BMI or weight gain. Adult weight gain is strongly associated with postmenopausal breast cancer only among non-HRT users in this study. These data illustrate the importance of examining breast cancer risk factors separately by HRT use; the effects of other risk factors may be attenuated or obscured among women taking HRT.

  5. Maintaining normal levels of ionized calcium during citrate-based renal replacement therapy is associated with stable parathyroid hormone levels.

    PubMed

    Raimundo, Mário; Crichton, Siobhan; Lei, Katie; Sanderson, Barnaby; Smith, John; Brooks, John; Ng, Josephine; Lemmich Smith, Joanna; McKenzie, Catherine; Beale, Richard; Dickie, Helen; Ostermann, Marlies

    2013-01-01

    Citrate is an effective anticoagulant during continuous renal replacement therapy (CRRT). Previous studies showed raised parathyroid hormone (PTH) levels when aiming for serum ionized calcium [Cai] between 0.8 and 1.1 mmol/l. Our objective was to assess whether citrate-based CRRT with physiologic target systemic [Ca(i)] between 1.12 and 1.20 mmol/l could maintain stable PTH levels. Measurement of intact PTH (PTHi) in 30 consecutive critically ill patients treated with citrate-based CRRT. Thirty patients [mean age: 70.4 (SD 11.3) years; 56.7% males] were enrolled. Mean serum [Ca(i)] was 1.16 mmol/l (SD 0.09), 1.13 mmol/l (SD 0.09), 1.17 mmol/l (SD 0.05) and 1.16 mmol/l (SD 0.04) at baseline, 12, 24 and 48 h, respectively (p = 0.29). Median PTHi levels (interquartile range) at baseline, 12, 24 and 48 h were 66.5 (43-111), 109 (59.5-151.5), 88.5 (47-133) and 85 pg/ml (53-140), respectively. The differences between baseline and 12 h and across all time points were statistically not significant (p = 0.16 and p = 0.49, respectively). In a mixed-effects model, each 0.1 mmol/l increase in serum [Ca(i)] was associated with a 31.2% decrease in PTHi (p < 0.001). Results were unchanged after adjustment for age, gender, magnesium, phosphate, arterial pH and time spent on CRRT. Maintaining systemic [Ca(i)] within the physiologic range was associated with stable PTHi levels. © 2013 S. Karger AG, Basel.

  6. Obesity, coffee consumption and CRP levels in postmenopausal overweight/obese women: Importance of hormone replacement therapy use

    PubMed Central

    Arsenault, Benoit J.; Earnest, Conrad P.; Després, Jean-Pierre; Blair, Steven N.; Church, Timothy S.

    2009-01-01

    Background/Objective Obesity is associated with an inflammatory state that is often characterized by elevated plasma C-reactive protein (CRP) levels. Although coffee is broadly consumed in Western societies, few studies have examined the relationship between obesity, coffee consumption and CRP levels. The objective of the present study was to assess the relationship between obesity, coffee consumption and variation in CRP in postmenopausal, overweight/obese women with or without hormone replacement therapy (HRT) use. Subjects/Methods Cross-sectional analyses of 344 healthy sedentary, overweight/obese postmenopausal women (mean age=57.1±6.4 years and mean body mass index [BMI]=36.1±3.9 kg/m2). Plasma CRP levels were measured by a highly sensitive immunoassay that used monoclonal antibodies coated with polystyrene particles. Diet was assessed using the Food Intake and Analysis System semi-quantitative food frequency questionnaire. Results Plasma CRP was positively associated with BMI (p<0.001) and negatively associated with coffee consumption (p≤0.05). In women using HRT, plasma CRP was positively associated BMI in women consuming less than one cup of coffee per month (r2=0.15 [p<0.001]), one cup per day (0.14 [p=0.02]) and more than one cup per day (0.12 [p=0.03]). In women who did not use HRT, CRP was associated BMI only in women consuming less than one cup of coffee per day (r2=0.16 [p<0.001]) but not in women consuming one cup per day (0.06 [p=0.10]) or more than one daily cup of coffee (0.03 [p=0.27]). Conclusion Among overweight/obese postmenopausal women coffee consumption is negatively associated with CRP. Coffee consumption appears to attenuate the association between BMI and CRP, but only in women not using HRT. PMID:19756031

  7. Inverse association of female hormone replacement therapy with age-related macular degeneration and interactions with ARMS2 polymorphisms.

    PubMed

    Edwards, Digna R Velez; Gallins, Paul; Polk, Monica; Ayala-Haedo, Juan; Schwartz, Stephen G; Kovach, Jaclyn L; Spencer, Kylee; Wang, Gaofeng; Agarwal, Anita; Postel, Eric A; Haines, Jonathan L; Pericak-Vance, Margaret; Scott, William K

    2010-04-01

    Purpose. To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCPs) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk. Methods. Related and unrelated female participants (n = 799) were examined and data were analyzed with generalized estimating equations with adjustment for age and smoking. Individuals with AMD grades 1 to 2 were considered to be unaffected (n = 239) and those with grades 3 to 5 were considered affected (n = 560). Results. When comparing all cases with controls, significant inverse associations were observed for HRT (odds ratio [OR] = 0.65, 95% CI 0.48-0.90, P = 0.008) and BCPs (OR = 0.60, 95% CI 0.36-0.10, P = 0.048). When analyses were stratified by AMD severity (early versus geographic atrophy versus neovascular), the inverse association remained significant (HRT OR = 0.45, 95% CI 0.30-0.66, P < 0.0001; BCP OR = 0.55, 95% CI 0.32-0.96, P = 0.036) only when comparing neovascular AMD with the control. All pair-wise HRT-genotype and BCP-genotype interactions were examined, to determine whether HRT or BCP modifies the effect of established genetic risk factors. The strongest interactions were observed for HRT x ARMS2 coding SNP (R73H) rs10490923 (P = 0.007) and HRT x ARMS2 intronic SNP rs17623531 (P = 0.019). Conclusions. These findings provide the first evidence suggesting that ARMS2 interacts with HRT to modulate AMD risk and are consistent with previous reports demonstrating a protective relationship between exogenous estrogen use and neovascular AMD. These results highlight the genetic and environmental complexity of the etiologic architecture of AMD; however, further replication is necessary to validate them.

  8. Volumetric quantification of the effect of aging and hormone replacement therapy on breast composition from digital mammograms.

    PubMed

    Hammann-Kloss, J S; Bick, U; Fallenberg, E; Engelken, F

    2014-07-01

    To assess the physiological changes in breast composition with aging using volumetric breast composition measurement from digital mammograms and to assess the effect of hormone replacement therapy (HRT). A total of 764 consecutive mammograms of 208 non-HRT using women and 508 mammograms of 134 HRT-using women were analyzed using a volumetric breast composition assessment software (Quantra™, Hologic Inc.). Fibroglandular tissue volume (FTV), breast volume (BV), and percent density (PD) were measured. For statistical analysis, women were divided into a premenopausal (<46 years), a perimenopausal (46-55 years), and a postmenopausal (>55 years) age group. More detailed graphical analysis was performed using smaller age brackets. Women using HRT were compared to age-matched controls not using HRT. Women in the postmenopausal age group had a significantly lower FTV and PD and a significantly higher BV than women in the premenopausal age group (FTV: 77 vs. 120 cm(3), respectively; PD: 16% vs. 28%, respectively; BV 478 vs. 406 cm(3), respectively; p<0.01 for all). Median FTV was nearly stable in consecutive mammograms in the premenopausal and postmenopausal age groups, but declined at a rate of 3.9% per year in the perimenopausal period. Median PD was constant in the premenopausal and postmenopausal age groups and declined at a rate of 0.57% per year in the perimenopausal age group. BV continuously increased with age. Women using HRT throughout the study had a 5% higher PD than women not using HRT (22% vs. 17%, respectively; p<0.001). Accurate knowledge of normal changes in breast composition are of particular interest nowadays due to the importance of breast density for breast cancer risk evaluation. FTV and PD change significantly during the perimenopausal period but remain relatively constant before and thereafter. Median total breast volume consistently increases with age and further contributes to changes in breast density. HRT use is associated with a significantly

  9. Risk of breast cancer in relation to combined effects of hormone therapy, body mass index, and alcohol use, by hormone-receptor status.

    PubMed

    Hvidtfeldt, Ulla Arthur; Tjønneland, Anne; Keiding, Niels; Lange, Theis; Andersen, Ingelise; Sørensen, Thorkild I A; Prescott, Eva; Hansen, Åse Marie; Grønbæk, Morten; Bojesen, Stig Egil; Diderichsen, Finn; Rod, Naja Hulvej

    2015-05-01

    Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high-risk" users is important for therapeutic reasons. We investigated interactions between hormone therapy use and alcohol-use/high BMI status in relation to invasive breast cancer risk, both overall and according to estrogen receptor (ER) status. Two Danish prospective cohorts were pooled, including 30,789 women ages 50+ years (study period 1981 to 2009). Information on risk factors was obtained in baseline questionnaires. We performed analyses using the Aalen additive hazards model. Serum estradiol and testosterone measurements were obtained in a subsample of approximately 1000 women. During 392,938 person-years of follow-up, 1579 women developed invasive breast cancer. Among nonusers of hormone therapy, the risk of breast cancer was slightly increased with overweight/obesity and increasing alcohol consumption. Compared with normal-weight nonusers, the risk of breast cancer was higher in hormone therapy users across all BMI strata (P for interaction = 0.003). A markedly higher risk of breast cancer was also observed for alcohol combined with hormone therapy use compared with abstinent nonusers (P for interaction = 0.02). These effects were primarily restricted to ER-positive cases. Combined effects of hormone therapy/high BMI and hormone therapy/alcohol on serum estradiol and testosterone supported the hypothesis of a hormonal pathway linking these exposures to breast cancer. These analyses suggest an increased risk of breast cancer associated with hormone therapy use-a risk that may be particularly strong among women consuming alcohol.

  10. Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.

    PubMed

    Hu, Jinbo; Zhang, Aiping; Yang, Shumin; Wang, Yue; Goswami, Richa; Zhou, Huang; Zhang, Yi; Wang, Zhihong; Li, Rong; Cheng, Qingfeng; Zhen, Qianna; Li, Qifu

    2016-07-01

    The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend  = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  11. Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

    PubMed

    Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

    2015-07-01

    Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

  12. The effects of castration and hormone replacement on the cross-sectional area of pubococcygeus muscle fibers in the female rat.

    PubMed

    Lara-García, Miguel; Alvarado, Mayvi; Cuevas, Estela; Cortés-sol, Albertina; Domínguez, Andrés; Tovar, Anibal; Pacheco, Pablo

    2011-07-01

    In this study, we analyzed the effect of ovariectomy and gonadal hormone replacement on the cross-sectional area of pubococcygeus (Pcm) fibers. It was found that in comparison to intact animals, ovariectomized animals [for 2 or 6 weeks] had an increased cross-sectional area average in Pcm fibers. Ovariectomy also reduced the percentage of fibers with smaller cross-sectional area. In ovariectomized animals after 4 weeks of hormone replacement with an empty Silastic capsule or filled with testosterone propionate or dihydrotestosterone, significantly increased the cross-sectional area average and the percentage of fibers with larger size. However, 17β-estradiol but not estradiol benzoate treatment reduced the cross-sectional area average and increased the percentage of Pcm fibers with smaller size. Progesterone did not have an effect on the cross-sectional area of this muscle. We conclude that Pcm fibers of female rats are sensitive to gonadal hormones, and contrary to male castration, ovariectomy promotes an increase in their cross-sectional area. Also, we discuss according to other studies that an external mechanism which lies within the neuromuscular periphery could also participate in the modulatory hormonal effect on mass or muscle fiber size. Furthermore, in this process, estradiol is likely to regulate the fiber cross-sectional area growing produced by androgens.

  13. The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

    ERIC Educational Resources Information Center

    Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

    2001-01-01

    Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

  14. The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

    ERIC Educational Resources Information Center

    Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

    2001-01-01

    Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

  15. A New Radioimmunoassay for Plasma l-Triiodothyronine: Measurements in Thyroid Disease and in Patients Maintained on Hormonal Replacement

    PubMed Central

    Surks, Martin I.; Schadlow, Alan R.; Oppenheimer, Jack H.

    1972-01-01

    A new procedure for the radioimmunoassay of l-triiodothyronine (T3) in human plasma is described in which the iodothyronines are separated from the plasma proteins before incubation with a specific antiserum to T3. The antibody bound and free T3 are separated with dextran-coated charcoal. In this system, the mean recovery of T3 added to plasma was 97.9% and both in vitro conversion of l-thyroxine (T4) to T3 and cross-reaction between T4 and the anti-T3 antibody were undetectable (less than 0.1%). The assay procedure allowed the measurement of T3 in up to 0.5 ml of plasma resulting in improved assay sensitivity (6 ng/100 ml). The mean plasma T3 in normal subjects was 146±24 ng/100 ml (sd). Mean T3 concentration was increased in hyperthyroidism (665±289 ng/100 ml) and decreased in hypothyroidism (44±26 ng/100 ml). In patients with severe hypothyroidism, plasma T3 was between 7 and 30 ng/100 ml. Plasma T3 concentration was relatively constant throughout the day in three euthyroid subjects. In contrast, in hypothyroid subjects on replacement therapy with T3, a T4: T3 combination or desiccated thyroid plasma T3 was markedly elevated for several hours after ingestion of the medication. Plasma T3 was unchanged throughout the day in patients treated with T4. Thus, insofar as plasma T3 levels are concerned, replacement therapy with T4 appears to mimic the euthyroid state more closely than other preparations. PMID:4539287

  16. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy.

    PubMed

    Berenson, J R; Hilger, J D; Yellin, O; Dichmann, R; Patel-Donnelly, D; Boccia, R V; Bessudo, A; Stampleman, L; Gravenor, D; Eshaghian, S; Nassir, Y; Swift, R A; Vescio, R A

    2014-07-01

    In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m(2) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m(2)), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).

  17. Recurrent infantile hypoglycemia due to combined fructose-1,6-diphosphatase deficiency and growth hormone deficiency.

    PubMed

    Takagi, Dania; Ben-Ari, Josef; Nemet, Dan; Zeharia, Avraham; Eliakim, Alon

    2013-01-01

    A 14-month-old female infant presented with recurrent episodes of acute gastroenteritis accompanied by severe metabolic acidosis and hypoglycemia. Physical examination showed hepatomegaly. Laboratory evaluation revealed elevated hepatic enzymes, prolonged prothrombin time, hyperuricemia, and extremely elevated lactate and alanine levels. Glucagon injection during hypoglycemia resulted in a further decrease of blood glucose. She was treated with glucose-containing intravenous fluids, with rapid improvement and normalization of her blood pH and glucose levels. Hormonal assessment during two episodes of hypoglycemia indicated growth hormone (GH) deficiency. However, as isolated GH deficiency could not explain all other concomitant features, such as severe lactic acidosis, hepatomegaly, impaired liver function, and hyperuricemia, the possibility of a combined defect was suggested. Further lymphocytic enzymatic investigation revealed fructose-1,6-diphosphatase deficiency and molecular genetic analysis demonstrated frame shift mutation in the FBP1 gene. This enzyme deficiency causes a rare metabolic disorder not previously described in combination with GH deficiency.

  18. Hormone Replacement Therapy advertising: sense and nonsense on the web pages of the best-selling pharmaceuticals in Spain

    PubMed Central

    2010-01-01

    Background The balance of the benefits and risks of long term use of hormone replacement therapy (HRT) have been a matter of debate for decades. In Europe, HRT requires medical prescription and its advertising is only permitted when aimed at health professionals (direct to consumer advertising is allowed in some non European countries). The objective of this study is to analyse the appropriateness and quality of Internet advertising about HRT in Spain. Methods A search was carried out on the Internet (January 2009) using the eight best-selling HRT drugs in Spain. The brand name of each drug was entered into Google's search engine. The web sites appearing on the first page of results and the corresponding companies were analysed using the European Code of Good Practice as the reference point. Results Five corporate web pages: none of them included bibliographic references or measures to ensure that the advertising was only accessible by health professionals. Regarding non-corporate web pages (n = 27): 41% did not include the company name or address, 44% made no distinction between patient and health professional information, 7% contained bibliographic references, 26% provided unspecific information for the use of HRT for osteoporosis and 19% included menstrual cycle regulation or boosting feminity as an indication. Two online pharmacies sold HRT drugs which could be bought online in Spain, did not include the name or contact details of the registered company, nor did they stipulate the need for a medical prescription or differentiate between patient and health professional information. Conclusions Even though pharmaceutical companies have committed themselves to compliance with codes of good practice, deficiencies were observed regarding the identification, information and promotion of HRT medications on their web pages. Unaffected by legislation, non-corporate web pages are an ideal place for indirect HRT advertising, but they often contain misleading information

  19. Hormone replacement therapy advertising: sense and nonsense on the web pages of the best-selling pharmaceuticals in Spain.

    PubMed

    Chilet-Rosell, Elisa; Martín Llaguno, Marta; Ruiz Cantero, María Teresa; Alonso-Coello, Pablo

    2010-03-16

    The balance of the benefits and risks of long term use of hormone replacement therapy (HRT) have been a matter of debate for decades. In Europe, HRT requires medical prescription and its advertising is only permitted when aimed at health professionals (direct to consumer advertising is allowed in some non European countries). The objective of this study is to analyse the appropriateness and quality of Internet advertising about HRT in Spain. A search was carried out on the Internet (January 2009) using the eight best-selling HRT drugs in Spain. The brand name of each drug was entered into Google's search engine. The web sites appearing on the first page of results and the corresponding companies were analysed using the European Code of Good Practice as the reference point. Five corporate web pages: none of them included bibliographic references or measures to ensure that the advertising was only accessible by health professionals. Regarding non-corporate web pages (n = 27): 41% did not include the company name or address, 44% made no distinction between patient and health professional information, 7% contained bibliographic references, 26% provided unspecific information for the use of HRT for osteoporosis and 19% included menstrual cycle regulation or boosting feminity as an indication. Two online pharmacies sold HRT drugs which could be bought online in Spain, did not include the name or contact details of the registered company, nor did they stipulate the need for a medical prescription or differentiate between patient and health professional information. Even though pharmaceutical companies have committed themselves to compliance with codes of good practice, deficiencies were observed regarding the identification, information and promotion of HRT medications on their web pages. Unaffected by legislation, non-corporate web pages are an ideal place for indirect HRT advertising, but they often contain misleading information. HRT can be bought online from Spain

  20. Menopause, Reproductive Life, Hormone Replacement Therapy, and Bone Phenotype at Age 60–64 Years: A British Birth Cohort

    PubMed Central

    Muthuri, S.; Cooper, R.; Moore, A.; Mackinnon, K.; Cooper, C.; Adams, J. E.; Hardy, R.; Ward, K. A.

    2016-01-01

    Context: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment. Objective: The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60–64 years. Design: This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. Setting: The study was conducted in England, Scotland, and Wales. Participants: Participants included 848 women with a known type of menopause and bone measures at 60–64 years. Main Outcome Measures: Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured. Results: A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%–15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%–11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%–9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%–1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography. Conclusions: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater

  1. Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

    PubMed

    Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

    2012-03-01

    Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception.

    PubMed

    Edelman, Alison; Micks, Elizabeth; Gallo, Maria F; Jensen, Jeffrey T; Grimes, David A

    2014-07-29

    The avoidance of menstruation through continuous or extended (greater than 28 days) administration of combination hormonal contraceptives (CHCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through extended or continuous use of CHCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school. To determine the differences between continuous or extended-cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active hormone compared with traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormones and 4 days of placebo). Our hypothesis was that continuous or extended-cycle CHCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with standard cyclic CHCs. We searched computerized databases (Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, POPLINE, LILACS) for trials using continuous or extended CHCs (oral contraceptives, contraceptive ring and patch) during the years 1966 to 2013. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references. All randomized controlled trials in any language comparing continuous or extended-cycle (greater than 28 days of active hormones) versus traditional cyclic administration (21 days of active hormones and 7 days of placebo, or 24 days of active hormones and 4 days of placebo) of CHCs for contraception. Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 5. Peto

  3. Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

    PubMed

    Kandemir, Nurgün; Vurallı, Doğuş; Taşkıran, Ekim; Gönç, Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Yılmaz, Engin

    2012-01-01

    Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

  4. A New Combined Technique Reducing the Risk of Paraplegia during Thoracoabdominal Aorta Replacement.

    PubMed

    Tozzi, Piergiorgio; Pralong, Etienne; Gronchi, Fabrizio; Siniscalchi, Giuseppe

    2017-03-01

    Acute spinal cord ischemia during thoracoabdominal aorta replacement is a dreadful complication. Existing tools (motor evoked potential [MEP] and somatosensory evoked potential [SSEP]) do not allow differentiating between central and peripheral paraplegia. Therefore, the surgeon often performs unnecessary reimplantation of intercostal arteries: this is time consuming, and significantly increases bleeding complications. We present a simple technique combining MEP and peripheral compound muscle action potential induced by posterior tibialis nerve stimulation, enabling the surgeon to quickly discriminate between central and peripheral neurologic injury. The surgeon has one more tool to drive in real time the optimal surgical strategy. This strategy guides the decision as to which side branches ought to be reimplanted, thus minimizing the risk of paraplegia. Georg Thieme Verlag KG Stuttgart · New York.

  5. Combined aortic valve replacement and coronary artery bypass grafting for a calcified ascending aorta.

    PubMed

    Baba, Hironori; Umesue, Masayoshi; Matsui, Kanzi

    2012-04-01

    Although a severely calcified ascending aorta is encountered infrequently, it presents formidable problems during cardiac surgery. We describe a case of severe aortic valve stenosis and coronary artery disease combined with a severely calcified ascending aorta. The patient was an 80-year-old man with a calcified ascending aorta. He successfully underwent an aortic valve replacement and a single coronary artery bypass graft (CABG) using a saphenous vein graft with the proximal end connected on a Dacron patch, which was used for aortoplasty of the calcified plate along the aortotomy. These procedures were performed under moderate hypothermia with aortic clamping. This patch aortoplasty can be a useful alternative in cases that require aortotomy and proximal anastomoses of a CABG on a calcified ascending aorta.

  6. Influence of hormonal replacement on the ventral lobe of the prostate of rats (Rattus norvegicus albinus) submitted to chronic ethanol treatment.

    PubMed

    Sáttolo, S; Carvalho, C A F; Cagnon, V H A

    2004-12-01

    The harmful influence of the chronic alcohol ingestion on the male reproductive system leads to important alterations including hypogonadism and feminization, besides the morphological and functional disorganization of the different sexual glands. So, the aim of this study was to analyse the structural changes on the ventral lobe of the prostate of rats with hormonal replacement associated to chronic alcohol ingestion. A total of 30 rats (Rattus norvegicus albinus) was divided into three groups: control-received water; alcoholic-received ethanol diluted to 20% and hormone-treated alcoholic-received ethanol diluted to 20% associated with the administering of testosterone (5mg/kg of weight) during the last 30 days of treatment. After 150 days of treatment, the animals were sacrificed, the prostate removed and submitted to transmission and scanning electron microscopies, histochemical analysis for acid phosphatase, testosterone level and stereologic analysis. In the alcoholic group the results demonstrated reduction of the total cellular volume and disorganization of the organelles involved in the secretory process. It was characterized a partial recovery of the cellular volume after treatment with testosterone. It was concluded that the ethanol impaired the cellular morphology and the hormonal replacement by itself did not bring about efficient remodeling of the organelles responsible for the secretory process.

  7. Combined hormonal contraception use in reproductive-age women with contraindications to estrogen use.

    PubMed

    Lauring, Julianne R; Lehman, Erik B; Deimling, Timothy A; Legro, Richard S; Chuang, Cynthia H

    2016-09-01

    The Centers for Disease Control and Prevention's US Medical Eligibility Criteria for Contraceptive Use recommends that combined hormonal contraceptives (ie, birth control pills, contraceptive patch, vaginal ring) should be avoided in women with specific medical conditions because of the increased risk of cardiovascular events associated with estrogen use. Whether women with category 3 (theoretical or proven risk usually outweigh the advantages) or category 4 (unacceptable health risk) contraindications are appropriately avoiding estrogen-containing combined hormonal contraceptives is unknown. We describe the prevalence of combined hormonal contraceptive use among a sample of reproductive-age women with medical contraindications to estrogen use. Our hypothesis was that women with categories 3 and 4 contraindications would use estrogen-containing contraception less often than women without medical contraindications. We also explored whether inappropriate estrogen-containing contraceptive use is related to contraceptive provider characteristics. Data are from the baseline survey of the MyNewOptions study, which included privately insured women residing in Pennsylvania aged 18-40 years, who were sexually active and not intending pregnancy in the next year. Women were surveyed about their medical conditions, contraceptive use, and characteristics of their contraceptive provider. Women were considered to have a contraindication to combined hormonal contraceptives if they reported a category 3 or category 4 contraindication: hypertension, smokers older than age 35 years, a history of venous thromboembolism, diabetes with complications, coronary artery disease, systemic lupus erythematosus with antiphospholipid antibodies, breast cancer, or migraine headaches with aura. χ(2) tests for general association were used to compare combined hormonal contraceptives use, contraceptive health provider characteristics, and sociodemographic data in women with and without

  8. Evaluation of various combinations of alternative protein feedstuffs to replace soybean meal in diets for pond-raised channel catfish

    USDA-ARS?s Scientific Manuscript database

    A study was conducted in earthen ponds to evaluate the use of combinations of two or three alternative protein sources to replace soybean meal in diets for Channel Catfish Ictalurus punctatus. Six 28% protein diets containing various combinations of alternative protein feedstuffs including cottonse...

  9. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    PubMed

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

  10. A LONGER INTERVAL WITHOUT GROWTH HORMONE REPLACEMENT AND FEMALE GENDER ARE ASSOCIATED WITH LOWER BONE MINERAL DENSITY IN ADULTS WITH CHILDHOOD ONSET GROWTH HORMONE DEFICIENCY - A KIMS DATABASE ANALYSIS

    PubMed Central

    Tritos, Nicholas A; Hamrahian, Amir H; King, Donna; Greenspan, Susan L; Cook, David M; Jönsson, Peter J; Wajnrajch, Michael P; Koltowska – Häggstrom, Maria; Biller, Beverly MK

    2016-01-01

    Objective Childhood onset growth hormone deficiency (COGHD) is associated with low bone mineral density (BMD). Adults with persistent COGHD may be at risk for insufficient bone accrual or bone loss during adulthood. The purpose of this study was to identify BMD predictors and characterize the effects of GH replacement on BMD in COGHD adults with persistent GHD. Design Retrospective analysis of the KIMS database. Methods Variables predicting standardized BMD (sBMD) were identified. The effect of GH replacement (3 years) on BMD was examined. Results 314 COGHD adults (148 women, 166 men; 62 non-naïve, 178 semi-naïve, and 74 true naïve, depending on length and timing of previous GH replacement), who had BMD measured in lumbar spine (LS) and femoral neck (FN) at study entry. In semi-naïve subjects, a longer gap in GH replacement between childhood and adulthood was predictive of lower sBMD in the FN (r= −0.18, P=0.038). Thyrotropin deficiency predicted lower sBMD in the LS (r= −0.16,P=0.052). In true naïve patients, a longer gap between onset of pituitary disease and study entry (r= −0.35,P=0.012) and female gender (r= −0.27,P=0.043) independently predicted lower sBMD in the FN. There were no differences in BMD increases between non-naïve, semi-naïve and true naïve subjects on GH replacement. Conclusions In semi-naïve subjects a longer interval off GH replacement was associated with lower sBMD in the FN. Among true naïve patients, a longer gap between the onset of pituitary disease and GH replacement, and female gender predicted lower sBMD in the FN. PMID:22711759

  11. Combining phase information in reciprocal space for molecular replacement with partial models.

    PubMed

    Millán, Claudia; Sammito, Massimo; Garcia-Ferrer, Irene; Goulas, Theodoros; Sheldrick, George M; Usón, Isabel

    2015-09-01

    ARCIMBOLDO allows ab initio phasing of macromolecular structures below atomic resolution by exploiting the location of small model fragments combined with density modification in a multisolution frame. The model fragments can be either secondary-structure elements predicted from the sequence or tertiary-structure fragments. The latter can be derived from libraries of typical local folds or from related structures, such as a low-homology model that is unsuccessful in molecular replacement. In all ARCIMBOLDO applications, fragments are searched for sequentially. Correct partial solutions obtained after each fragment-search stage but lacking the necessary phasing power can, if combined, succeed. Here, an analysis is presented of the clustering of partial solutions in reciprocal space and of its application to a set of different cases. In practice, the task of combining model fragments from an ARCIMBOLDO run requires their referral to a common origin and is complicated by the presence of correct and incorrect solutions as well as by their not being independent. The F-weighted mean phase difference has been used as a figure of merit. Clustering perfect, non-overlapping fragments dismembered from test structures in polar and nonpolar space groups shows that density modification before determining the relative origin shift enhances its discrimination. In the case of nonpolar space groups, clustering of ARCIMBOLDO solutions from secondary-structure models is feasible. The use of partially overlapping search fragments provides a more favourable circumstance and was assessed on a test case. Applying the devised strategy, a previously unknown structure was solved from clustered correct partial solutions.

  12. [Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

    PubMed

    Vyshnevs'ka, O A; Bol'shova, O V

    2013-06-01

    Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

  13. [Effect of combined hormonal oral contraception on the somatic and psychic status of women of reproductive age].

    PubMed

    Vertkin, A L; Nosova, A V

    2012-01-01

    The paper is devoted to the topical problem of maintaining somatic and psychic health of the women of reproductive age by rational pregnancy planning and prevention of abortions by modern methods of contraception including combined oral hormonal contraception. Unfortunately, this approach is rarely employed in this country (5-6%). Results of retrospective analysis of medical documentation, clinical efficacy and safety of modern combined oral hormonal contraception are presented.

  14. Combined Sewer Overflows: An Environmental Source of Hormones and Wastewater Micropollutants

    PubMed Central

    2012-01-01

    Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency. PMID:22540536

  15. Combined Sewer Overflows as a Source of Hormones to Surface Water

    NASA Astrophysics Data System (ADS)

    Phillips, P.; Chalmers, A.; Gray, J. L.; Foreman, W.; Kolpin, D. W.; Wall, G.; Esposito, K.

    2009-12-01

    Some sources of hormones to surface water, such as wastewater-treatment-plant (WWTP) effluent, have been well documented, but other sources, particularly wet-weather discharges from combined-sewer-overflows (CSOs), are not well characterized. Flow-weighted composite samples of secondarily treated WWTP effluent and untreated sewage discharges from WWTP inflows and CSO discharges were collected during 12 storms and 6 non-storm conditions from November 2007-December 2008 at the main Burlington Vermont WWTP. Concentrations of many androgens and estrogens were highest in samples from untreated sewage, and lower in samples from treated sewage. For example, concentrations of estriol in CSO samples ranged from 5 to over 100 ng/L (nanograms per liter), but were generally less than 1 ng/L in treated sewage. Many androgens were detected in CSO discharge samples in concentrations ranging from 1 to over 1000 ng/L, but were not detected above 1 ng/L in treated samples. For many of the hormones, including androgens and estriol, CSO discharges comprised over half of the total load discharged by the WWTP, even though annual CSO discharge is less than 10% of the treated plant discharge. These results indicate that untreated discharges during CSO events can be a major source of some hormones and other wastewater compounds to the environment.

  16. Combined sewer overflows: an environmental source of hormones and wastewater micropollutants

    USGS Publications Warehouse

    Phillips, P.J.; Chalmers, A.T.; Gray, J.L.; Kolpin, D.W.; Foreman, W.T.; Wall, G.R.

    2012-01-01

    Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.

  17. An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

    DTIC Science & Technology

    2008-04-01

    breast cancer risk to be modestly associated with one SNPs in each GSTP1 (rs1695: OR = 1.4 [95% CI: 1.02-1.9] for carriers of A allele); CYP1B1 ...In a multi-gene model including two genes with single gene effects within the estrogen pathway ( CYP1B1 *2 and GSTP1), breast cancer risk was 1.6 (95...pathways. 15. SUBJECT TERMS Genetic polymorphisms , epidemiology, exogenous risk factors, gene-environment interactions, hormonal pathway, estrogen

  18. An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

    DTIC Science & Technology

    2008-10-01

    1.02-1.9] for carriers of A allele); CYP1B1 (rs1056827: OR = 1.7 ]95% CI:1.2-2.5] for T homozygotes); SRD5A1 (rs248793: OR=1.2 [95% CI: 1.02-1.5... CYP1B1 *2 and GSTP1), breast cancer risk was 1.6 (95% CI: 1.03-2.4) times higher for carriers of 1 high risk genotype and 2.8 (95% CI: 1.5-5.3) times...is modified by variation in genes within hormonal pathways. 15. SUBJECT TERMS Genetic polymorphisms , epidemiology, exogenous risk factors, gene

  19. Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.

    PubMed

    Chen, Li-Shiun; Baker, Timothy B; Jorenby, Douglas; Piper, Megan; Saccone, Nancy; Johnson, Eric; Breslau, Naomi; Hatsukami, Dorothy; Carney, Robert M; Bierut, Laura J

    2015-09-01

    Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings. Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Therapy of Severe Heatshock in Combination With Multiple Organ Dysfunction With Continuous Renal Replacement Therapy

    PubMed Central

    Chen, Guang-Ming; Chen, Yang-Hong; Zhang, Wei; Yu, Yi; Chen, Jin-Hua; Chen, Jian

    2015-01-01

    Abstract This study aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) and routine therapy in heatshock (HS) patients. We retrospectively reviewed the clinical information of 33 severe exertional HS patients who were treated from February 1998 to October 2013. On the basis of whether or not CRRT therapy was used in addition to conventional therapy, patients were divided into a CRRT group (n = 15) and a control group (n = 18). Body temperature, blood gas analysis, routine blood tests, blood eletrolytes, enzymes and kidney function data, and APACHE II scores were obtained and compared between the 2 groups on admission and 3, 5, and 7 days after admission. Mortality was also compared between the 2 groups. CRRT treatment combined with conventional treatment resulted in a higher hospital-discharge rate, a faster return to normal of body temperature, greater increase in platelets, a greater decrease in WBC, neutrophils, and serum markers for liver and kidney dysfunction, greater improvement of organ dysfunction, and lower APACHE II scores than conventional treatment used alone. The addition of CRRT to conventional treatment for HS improves survival and causes a faster return to normal of serum markers and organ function. PMID:26252279

  1. Predictors of the effects of 4 years of growth hormone replacement on bone mineral density in patients with adult-onset growth hormone deficiency – a KIMS database analysis

    PubMed Central

    Tritos, Nicholas A.; Hamrahian, Amir H.; King, Donna; Greenspan, Susan L.; Cook, David M.; Jonsson, Peter J.; Koltowska-Haggstrom, Maria; Biller, Beverly M.K.

    2016-01-01

    Summary Objective Growth hormone (GH) replacement may increase bone mineral density (BMD) in GH-deficient (GHD) adults. The goal of this study was to identify predictors of BMD response to GH replacement in GH na ve adults. Design and measurements This was a retrospective analysis of data extracted from KIMS (Pfizer International Metabolic Database), an international pharmacoepidemiological survey of adult GHD patients from 31 countries. Patients A total of 231 GH naive adults were identified (115 women and 116 men) who had BMD measured on the same densitometer in the lumbar spine (LS) and/or femoral neck (FN) both at baseline and after 4 years of GH replacement. Results After 4 years, there was a median (10th, 90th percentile) 4.6% (−5.2%, 12.2%) increase in LS BMD over baseline (P = 00001). There was a positive correlation between per cent change in LS BMD and age at the onset of pituitary disease (r = 025, P = 0001). There was no change in FN BMD over baseline [0.0% (−7.3%, 8.5%)]. On multivariate analysis, older age at the onset of pituitary disease predicted a greater increase in LS BMD on GH replacement (r = 0.55, P < 0.0001). Conclusions In a population of GH na ve adults, GH replacement led to a significant increase in LS BMD over baseline, but no change in FN BMD. The potential for greater BMD improvement on GH replacement therapy in adults with disease of later onset should be considered when making treatment decisions in this patient population. PMID:23278636

  2. A case of extensive genitourinary tuberculosis: combined augmentation ileo-cystoplasty, ureteric ileal replacement and buccal mucosal graft urethroplasty.

    PubMed

    Singh, Onkar; Gupta, Shilpi Singh; Arvind, Nand Kishore

    2013-09-01

    Genitourinary tuberculosis (GUTB) is the second most common form of extrapulmonary TB after lymph nodes. Advanced GUTB leading to strictures of ureters and urethra, and bladder contracture frequently need surgical management. These are usually treated by ileal replacement of ureter, substitution urethroplasty using buccal mucosal graft (BMG) and augmentation ileo-cystoplasty, respectively. These procedures have been well demonstrated individually but all these three procedures have never been combined as single procedure in the same patient. We report a case of advanced GUTB with ureteric and urethral strictures, and bladder contracture which was treated by the ileal replacement of ureter, augmentation ileo-cystoplasty combined with BMG substitution urethroplasty in a single sitting.

  3. Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

    PubMed

    Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

    2012-04-01

    Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.

  4. Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

    PubMed

    van Bunderen, Christa C; van den Dries, Carline J; Heymans, Martijn W; Franken, Anton A M; Koppeschaar, Hans P F; van der Lely, Aart J; Drent, Madeleine L

    2014-08-01

    Isolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment. A nationwide surveillance study was carried out to describe the difference in the clinical presentation and responsiveness to GH treatment of patients with IGHD and MPHDs. The Dutch National Registry of GH Treatment in Adults was founded in 1998 to gain more insight into long-term efficacy and safety of GH therapy. Out of 2891 enrolled patients, 266 patients with IGHD at the start of GH treatment were identified and compared with 310 patients with MPHDs. Cardiovascular indices will be investigated at baseline and during long-term follow-up, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity. Patients with IGHD and MPHDs were demonstrated to be different entities at clinical presentation. Metabolically, patients with MPHDs had a larger waist circumference, lower HDL cholesterol level, and higher triglyceride level. The effect of GH treatment was comparable between patient groups. GH seems to protect against rising lipid levels and blood pressure, even after excluding patients using corresponding concomitant medication. The risk for cardiovascular disease or diabetes mellitus during follow-up was not different between patients with IGHD and MPHDs. Patients with IGHD had a less impaired metabolic profile than patients with MPHDs at baseline. Influence of other pituitary hormone replacement therapies on the effect of GH treatment is not demonstrated. © 2014 European Society of Endocrinology.

  5. Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer: efficacy in combination with hormonal therapy

    PubMed Central

    2012-01-01

    Background Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT. Methods Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not. Results Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev. Conclusion Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents. PMID:23083011

  6. Reconciliation of the paradox that testosterone replacement prevents the postcastration hypersecretion of follicle-stimulating hormone in male rhesus monkeys (Macaca mulatta) with an intact central nervous system but not in hypothalamic-lesioned, gonadotropin-releasing hormone-replaced animals.

    PubMed

    Abeyawardene, S A; Plant, T M

    1989-03-01

    Testosterone (T) replacement suppresses the postcastraction hypersection of follicle-stimulating hormone (FSH) in monkeys with an intact central nervous system (CNS), but not in hypothalamic-lesioned animals in which the pituitary-testicular axis is driven by an i.v. infusion of gonadotropin-releasing hormone (GnRH). One possible explanation for this finding is that T replacement markedly reduces the frequency of pulsatile GnRH release in CNS-intact animals. Under such a state of compromised hypophysiotropic drive to the gonadotropes, removal of a specific FSH-inhibiting factor would not be expected to lead to a hypersecretion of FSH. To test this hypothesis indirectly, adult monkeys were orchidectomized and immediately implanted with T-containing Silastic capsules to maintain circulating T concentrations in the upper physiological range, thereby preventing the postcastration hypersecretion of luteinizing hormone (LH) and FSH. An intermittent i.v. infusion of GnRH, identical to that used in studies with the hypothalamic-lesioned, GnRH-replaced model (1 microgram/min for 3 min every 3 h), was initiated 1 wk after castration and T replacement; subsequently, plasma LH and FSH concentrations were determined on Days 8 and 16-18 of GnRH treatment in samples collected every 20 min for 9 h. This GnRH stimulus resulted in a striking elevation in FSH concentrations from 5.2 +/- 1.5 ng/ml (mean +/- SE) before GnRH treatment to 62.6 +/- 20.8 and 118.3 +/- 33.1 ng/ml on Days 8 and 16-18 of GnRH treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Regression of prostate tumors upon combination of hormone ablation therapy and celecoxib in vivo.

    PubMed

    Abedinpour, Parisa; Baron, Véronique T; Welsh, John; Borgström, Per

    2011-06-01

    Hormonal ablation is the standard of treatment for advanced androgen-dependent prostate cancer. Although tumor regression is usually achieved at first, the cancer inevitably evolves toward androgen-independence, in part because of the development of mechanisms of resistance and in part because at the tissue level androgen withdrawal is not fully attained. Current research efforts are focused on new therapeutic strategies that will increase the effectiveness of androgen withdrawal and delay recurrence. We used a syngeneic pseudo-orthotropic mouse model of prostate cancer to test the efficacy of combining androgen withdrawal with FDA-approved COX-2 inhibitor celecoxib. GFP-tagged TRAMP-C2 cells were co-implanted with prostate tissue in the dorsal chamber model and tumors were allowed to establish and vascularize. Tumor growth and angiogenesis were monitored in real-time using fluorescent intravital microscopy (IVM). Androgen withdrawal in mice was achieved using surgical castration or chemical hormonal ablation, alone or in combination with celecoxib (15 mg/kg, twice daily). Celecoxib alone decreased the growth of prostate tumors mostly by inducing mitotic failure, which resulted in increased apoptosis. Surprisingly, celecoxib did not possess significant angiostatic activity. Surgical or chemical castration prevented the growth of prostate tumors and this, on the other hand, was associated with disruption of the tumor vasculature. Finally, androgen withdrawal combined with celecoxib caused tumor regression through decreased angiogenesis and increased mitosis arrest and apoptosis. Celecoxib, a relatively safe COX-2-selective anti-inflammatory drug, significantly increases the efficacy of androgen withdrawal in vivo and warrants further investigation as a complement therapy for advanced prostate cancer. Copyright © 2010 Wiley-Liss, Inc.

  8. [Impact of contraception counseling on choice of combined hormonal methods in Colombia].

    PubMed

    Gómez Sánchez, Pío; Lozano, Fidel; Velásquez, Andrés; Marrugo, Martha; Torres, Luz

    2015-06-01

    Determine the impact of informed contraceptive counseling on choice of contraceptive method. Multicenter descriptive study using before-and-after evaluation in nine cities in Colombia. Women considering use of self-administered combined hormonal methods at the time of consultation were invited to participate. They were asked about contraceptive method use and preference, following signing of informed consent. Later, they were given standardized medical advice on contraception and then asked again about contraceptive preference and reasons for their choice. The study enrolled 858 women. At the beginning of the study, 538 (62.7%) women were using the combined pill and 281 (32.8%) were not using any contraceptive method. Before receiving counseling, women showed a preference for the pill (62.7%), followed by the intravaginal ring (28.4%), and transdermal patch (14%). After counseling, preferences were as follows: pill (40.8%), intravaginal ring (31.5%), and transdermal patch (11.3%). After counseling, 32.5%, 26.8%, and 7.5% of those considering the pill, patch, and ring, respectively, changed their intended choice. Region of origin, employment status, desire to conceive a child in the future, and having a stable relationship showed a statistical relationship to choice of method. However, age, number of children, and level of education were not determining factors. Medical advice has an impact on choice of self-administered combined hormonal contraceptives, which helps women to use the method of their choice and improves adherence to the method in accordance with its particular conditions.

  9. Behavioural and hormonal effects of member replacement in captive groups of blue-fronted amazon parrots (Amazona aestiva).

    PubMed

    Silva de Souza Matos, Laerciana; Palme, Rupert; Silva Vasconcellos, Angélica

    2017-03-09

    Social species in captivity may face allostatic overload due to artificial grouping and other social constraints. In rescue centres, groups of psittacines are constantly mixed due to the arrival and/or release of individuals; this procedure is potentially harmful to animal welfare. This study aimed at evaluating the possible impacts of mate replacement on the stress levels of captive blue-fronted amazon parrots (Amazona aestiva). During five weeks, we recorded agonistic interactions and dropping-glucocorticoid metabolites (GCM) concentrations of individuals allocated in a group whose members were kept constant and in a group subjected to frequent member replacement. In both groups, non-linear hierarchies developed, without sex differences regarding aggression or hierarchical positions. The replacement of individuals had no effect on the number of agonistic interactions or on the animals' stress levels. In both groups, higher-ranking individuals had higher stress loads than subordinates. Our study, the first to investigate the social dynamics of A. aestiva, indicated that introducing or removing individuals in captive groups does not seem to affect the welfare of the birds in the short term. This information favours release and reintroduction programs and is relevant for conservation management of this, and possibly other parrot species with similar environmental requirements.

  10. Fatal breast cancer risk in relation to use of unopposed estrogen and combined hormone therapy.

    PubMed

    Pocobelli, Gaia; Newcomb, Polly A; Li, Christopher I; Cook, Linda S; Barlow, William E; Weiss, Noel S

    2014-06-01

    Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. To address this question, we conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). A total of 1,288 cases and 12,535 controls were included in the analyses. Exclusive use of EHT was not associated with fatal breast cancer risk, either overall or within categories of recency or duration [odds ratio (OR) for current vs. never use = 1.1; 95 % confidence interval (CI) 0.8-1.3]. Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current vs. never use = 0.9; 95 % CI 0.7-1.3), except for a suggestion of an increased risk with current long-term use. Consistent with prior studies, we observed no increased risk of fatal breast cancer associated with use of EHT. To date only a few studies have evaluated fatal breast cancer risk in relation to use of CHT, and collectively the results are inconsistent.

  11. Fatal Breast Cancer Risk in Relation to Use of Unopposed Estrogen and Combined Hormone Therapy

    PubMed Central

    Pocobelli, Gaia; Newcomb, Polly A.; Li, Christopher I.; Cook, Linda S.; Barlow, William E.; Weiss, Noel S.

    2014-01-01

    Background Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. Methods We conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). Results A total of 1,288 cases and 12,535 controls were included in the analyses. Exclusive use of EHT was not associated with fatal breast cancer risk, either overall or within categories of recency or duration (odds ratio (OR) for current versus never use=1.1; 95% CI (confidence interval), 0.8–1.3). Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current versus never use=0.9; 95% CI, 0.7–1.3), except for a suggestion of an increased risk with current long-term use. Conclusion Consistent with prior studies, we observed no increased risk of fatal breast cancer associated with use of EHT. To date only a few studies have evaluated fatal breast cancer risk in relation to use of CHT, and collectively the results are inconsistent. PMID:24671356

  12. The influence of growth hormone (GH) deficiency and GH replacement on quality of life in GH-deficient patients.

    PubMed

    Deijen, J B; van der Veen, E A

    1999-01-01

    The total absence of hormones such as cortisol or thyroxine causes death within weeks. Lack of estrogen or testosterone is followed by infertility and impaired sexual functioning. Relative deficiencies of almost all classical hormones have a substantial impact on quality of life (QOL). However, in contrast to virtually all aspects of metabolism, QOL is difficult to measure. Only recently have tests been developed to assess general QOL, whereas specific tests address those aspects of QOL affected only in specific situations or disease states. For example, in rheumatoid arthritis and other chronic disabling diseases, the use of measures of QOL to assess treatment modalities is almost routine. In diseases with overt metabolic disturbances attention is generally focused on changes in metabolic parameters and the issue of QOL is neglected. Although very few practising endocrinologists will not support the idea that they specialize in improving QOL, its assessment in patients with endocrinological disorders began only recently--in patients with growth hormone (GH) deficiency only 10 years ago. It became apparent that GH deficiency in adult life is unmistakably followed by changes in parameters that determine QOL. In adults with childhood-onset GH deficiency, the unemployment rate is higher and the marriage rate lower than in the general population. Another symbol of success in life, the possession of a driver's licence, is less frequently attained by these patients. Most patients with adult-onset GH deficiency score unfavourably in questionnaires such as the Nottingham Health Profile. GH substitution is now available on a scale large enough to enable studies to be made of the effects on QOL in adults. The first studies were reported in 1989. However, only in the last few years have studies appeared in which sufficient number of patients and sufficient length of treatment were reported to allow a more objective judgement of the effectiveness of GH substitution. Although

  13. TRADITIONAL CHINESE MEDICINE COMBINED WITH HORMONE THERAPY TO TREAT PREMATURE OVARIAN FAILURE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

    PubMed

    Kou, Mei-Jing; Ding, Xiu-Fang; Chen, Jia-Xu; Liu, Yan; Liu, Yue-Yun

    2016-01-01

    This meta-analysis aimed to provide critically estimated evidence for the advantages and disadvantages of Chinese herbal medicines used for premature ovarian failure (POF), which could provide suggestions for rational treatments. The databases searched included MEDLINE, EMBASE, CNKI, VIP, China Dissertation Database, China Important Conference Papers Database, and online clinical trial registry websites. Published and unpublished randomized controlled trials of traditional Chinese medicine (TCM) combined with hormone therapy (HT) and HT alone for POF were assessed up to December 30, 2015. Two authors extracted data and assessed trial quality independently using Cochrane systematic review methods. Meta-analysis was used to quantitatively describe serum hormone levels and Kupperman scores associated with perimenopause symptoms. Seventeen randomized controlled trials involving 1352 participants were selected. Compared with HT alone, although no significant effects were observed in the levels of luteinizing hormone, therapy with TCM combined with HT compared to HT alone effectively altered serum hormone levels of follicle stimulating hormone (P<0.01) and estradiol (P < 0.01), and improved Kupperman index scores (P< 0.01). The reported favorable effects of TCM combined with HT for treating POF patients are better than HT alone.However, the beneficial effects derived from this combination therapy cannot be viewed conclusive. In order to better support the clinical use, more rigorously designed trials are required to provide.

  14. Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy.

    PubMed

    Dören, M; Rübig, A; Coelingh Bennink, H J; Holzgreve, W

    2001-03-01

    To determine serum parameters reflective of androgen status in postmenopausal women using two types of hormone replacement therapy (HRT). Randomized, double-blind, prospective 1-year trial of two oral HRT regimens. University hospital, department of obstetrics and gynecology, menopause clinic. 100 postmenopausal women > or = 45 years. Daily use of the progestogen tibolone (2.5 mg; n = 50) or continuous combined 17-beta-estradiol (2 mg) and norethindrone acetate (E+NA, 1 mg; n = 50). Measurements of total testosterone (total T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), FSH, and sex-hormone-binding globulin (SHBG), and calculations of free testosterone (free T). Assessment of changes from baseline within and between groups after 6 and 12 months. We found significant differences (% changes) in the tibolone group compared to baseline within the groups after both 6 and 12 months, respectively. Levels of free T doubled, total T decreased slightly, and SHBG decreased by half; DHEAS increased by approximately 20%; and FSH decreased. In the E+NA group, levels of free T, total T, androstenedione, and FSH all decreased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were significantly higher in the E+NA group. Between groups throughout the study, the changes from baseline were significant due to the different extent of FSH reduction, and opposite changes of free T, SHBG, and DHEAS. Both regimens modify plasma androgens, DHEAS, and SHBG differently. Tibolone decreased the levels of SHBG, and substantially increased free T and to a lesser extent increased DHEAS; this may reflect a modification of adrenal androgen production. Continuous combined estradiol and norethindrone acetate HRT suppressed the peripheral plasma androgens mediated by increased levels of SHBG.

  15. LacZ Expression in Fut2-LacZ Reporter Mice Reveals Estrogen Regulated Endocervical Glandular Expression During Estrous Cycle, Hormone Replacement, and Pregnancy

    PubMed Central

    DOMINO, STEVEN E.; HURD, ELIZABETH A.

    2006-01-01

    The “Secretor” gene (FUT2) encodes an α(1,2)fucosyltransferase (E.C. 2.4.1.69) that elaborates α(1,2)fucose residues on mucosal epithelium and secreted mucins. While uterine α(1,2)fucosylated glycans have proposed to be involved in embryo adhesion, mice with a homozygous null mutation of Fut2 displayed normal fertility. To help develop alternative hypotheses for function, the cell type and regulation of Fut2 expression during the estrous cycle, hormone replacement, and pregnancy was examined in Fut2-LacZ reporter mice containing targeted replacement of Fut2 with bacterial lacZ. LacZ expression in the reproductive tract of Fut2-LacZ mice is most prominent in the glandular epithelium of the endocervix during estrus and pregnancy. Nuclear LacZ expression identifies cell specific expression of Fut2 in mucus secreting cells of the endocervix, uterine glands, foveolar pit and chief cells of the stomach, and goblet cells of the colon. In ovariectomized Fut2-LacZ mice, estradiol treatment stimulates X-gal staining in endocervix and uterus, but does not affect expression in stomach and colon. Northern blot analysis in wild type mice shows 15-fold elevations of Fut2 steady-state mRNA with estradiol treatment, while Fut1 varies little. Fut2 levels in the glandular stomach and distal colon remain constant while uterine Fut2 levels vary 8-fold during the estrous cycle. These data represent the first demonstration of a glycosyltransferase gene under tissue-specific hormonal regulation in a LacZ reporter mouse model. Endocervical expression of Fut2 in estrus and pregnancy may modify cervical mucus barrier properties from microbial infection analogous to the potential role of mucosal glycans in humans. PMID:14576173

  16. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

    PubMed

    Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

    2016-08-01

    Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

  17. Moving toward an understanding of hormone replacement therapy in adolescent girls: looking through the lens of Turner syndrome.

    PubMed

    Davenport, Marsha L

    2008-01-01

    Turner syndrome (TS) is a relatively common disorder of phenotypic females caused by loss of all or part of the second sex chromosome. Most individuals with TS have short stature and gonadal dysgenesis and are at risk for many other medical and learning problems. In the 45,X ovary, germs cells multiply quite normally during fetal development, but there is accelerated atresia of oocytes in the second half of pregnancy that produces gonadal insufficiency by birth. In girls with other karyotypes, especially those mosaic for 45,X/46,XX, gonadal function may be normal or near-normal. In this chapter, management goals for gonadal insufficiency in girls with TS are presented. The effects of estrogen deficiency and its replacement on three specific problems associated with TS-short stature, cardiovascular disease, and developmental differences in brain structure and function-are explored. General guidelines for estrogen replacement therapy using transdermal estrogen, the most physiologic option, are provided and future research goals are outlined.

  18. Prevalence and incidence of diabetes mellitus in adult patients on growth hormone replacement for growth hormone deficiency: a surveillance database analysis.

    PubMed

    Attanasio, Andrea F; Jung, Heike; Mo, Daojun; Chanson, Philippe; Bouillon, Roger; Ho, Ken K Y; Lamberts, Steven W J; Clemmons, David R

    2011-07-01

    GH replacement in adult GH-deficient patients may cause insulin resistance, raising concerns of potential increased risk of developing diabetes mellitus (DM). Our objective was to assess DM prevalence and incidence in the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database. GH-treated patients enrolled into HypoCCS (2922 U.S. and 3709 European patients) were assessed for DM, defined as recorded on the clinical report form, reported as adverse events, fasting glucose at least 7 mmol/liter recorded at least twice, or insulin treatment reported. DM prevalence was 8.2% [95% confidence interval (CI) = 7.6-8.9] overall, 11.3% in the United States and 5.7% in Europe. Incidence (n/1000 patient-years) was 9.7 (95% CI = 8.4-10.9) overall, 14.1 (11.5-16.7) in the United States, and 7.0 (5.6-8.3) in Europe. Overall incidence was 2.1 (0.9-3.3) for patients with body mass index (BMI) below 25 kg/m(2) increasing to 16.4 (13.7-19.1) for BMI over 30 kg/m(2). Obesity (BMI > 30 kg/m(2)) prevalence was higher in the United States than Europe and higher in U.S. patients than a U.S. reference population. After age, gender, and BMI adjustment, U.S. HypoCCS DM incidence was 10.6 (8.1-13.0), compared with 7.1 (6.0-8.1) in the National Health Interview Survey. In Europe, incidence for French and German patients was comparable to reference populations; for Sweden, the point estimate was higher than the reference population, but 95% CI overlapped. GH dose was not correlated with DM incidence. The present analysis showed no evidence for increased DM incidence in GH-treated adult hypopituitary patients. However, those more prone to develop DM exhibited a higher than normal prevalence of obesity.

  19. Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

    PubMed

    Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

    2017-02-01

    To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

  20. Luteininzing hormone releasing hormones analogs in combination with tamoxifen for the adjuvant treatment of premenopausal women with hormone receptor positive breast cancer.

    PubMed

    Conte, Benedetta; Poggio, Francesca; Del Mastro, Lucia

    2017-09-01

    The role of ovarian function suppression (OFS) through luteinizing hormone-releasing hormone agonists (LHRHa) in addition to tamoxifen has been questioned until recently. In 2015, two large clinical trials led to a paradigm shift in the adjuvant endocrine treatment of premenopausal women, introducing the use of LHRHa plus tamoxifen (or aromatase inhibitor, AI) into current clinical practice. Areas covered: The present review aims to provide an in-depth overview of the role of LHRHa+tamoxifen for the adjuvant treatment of premenopausal women with hormone receptor positive breast cancer (HR+BC). Expert opinion: The addition of LHRHa to endocrine treatment (either tamoxifen or AI) is effective in premenopausal women who are at high risk of relapse. To date, no clear recommendations are available for the choice between LHRHa+tamoxifen and LHRH+AI. Although recent data showed better DFS with LHRHa+AI, other issues should be considered: 1) approximately 20 out of 100 women do not reach complete OFS with LHRHa+AI; 2) there is no extended endocrine therapy option that can be applied to women who received 5 years of LHRHa+AI and remained premenopausal at the end of the fifth year. Long-term results of the SOFT-TEXT study are needed to establish if LHRHa+AI is superior to LHRHa+tamoxifen.

  1. Linear growth, growth-hormone secretion and IGF-I generation in children with neglected hypothyroidism before and after thyroxine replacement.

    PubMed

    Soliman, Ashraf T; Omar, Magdy; El Awwa, Ahmad; Rizk, Mostafa M; El Alaily, Rania K; Bedair, Elsaid M A

    2008-10-01

    We studied growth hormone (GH) stimulation and insulin-like growth factor -I (IGF-I) generation tests in 15 children with neglected congenital hypothyroidism (CH) (age = 6.4 +/- 4.2 years) and measured their growth parameters for >1 years after starting thyroxine (T4) replacement. One year after treatment, height SDS (HtSDS) increased from -4.3 +/- 2.5 to -2.7 +/- 2.3. Peak GH response to clonidine increased from 3.2 +/- 1.2 ng ml(-1) to 7.62 +/- 1.38 ng ml(-1) after treatments. Basal and peak IGF-I response to GH increased from (34.66 +/- 17.3 ng ml(-1) and 58.4 +/- 36.99 ng ml(-1), respectively) before treatment to (130.6 +/- 97.8 ng ml(-1) and 193.75 +/- 122.5 ng ml(-1), respectively). HtSDS increments were correlated significantly with basal free T4 concentrations (r = 0.622, P < 0.01). In summary, after long period of hypothyroidism, T4 replacement produced significant, although incomplete, catch-up growth through a partial recovery of GH- IGF-I axis.

  2. Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

    PubMed

    Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

    2016-01-01

    Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p < 0.001). There was a significant positive correlation between baseline serum thyroid stimulating hormone (TSH) level and EAT thickness in the SCH group. There was a significant reduction in mean EAT thickness in response to L-thyroxine treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p < 0.001). The decrease in EAT thickness after L-thyroxine treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

  3. Combined effects of venlafaxine, nicotine replacement, and brief counseling on smoking cessation.

    PubMed

    Cinciripini, Paul M; Tsoh, Janice Y; Wetter, David W; Lam, Cho; de Moor, Carl; Cinciripini, Lynn; Baile, Walter; Anderson, Cheryl; Minna, John D

    2005-11-01

    In this study, 147 smokers were randomly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling (9 weekly sessions) and transdermal nicotine replacement therapy (22 mg/day). Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting, with the daily dose titrated from 150 to 225 mg. in response to symptoms of negative affect and relapse. The results showed no main effect of treatment on abstinence. Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen. Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation. The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers, in addition to the expected benefits of nicotine replacement therapy and behavioral counseling. Copyright 2005 APA, all rights reserved.

  4. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

    PubMed

    Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

    2014-04-01

    Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body

  5. [Electroacupuncture intervention combined with general anesthesia for 80 cases of heart valve replacement surgery under cardiopulmonary bypass].

    PubMed

    Chi, Hao; Zhou, Wen-Xiong; Wu, Yao-Yao; Chen, Tong-Yu; Ge, Wen; Yuan, Lan; Shen, Wei-Dong; Zhou, Jia

    2014-02-01

    To determine whether electroacupuncture (EA) intervention combined with general anesthesia (GA) strategy can reduce early post-operative morbidity and medical costs in patients undergoing heart valve replacement operation under cardiopulmonary bypass. A total of 160 heart valve replacement surgery patients undergoing cardiopulmonary bypass were randomly divided into GA and EA + GA groups (n = 80 in each group). Patients of the GA group were given with intravenous injection of Fentanyl, Midazolam, Vecuronium Bromide, etc. and routine tracheal intubation. EA (3-4 Hz, 2.0-2.2 mA) was applied to bilateral Zhongfu (LU 1), Chize (LU 5) and Ximen (PC 4) beginning about 20 mm before the surgery in the EA + GA group. Endotracheal intubation was not employed but only prepared as a standby for patients of the EA + GA group. The dosage of narcotic drugs, duration of surgery, duration of aertic blockage, rate of cardiac re-beating, volumes of post-operative blood transfusion, discharge volume, cases of post-operative pulmonary infection, vocal cord injury, and the time of first bed-off, first eating and duration in intensive care unit (IOU) residence. etc. were recorded. The successful rates of heart valve replacement surgery were similar in both GA and EA + GA groups. Compared with the GA group, the dosages of Fentanyl, Midazolam and Vecuronium of the EA + GA group were significantly lower (P < 0.05, P < 0.01), the numbers of patients needing blood-transfusion, antibiotics treatment, and suffering from pulmonary infection were fewer, the time of first bed-off and duration of hospitalizetion and IOU residence were considerably shorter (P < 0.05, P < 0.01) and the total medical cost was obviously lower (P < 0.05) in the EA + GA group. EA combined with general anesthesia strategy for heart valve replacement surgery without endotracheal intubation is safe and can reduce post-operative morbidity and medical costs in patients undergoing heart valve replacement surgery under

  6. Synchronous esthesioneuroblastoma and growth-hormone-secreting pituitary macroadenoma: combined open and endoscopic management.

    PubMed

    Valdes, Costanza J; Tewfik, Marc A; Guiot, Marie-Christine; Di Maio, Salvatore

    2014-12-01

    Background Esthesioneuroblastoma is an uncommon malignant neoplasm that arises from the olfactory neuroepithelium. In this article we report a case of esthesioneuroblastoma presenting concomitantly with a growth-hormone (GH)-secreting pituitary macroadenoma. Results A 52 year old woman underwent surgery for suspected nasal polyps. Intralesional debulking of an intranasal tumor disclosed a low-grade esthesioneuroblastoma. Magnetic resonance imaging (MRI) demonstrated a large nasal and intracranial tumor, in addition to a separate sellar and suprasellar tumor. The patient was frankly acromegalic. She underwent a first-stage gross total resection of the esthesioneuroblastoma via a combined extended subfrontal and extended endonasal approach, followed by focused radiation therapy. She then returned for endoscopic removal of the GH-secreting pituitary macroadenoma. Conclusion The combined open and endoscopic management of this patient is described and a review of the literature presented. To our knowledge this is the first case of synchronous esthesioneuroblastoma and macroadenoma, in this case GH secreting, described in the literature.

  7. Epidermal growth factor and growth hormone-releasing peptide-6: combined therapeutic approach in experimental stroke.

    PubMed

    García Del Barco-Herrera, Diana; Martínez, Nelvys Subirós; Coro-Antich, Rosa María; Machado, Jorge Martín; Alba, José Suárez; Salgueiro, Sandra Rodríguez; Acosta, Jorge Berlanga

    2013-01-01

    Stroke is the second cause of mortality worldwide, with a high incidence of disability in survivors. Promising candidate drugs have failed in stroke trials. Combined therapies are attractive strategies that simultaneously target different points of stroke pathophysiology. The aim of this work is to determine whether the combined effects of epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP6) can attenuate clinical signs and pathology in an experimental stroke model. Brain global ischemia was generated in Mongolian gerbils by 15 minutes of carotid occlusion. After reperfusion, EGF, GHRP6 or EGF+GHRP6 were intraperitoneally administered. Clinical manifestations were monitored daily. Three days after reperfusion, animals were anesthetized and perfused with an ink solution. The anatomy of the Circle of Willis was characterized. Infarct volume and neuronal density were analyzed. EGF+GHRP6 co-administration reduced clinical manifestations and infarct volume and preserved neuronal density. No correlation was observed between the grade of anastomosis of the Circle of Willis and clinical manifestations in the animals receiving EGF+GHRP6, as opposed to the vehicle-treated gerbils. Co-treatment with EGF and GHRP6 affects both the clinical and pathological outcomes in a global brain ischemia model, suggesting a suitable therapeutic approach for the acute management of stroke.

  8. Designed nanostructured pt film for electrocatalytic activities by underpotential deposition combined chemical replacement techniques.

    PubMed

    Huang, Minghua; Jin, Yongdong; Jiang, Heqing; Sun, Xuping; Chen, Hongjun; Liu, Baifeng; Wang, Erkang; Dong, Shaojun

    2005-08-18

    Multiple-deposited Pt overlayer modified Pt nanoparticle (MD-Pt overlayer/PtNPs) films were deliberately constructed on glassy carbon electrodes through alternately multiple underpotential deposition (UPD) of Ag followed redox replacement reaction by Pt (II) cations. The linear and regular growth of the films characterized by cyclic voltammetry was observed. Atomic force spectroscopy (AFM) provides the surface morphology of the nanostructured Pt films. Rotating disk electrode (RDE) voltammetry and rotating ring-disk electrode (RRDE) voltammetry demonstrate that the MD-Pt overlayer/PtNPs films can catalyze an almost four-electron reduction of O(2) to H(2)O in air-saturated 0.1 M H(2)SO(4). Thus-prepared Pt films behave as novel nanostructured electrocatalysts for dioxygen reduction and hydrogen evolution reaction (HER) with enhanced electrocatalytic activities, in terms of both reduction peak potential and peak current, when compared to that of the bulk polycrystalline Pt electrode. Additionally, it is noted that after multiple replacement cycles, the electrocatalytic activities improved remarkably, although the increased amount of Pt is very low in comparison to that of pre-modified PtNPs due to the intrinsic feature of the UPD-redox replacement technique. In other words, the electrocatalytic activities could be improved markedly without using very much Pt by the technique of tailoring the catalytic surface. These features may provide an interesting way to produce Pt catalysts with a reliable catalytic performance as well as a reduction in cost.

  9. Modulation of nociceptive threshold by combined hormonal contraceptives in women with oestrogen-withdrawal migraine attacks: a pilot study.

    PubMed

    De Icco, Roberto; Cucinella, Laura; De Paoli, Irene; Martella, Silvia; Sances, Grazia; Bitetto, Vito; Sandrini, Giorgio; Nappi, Giuseppe; Tassorelli, Cristina; Nappi, Rossella E

    2016-12-01

    Menstrually-related headache and headaches associated with oestrogen withdrawal are common conditions, whose pathophysiology has not been completely elucidated. In this study we evaluated the influence of combined hormonal contraceptives (CHC) on pain threshold in women presenting migraine attacks during hormone-free interval. Eleven women with migraine attacks recurring exclusively during the oestrogen-withdrawal period were studied with the nociceptive flexion reflex, a neurophysiological assessment of the pain control systems, during the third week of active treatment and during the hormone-free interval. During the hormone-free interval, nociceptive withdrawal reflex threshold was significantly lower (12.8 ± 8.0 mA) as compared to the third week of hormonal treatment (15.6 ± 6.6 mA) (p = 0.02). No change was observed in the pain perceived and in the temporal summation. Oestrogen withdrawal may mediate an increased sensitivity to somatosensory stimuli in women with migraine attacks recurring during the hormone-free interval.

  10. The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

    PubMed

    Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

    2015-04-01

    Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. The cost-effectiveness of growth hormone replacement therapy (Genotropin®) in hypopituitary adults in Sweden

    PubMed Central

    2013-01-01

    Background To evaluate the cost-effectiveness of growth hormone (GH) treatment (Genotropin®) compared with no GH treatment in adults with GH deficiency in a Swedish societal setting. Methods A Markov-type cost-utility simulation model was constructed and used to simulate, for men and women, morbidity and mortality for GH-treated and -untreated individuals over a 20-year period. The calculations were performed using current available prices concerning morbidity-related healthcare costs and costs for Genotropin®. All costs and treatment effects were discounted at 3%. Costs were expressed in Euro (1€ = 9.03 SEK). GH-treated Swedish patients (n = 434) were identified from the KIMS database (Pfizer International Metabolic Database) and untreated patients (n = 2135) from the Swedish Cancer Registry and the Hospital Discharge Registry. Results The results are reported as incremental cost per quality-adjusted life year (QALY) gained, including both direct and indirect costs for GH-treated versus untreated patients. The weighted sum of all subgroup incremental cost per QALY was €15,975 and €20,241 for men and women, respectively. Including indirect cost resulted in lower cost per QALY gained: €11,173 and €10,753 for men and women, respectively. Key drivers of the results were improvement in quality of life, increased survival, and intervention cost. Conclusions The incremental cost per QALY gained is moderate when compared with informal thresholds applied in Sweden. The simulations suggest that GH-treatment is cost-effective for both men and women at the €55,371 (SEK 500,000 – the informal Swedish cost-effectiveness threshold) per QALY threshold. PMID:24079522

  12. Replacement of insulin receptor tyrosine residues 1162 and 1163 does not alter the mitogenic effect of the hormone

    SciTech Connect

    Debant, A.; Clauser, E.; Ponzio, G.; Filloux, C.; Auzan, C.; Contreres, J.O.; Rossi, B. )

    1988-11-01

    Chinese hamster ovary transfectants that express insulin receptors in which tyrosine residues 1162 and 1163 were replaced by phenylalanine exhibit a total inhibition of the insulin-mediated tyrosine kinase activity toward exogenous substrates; this latter activity is associated with total inhibition of the hypersensitivity reported for insulin in promoting 2-deoxyglucose uptake. The authors now present evidence that the twin tyrosines also control the insulin-mediated stimulation of glycogen synthesis. Surprisingly, this type of Chinese hamster ovary transfectant is as hypersensitive to insulin for its mitogenic effect as are Chinese hamster ovary cells expressing many intact insulin receptors. Such data suggest that (i) the insulin mitogenic effect routes through a different pathway than insulin uses to activate the transport and metabolism of glucose and (ii) the mitogenic effect of insulin is not controlled by the twin tyrosines. At the molecular level, the solubilized mutated receptor has not insulin-dependent tyrosine kinase activity, whereas this receptor displays measurable insulin-stimulated phosphorylation of its {beta} subunit in {sup 32}P-labeled cells. The authors therefore propose that the autocatalytic phosphorylating activity of the receptor reports a cryptic tyrosine kinase activity that cannot be visualized by the use of classical exogenous substrates.

  13. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    ClinicalTrials.gov

    2017-03-28

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  14. A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

    PubMed Central

    Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

    2012-01-01

    Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P < 0.0001) and T + NES 12 mg (88%, P = 0.0002) compared with T + NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

  15. Unicompartmental knee replacement: a comparison of four techniques combining less invasive approach and navigation.

    PubMed

    Jenny, Jean-Yves

    2008-10-01

    We developed a nonimage-guided navigation system for unicompartmental knee replacement, suitable for both conventional and minimally invasive approaches. We performed a radiologic analysis of the accuracy of implantation with conventional nonnavigated instrumentation, conventional, open navigated instrumentation, minimally invasive navigated experimental instrumentation derived from conventional instruments, and minimally invasive navigation-dedicated instrumentation. Navigated technique allowed improving the accuracy of the radiologic implantation. Minimally invasive implantation was effective, but the accuracy may not reach that of the conventional navigated technique. Minimal invasive techniques have to be validated, because a loss of accuracy will negatively influence longterm outcomes.

  16. Effects of combined hormonal contraception on health and wellbeing: women's knowledge in northern Italy.

    PubMed

    Nappi, Rossella E; Pellegrinelli, Alice; Campolo, Federica; Lanzo, Gabriele; Santamaria, Valentina; Suragna, Alessandro; Spinillo, Arsenio; Benedetto, Chiara

    2015-02-01

    We investigated levels of knowledge of the effects of combined hormonal contraceptives (CHCs) on general/reproductive health and physical/psychosexual wellbeing. A cross-sectional study was conducted in two university hospitals in northern Italy. Healthy current-, past- and never CHC users (n = 545; age 18-44 years) completed a self-administered questionnaire. Ninety-three percent of current-, 74% of past-, and 56% of never users believed they were sufficiently informed (χ(2): 67.1; p = 0.001) about the benefits and risks of CHCs. Respondents mentioned: (i) a reduced risk of ovarian (67%) and endometrial (53%) cancer; (ii) an increased risk of thrombosis (82%); (iii) an increased risk of breast cancer (45%); (iv) a decreased fertility (19%) and no influence on risk of sexually transmitted infections (48%); (v) a reduced risk of menstrual abnormalities (77%) and acne (79%); (vi) less dysmenorrhoea (83%) and more headache (56%), weight gain (74%), increased appetite (51%), leg cramps (77%), mood swings (45%), vaginal dryness (47%), and low sex drive (48%). Beliefs about diseases/conditions and symptoms were influenced by CHC use. CHC use is linked to good knowledge of risks and benefits. Our data suggest HCPs must be proactive in providing relevant information so that women can choose their contraception with a balanced insight of side effects.

  17. Knowledge-attitude-practice survey among Portuguese gynaecologists regarding combined hormonal contraceptives methods.

    PubMed

    Bombas, Teresa; Costa, Ana Rosa; Palma, Fátima; Vicente, Lisa; Sá, José Luís; Nogueira, Ana Maria; Andrade, Sofia

    2012-04-01

    ABSTRACT Objectives To evaluate knowledge, attitude and practices of Portuguese gynaecologists regarding combined hormonal contraceptives. Methods A cross-sectional survey was conducted among 303 gynaecologists. Results Ninety percent of the gynaecologists considered that deciding on contraceptive methods is a process wherein the woman has her say. Efficacy, safety and the woman's preference were the major factors influencing gynaecologists, while efficacy, tolerability and ease of use were the major factors perceived by the specialists to influence the women's choice. Gynaecologists believed that only 2% of women taking the pill were 100% compliant compared to 48% of those using the patch and 75% of those using the ring. The lower risk of omission was the strong point for the latter methods. Side effects were the main reason to change to another method. Vaginal manipulation was the most difficult topic to discuss. Conclusions Most gynaecologists decided with the woman on the contraceptive method. The main reasons for the gynaecologist's recommendation of a given contraceptive method and the women's choice were different. Counselling implies an open discussion and topics related to sexuality were considered difficult to discuss. Improving communication skills and understanding women's requirements are critical for contraceptive counselling.

  18. Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy.

    PubMed

    Wu, Fiona; Ames, Ruth; Clearwater, Judy; Evans, Margaret C; Gamble, Greg; Reid, Ian R

    2002-06-01

    To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. Prospective, observational study. One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). Bone density is highly predictable over an extended period of time in normal

  19. Combined sprint and resistance training abrogates age differences in somatotropic hormones

    PubMed Central

    Sellami, Maha; Dhahbi, Wissem; Hayes, Lawrence D.; Rhibi, Fatma; Djemail, Hanen; Chaouachi, Anis

    2017-01-01

    The aim of this investigation was to compare serum growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in response to a combined sprint and resistance training (CSRT) program in young and middle-aged men.Thirty-eight healthy, moderately trained men participated in this study. Young and middle-aged men were randomly assigned to, a young training group (YT = 10, 21.4±1.2yrs) ora young control group (YC = 9, 21.6±1.8 yrs), a middle-aged training group (MAT = 10, 40.4±2.1 yrs) or a middle-aged control group (MAC = 9, 40.5±1.8 yrs). Participants performed the Wingate Anaerobic Test (WAnT) before and after a 13-week CSRT program (three sessions per week). Blood samples were collected at rest, after warm-up, immediately post-WAnT, and 10 min post-WAnT. CSRT induced increases in GH at rest and in response to the WAnT in YT and MAT (P<0.05). CSRT-induced increases were observed for IGF-1 and IGFBP-3 at rest in MAT only (P<0.05). Pre-training, GH, IGF-1 and IGFBP-3 were significantly higher at rest and in response to the WAnT in young participants as compared to their middle-aged counterparts (P<0.05). Post-training, YT and MAT had comparable basal GH (P>0.05). In response to the WAnT, amelioration of the age-effect was observed between YT and MAT for IGF-1 and IGF-1/IGFBP-3 ratio following CSRT (P>0.05). These data suggest that CSRT increases the activity of the GH/IGF-1 axis at rest and in response to the WAnT in young and middle-aged men. In addition, CSRT reduces the normal age-related decline of somatotropic hormones in middle-age men. PMID:28800636

  20. The state of hormonal contraception today: benefits and risks of hormonal contraceptives: combined estrogen and progestin contraceptives.

    PubMed

    Shulman, Lee P

    2011-10-01

    Discussion of effective birth control methods can be a challenging process for clinicians because the adoption and consistent use of contraception may be influenced by patients' fears, myths, and misperceptions. Over the years, new progestins have been included in combination contraceptives or are used alone to provide effective contraception as well as to decrease androgenic side effects and ameliorate the symptoms of premenstrual dysphoric disorder. Alternative delivery systems and regimens have also been introduced to improve tolerability and continuance and convenience of use. This is a review of estrogen and progestin combinations and their effects.

  1. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the

  2. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Kook, A I; Monje, E; Redding, T W; Paz-Bouza, J I

    1986-01-01

    The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these

  3. Combined heat shock protein 90 and ribosomal RNA sequence phylogeny supports multiple replacements of dinoflagellate plastids.

    PubMed

    Shalchian-Tabrizi, Kamran; Minge, Marianne A; Cavalier-Smith, Tom; Nedreklepp, Joachim M; Klaveness, Dag; Jakobsen, Kjetill S

    2006-01-01

    Dinoflagellates harbour diverse plastids obtained from several algal groups, including haptophytes, diatoms, cryptophytes, and prasinophytes. Their major plastid type with the accessory pigment peridinin is found in the vast majority of photosynthetic species. Some species of dinoflagellates have other aberrantly pigmented plastids. We sequenced the nuclear small subunit (SSU) ribosomal RNA (rRNA) gene of the "green" dinoflagellate Gymnodinium chlorophorum and show that it is sister to Lepidodinium viride, indicating that their common ancestor obtained the prasinophyte (or other green alga) plastid in one event. As the placement of dinoflagellate species that acquired green algal or haptophyte plastids is unclear from small and large subunit (LSU) rRNA trees, we tested the usefulness of the heat shock protein (Hsp) 90 gene for dinoflagellate phylogeny by sequencing it from four species with aberrant plastids (G. chlorophorum, Karlodinium micrum, Karenia brevis, and Karenia mikimotoi) plus Alexandrium tamarense, and constructing phylogenetic trees for Hsp90 and rRNAs, separately and together. Analyses of the Hsp90 and concatenated data suggest an ancestral origin of the peridinin-containing plastid, and two independent replacements of the peridinin plastid soon after the early radiation of the dinoflagellates. Thus, the Hsp90 gene seems to be a promising phylogenetic marker for dinoflagellate phylogeny.

  4. Patient selection for transcatheter aortic valve replacement: A combined clinical and multimodality imaging approach

    PubMed Central

    Cocchia, Rosangela; D’Andrea, Antonello; Conte, Marianna; Cavallaro, Massimo; Riegler, Lucia; Citro, Rodolfo; Sirignano, Cesare; Imbriaco, Massimo; Cappelli, Maurizio; Gregorio, Giovanni; Calabrò, Raffaele; Bossone, Eduardo

    2017-01-01

    Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview on TAVR clinical and technical aspects essential for adequate selection. PMID:28400918

  5. Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

    PubMed

    Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

    2016-10-01

    This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

  6. Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

    PubMed

    Behre, Hermann M; Zitzmann, Michael; Anderson, Richard A; Handelsman, David J; Lestari, Silvia W; McLachlan, Robert I; Meriggiola, M Cristina; Misro, Man Mohan; Noe, Gabriela; Wu, Frederick C W; Festin, Mario Philip R; Habib, Ndema A; Vogelsong, Kirsten M; Callahan, Marianne M; Linton, Kim A; Colvard, Doug S

    2016-12-01

    The development of a safe and effective reversible method of male contraception is still an unmet need. Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Prospective multicentre study. Ten study centers. Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

  7. Effects of Botanicals and Combined Hormone Therapy on Cognition in Postmenopausal Women

    PubMed Central

    Maki, Pauline M.; Rubin, Leah H.; Fornelli, Deanne; Drogos, Lauren; Banuvar, Suzanne; Shulman, Lee P.; Geller, Stacie E.

    2009-01-01

    Objective To characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. Design In a Phase II randomized, double-blind, placebo-controlled study, 66 midlife women (out of 89 from a parent study; mean age=53 y) with ≥ 35 weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), CEE/MPA (0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. Results There was no impact of either of the botanical treatments on any cognitive measure. Compared to placebo, CEE/MPA led to greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (p=0.057) in unadjusted analyses, but reached significance (p=.02) after adjusting for vasomotor symptoms. Neither botanical treatment group showed a change in verbal memory that differed from the placebo group (ps>0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. Conclusions Results indicate no effects of a red clover (phytoestrogen) supplement or black cohosh on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory. PMID:19590458

  8. Bumblebees can be used in combination with juvenile hormone analogues and ecdysone agonists.

    PubMed

    Mommaerts, Veerle; Sterk, Guido; Smagghe, Guy

    2006-08-01

    This study examined the lethal and sublethal effects on the beneficial insect Bombus terrestris by two classes of insect growth regulators (IGRs) that are commercially used in agriculture to control pest insects. Three juvenile hormones analogues (JHAs) (pyriproxyfen, fenoxycarb and kinoprene) and two ecdysone agonists or moulting accelerating compounds (MACs) (tebufenozide and methoxyfenozide) were tested. The bumblebee workers were exposed to the insecticides via three different routes of exposure: dermally by topical contact, and orally via the drinking sugar water or the pollen. In the first series of experiments the IGRs were applied at their respective maximum field recommended concentration (MFRC). These risk hazard tests showed that the tested IGRs caused no acute toxicity on the workers, and any compound had an adverse effect on reproduction (production of males). In addition, larval development was followed in the treated nests compared with the controls. After application of the two MACs and the JHA fenoxycarb no adverse effects were observed on larval development. However, in the nests where the workers were exposed to the JHAs pyriproxyfen and kinoprene higher numbers of dead larvae were scored. These larvae were third and fourth instars, implying a lethal blockage of development before metamorphosis. In a second test, a series of dilutions was made for kinoprene, and these results revealed that only the MFRC caused a toxic effect on the larval development. On the other hand, kinoprene at lower concentrations (0.0650 mg ai/l) had a stimulatory effect on brood production. It was remarkable that ovaries of such treated dominant workers were longer and contained more eggs than in the controls. In a last experiment, the cuticular uptake was determined for a JHA and MAC to evaluate to what extent worker bees accumulate these classes of IGRs. Cuticular uptake ranged from 34 to 83% at 24 h after topical application. Overall, the obtained results indicate that

  9. Combination of Alpha-Melanocyte Stimulating Hormone with Conventional Antibiotics against Methicillin Resistant Staphylococcus aureus

    PubMed Central

    Singh, Madhuri; Gadepalli, Ravisekhar; Dhawan, Benu; Mukhopadhyay, Kasturi

    2013-01-01

    Our previous studies revealed that alpha-melanocyte stimulating hormone (α-MSH) is strongly active against Staphylococcus aureus (S. aureus) including methicillin resistant S. aureus (MRSA). Killing due to α-MSH occurred by perturbation of the bacterial membrane. In the present study, we investigated the in vitro synergistic potential of α-MSH with five selected conventional antibiotics viz., oxacillin (OX), ciprofloxacin (CF), tetracycline (TC), gentamicin (GM) and rifampicin (RF) against a clinical MRSA strain which carried a type III staphylococcal cassette chromosome mec (SCCmec) element and belonged to the sequence type (ST) 239. The strain was found to be highly resistant to OX (minimum inhibitory concentration (MIC) = 1024 µg/ml) as well as to other selected antimicrobial agents including α-MSH. The possibility of the existence of intracellular target sites of α-MSH was evaluated by examining the DNA, RNA and protein synthesis pathways. We observed a synergistic potential of α-MSH with GM, CF and TC. Remarkably, the supplementation of α-MSH with GM, CF and TC resulted in ≥64-, 8- and 4-fold reductions in their minimum bactericidal concentrations (MBCs), respectively. Apart from membrane perturbation, in this study we found that α-MSH inhibited ∼53% and ∼47% DNA and protein synthesis, respectively, but not RNA synthesis. Thus, the mechanistic analogy between α-MSH and CF or GM or TC appears to be the reason for the observed synergy between them. In contrast, α-MSH did not act synergistically with RF which may be due to its inability to inhibit RNA synthesis (<10%). Nevertheless, the combination of α-MSH with RF and OX showed an enhanced killing by ∼45% and ∼70%, respectively, perhaps due to the membrane disrupting properties of α-MSH. The synergistic activity of α-MSH with antibiotics is encouraging, and promises to restore the lost potency of discarded antibiotics. PMID:24040081

  10. [Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

    PubMed

    Péter, Ferenc; Muzsnai, Agota

    2013-05-12

    Bevezetés: Igazolt hypothyreosisban a hormonpótlás általánosan l-tiroxinnal történik. Az utóbbi években egyre több közlemény veti fel az l-trijód-tironin-kiegészítés esetenkénti szükségességét szerzett hypothyreosisban. Cél: Kombinált l-tiroxin- és l-trijód-tironin-kezelés szerepének tanulmányozása hypothyreosis congenitalis formájának egyes eseteiben. Módszer: A szerzők 16 beteg (életkor: 11,9±6,3 év) adatait dolgozták fel, akiknél a referenciatartomány felső határa körüli vagy azt meghaladó szérumszabadtiroxin-szintek (21,16±2,5 pmol/l) ellenére tartósan magas szérum-TSH-értéket találtak (15,7±5,7 mIU/l) és ezért napi egyszeri l-trijód-tironin- (0,18±0,09 μg/kg) kiegészítést kaptak. Eredmények: A két hormon együttes adása a paraméterek gyors javulását okozta (TSH: 4,2±3,15 mIU/l, szabad tiroxin: 16,55±2,4, trijód-tironin: 7,4±1,8 pmol/l). Az eredményesség 10, tartósan kezelt beteg (kezelési időtartam: 2,9±2,0 év) esetében még kifejezettebb volt (TSH: 4,33±3,2 mIU/l, szabad tiroxin: 16,85±3,1, trijód-tironin: 6,4±0,85 pmol/l). Napi l-tiroxin-adagjuk 2,6±0,9 μg/kg-ról 2,18±0,6 μg/kg-ra csökkent, a két hormon aránya 5:1 és 19:1 között volt, szabad frakcióik hányadosa pedig 3,8±0,4-ről 2,6±0,3-re normalizálódott az l-trijód-tironin-kezelés alatt. Következtetések: A szerzők megfigyelése szerint újszülöttkortól hormonpótlásra szoruló hypothyreoticus gyermekekben előfordul (>5%), hogy éveken át működő feed-back mechanizmusuk súlyos zavara alakul ki, ami magas tiroxinszint mellett sem szupprimálódó, fokozott TSH-elválasztásban nyilvánul meg. A bemutatott betegek hormonparaméterei a kombinált kezelés hatására javultak, majd rendeződtek. A szerzők adatai azok felfogását támogatják, akik szerint hypothyreosis egyes eseteiben szükség lehet az l-tiroxin-pótlás kiegészítésére l-trijód-tironinnal. Orv. Hetil., 2013, 154, 738–744.

  11. Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

    PubMed

    Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

    2015-08-01

    Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

  12. Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

    PubMed

    Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N

    2016-01-01

    The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

  13. Ceramide--antiestrogen nanoliposomal combinations--novel impact of hormonal therapy in hormone-insensitive breast cancer.

    PubMed

    Morad, Samy A F; Levin, Jonathan C; Shanmugavelandy, Sriram S; Kester, Mark; Fabrias, Gemma; Bedia, Carmen; Cabot, Myles C

    2012-11-01

    Although the sphingolipid ceramide exhibits potent tumor suppressor effects, efforts to harness this have been hampered by poor solubility, uptake, bioavailability, and metabolic conversion. Therefore, identification of avenues to improve efficacy is necessary for development of ceramide-based therapies. In this study, we used mutant p53, triple-negative breast cancer (TNBC) cells, a type of breast cancer highly refractory to treatment, and cell-permeable nanoliposomal C6-ceramide in conjunction with the antiestrogen tamoxifen, which has been shown to be an effective modulator of ceramide metabolism. We show for the first time that nanoliposomal tamoxifen enhances nanoliposomal C6-ceramide cytotoxicity in cultured TNBC cells, a response that was accompanied by induction of cell-cycle arrest at G(1) and G(2), caspase-dependent induction of DNA fragmentation, and enhanced mitochondrial and lysosomal membrane permeability at 18 and 2 hours, respectively. Tamoxifen metabolites were also effective. Only tamoxifen promoted lysosomal membrane permeability. In addition, we show for the first time that tamoxifen inhibits acid ceramidase, as measured in intact cell assays; this effect was irreversible. Together, our findings show that tamoxifen magnifies the antiproliferative effects of C6-ceramide via combined targeting of cell-cycle traverse and lysosomal and mitochondrial integrity. We adduce that C6-ceramide-induced apoptosis is amplified by tamoxifen's impact on lysosomes and perhaps accompanying inhibition of acid ceramidase, which could result in decreased levels of sphingosine 1-phosphate. This drug regimen could serve as a promising therapy for chemoresistant and triple-negative types of breast cancer, and thus represents an indication for tamoxifen, irrespective of estrogen receptor status. ©2012 AACR.

  14. Ceramide-antiestrogen nanoliposomal combinations – novel impact of hormonal therapy in hormone-insensitive breast cancer

    PubMed Central

    Morad, Samy A.F.; Levin, Jonathan; Shanmugavelandy, Sriram S.; Kester, Mark; Fabrias, Gemma; Bedia, Carmen; Cabot, Myles C.

    2012-01-01

    Although the sphingolipid ceramide exhibits potent tumor suppressor effects, efforts to harness this have been hampered by poor solubility, uptake, bioavailability, and metabolic conversion. Therefore, identification of avenues to improve efficacy is necessary for development of ceramide-based therapies. In this study we used mutant p53, triple negative breast cancer (TNBC) cells, a type of breast cancer highly refractory to treatment, and cell-permeable nanoliposomal C6-ceramide in conjunction with the antiestrogen tamoxifen, which has been shown to be an effective modulator of ceramide metabolism. We show for the first time that nanoliposomal tamoxifen enhances nanoliposomal C6-ceramide cytotoxicity in cultured TNBC cells, a response that was accompanied by induction of cell cycle arrest at G1 and G2, caspase-dependent induction of DNA fragmentation, and enhanced mitochondrial and lysosomal membrane permeability, at 18 and 2 hr, respectively. Tamoxifen metabolites were also effective. Only tamoxifen promoted lysosomal membrane permeability. In addition, we demonstrate for the first time that tamoxifen inhibits acid ceramidase, as measured in intact cell assays; this effect was irreversible. Together, our findings show that tamoxifen magnifies the antiproliferative effects of C6-ceramide via combined targeting of cell cycle traverse and lysosomal and mitochondrial integrity. We adduce that C6-ceramide-induced apoptosis is amplified by tamoxifen's impact on lysosomes and perhaps accompanying inhibition of acid ceramidase, which could result in decreased levels of sphingosine 1-phosphate. This drug regimen could serve as a promising therapy for chemoresistant and triple negative types of breast cancer, and thus represents an indication for tamoxifen, irrespective of estrogen receptor status. PMID:22962326

  15. Combined coronary artery bypass grafting and aortic valve replacement with minimal extracorporeal closed circuit circulation versus standard cardiopulmonary bypass.

    PubMed

    Yilmaz, Alaadin; Sjatskig, Jelena; van Boven, Wim J; Waanders, Frans G; Kelder, Johannes C; Sonker, Uday; Kloppenburg, Geoffrey T L

    2010-12-01

    Isolated aortic valve replacement (AVR) or coronary artery bypass grafting (CABG) using minimized extracorporeal circulation (MECC) has been shown to have less deleterious effects than standard cardiopulmonary bypass (CPB). In this prospective cohort study, we evaluated and compared clinical results of combined AVR with CABG using MECC. We prospectively collected preoperative, intraoperative, postoperative and follow-up data of 65 patients who underwent combined AVR with CABG using MECC and compared these with 135 patients undergoing combined AVR with CABG using standard CPB. No significant differences were seen in patients demographic characteristics or intraoperative data. Patients in the MECC group experienced a smaller preoperative haemoglobin drop (4.5±0.8 g/dl vs. 5.0±0.5 g/dl, P=0.002) resulting in higher haemoglobin at discharge (11.3±1.3 g/dl vs. 10.8±1.1 g/dl, P=0.03). They had decreased blood products requirements (P=0.004) compared to patients in the standard CPB group. No differences were noted in pulmonary complications, neurological events or mortality. We present for the first time data showing that combined AVR with CABG using MECC is feasible and provides better clinical results compared to standard CPB with regard to blood products requirements, without compromising operative morbidity or mortality.

  16. Effect of growth hormone, hyperbaric oxygen and combined therapy on the gastric serosa

    PubMed Central

    Adas, Gokhan; Adas, Mine; Arikan, Soykan; Sarvan, Ahu Kemik; Toklu, Akin Savas; Mert, Selva; Barut, Gul; Kamali, Sedat; Koc, Bora; Tutal, Firat

    2013-01-01

    AIM: To investigate the role of growth hormone (GH), hyperbaric oxygen therapy (HBOT) and combined therapy on the intestinal neomucosa formation of the gastric serosa. METHODS: Forty-eight male Wistar-albino rats, weighing 250-280 g, were used in this study. The rats were divided into four groups (n = 12): Group 1, control, gastric serosal patch; Group 2, gastric serosal patch + GH; Group 3, gastric serosal patch + HBOT; and Group 4, gastric serosal patch + GH + HBOT. Abdominal access was achieved through a midline incision, and after the 1-cm-long defect was created in the jejunum, a 1 cm × 1 cm patch of the gastric corpus was anastomosed to the jejunal defect. Venous blood samples were taken to determine the insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) basal levels. HBOT was performed in Groups 3 and 4. In Groups 2 and 4, human GH was given subcutaneously at a dose of 2 mg per kg/d for 28 d, beginning on the operation day. All animals were sacrificed 60 d after surgery. The jejunal segment and the gastric anastomotic area were excised for histological examination. The inflammatory process, granulation, collagen deposition and fibroblast activity at the neomucosa formation were studied and scored. Additionally, the villus density, villus height, and crypt depth were counted and recorded. The measurements of villus height and crypt depth were calculated with an ocular micrometer. New vessel growth was determined by calculatingeach new vessel in a 1 mm2 area. RESULTS: In the histological comparison of groups, no significant differences were observed between the control group and Groups 2 and 3 with respect to epithelialization, granulation, fibroblastic activity and the inflammatory process, but significant differences were present between the control group and all others groups (Groups 2-4) with respect to angiogenesis (P < 0.01) and collagen deposition (P < 0.05, P < 0.01). Significant differences between the

  17. An unusual combination of Klinefelter syndrome and growth hormone deficiency in a prepubertal child.

    PubMed

    Ramesh, Jayanthy; Nagasatyavani, Mudiganti; Venkateswarlu, Javvadii; Nagender, Jakka

    2014-09-01

    Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in males. It is very difficult to diagnose this disorder in childhood due to absence of significant manifestations before puberty. These patients usually present with tall stature. We report a case of KS with short stature due to growth hormone deficiency. The boy's height was below the 3rd centile with significant delay in bone age. He responded well to growth hormone injections. In view of mental subnormality karyotyping was done, which revealed KS (47XXY).

  18. Psychological and clinical factors implicated in decision making about a trial of low-dose tamoxifen in hormone replacement therapy users.

    PubMed

    Rondanina, Gabriella; Puntoni, Matteo; Severi, Gianluca; Varricchio, Clara; Zunino, Anna; Feroce, Irene; Bonanni, Bernardo; Decensi, Andrea

    2008-03-20

    To assess the sociodemographic, health-related, and psychological factors that influence the decision of women on hormone replacement therapy (HRT) to participate in a phase III trial of low-dose tamoxifen. Clinical and psychological factors were assessed in 265 women who accepted and 192 women who refused to participate in a proposed trial. Health-related and sociodemographic factors included age, Gail risk, body mass index, education, current HRT use, regular mammographic screening, smoking habit, physical activity, alcohol use, concern about adverse effects, and physician recommendation. Psychological factors included breast cancer-related worry, absolute and comparative cancer risk perception, anxiety, and depression. The most frequent reasons for entry were willingness to participate in a research program (60%), the need/desire to receive frequent medical care (58%), and the desire to contribute to medical knowledge (44%); whereas reasons for refusal included fear of medication abuse (33%), concern about adverse effects (31%), and physician advice against enrollment (24%). In a logistic model, after adjusting for current HRT use, the trial participation was directly associated with satisfaction with clearly explained study objectives (odds ratio [OR] = 9.33; 95% CI, 4.04 to 21.55) and inversely associated with high breast cancer worry (OR = 0.15; 95% CI, 0.03 to 0.77) and age > or = 60 years (OR = 0.40; 95% CI, 0.22 to 0.73). Participation in a chemoprevention trial among HRT users is associated with a younger age, no breast cancer worry, and satisfaction with health care providers, suggesting a condition of psychological well-being as a promoting factor and emphasizing the importance of thorough counseling at study presentation.

  19. Media coverage of women's health issues: is there a bias in the reporting of an association between hormone replacement therapy and breast cancer?

    PubMed

    Whiteman, M K; Cui, Y; Flaws, J A; Langenberg, P; Bush, T L

    2001-01-01

    Media coverage of scientific research plays a major role in shaping public opinion and influencing medical practice. When an association is controversial, such as with hormone replacement therapy (HRT) and breast cancer, it is important that a balanced picture of the scientific literature be reported. The objective of this study was to assess whether scientific publications that do and do not support an HRT/breast cancer association were cited in the media in proportions similar to those with which they appear in the scientific literature. Scientific publications reporting on the HRT/breast cancer association published from January 1, 1995, to June 30, 2000, were identified through a systematic Medline search. Media reports from newspapers, magazines, television, and radio that reported on HRT and breast cancer were retrieved from an online database. Investigators independently recorded characteristics of the scientific publications and media reports. A total of 32 scientific publications were identified: 20 (62.5%) concluded there was an increased risk of breast cancer associated with HRT (positive publications), and 12 (37.5%) concluded there was no evidence for an association (null publications). Nearly half (47%) of the scientific publications were not cited by the media. There were 203 media citations of scientific publications: 82% were of positive publications and 18% were of null publications, representing a significant excess of citations of positive publications (p < 0.01). Media coverage of this controversial issue is based on a limited sample of the scientific publications. Moreover, the excess of media citations for positive scientific publications suggests a bias against null scientific publications.

  20. Cost-effectiveness of hormone replacement therapy for fracture prevention in young postmenopausal women: an economic analysis based on a prospective cohort study.

    PubMed

    Fleurence, R; Torgerson, D J; Reid, D M

    2002-08-01

    A recent systematic review of randomized controlled trials has shown that hormone replacement therapy (HRT) prevents fractures when taken soon after the menopause. HRT for treatment of menopausal symptoms is relatively cost-effective, but whether its use for prevention of perimenopausal fractures is economically efficient is unknown. We undertook a 6-year follow-up of 3645 perimenopausal women who had a bone mineral density (BMD) measurement with recommendation to use HRT if low BMD was present. Data were collected on incident fractures and costs. After an average of 6.2 years of follow-up HRT use significantly reduced incident fractures by 52% (95% CI: 67% to 18%). However, costs were increased by an average of pounds sterling 275 (95% CI: pounds sterling 228 to pounds sterling 330) for the group as a whole; for hysterectomized women costs were increased less (pounds sterling 138), but this was still significantly greater than for non-HRT users (95% CI: pounds sterling 6 to pounds sterling 275). The cost per averted fracture was about pounds sterling 11 000 (95% CI: pounds sterling 8625 to pounds sterling 13 872) for the whole group and for hysterectomized women the corresponding figure was substantially less (pounds sterling 1784; 95% CI: pounds sterling 59 to pounds sterling 3532). HRT given to women at or shortly after the menopause is therefore associated with a halving of fracture incidence. Such a policy for hysterectomized women without menopausal symptoms may be cost-effective as such women are at elevated risk of fracture and need cheaper, unopposed, estrogens.

  1. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

    PubMed

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

    2017-03-01

    Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Peripheral quantitative computed tomography (pQCT) is useful for monitoring bone mineral density of the patients who receive hormone replacement therapy.

    PubMed

    Sawada, Kenjiro; Morishige, Ken-Ichirou; Ohmichi, Masahide; Nishio, Yukihiro; Yamamoto, Toshiya; Hayakawa, Jun; Mabuchi, Seiji; Isobe, Aki; Sasaki, Hiroshi; Sakata, Masahiro; Tasaka, Keiichi; Murata, Yuji

    2007-04-20

    A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.

  3. Association of the Joint Effect of Menopause and Hormone Replacement Therapy and Cancer in African American Women: The Jackson Heart Study

    PubMed Central

    Campbell Jenkins, Brenda W.; Addison, Clifton; Wilson, Gregory; Liu, Jiankang; Fortune, Melody; Robinson, Kiana; White, Monique; Sarpong, Daniel

    2011-01-01

    Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p < 0.0001), but not HRT (p = 0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases. PMID:21776241

  4. Association of the joint effect of menopause and hormone replacement therapy and cancer in African American women: the Jackson Heart Study.

    PubMed

    Campbell Jenkins, Brenda W; Addison, Clifton; Wilson, Gregory; Liu, Jiankang; Fortune, Melody; Robinson, Kiana; White, Monique; Sarpong, Daniel

    2011-06-01

    Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p<0.0001), but not HRT (p=0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases.

  5. Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass.

    PubMed

    Bahl, Aileen; Pöllänen, Eija; Ismail, Khadeeja; Sipilä, Sarianna; Mikkola, Tuija M; Berglund, Eva; Lindqvist, Carl Mårten; Syvänen, Ann-Christine; Rantanen, Taina; Kaprio, Jaakko; Kovanen, Vuokko; Ollikainen, Miina

    2015-12-01

    The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

  6. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

    PubMed

    Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

    2017-03-09

    A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10(6) hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4(th) week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that

  7. Separate and Combined Effects of Very Low Nicotine Cigarettes and Nicotine Replacement in Smokers with Schizophrenia and Controls

    PubMed Central

    Rohsenow, Damaris J.; Kaplan, Gary B.; Swift, Robert M.; AhnAllen, Christopher G.

    2013-01-01

    Introduction: The prevalence of smoking among people with schizophrenia in the United States is about 3 times that of the general population. Novel approaches are needed to reduce rates of smoking-related morbidity and mortality among these smokers. Methods: This study used a within-subjects design to investigate the separate and combined effects of sensorimotor replacement for smoking (very low nicotine content [VLNC] cigarettes vs. no cigarettes) and transdermal nicotine replacement (42 mg nicotine [NIC] vs. placebo [PLA] patches) in smokers with schizophrenia (SS; n = 30) and control smokers without psychiatric illness (CS; n = 26). Each session contained a 5-hr controlled administration period in which participants underwent the following conditions, in counterbalanced order: VLNC + NIC, VLNC + PLA, no cigarettes + NIC, no cigarettes + PLA, usual-brand cigarettes + no patches. Next, participants completed measures of cigarette craving, nicotine withdrawal, smoking habit withdrawal, and cigarette subjective effects, followed by a 90-min period of ad libitum usual-brand smoking. Results: Smoking VLNC cigarettes during the controlled administration periods reduced cigarette craving, nicotine withdrawal symptoms, habit withdrawal symptoms, and usual-brand smoking in SS and CS relative to the no cigarette conditions. VLNC cigarettes were well accepted by both groups and did not affect psychiatric symptom levels in SS. Transdermal nicotine significantly reduced cigarette craving but did not affect usual-brand smoking. Conclusions: These findings suggest that reducing the nicotine content of cigarettes to nonaddictive levels may be a promising approach for reducing nicotine dependence among people with schizophrenia. PMID:22517190

  8. Noncontraceptive use of oral combined hormonal contraceptives in polycystic ovary syndrome-risks versus benefits.

    PubMed

    Dokras, Anuja

    2016-12-01

    The use of steroid sex hormones for noncontraceptive benefits has been endorsed by several medical societies. In women with polycystic ovary syndrome (PCOS), hormonal contraceptives are first-line therapy for concurrent treatment of menstrual irregularity, acne, and hirsutism. The association of PCOS with obesity, diabetes, and dyslipidemia frequently brings up the debate regarding risks versus benefits of hormonal contraceptives in this population. In women with PCOS, the lack of large-scale studies evaluating the risks with varying doses of ethinyl estradiol, types of progestins, and presence of confounding factors such as obesity, smoking, and other cardiometabolic comorbidities is a significant limitation in these deliberations. Although it is important to assess the absolute risk for major morbidities including cardiovascular events, currently, there are a paucity of long-term data for these outcomes in PCOS. Most of the current studies do not suggest an increase in risk of prediabetes/diabetes, clinically significant dyslipidemia, inflammatory changes, or depressive/anxiety symptoms with oral contraceptive pill use. Screening of women with PCOS for cardiometabolic and psychiatric comorbidities is routinely recommended. This information should be used by health care providers to individualize the choice of hormonal contraceptive treatment, adequately counsel patients regarding risks and benefits, and formulate an appropriate follow-up plan.

  9. Value of combined cross sectional and Doppler echocardiography in the detection of left ventricular pseudoaneurysm after mitral valve replacement.

    PubMed Central

    Kupari, M; Verkkala, K; Maamies, T; Härtel, G

    1987-01-01

    The development of a left ventricular pseudoaneurysm is a rare complication of heart surgery. Until recently it has been impossible to detect without an angiographic study of the left ventricle. A combination of cross sectional and Doppler ultrasound studies led to the correct diagnosis in two patients with left ventricular pseudoaneurysms after mitral valve replacement. Cross sectional echocardiography showed a posterolateral echo-free space confined only by the pericardium and communicating with the left ventricle through a defect in the ventricular wall, and Doppler echocardiography confirmed the presence of blood flow in this cavity. This Doppler finding is critical if the perforation is too small to be identified reliably by cross sectional imaging. Surgical repair of the pseudoaneurysm can be undertaken without invasive studies if the echocardiographic findings are unequivocal and there is no reason to suspect the integrity of the circumflex coronary artery. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:3620242

  10. Successful treatment of Listeria monocytogenes prosthetic valve endocarditis using rifampicin and benzylpenicillin in combination with valve replacement

    PubMed Central

    Chik, William; Chen, Sharon; Kok, Jen

    2017-01-01

    Introduction. Listeria monocytogenes is an uncommon cause of prosthetic valve endocarditis (PVE). Recommended antimicrobial therapy typically includes intravenous β-lactams with or without synergistic aminoglycosides. In vitro studies have previously identified antagonism when rifampicin has been used in combination with β-lactams. However, in vivo data of rifampicin use are limited despite its enhanced anti-biofilm activity. Case presentation. A 63-year-old male presented with fever and back pain. L. monocytogenes bacteraemia and bioprosthetic aortic valve endocarditis was confirmed, along with spinal discitis and osteomyelitis. He was successfully treated with benzylpenicillin and rifampicin, in conjunction with valve replacement. Conclusion. Rifampicin remains an alternate agent to use, when there are contraindications to traditional aminoglycoside therapy. Further data on rifampicin use in L. monocytogenes PVE are awaited. PMID:28348807

  11. A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

    PubMed

    Januszkiewicz, A; Essén, P; McNurlan, M A; Ringdén, O; Garlick, P J; Wernerman, J

    2001-11-01

    In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

  12. Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

    PubMed Central

    Schirra, Horst Joachim; Anderson, Cameron G.; Wilson, William J.; Kerr, Linda; Craik, David J.; Waters, Michael J.; Lichanska, Agnieszka M.

    2008-01-01

    Background Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. Methodology/Principal Findings The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. Conclusions/Significance The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone receptor, and

  13. Independent and combined effects of eating rate and energy density on energy intake, appetite, and gut hormones.

    PubMed

    Karl, J Philip; Young, Andrew J; Rood, Jennifer C; Montain, Scott J

    2013-03-01

    Energy density (ED) and eating rate (ER) influence energy intake; their combined effects on intake and on postprandial pancreatic and gut hormone responses are undetermined. To determine the combined effects of ED and ER manipulation on voluntary food intake, subjective appetite, and postprandial pancreatic and gut hormone responses. Twenty nonobese volunteers each consumed high (1.6 kcal g(-1) ; HED) and low (1.2 kcal g(-1) ; LED) ED breakfasts slowly (20 g min(-1) ; SR) and quickly (80 g min(-1) ; FR) ad libitum to satiation. Appetite, and pancreatic and gut hormone concentrations were measured periodically over 3 h. Ad libitum energy intake during the subsequent lunch was then measured. Main effects of ED and ER on energy intake and a main effect of ER, but not ED, on mass of food consumed were observed, FR and HED being associated with increased intake (P < 0.05). Across all conditions, energy intake was highest during FR-HED (P ≤ 0.01). Area under the curve (AUC) of appetite ratings was not different between meals. Main effects of ED and ER on insulin, peptide-YY, and glucagon-like peptide-1 AUC (P < 0.05) were observed, FR and HED being associated with larger AUC. No effects on active or total ghrelin AUC were documented. Total energy intake over both meals was highest during the FR-HED trial with the greatest difference between FR-HED and SR-LED trials (P ≤ 0.01). Consuming an energy dense meal quickly compounds independent effects of ER and ED on energy intake. Energy compensation at the following meal may not occur despite altered gut hormone responses. Copyright © 2013 The Obesity Society.

  14. Acute Hormonal and Force Responses to Combined Strength and Endurance Loadings in Men and Women: The “Order Effect”

    PubMed Central

    S. Taipale, Ritva; Häkkinen, Keijo

    2013-01-01

    Purpose To examine acute responses and recovery of serum hormones and muscle force following combined strength (S) and endurance (E) loading sessions in which the order of exercises is reversed (ES vs. SE). Methods This cross-over study design included recreationally endurance trained men and women (age 21–45 years, n = 12 men n = 10 women) who performed both loadings. Maximal bilateral isometric strength (MVC), isometric rate of force development (RFD) and serum concentrations of testosterone (T), cortisol (C), growth hormone (GH), insulin-like growth factor 1 (IGF-1), binding protein 3 (IGFBP3) and sex hormone binding globulin (SHBG) were measured during and after both loadings. Results Both of the present combined (ES and SE) loadings led to a greater acute decrease in MVC in men than in women, while RFD was slightly affected only in men. Recovery of MVC and RFD to baseline was complete at 24 h regardless of the order of exercises. In men, neuromuscular fatigue was accompanied by increased C concentrations observed post SE. This was followed by decreased concentrations of T at 24 h and 48 h that were significantly lower than those observed following ES. GH response in men also differed significantly post loadings. In women, only a significant difference in T between ES and SE loadings was observed at post. Conclusion These observed differences in hormonal responses despite similarities in neuromuscular fatigue in men indicate the presence of an order effect as the body was not fully recovered at 48 h following SE. These findings may be applicable in training prescription in order to optimize specific training adaptations. PMID:23408956

  15. [The influence of hormonal replacement therapy on bone density in postmenopausal women depending on polymorphism of vitamin D receptor (VDR) and estrogen receptor (ER) genes].

    PubMed

    Brodowska, Agnieszka

    2003-01-01

    genes? 3. What estrogen concentration is necessary to protect bone tissue depending on the polymorphism of VDR and ER genes? The study group included 44 postmenopausal women aged 44-75 years with primary osteoporosis on cyclic HRT (hormonal replacement therapy). Two hormonal preparations were administered: Systen 50 (Jansen Cilag) transdermal system twice per week between day 1 and 21 of the cycle; Provera (Upjohn) 5 mg tablets daily between day 16 and 27 of the cycle. This therapy was supplemented with vitamin D analogue (Alphacalcidolum, Glaxo-Poznan) orally at 0.25 microg per day, calcium-enriched (1200 mg daily) diet and regular physical exercise. Patients were qualified to the study on the basis of a questionnaire. Women with secondary osteoporosis were excluded. TSH, FT3, and FT4 concentrations, as well as fasting glucose were measured. 24 h glycemia was established in women with elevated glucose levels. Polymorphism of the ER gene was studied with Xba I and Pvu II restrictases. Polymorphism of the VDR gene was studied with Bsm I restrictase. Age and BMI were recorded. Spine BMD was determined with DEXA (Dual Energy X-ray Absorptiometry (Lunar instrument) before treatment and after 12 months of HRT. Serum estradiol concentrations were measured before treatment and after 2 months of HTR. The following conclusions were drawn: 1. There is no connection between VDR and ER gene polymorphism and degree of osteoporosis before treatment. 2. XX, PP and Bb markers or X, P, B alleles are associated with a significant decrease in therapeutic efficacy. Nevertheless, satisfactory results were achieved in each woman with primary osteoporosis. 3. Estradiol concentration in serum before and during HRT does not depend on the polymorphism of VDR and ER genes.

  16. Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients.

    PubMed

    Lombardi, Celestino Pio; Bocale, Raffaella; Barini, Angelina; Barini, Antonella; D'Amore, Annamaria; Boscherini, Mauro; Bellantone, Rocco

    2017-01-01

    Following thyroid surgery, levothyroxine therapy is used to replace deficient thyroid hormones and prevent postoperative thyroid hypofunction. We compared the effects of replacement therapy with either liquid or tablet formulation of levothyroxine on mood states, self-perceived mental well-being and thyroid hormone profile in recently thyroidectomized patients. Profile of mood states, General Heath Questionnaire 12-items and thyroid hormone profile were assessed in recently (5-7 days) thyroidectomized patients at baseline and 2 months after randomization to replacement therapy with either liquid (n = 77) or tablet (n = 78) formulation of levothyroxine. After 2 months under levothyroxine replacement treatment, significant improvements of Positive Affect Scale (p < 0.001) and Negative Affect Scale (p < 0.001) of Profile of mood states, as well as of General Heath Questionnaire 12-items (p < 0.001) were observed in the study population. However, there were greater variations observed in patients assigned to liquid levothyroxine formulation in comparison to those who were assigned to levothyroxine in the form of tablet (time × treatment interaction: Positive Affect Scale of Profile of mood states, p = 0.030; Negative Affect Scale of Profile of mood states, p < 0.0001; General Heath Questionnaire 12-items, p = 0.003). As expected, circulating TSH levels significantly decreased (p <0.001) while FT3 and FT4 levels significantly increased (p < 0.0001 for both) under levothyroxine replacement therapy. These changes were significantly greater in patients treated with liquid levothyroxine formulation (time × treatment interaction: TSH, p = 0.011; FT3, p = 0.016; FT4, p = 0.028). Our data indicate a greater efficacy of liquid formulation of levothyroxine in ameliorating mood states and self-perception of mental well-being and thyroid hormone profile after 2 months of replacement therapy in recently thyroidectomized

  17. Thyroid-stimulating hormone suppression therapy for differentiated thyroid cancer: The role for a combined T3/T4 approach.

    PubMed

    Fussey, Jonathan Mark; Khan, Habib; Ahsan, Farhan; Prashant, Ravi; Pettit, Laura

    2017-09-27

    In the management of differentiated thyroid carcinoma, surgery with or without postoperative radioiodine, and thyroid-stimulating hormone (TSH) suppression is the standard of care in most patients. Levothyroxine is recommended for long-term TSH suppression. For some patients, this may be difficult to tolerate due to adverse effects, such as impaired cognitive function. This article reviews the evidence for the role of combination treatment with triiodothyronine (T3) and levothyroxine (T4) in these patients. The evidence for combination T3 and T4 treatment comes mainly from studies on hypothyroidism, and research into its use for TSH suppression is limited. Although the evidence base is not strong, there is a small group of patients who may benefit from combination T3 and T4 treatment due to difficulty tolerating thyroxine. Until further evidence is available, a case-by-case approach is recommended. © 2017 Wiley Periodicals, Inc.

  18. Evaluation of the coagulation profile among oral and vaginal combined hormonal contraceptive users using sonoclot coagulation analyzer.

    PubMed

    Brandy, Kyle R; Meyer, Rachel M; Luo, Xianghua; Rao, Gundu H; Datta, Yvonne H; Divani, Afshin A

    2012-11-01

    Combined hormonal contraceptives possess an inherent risk of thrombus-related events. The purpose of this study is to elucidate alterations in the coagulation profile among young women using combined oral contraceptive (COC) or combined vaginal contraceptive (CVC) compared to a normal, healthy, female control group using the Sonoclot coagulation analyzer. We enrolled 159 participants (64 control individuals, 51 COC users, and 44 CVC users). Each participant completed a survey of medical history, family medical history, and lifestyle choices. Citrated venous whole blood was collected and analyzed using the Sonoclot coagulation analyzer. After adjusting for age, race, alcohol consumption, sleeping habits, and family history of cardiovascular disease, and stroke, we observed COC and CVC users had mostly similar coagulation profiles except when compared to the control, and COC and CVC users had an elevated glass bead peak signal while COC users had a shorter peak time.

  19. Combined total ankle replacement and modified bridle tendon transfer for end-stage ankle joint arthrosis with paralytic dropfoot: report of an unusual case.

    PubMed

    Bibbo, Christopher; Baronofsky, Hyim J; Jaffe, Leland

    2011-01-01

    In recent years, total ankle replacement has become a reasonable option for many patients with end-stage ankle arthrosis. In order to be successful, total ankle replacement requires a relatively balanced alignment of the foot in relation to the leg. Such alignment is traditionally achieved surgically by means of stabilization of the hindfoot in conjunction with relocation osteotomy of the calcaneus and/or tibia. In this report, we describe the unconventional combination of total ankle replacement in an adult patient with concomitant paralysis that was addressed by means of tendon transfer.

  20. Combined small cell carcinoma of the sinonasal tract associated with syndrome of inappropriate secretion of antidiuretic hormone: A case report

    PubMed Central

    KAYAKABE, MIKIKO; TAKAHASHI, KATSUMASA; OKAMIYA, TOMOFUMI; SEGAWA, ATSUKI; OYAMA, TETSUNARI; CHIKAMATSU, KAZUAKI

    2014-01-01

    Combined small cell carcinoma (SmCC) and squamous cell carcinoma (SqCC) is a rare malignant neoplasm in the head and neck. This study presents the first reported case of combined SmCC and SqCC originating from the sinonasal tract accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH). An 80-year-old female presented with a four-week history of right nasal discharge, nasal obstruction and left neck swelling. Imaging studies revealed a tumorous lesion in the maxillary sinus encroaching upon the right nasal cavity and left cervical lymph node (LN) swelling. An incisional biopsy carried out from the right maxillary sinus and LNs resulted in a diagnosis of combined SmCC with SqCC, staged as T4aN2cM0. Clinical examination revealed a sustained increase of antidiuretic hormone, hyponatremia with urinary sodium increase, and serum hypo-osmosis, resulting in SIADH. Water restriction to <1,000 ml/day was effective in improving sodium and osmotic imbalance. Curative treatment for the tumor was not prescribed due to the poor condition of the patient. Palliative treatment was administered and the patient succumbed to cachexia five months after histological diagnosis. The presence of SIADH may have marked implications for the treatment and prognosis of this disease. PMID:24944702

  1. Combined small cell carcinoma of the sinonasal tract associated with syndrome of inappropriate secretion of antidiuretic hormone: A case report.

    PubMed

    Kayakabe, Mikiko; Takahashi, Katsumasa; Okamiya, Tomofumi; Segawa, Atsuki; Oyama, Tetsunari; Chikamatsu, Kazuaki

    2014-04-01

    Combined small cell carcinoma (SmCC) and squamous cell carcinoma (SqCC) is a rare malignant neoplasm in the head and neck. This study presents the first reported case of combined SmCC and SqCC originating from the sinonasal tract accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH). An 80-year-old female presented with a four-week history of right nasal discharge, nasal obstruction and left neck swelling. Imaging studies revealed a tumorous lesion in the maxillary sinus encroaching upon the right nasal cavity and left cervical lymph node (LN) swelling. An incisional biopsy carried out from the right maxillary sinus and LNs resulted in a diagnosis of combined SmCC with SqCC, staged as T4aN2cM0. Clinical examination revealed a sustained increase of antidiuretic hormone, hyponatremia with urinary sodium increase, and serum hypo-osmosis, resulting in SIADH. Water restriction to <1,000 ml/day was effective in improving sodium and osmotic imbalance. Curative treatment for the tumor was not prescribed due to the poor condition of the patient. Palliative treatment was administered and the patient succumbed to cachexia five months after histological diagnosis. The presence of SIADH may have marked implications for the treatment and prognosis of this disease.

  2. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    SciTech Connect

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions.

  3. Zonal corticosteroid hormone biosynthesis in the adrenal cortex in rats exposed to emotional stress combined with salt loading

    SciTech Connect

    Shul'ga, V.A.

    1987-07-01

    The authors study the pattern of biosynthesis of corticosteroid hormones in the zona glomerulosa and the combined zona fasciculata + zona reticularis of the adrenals, which are responsible for the mineralocorticoid and glucocorticoid function of the glands, during simultaneous exposure of animals to salt loading and emotional stress. Experiments were carried out on rats. The adrenals were divided into parts and samples were incubated in vitro with the addition of /sup 3/H-progesterone to each sample. The specific activity of the /sup 3/H-labeled corticosteroids decreased significantly in rats with a normal salt intake exposed to emotional stress.

  4. Combined Hypofractionated Radiation and Hormone Therapy for the Treatment of Intermediate-Risk Prostate Cancer

    SciTech Connect

    Yassa, Michael; Fortin, Bernard; Fortin, Marie-Andree; Lambert, Carole; Van Nguyen, Thu; Bahary, Jean-Paul

    2008-05-01

    Purpose: Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. Methods and Materials: Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. Results: Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. Conclusions: Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

  5. Combined effects of O3 and UV radiation on secondary metabolites and endogenous hormones of soybean leaves.

    PubMed

    Mao, Bing; Yin, Hong; Wang, Yan; Zhao, Tian-Hong; Tian, Rong-Rong; Wang, Wei; Ye, Jia-Shu

    2017-01-01

    Enhanced ultraviolet radiation (UV) and elevated tropospheric ozone (O3) may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day) and enhanced UV radiation (1.73 kJ h-1 m-2) significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone.

  6. Combined effects of O3 and UV radiation on secondary metabolites and endogenous hormones of soybean leaves

    PubMed Central

    Wang, Yan; Tian, Rong-Rong; Wang, Wei; Ye, Jia-Shu

    2017-01-01

    Enhanced ultraviolet radiation (UV) and elevated tropospheric ozone (O3) may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day) and enhanced UV radiation (1.73 kJ h-1 m-2) significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone. PMID:28806739

  7. Concomitant therapies (glucocorticoids and sex hormones) in adult patients with growth hormone deficiency.

    PubMed

    Scaroni, C; Ceccato, F; Rizzati, S; Mantero, F

    2008-09-01

    Adult-onset GH deficiency (GHD), mostly due to organic lesions of the pituitary-hypothalamic region, is frequently associated with multiple anterior pituitary deficiencies that need long-term substitutive treatment. The GH-IGF-I axis may play an important role in modulating peripheral metabolism of hormones (adrenal, thyroid, and sex hormones) and these interactions may have clinically significant implications on the phenotypes of adult GHD patients and on the effects of the combined replacement hormonal treatment of this condition. By accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients; estrogen replacement blunts the response to GH in women whereas in men with androgen substitution the responsivity increases over time. Endocrinologists should be mindful of these phenomena when starting patients with hypopituitarism on GH replacement therapy.

  8. En bloc aortic and mitral valve replacement and left ventricular outflow tract enlargement using a combined transaortic and trans-septal atrial approach.

    PubMed

    Hassan, Mohammed; Windsor, Jimmy; Ricci, Marco

    2015-12-01

    Aortic and mitral valve replacement with division and reconstruction of the inter-valvular fibrous body has been described in clinical situations involving infective endocarditis, extensive annular calcifications and diminutive valve annuli. Herein, we describe a combined transaortic and trans-septal approach with division of the inter-valvular fibrosa for combined aortic and mitral valve replacement. The reconstruction of the inter-valvular fibrous body, atrial walls and aortic root was carried out using a 'three-patch' technique with bovine pericardium.

  9. Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination.

    PubMed

    Cengiz, Ercument; Karaca, Burcak; Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Gul, Mustafa K; Erten, Cigdem; Atmaca, Harika; Uzunoglu, Selim; Karabulut, Bulent; Sanli, Ulus A; Uslu, Ruchan

    2010-03-01

    Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose- and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated >or=3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers.

  10. Colostrum replacer feeding regimen, addition of sodium bicarbonate, and milk replacer: the combined effects on absorptive efficiency of immunoglobulin G in neonatal calves.

    PubMed

    Cabral, R G; Cabral, M A; Chapman, C E; Kent, E J; Haines, D M; Erickson, P S

    2014-01-01

    Eighty Holstein and Holstein cross dairy calves were blocked by birth date and randomly assigned to 1 of 8 treatments within each block to examine the effect of a colostrum replacer (CR) feeding regimen, supplementation of CR with sodium bicarbonate (NaHCO3), and provision of a milk replacer (MR) feeding on IgG absorption. Calves were offered a CR containing 184.5g/L of IgG in either 1 feeding at 0h (within 30 min of birth), with or without 30g of NaHCO3, with or without a feeding of MR at 6h of age, or 2 feedings of CR (123g of IgG at 0h with or without 20g of NaHCO3 and 61.5g of IgG at 6h with or without 10g of NaHCO3), with or without a MR feeding at 12h. Therefore, treatments were (1) 1 feeding of CR; (2) 2 feedings of CR; (3) 1 feeding of CR + 30g of NaHCO3; (4) 2 feedings of CR + 30g of NaHCO3; (5) 1 feeding of CR + MR feeding; (6) 2 feedings of CR + MR feeding; (7) 1 feeding of CR + 30g NaHCO3 + MR feeding; and (8) 2 feedings of CR + 30g NaHCO3 + MR feeding. Blood samples were obtained at 0, 6, 12, 18, and 24h after birth and were analyzed for IgG via radial immunoassay. Results indicated that CR feeding schedule, MR feeding, and the interactions CR × Na, CR × MR, and CR × Na × MR were similar for 24-h serum IgG, apparent efficiency of absorption, or area under the curve. Serum IgG at 24h, apparent efficiency of absorption, and area under the curve were decreased with addition of NaHCO3 compared with calves not supplemented with NaHCO3. These data indicate that supplementation of CR with NaHCO3 is not beneficial to IgG absorption and feeding MR within 6h of CR feeding does not affect IgG absorption. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995-2009.

    PubMed

    Petersen, J F; Bergholt, T; Nielsen, A K; Paidas, M J; Løkkegaard, E C L

    2014-07-03

    Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15-49 during the period of 1995-2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.

  12. Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders.

    PubMed

    Zucchini, Stefano; Iafusco, Dario; Vannelli, Silvia; Rabbone, Ivana; Salzano, Giuseppina; Pozzobon, Gabriella; Maghnie, Mohamad; Cherubini, Valentino; Bizzarri, Carla; Bonfanti, Riccardo; D'Annunzio, Giuseppe; Lenzi, Lorenzo; Maggio, Maria Cristina; Marigliano, Marco; Scaramuzza, Andrea; Tumini, Stefano; Iughetti, Lorenzo

    2014-01-01

    Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.

  13. Pharmacokinetics of the first combination 17β-estradiol/progesterone capsule in clinical development for menopausal hormone therapy.

    PubMed

    Pickar, James H; Bon, Charles; Amadio, Julia M; Mirkin, Sebastian; Bernick, Brian

    2015-12-01

    This study aims to compare the pharmacokinetics and oral bioavailability of a capsule combining 17β-estradiol and progesterone in a non-peanut oil-containing formulation with those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women. This was an open-label, balanced, randomized, single-dose, two-treatment, three-period, three-sequence, cross-over, partial-replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were randomly assigned to one of three dosing sequences of test and reference products (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference product), with each of the three periods separated by a 14-day washout. The primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the test and reference products, assessed for bioequivalence using the scaled average bioequivalence or unscaled average bioequivalence method. Safety was assessed by clinical observation, participant-reported adverse events, and laboratory data, including blood levels of hormones. Sixty-six women were randomly assigned, and 62 women (94.0%) completed all three study periods. All AUC and Cmax parameters met bioequivalence criteria for all analytes (estradiol, progesterone, and estrone), except Cmax for total estrone. The extent of estradiol and progesterone absorption was similar between the test product and the reference products. Four adverse events--all considered mild and unrelated to the study drugs--were reported. The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation.

  14. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice.

    PubMed

    Han, Hao; Xin, Peng; Zhao, Lina; Xu, Jian; Xia, Yun; Yang, Xuefeng; Sun, Xiufa; Hao, Liping

    2012-06-01

    The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.

  15. Pharmacokinetics of the first combination 17β-estradiol/progesterone capsule in clinical development for menopausal hormone therapy

    PubMed Central

    Pickar, James H.; Bon, Charles; Amadio, Julia M.; Mirkin, Sebastian; Bernick, Brian

    2015-01-01

    Abstract Objective: This study aims to compare the pharmacokinetics and oral bioavailability of a capsule combining 17β-estradiol and progesterone in a non–peanut oil–containing formulation with those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women. Methods: This was an open-label, balanced, randomized, single-dose, two-treatment, three-period, three-sequence, cross-over, partial-replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were randomly assigned to one of three dosing sequences of test and reference products (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference product), with each of the three periods separated by a 14-day washout. The primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the test and reference products, assessed for bioequivalence using the scaled average bioequivalence or unscaled average bioequivalence method. Safety was assessed by clinical observation, participant-reported adverse events, and laboratory data, including blood levels of hormones. Results: Sixty-six women were randomly assigned, and 62 women (94.0%) completed all three study periods. All AUC and Cmax parameters met bioequivalence criteria for all analytes (estradiol, progesterone, and estrone), except Cmax for total estrone. The extent of estradiol and progesterone absorption was similar between the test product and the reference products. Four adverse events—all considered mild and unrelated to the study drugs—were reported. Conclusions: The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation. PMID:25944519

  16. The role of rosiglitazone treatment in the modulation of islet hormones and hormone-like peptides: a combined in situ hybridization and immunohistochemical study.

    PubMed

    Yildirim, Sukriye; Bolkent, Sema; Sundler, Frank

    2008-12-01

    Rosiglitazone, peroxisome proliferator-activated receptor-gamma agonist, is an insulin sensitizing agent in peripheral tissues. This study investigated islet hormones and hormone-like peptides expression patterns in rosiglitazone treated streptozotocin (STZ)-diabetic rats by using immunohistochemistry and in situ hybridization methods. Animals were divided into four groups. I. Group: Intact control rats. II. Group: Rosiglitazone-treated controls. III. Group: STZ-diabetic rats. IV. Group: Rosiglitazone-treated diabetic animals. Rosiglitazone was given for 7 days at a dose of 20 mg/kg body weight. In the STZ-diabetic group, there were significant differences in islet hormones and hormone like peptides cell numbers compared to rosiglitazone control group and intact control group. There were significant differences in cocaine- and amphetamine-regulated transcript (CART) and pancreatic polypeptide (PP) cell numbers between rosiglitazone control group and rosiglitazone + STZ-diabetic group. We detected a significant decrease in glucagon mRNA signals in rosiglitazone-treated control group compared to intact controls. We found a statistically significant difference in islet amyloid polypeptide (IAPP) mRNA signals between the STZ-diabetic group and the rosiglitazone + STZ-diabetic group. Besides, we also demonstrated co-localization of peptides by using double and triple histochemistry. In conclusion, our results show that short-term rosiglitazone treatment had a preservative effect to some extent on the expression of islet hormones and hormone-like peptides to maintain the islet function.

  17. Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing

    PubMed Central

    Blair, Jeffrey A.; Palm, Russell; Chang, Jaewon; McGee, Henry; Zhu, Xiongwei; Wang, Xinglong; Smith, Gemma Casadesus

    2015-01-01

    Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer’s disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4 month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss. PMID:26497249

  18. Artificial disk replacement combined with midlevel ACDF versus multilevel fusion for cervical disk disease involving 3 levels.

    PubMed

    Kang, Liangqi; Lin, Dasheng; Ding, Zhenqi; Liang, Bowei; Lian, Kejian

    2013-01-01

    The optimal surgical approach for cervical disk disease remains a matter of debate, especially for multilevel disease. The purpose of this study was to compare the results of 2 surgical strategies for cervical disk disease involving 3 levels: hybrid constructs, artificial disk replacement combined with midlevel anterior cervical diskectomy and fusion (ACDF), and 3-level ACDF. The authors prospectively compared patients who had cervical disk disease involving 3 levels that was treated with hybrid constructs or with 3-level ACDF. Patients were asked to use the Neck Disability Index (NDI) to grade their pain intensity preoperatively and at routine postoperative intervals of 1, 3, 6, 12, and 24 months. Dynamic flexion and extension lateral cervical radiographs were obtained while in the standing position preoperatively and at the postoperative intervals. The angular range of motion for C2-C7 and the adjacent segments was measured using the Cobb method. Twenty-four patients were treated, 12 with hybrid constructs and 12 with 3-level ACDF. Both groups had significant postoperative improvement in NDI scores and neck pain (P<.05). However, no significant difference was found between the groups (P>.05). The hybrid constructs group showed faster recovery of C2-C7 range of motion. Mean C2-C7 range of motion of the hybrid constructs group recovered to that of the preoperative value, but that of the 3-level ACDF group did not (P<.05). Range of motion of the superior and inferior adjacent segments showed significant differences between the 2 groups at 12 and 24 months postoperatively (P<.05). These findings suggest that the hybrid constructs is a safe and effective alternative for cervical disk disease involving 3 levels. The definite stabilization and maintained range of motion can be achieved right away, which can ensure a good preliminary clinical outcome.

  19. Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.

    PubMed

    Chang, Kee-Lung; Cheng, Hsiao-Ling; Huang, Li-Wen; Hsieh, Bau-Shan; Hu, Yu-Chen; Chih, Tsai-Tung; Shyu, Huey-Wen; Su, Shu-Jem

    2009-04-08

    Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

  20. Combination Treatment with Progesterone and Vitamin D Hormone May Be More Effective than Monotherapy for Nervous System Injury and Disease

    PubMed Central

    Cekic, Milos; Sayeed, Iqbal; Stein, Donald G.

    2010-01-01

    More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems. Emerging data on 1,25-dihydroxyvitamin D3 (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment. PMID:19394357

  1. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency.

    PubMed

    Müller, Julia; Mayerl, Steffen; Visser, Theo J; Darras, Veerle M; Boelen, Anita; Frappart, Lucien; Mariotta, Luca; Verrey, Francois; Heuer, Heike

    2014-01-01

    The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we speculated that Mct10 inactivation may compromise the tissue-specific TH homeostasis as well. However, analysis of Mct10 knockout (ko) mice revealed normal serum TH levels and tissue TH content in contrast to Mct8 ko mice that are characterized by high serum T3, low serum T4, decreased brain TH content, and increased tissue TH concentrations in the liver, kidneys, and thyroid gland. Surprisingly, mice deficient in both TH transporters (Mct10/Mct8 double knockout [dko] mice) showed normal serum T4 levels in the presence of elevated serum T3, indicating that the additional inactivation of Mct10 partially rescues the phenotype of Mct8 ko mice. As a consequence of the normal serum T4, brain T4 content and hypothalamic TRH expression were found to be normalized in the Mct10/Mct8 dko mice. In contrast, the hyperthyroid situation in liver, kidneys, and thyroid gland of Mct8 ko mice was even more severe in Mct10/Mct8 dko animals, suggesting that in these organs, both transporters contribute to the TH efflux. In summary, our data indicate that Mct10 indeed participates in tissue-specific TH transport and also contributes to the generation of the unusual serum TH profile characteristic for Mct8 deficiency.

  2. Optimization of hormone combinations for root growth and bud germination in Chinese fir (Cunninghamia lanceolata) clone leaf cuttings.

    PubMed

    Li, Shubin; Huang, Peng; Ding, Guochang; Zhou, Lili; Tang, Piao; Sun, Min; Zheng, Yingying; Lin, Sizu

    2017-07-11

    In order to ascertain the optimal hormone combination for Chinese fir (Cunninghamia lanceolata) leaf cuttings, an L16(4)(4) orthogonal test of 6-benzylaminopurine (6-BA), 1-naphthaleneacetic acid (NAA), and indole-3-butyric acid (IBA) (0, 10, 30, or 50 mg · L(-1) of each exogenous hormone) immersion for 5, 10, 15, or 20 min was conducted. Callus initiation rate and rooting promotion rate were mainly affected by treatment time, root length increase by 6-BA concentration, and bud germination rate and plantlet formation rate by NAA concentration. The expected optimal combination for callus initiation rate was 50 mg · L(-1) 6-BA + 0 mg · L(-1) NAA + 30 mg · L(-1) IBA + 10 min; for rooting promotion rate, it was 0-10 mg · L(-1) 6-BA + 10 mg · L(-1) NAA + 30 mg · L(-1) IBA + 20 min; for bud germination rate, it was 50 mg · L(-1) 6-BA + 0-10 mg · L(-1) NAA + 0-30 mg · L(-1) IBA + 20 min; and for seedling formation rate for No. 4, it was 10 mg · L(-1) 6-BA + 10 mg · L(-1) NAA + 0 mg · L(-1) IBA + 20 min. Light microscopy image analysis revealed that a cluster of primordial cells was produced 40 days after cutting, and mastoid cells developed into peninsula cells in calli that were cultured for 50 days.

  3. Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period.

    PubMed

    Boguszewski, Cesar L; Lacerda, Claudio Silva de; Lacerda Filho, Luiz de; Carvalho, Julienne A R de; Boguszewski, Margaret C S

    2013-12-01

    To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

  4. Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1.

    PubMed

    Osorio, M G; Kopp, P; Marui, S; Latronico, A C; Mendonca, B B; Arnhold, I J

    2000-08-01

    Mutations in the pituitary-specific paired-like homeodomain transcription factor, PROP-1, result in combined pituitary hormone deficiency. We studied a Brazilian girl, offspring of first cousins, who presented with short stature and deficiencies of GH, TSH, PRL, LH, and FSH. Her cortisol response to hypoglycemia was determined at age 4.9, 10.7, and 14.1 yr and remained normal. Magnetic resonance imaging at the age of 9 yr revealed an anterior pituitary lobe of diminished height (3 mm; normal, 4.5 +/- 0.6), but radiography revealed a sella turcica volume above the normal mean. Direct sequencing of the PROP-1 gene revealed homozygosity for a novel 263T>C transition that results in the replacement of a highly conserved phenylalanine by serine at codon 88 (F88S). F88 constitutes the hydrophobic core of the first helix of the homeodomain of PROP-1, and the substitution by the polar residue serine is expected to alter the secondary structure and impair binding of the mutated PROP-1 to DNA target sequences. The F88S mutation (which corresponds to murine F85S) was introduced into the murine Prop-1 complementary DNA and its consequences on DNA binding and trans-activation were assessed in vitro. In contrast to wild-type Prop-1, the F88S mutant showed no significant DNA binding to a PRDQ9 Prop-1 response element in gel shift assays. Transcriptional activation of a luciferase reporter gene containing a PRDQ9 site upstream of a simian virus 40 promoter was reduced to approximately 34% compared with that of wild-type Prop-1 in transiently transfected TSA-201 human embryonic kidney cells. The F88S mutation further expands the repertoire of mutations in PROP-1.

  5. Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism.

    PubMed

    Fujikawa, M; Okamura, K; Sato, K; Mizokami, T; Shiratsuchi, M; Fujishima, M

    1999-06-01

    We describe a 51-year-old woman with long-standing young-onset primary hypothyroidism. Serum cortisol, adrenocorticotropin, and arginine vasopressin levels were normal, but urinary excretion of 17-hydroxycorticosteroid was decreased. Administration of a very small initial dose of thyroid hormone induced severe acute complications including fever, palpitation, and sweating associated with a rapid decrease in serum thyrotropin level, a dramatic increase in serum alkaline-phosphatase level, and a decrease in serum total cholesterol level. A week later, the late complications of nausea, severe hyponatremia, and eosinophilia occurred. Serum cortisol level decreased slightly but remained within normal limits during this hyponatremic period. This rare case suggests that increased sensitivity to thyroid hormone can occur in long-standing primary hypothyroidism with biphasic clinical course of acute thyrotoxic complications followed by severe hyponatremia resembling hypoadrenocorticism.

  6. Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months.

    PubMed

    Frank, Denise H; Kimler, Bruce F; Fabian, Carol J; Ranger-Moore, James; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S; Bartels, Peter H

    2009-06-01

    Aromatase inhibitors are currently being evaluated as preventive agents in post-menopausal women at high risk for breast cancer. A phase II trial of 42 women on hormone replacement therapy (HRT) treated with letrozole for 6 months showed Ki-67 was reduced by 66% but showed no change in cytomorphology or Masood score. Subsequent image analytical procedures (karyometry) conducted on a subset of the samples captured subvisual information that showed reduced cellular abnormality after 6 months of letrozole. In the present study we expanded on the preliminary karyometry study to determine if the change in karyometric measurements corresponded to changes in risk biomarkers quantified in the Phase II trial; and secondly, whether these biomarkers might be used together to serve as markers of response in individual cases. Pap stained slides from the Phase II trial were used. Epithelial cell images were digitized on a CCD video-microphotometer and the nuclei were segmented from the field using a semiautomatic algorithm. Nine out of 37 cases analyzed showed a numerical decrease in all three markers, although only three of these exhibited changes substantial enough to be considered as an improvement. However, 12 cases showed improvement by cytology (a decrease in Masood score of at least 2), an additional 13 cases demonstrated a reduction in Ki-67 expression by 50% of the median baseline value, and an additional five cases exhibited a decrease of at least 10% in abnormal cells by nuclear morphometry. Thus, a total of 30 of 37 cases (81%) showed improvement in at least one marker. There was no correlation between changes in Ki-67%, karyometric abnormality, and Masood score change other than specimens that exhibited an improvement in cytology also displayed greater decreases in nuclear morphometry abnormalities. Given the heterogeneity of mechanisms leading to malignancy, the quantitative analysis of nuclear chromatin patterns may be valuable as a global, or integrating

  7. Effect of different hormonal combinations on follicular wave emergence and superovulatory response in sheep.

    PubMed

    Souza-Fabjan, Joanna Maria Gonçalves; da Rosa, Rômulo Mendonça; Balaro, Mário Felipe Alvarez; Pinto, Pedro Henrique Nicolau; Dos Santos, Gustavo Bervian; Arashiro, Eduardo Kenji Nunes; da Fonseca, Jeferson Ferreira; Ungerfeld, Rodolfo; Brandão, Felipe Zandonadi

    2017-11-01

    The aim of the present study was to compare hormonal treatments to induce and synchronize follicular wave emergence to improve the results of superovulatory (SOV) treatments in ewes. In Experiment 1 (n = 66), ewes were treated with a progesterone intravaginal implant plus a PGF2α analogue (group GP4), or with the same treatment plus estradiol benzoate (GP4+EB), a GnRH agonist (GP4+GnRH), or both, estradiol benzoate and a GnRH agonist (GP4+EB+GnRH) in a 2 × 2 factorial arrangement. Follicular wave emergence was determined by ultrasound. Follicular wave did not emerge during the studied period in 10 females (one from GP4, six from GP4+EB and three from GP4+EB+GnRH). Follicular emergence was less synchronized (P = 0.007) when estradiol was administered (GP4+EB: 103.6 ± 22.0 h), without any interaction with GnRH treatment (GP4+EB+GnRH: 80.1 ± 21.4 h, GP4+GnRH: 52.5 ± 8.7 h, GP4: 56.6 ± 10.4 h). Estradiol administration delayed the moment of follicular emergence (P = 0.007) and the follicular wave emergence moment in which follicular dominance was achieved (P = 0.009), without interactions between estradiol and GnRH in the moment of follicular wave emergence or dominance. In Experiment 2 (n = 22), two SOV protocols were compared: the best treatment of Experiment 1 (GP4) was used to synchronize follicular wave emergence, initiating the SOV treatment 2.5 days later; in the control treatment, SOV treatment started 80 h after a short-term protocol to synchronize ovulation (Gcontrol). The number of corpora lutea (CL) and the evaluation of the collected embryos were performed six days after estrus. Blood samples were collected daily for plasma progesterone determination. Although the number of CL was similar in Gcontrol (7.1 ± 1.0) and GP4 (6.9 ± 5.1), the number of structures and viable embryos recovered were greater in Gcontrol (P < 0.05). The occurrence of luteal premature regression was significantly greater in GP4 (60%) than in

  8. Clinical and hormonal effects of ethinylestradiol combined with gestodene and desogestrel in young women with acne vulgaris.

    PubMed

    Mango, D; Ricci, S; Manna, P; Miggiano, G A; Serra, G B

    1996-03-01

    The effect of gestodene 75 micrograms (GTD) versus desogestrel 150 micrograms (DSG) combined with 30 micrograms of ethinylestradiol (EE) on acne lesions and plasma androstenedione (A), total testosterone (T), sex hormone binding globulin (SHBG) and "free androgen index" (FAI) was evaluated in an open study on 19 patients aged 18-35 years affected with postpubertal or persistent non-severe acne vulgaris. The patients were randomly allocated into two groups receiving EE-GTD (n = 8) and EE-DSG (n = 11), 21 tablets per cycle for 9 consecutive cycles. Clinical and hormonal evaluations were made between days 17-21 in the cycle before treatment and between days 17-21 of the cycle 3, 6 and 9 of treatment. During treatment, acne improved in most patients, reaching at cycle 9 a low score (absent or minimal) in 62% of the cases in the GTD group (mean acne score = 1.25) and in 90% of the cases in the DSG group (mean acne score = 0.90). Before treatment, about 75% of the patients showed one or more signs of biochemical hyperandrogenism, including elevated FAI (57%), elevated A (15%), elevated total T (15%) and decreased SHBG (21%), and there was evidence of inverse correlation between SHBG and acne scores (p < 0.05). The echogenic texture of the ovaries was multifollicular in 55% of the cases. By the end of the third cycle of treatment, the hormonal changes observed in both groups included significant decreases, with normalization of individual elevated levels of T, and a 3-fold rise of the initial values of plasma SHBG, which showed a further gradual increase at cycle 9 of EE-DSG administration. At cycle 9, normalization of the echogenic ovarian texture was observed. Acne improvement under treatments with estrogen and progestin (EP) could be significantly correlated with the normalization of biochemical hyperandrogenism. In conclusion, the biochemical and clinical efficacy of EE-GTD and EE-DSG indicate that both these preparations can be a good choice in the therapy of acne

  9. Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits.

    PubMed Central

    Haarbo, J; Leth-Espensen, P; Stender, S; Christiansen, C

    1991-01-01

    Cardiovascular disease is currently the leading cause of death among women in the United States. To investigate the effect of postmenopausal hormone therapy on atherogenesis, we studied 75 cholesterol-fed female rabbits for 19 wk. The rabbits were randomly assigned to five groups. Four groups underwent bilateral ovariectomy followed by treatment with either 17 beta-estradiol, 17 beta-estradiol plus norethisterone acetate, 17 beta-estradiol plus levonorgestrel, or placebo. The fifth group had a sham operation and received placebo. The hormone groups had only one-third of the aortic accumulation of cholesterol found in the placebo groups, a difference that was highly statistically significant (P less than 0.0001). No significant differences in aortic accumulation of cholesterol were found in the hormone groups. This indicates that estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits and that two commonly prescribed progestogens do not counteract the effect. The beneficial effect of estradiol could only partly be explained by its lowering effects on serum total cholesterol or VLDL cholesterol, which implies that estradiol possesses additional beneficial effects, possibly a direct action on the arterial wall. Images PMID:1901319

  10. Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

    PubMed

    Ziemnicka, Katarzyna; Gut, Paweł; Gołąb, Monika; Dworacki, Grzegorz; Wrotkowska, Elżbieta; Stajgis, Marek; Katulska, Katarzyna; Rabska-Pietrzak, Barbara; Obara-Moszyńska, Monika; Niedziela, Marek; Budny, Bartłomiej; Kałużna, Małgorzata; Waśko, Ryszard; Ruchała, Marek

    2016-12-01

    The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

  11. Inappropriate use of combined hormonal contraceptives for birth control among women of reproductive age in the United States.

    PubMed

    Yu, Jingbo; Hu, X Henry

    2013-07-01

    To describe the extent of inappropriate use of combined hormonal contraceptives (CHC) according to the United States Medical Eligibility Criteria (U.S. MEC). We analyzed Kantar Health's 2010 U.S. National Health and Wellness Survey data, which is an annual population-based survey of 75,000 U.S. adults via internet. A stratified random sampling framework was used to construct a sample that reflects the U.S. census by age, gender, and ethnicity. The analysis included nonpregnant females aged 18-44 years who used CHC, including oral, patch, or vaginal rings in the past 6 months. Women classified into category 3 (theoretical or proven risks usually outweigh the advantages of using the method) or 4 (unacceptable health risk) according to the U.S. MEC were defined as having high-risk conditions, or inappropriate CHC use. The proportions of women who had inappropriate CHC use were then projected to the U.S. population by diseases/conditions and demographic characteristics incorporating sampling weights. We identified 2963 adult females of reproductive age (mean 29.3±6.0) (i.e., 20.4% of all adult females of reproductive age in the database) as being CHC users. Among them, 23.7% (95% CI: 22.8%-24.5%) had at least one high-risk condition and 9.3% (95% CI: 9.2%-9.4%) had at least one condition of unacceptable risk. The three most common high-risk conditions were migraine (12.7%), multiple risk factors for arterial cardiovascular disease (9.3%), and hypertension (6.1%). Women with relatively higher proportions of inappropriate CHC use were age ≥35, not finished college, and Medicaid recipients. A large portion of women used CHC inappropriately. Hormone-free and progestin-only contraceptives are available options with potentially less risk for them.

  12. Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones.

    PubMed

    Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

    2015-11-16

    BACKGROUND The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11b-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. MATERIAL AND METHODS Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. RESULTS Hill's equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57-0.0247×(CDEX-4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. CONCLUSIONS Combined use of DEX and ETO reduced ETO's inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones.

  13. Combination Effects of (Tri)Azole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line

    PubMed Central

    Rieke, Svenja; Koehn, Sophie; Hirsch-Ernst, Karen; Pfeil, Rudolf; Kneuer, Carsten; Marx-Stoelting, Philip

    2014-01-01

    Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (tri)azole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl) were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol) and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP) enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence of this effect. PMID

  14. Combination effects of (tri)azole fungicides on hormone production and xenobiotic metabolism in a human placental cell line.

    PubMed

    Rieke, Svenja; Koehn, Sophie; Hirsch-Ernst, Karen; Pfeil, Rudolf; Kneuer, Carsten; Marx-Stoelting, Philip

    2014-09-17

    Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (tri)azole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl) were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol) and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP) enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this effect.

  15. Effect of a combined treatment with growth hormone and melatonin in the cardiological aging on male SAMP8 mice.

    PubMed

    Forman, Katherine; Vara, Elena; García, Cruz; Kireev, Roman; Cuesta, Sara; Escames, Germaine; Tresguerres, J A F

    2011-08-01

    The effect of a chronic combined treatment with growth hormone (GH) plus melatonin (Mel) on different age-related processes in cytosolic and nuclear fractions of hearts from SAMP8 mice (2 and 10 months) has been investigated. The parameters studied have been messenger RNA expressions of IL-1, IL-10, NFkBp50, NFkBp52, TNFα, eNOS, iNOS, HO-1, HO-2, BAD, BAX, and Bcl2 and protein expressions of iNOS, eNOS, TNFα, IL-1, IL-10, NFkBp50, NFKbp52, and caspase activity (3 and 9). Our results supported the existence of a proapoptotic and oxidative status together with inflammatory processes in the heart of old mice, with increases of inflammatory cytokines, caspase activity, HO-1, BAX, NFkBp50, and NFkBp52 and decreases of eNOS and Bcl2. Also, we were able to observe the translocation of NFkB to nuclei. The combined treatment was able to partially reduce the incidence of these deleterious changes, showing differences with the separated treatments with GH and Mel as were investigated in previous articles from our group.

  16. Effect of various growth hormone concentration and combination on callus induction, nature of callus and callogenic response of Nerium odorum.

    PubMed

    Rashmi, Runa; Trivedi, Maheshwar Prasad

    2014-03-01

    Nerium odorum, Linn. (Apocynaceae) is an important evergreen shrub. It is heat, salinity and drought tolerant. Plants with milky sap have medicinal value, mainly cardenolides, flavonoids and terpenes. It is used for wastewater purification and for restoration of riparian woodlands. In view of these facts, the study was conducted for micropropagation of N. odorum. Murashige and Skoog (MS) media supplemented with different concentrations (0.5-10.0 mg/l) of 1-naphthaleneacetic acid (NAA), 2,4-dichlorophenoxyacetic acid (2,4-D), 6-benzylaminopurine (BAP) and kinetin (Kin) were used singly and in combinations. Among all the growth hormones, 2,4-D was the best for callus induction (75% in stem and 79% in leaf) and in combination 2,4-D and BAP (78% in stem and 81% in leaf). The day of callus induction started from the 19th to the 37th day. This variation is due to the differences in culture conditions and the age of explants. The fresh and dry weight and moisture content showed good growth of callus, which is used in further studies of alkaloid production. Micropropagation of this plant allows the production of clones at a fast rate and in continuous manner. This work can lead to the development of an efficient protocol for callus induction and other issues.

  17. Adenopituitary hormone response to exercise combined with propranolol infusion in man.

    PubMed

    Jezová, D; Vigas, M; Klimes, I; Jurcovicová, J

    1983-06-01

    The effect of non-selective beta-blocker propranolol on the changes of plasma GH, prolactin and cortisol level during physical exercise in healthy untrained men has been evaluated. Acute i.v. pretreatment with propranolol resulted in an increased response of plasma GH level to the exercise on a bicycle ergometer. Propranolol significantly potentiated also the response of plasma cortisol level to submaximal exercise. No changes in urinary excretion of free cortisol and 17-OHCS during exercise combined with propranolol infusion as compared to that during exercise alone were observed. The increase of plasma prolactin level after exercise was not altered by propranolol administration. It is suggested that central beta-adrenoreceptors may play an inhibitory role in the control of GH and ACTH secretion during exercise. However, the interaction of propranolol with other central neurotransmitters as well as its peripheral effects, particularly the reduction in physical performance, must also be taken into consideration.

  18. Proposal to replace the illegitimate genus name Bryantella Wolin et al. 2004VP with the genus name Marvinbryantia gen. nov. and to replace the illegitimate combination Bryantella formatexigens Wolin et al. 2004VP with Marvinbryantia formatexigens comb. nov.

    PubMed

    Wolin, Meyer J; Miller, Terry L; Lawson, Paul A

    2008-03-01

    The prokaryote generic name Bryantella Wolin et al. 2004(VP) is illegitimate because it is a later homonym of Bryantella Chickering, 1946 (Animalia, Arthropoda, Arachnida, Araneae, Salticidae, Dendryphantinae, Dendryphantini) and a later homonym of Bryantella Britton, 1957 (Animalia, Arthropoda, Scarabaeoidea, Scarabaeidae, Melolonthinae) [Principle 2, Rule 51b(4) of the Bacteriological Code (1990 Revision)]. Bryantella represents a genus of jumping spiders within the family Salticidae and a genus of melolonthine scarab beetles within the family Scarabaeidae. Therefore, a new genus name, Marvinbryantia gen. nov., is proposed for this taxon. As a result, a new combination, Marvinbryantia formatexigens comb. nov., is required for the type species to replace the illegitimate combination Bryantella formatexigens Wolin et al. 2004(VP).

  19. [Long-term use of combined hormonal contraception--myths and reality].

    PubMed

    Novotná, M; Huvar, I; Bláha, O

    2002-09-01

    To assess relationship of long-term use of combined oral contraception (COC) and women health, discussion about myths connected with use of COC. Review of literature. Department of Obstetrics and Gynaecology, Hospital of Merciful Brothers, Brno, Czech Republic. Identification of studies able to address the topic using Medline database search. Besides reliable control of fertility COC protect women against dysmenorrhea, iron deficiency anemia, ovarian cysts and uterine fibroids. COC plays very important role in gynecologic endocrinology suppressing effectively hyperandrogenism, which has not only cosmetic effect but brings also improvement in cardiovascular health of affected perimenopausal women. Premenopausal using of COC could help preserve bone mineral density and can reduce the risk of developing Alzheimer's disease. The most important feature is protective effect against endometrial (by 70%) and ovarian (by 50%) cancer which increases with duration of COC use and is long lasting and may be observed 15 to 20 years after stopping use. Association of use COC with increased risk neither of cervical cancer nor breast cancer has not been confirmed. Controversy still persists over the association of long-term (longer than 8 years) COC use by young nulliparas and breast cancer. The risk in this group of users is probably slightly increased. But no authorities recommended any restriction of COC's prescription. Some studies have suggested an inverse relationship between use of COC and risk of colorectal cancer. The only established evidence of direct association between OC use and cancer risk is the increased risk for hepatocellular carcinoma in the absence of hepatitis B (but maximum by 4 cases per 1,000,000 users per year). Most non-contraceptive health benefits of COC are still not widely appreciated in spite of much evidence. The final decision of contraception method is upon well and adequate informed user by well educated doctor.

  20. Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives.

    PubMed

    Fels, Heather; Steward, Rachel; Melamed, Alexander; Granat, Anna; Stanczyk, Frank Z; Mishell, Daniel R

    2013-06-01

    This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens. This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI. From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01). This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Individual and combined effects of noise-like whole-body vibration and parathyroid hormone treatment on bone defect repair in ovariectomized mice.

    PubMed

    Matsumoto, Takeshi; Sato, Daisuke; Hashimoto, Yoshihiro

    2016-01-01

    The effectiveness of intermittent administration of parathyroid hormone and exposure to whole-body vibration on osteoporotic fracture healing has been previously investigated, but data on their concurrent use are lacking. Thus, we evaluated the effects of intermittent administration of parathyroid hormone, whole-body vibration, and their combination on bone repair in osteoporotic mice. Noise-like whole-body vibration with a broad frequency range was used instead of conventional sine-wave whole-body vibration at a specific frequency. Mice were ovariectomized at 9 weeks of age and subjected to drill-hole surgery in the right tibial diaphysis at 11 weeks. The animals were divided into four groups (n = 12 each): a control group, and groups treated with intermittent administration of parathyroid hormone, noise-like whole-body vibration, and both. From postoperative day 2, the groups treated with intermittent administration of parathyroid hormone and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were subcutaneously administered parathyroid hormone at a dose of 30 µg/kg/day. The groups treated with noise-like whole-body vibration and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were exposed to noise-like whole-body vibration at a root mean squared acceleration of 0.3g and frequency components of 45-100 Hz for 20 min/day. Following 18 days of interventions, the right tibiae were harvested, and the regenerated bone was analyzed by micro-computed tomography and nanoindentation testing. Compared with the control group, callus volume fraction was 40% higher in groups treated with intermittent administration of parathyroid hormone and 73% higher in groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration, and callus thickness was 35% wider in groups treated with both

  2. [Histopathological effect and its predictors of neoadjuvant hormonal therapy by combined androgen blockade].

    PubMed

    Ito, T; Mamiya, Y; Aizawa, T; Akiyama, A; Yamamoto, S; Tsuzuki, M; Yoshimasa, O; Miki, M; Furusato, M

    1999-09-01

    Combined androgen blockade (CAB) uning LH-RH agonist and flutamide has been performed as neoadjuvant therapy for T 2, 3 prostate cancers (CaP). The histological effects of neoadjuvant CAB therapy and influential factors were investigated. Materials were 20 CaP cases which were underwent radical prostatectomy (RP) after neoadjuvant CAB therapy. All cases were diagnosed by echo-guided sextant needle biopsies. RP was performed after serum PSA was decreased to undetectable level. Histological effect was evaluated by general rule for clinical and pathological studies on prostate cancer (Japanese Urological Association). All cases were divided 2 groups by histological effects as follows: Group A (poor effect group): G 0 and G 1, Group B (good effect group): G 2 and G 3. Immunostaining of p 53 (mutant type), bcl-2 and Chromogranin A (ChA) were performed for both pretreatment needle biopsy and RP specimen. In addition, pretreatment serum PSA and Gleason grade were also investigated. Down grading were found in 30%. Down staging were found in 35% (7 cases). All 7 cases were negative surgical margins and 5 of 7 were clinical T 3. Negative bcl-2 of biopsy specimen was correlation with down grading (p = 0.008). In the histopathological evaluation, G 0 was 1, G 1 were 10, G 2 were 6 and G 3 were 3 cases. Gleason 4 or 5 elements of biopsy were found in 9/11 cases in Group A but only 3/9 cases in Group B (p = 0.027). The bcl-2 positive cells of biopsy were found in 8/11 cases in Group A but only 1/9 cases in Group B (p = 0.006). The p 53 and/or bcl-2 positive cells of biopsy were found in 10/11 cases in Group A but only 3/9 cases in Group B (p = 0.007). Serum PSA and ChA were not correlation with histological effect of neoadjuvant CAB therapy. But, in 3 cases, ChA positive cell appeared after neoadjuvant therapy. We could not expect more than 50% cases to show the down grading and down staging. But, in T 3 case, surgical failure could be decrease. We could expect prostate cancer

  3. Effect of combined treatment with zoledronic acid and parathyroid hormone on mouse bone callus structure and composition.

    PubMed

    Casanova, Michele; Herelle, Janelle; Thomas, Marcel; Softley, Rowan; Schindeler, Aaron; Little, David; Schneider, Philipp; Müller, Ralph

    2016-11-01

    In recent years, great interest in combined treatment of parathyroid hormone (PTH) with anti-resorptive therapy has emerged. PTH has been suggested to aid bridging of atrophic fractures and improve strength in closed fracture models. Bisphosphonate treatments typically result in a larger woven bone callus that is slower to remodel. The combination of both drugs has been demonstrated to be effective for the treatment of osteoporotic bone loss in many preclinical studies. However, the effect of combined treatment on fracture repair is still largely unexplored. In this study, we aimed to compare these drugs as single-agent and in combination in a murine closed fracture model. We wanted to assess potential differences in material properties, morphometry and in the development of the lacuno-canalicular network. A total of 40 female, 11-week-old wild type mice underwent a closed fracture on the midshaft of the tibia and were assigned to four groups (n=8-10 per group). Beginning on post-operative day 8, animals received different subcutaneous injections. Group 1 received a single injection of saline solution and Group 2 of zoledronic acid (ZA). Group 3 received daily dosing of PTH. Group 4 received a dual treatment, starting with a single dose of ZA followed by daily injection of PTH. Three weeks after fracture, all animals were euthanized and tibiae were assessed using micro-computed tomography (micro-CT), high-resolution micro-CT (HR micro-CT), Raman spectroscopy, quantitative histomorphometry, and deconvolution microscopy (DV microscopy). Combined treatment showed a significant increase of 41% in bone volume fraction and a significant decrease of 61% in the standard deviation of the trabecular spacing compared to vehicle, both known to be strong predictors of callus strength. An analysis via HR micro-CT showed similar results on all groups for lacunar numerical density, whereas mean lacuna volume was found to be higher compared to vehicle in treated groups, but only

  4. The effect of growth hormone (GH) replacement on blood glucose homeostasis in adult nondiabetic patients with GH deficiency: real-life data from the NordiNet(®) International Outcome Study.

    PubMed

    Weber, Matthias M; Biller, Beverly M K; Pedersen, Birgitte Tønnes; Pournara, Effie; Christiansen, Jens Sandahl; Höybye, Charlotte

    2017-02-01

    To assess the effect of 4 years' growth hormone (GH) replacement on glucose homeostasis and evaluate factors affecting glycosylated haemoglobin (HbA1c ) in adults with growth hormone deficiency (GHD). NordiNet(®) International Outcome Study, a noninterventional study, monitors long-term effectiveness and safety of GH replacement [Norditropin(®) (somatropin), Novo Nordisk A/S] in real-life clinical practice. Nondiabetic patients (n = 245) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH replacement and HbA1c values at baseline and 4 years were included in the analysis. Changes from baseline (∆) to 4 years in HbA1c , fasting plasma glucose (FPG), IGF-I, lipids (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides), waist circumference, glycaemic (HbA1c <5·7%; HbA1c , 5·7-6·5%; HbA1c , ≥6·5%) and metabolic health status were evaluated. Effects of baseline HbA1c , gender, baseline age, average GH dose and baseline body mass index (BMI) on ΔHbA1c were investigated. The models were adjusted for concomitant medication use. Mean (standard deviation) baseline HbA1c was 5·13 (0·65)% and remained at the same level at 4 years. Age at treatment start (P = 0·0094) and BMI (P = 0·0008) had a significant impact on ∆HbA1c . At 4 years, 85% of patients with HbA1c <5·7% (normal levels) at baseline and 55% of patients with HbA1c 5·7-6·5% (impaired glucose tolerance) at baseline remained in the same glycaemic health category. Nineteen patients improved from impaired glucose tolerance to normal HbA1c . Seven patients developed diabetes. These data demonstrate that 4 years' GH replacement therapy did not adversely affect glucose homeostasis in the majority of adults with GHD. © 2016 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

  5. Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency.

    PubMed

    Esposito, Andrea; Capalbo, Donatella; De Martino, Lucia; Rezzuto, Martina; Di Mase, Raffaella; Pignata, Claudio; Salerno, Mariacarolina

    2016-07-01

    The aim of our prospective case-control study was to evaluate long-term effects of GH replacement therapy on erythrocytes parameters, leukocytes, and platelets numbers in a large cohort of children with isolated GH deficiency (GHD). Hemoglobin (Hb) concentration, hematocrit (Hct), mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, number of erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes and platelets, ferritin, and C-reactive protein were evaluated in 85 children with isolated GHD (10.20 ± 3.50 years) before and annually during the first 5 years of GH replacement therapy and in 85 healthy children age and sex comparable to patients during 5 years of follow-up. Compared with controls, GHD children at study entry showed lower Hb (-1.18 ± 0.87 vs. -0.40 ± 0.90 SDS, p < 0.0001), red cells number (-0.24 ± 0.81 vs. 0.25 ± 1.14 SDS, p < 0.0001), and Hct (-1.18 ± 0.86 vs. -0.68 ± 0.99 SDS, p < 0.0001). Twelve GHD patients (14 %) showed a normocytic anemia. GH therapy was associated with a significant increase in Hb, Hct, and red cells number which became all comparable to controls within the first 2 years of treatment. Moreover, hemoglobin levels normalized in all anemic GHD patients after 5 years of therapy. No difference between patients and controls was found in leukocytes and platelets numbers neither at baseline nor during the study. GHD in childhood is associated with an impairment of erythropoiesis which causes a normocytic anemia in a considerable percentage of patients. GH replacement therapy exerts a beneficial effect leading to a significant increase of erythrocytes parameters and recovery from anemia. Neither GHD nor GH replacement treatment exerts effects on leukocytes or platelets numbers.

  6. Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood.

    PubMed

    Nass, R; Huber, R M; Klauss, V; Müller, O A; Schopohl, J; Strasburger, C J

    1995-02-01

    The effects of 6 months of replacement therapy with recombinant human GH (hGH) on physical work capacity and cardiac structure and function were investigated in 20 patients with hGH deficiency of adult onset in a double blind, placebo-controlled trial. The GH dose of 12.5 micrograms/kg BW was self-administered daily sc. Oxygen consumption (VO2), CO2 production, and ventilatory volumes were measured during exercise on a bicycle spiroergometer. M-Mode echocardiography was performed using standard techniques. The VO2 max data, expressed per kg BW (mL/min.kg BW) showed a significant increase from 23.2 +/- 2.4 to 30.0 +/- 2.3 (P < 0.01) in the hGH-treated group, whereas the VO2 max data, expressed per lean body mass (milliliters per min/kg lean body mass) did not change significantly in either group. Maximal O2 pulse (milliliters per beat) increased significantly from 15.2 +/- 5.6 to 19.6 +/- 3.3 mL/beat (P < 0.01), but remained constant in the placebo group. The maximal power output (watts +/- SE) increased significantly (P < 0.01) from 192.5 +/- 13.5 to 227.5 +/- 11.5 in the hGH-treated group, but remained constant in the placebo group. Cardiac structure (left ventricular posterior wall, interventricular septum thickness, left ventricular mass, left ventricular end-systolic dimension, and left ventricular end-diastolic dimension) as well as echocardiographically assessed cardiac function did not change significantly after 6 months of treatment in either group. We conclude that hGH replacement in hGH-deficient adults improves oxygen uptake and exercise capacity. These improvements in pulmonary parameters might be due to an increase in respiratory muscle strength and partly to the changes in muscle volume per se observed during hGH replacement therapy. Furthermore, an increased cardiac output might contribute to the improvement in exercise performance during hGH treatment. According to our data, hGH replacement therapy leads to an improvement of exercise capacity and

  7. Mortality of Combined Serum Phosphorus and Parathyroid Hormone Concentrations and their Changes over Time in Hemodialysis Patients

    PubMed Central

    Streja, Elani; Wang, Hsin-Yi; Lau, Wei-Ling; Molnar, Miklos Z; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar; Park, Jongha

    2014-01-01

    Background Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD). Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management. Methods A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6 months, in particular discordant changes, were also modeled with mortality. Results HD patients were 64±15 (mean±SD) years old and included 45% women, 33% African–American, and 59% diabetic. Compared with serum P level ≥7.0 mg/dL and PTH level ≥600 pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5–<5.5 mg/dL combined with PTH level of 150–<300 pg/mL (HR 0.64, 95% confidence interval 0.61–0.67). A change over time in serum P level towards the 3.5–<5.5 mg/dL range from higher or lower ranges was associated with a decreased mortality, whereas only change in PTH level from <150 pg/mL to 150–<300 pg/mL range was associated with a lower risk of mortality. Upon discordant changes of PTH and P, i.e., decrease in one of the two measures while the other increased, no change in mortality risk was observed. Conclusion In CKD–MBD management, patent survival is the greatest with controlling both serum P and PTH levels in balance. Tailoring an individualized treatment strategy in CKD-MBD may benefit patients. Further studies are needed. PMID:24486956

  8. Mortality of combined serum phosphorus and parathyroid hormone concentrations and their changes over time in hemodialysis patients.

    PubMed

    Streja, Elani; Wang, Hsin-Yi; Lau, Wei Ling; Molnar, Miklos Z; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar; Park, Jongha

    2014-04-01

    Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD) Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management. A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6months, in particular discordant changes, were also modeled with mortality. HD patients were 64±15 (mean±SD)years old and included 45% women, 33% African-American, and 59% diabetic. Compared with serum P level ≥7.0mg/dL and PTH level ≥600pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5-<5.5mg/dL combined with PTH level of 150-<300pg/mL (HR 0.64, 95% confidence interval 0.61-0.67). A change over time in serum P level towards the 3.5-<5.5mg/dL range from higher or lower ranges was associated with a decreased mortality, whereas only change in PTH level from <150pg/mL to 150-<300pg/mL range was associated with a lower risk of mortality. Upon discordant changes of PTH and P, i.e., decrease in one of the two measures while the other increased, no change in mortality risk was observed. In CKD-MBD management, patent survival is the greatest with controlling both serum P and PTH levels in balance. Tailoring an individualized treatment strategy in CKD-MBD may benefit patients. Further studies are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males.

    PubMed

    Seimon, Radhika V; Feltrin, Kate L; Meyer, James H; Brennan, Ixchel M; Wishart, Judith M; Horowitz, Michael; Feinle-Bisset, Christine

    2009-04-01

    Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures (r = 0.76, P < 0.01), plasma CCK (r = 0.66, P < 0.01), and PYY (r = 0.98, P < 0.001), and reduced suppression of antral (r = -0.64, P < 0.05) and duodenal (r = -0.69, P < 0.05) pressure waves, desire-to-eat (r = -0.8, P < 0.001), and energy intake (r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

  10. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  11. Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study.

    PubMed

    Clarke, Bart L; Vokes, Tamara J; Bilezikian, John P; Shoback, Dolores M; Lagast, Hjalmar; Mannstadt, Michael

    2017-01-01

    In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2.0-2.2 mmol/L). Predefined endpoints related to phosphate homeostasis and vitamin D metabolism were analyzed. Serum phosphate levels decreased rapidly from the upper normal range and remained lower with rhPTH(1-84) (P < 0.001 vs. placebo). At week 24, serum calcium-phosphate product was lower with rhPTH(1-84) vs. placebo (P < 0.001). rhPTH(1-84) treatment resulted in significant reductions in oral calcium dose compared with placebo (P < 0.001) while maintaining serum calcium. After pretreatment optimization, baseline serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels were within the normal range in both groups. After 24 weeks, 1,25(OH)2D levels were unchanged in both treatment groups, despite significantly greater reductions in active vitamin D dose in the rhPTH(1-84) group. In hypoparathyroidism, rhPTH(1-84) reduces serum phosphate levels, improves calcium-phosphate product, and maintains 1,25(OH)2D and serum calcium in the normal range while allowing significant reductions in active vitamin D and oral calcium doses.

  12. Crude Glycerol as Cost-Effective Fuel for Combined Heat and Power to Replace Fossil Fuels, Final Technical Report

    SciTech Connect

    Roberts, William L

    2012-10-31

    The primary objectives of this work can be summed into two major categories. Firstly, the fundamentals of the combustion of glycerol (in both a refined and unrefined form) were to be investigated, with emphasis of the development of a system capable of reliably and repeatedly combusting glycerol as well as an analysis of the emissions produced during glycerol combustion. Focus was placed on quantifying common emissions in comparison to more traditional fuels and this work showed that the burner developed was able to completely combust glycerol within a relatively wide range of operating conditions. Additionally, focus was placed on examining specific emissions in more detail, namely interesting NOx emissions observed in initial trials, acrolein and other volatile organic emissions, and particulate and ash emissions. This work showed that the combustion of crude glycerol could result in significantly reduced NOx emissions as a function of the high fuel bound oxygen content within the glycerol fuel. It also showed that when burned properly, the combustion of crude glycerol did not result in excessive emissions of acrolein or any other VOC compared to the combustion from more traditional fuels. Lastly however, this work has shown that in any practical application in which glycerol is being burned, it will be necessary to explore ash mitigation techniques due to the very high particulate matter concentrations produced during glycerol combustion. These emissions are comparable to unfiltered coal combustion and are directly tied to the biodiesel production method. The second focus of this work was directed to developing a commercialization strategy for the use of glycerol as a fuel replacement. This strategy has identified a 30 month plan for the scaling up of the laboratory scale burner into a pre-pilot scale system. Additionally, financing options were explored and an assessment was made of the economics of replacing a traditional fuel (namely natural gas) with crude

  13. Effect of Combined Single-Injection Femoral Nerve Block and Patient-Controlled Epidural Analgesia in Patients Undergoing Total Knee Replacement

    PubMed Central

    Lee, Ae-Ryung; Choi, Duck-Hwan; Choi, Soo-Joo; Hahm, Tae-Soo; Kim, Ga-Hyun; Moon, Young-Hwan

    2011-01-01

    Purpose Total knee replacement is one of the most painful orthopedic procedures, and effective pain relief is essential for early mobility and discharge from hospital. The aim of this study was to evaluate whether addition of single-injection femoral nerve block to epidural analgesia would provide better postoperative pain control, compared to epidural analgesia alone, after total knee replacement. Materials and Methods Thirty-eight patients received a single-injection femoral nerve block with 0.25% levobupivacaine (30 mL) combined with epidural analgesia (femoral nerve block group) and 40 patients received epidural analgesia alone (control group). Pain intensity and volume of patient-controlled epidural analgesia medication and rescue analgesic requirements were measured in the first 48 hours after surgery at three time periods; 0-6 hours, 6-24 hours, and 24-48 hours. Also, side effects such as nausea, vomiting, and pruritus were evaluated. Results Median visual analog scale at rest and movement was significantly lower until 48 hours in the femoral nerve block group. Patient-controlled epidural analgesia volume was significantly lower throughout the study period, however, rescue analgesia requirements were significantly lower only up to 6 hours in the femoral nerve block group. The incidences of nausea and vomiting and rescue antiemetic requirement were significantly lower in the femoral nerve block group up to 6 hours. Conclusion The combination of femoral nerve block with epidural analgesia is an effective pain management regimen in patients undergoing unilateral total knee replacement. PMID:21155047

  14. Differential effects on visual and spatial recognition memory of a novel hormone therapy regimen of estrogen alone or combined with progesterone in older surgically menopausal monkeys.

    PubMed

    Voytko, M L; Higgs, C J; Murray, R

    2008-07-17

    Building upon our initial studies in young adult surgically menopausal monkeys, this study examined the effects of a novel schedule of administration of estradiol therapy alone, or in combination with progesterone, on visual and spatial recognition memory in older monkeys. Monkeys were preoperatively trained on a delayed matching-to-sample task and a delayed response task. At the time of ovariectomy, monkeys began their hormonal treatments and were cognitively assessed at 2, 12 and 24 weeks following treatment initiation. A schedule of hormone administration was used that closely modeled the normal fluctuations of hormones during the course of a normal primate menstrual cycle. Monkeys receiving placebo had lower levels of accuracy than monkeys receiving estrogen therapies on the delayed matching-to-sample task that were not apparent until 12 weeks following initiation of therapy and were no longer detected at the 24-week assessment. There was no effect of hormone therapy on accuracy in the delayed response task at any of the postoperative assessments. In both tasks, monkeys treated with estrogen plus progesterone had longer choice response latencies, especially on trials in which they made errors; however these effects did not influence accuracy measures in these animals. Our findings indicate that visual recognition ability may be more sensitive than spatial recognition memory to this novel hormone therapy regimen, that treatment with estradiol plus progesterone was equivalent to that of estradiol alone, and that neither therapy had significant negative impact on memory profiles.

  15. Hormone therapy in acne.

    PubMed

    Lakshmi, Chembolli

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  16. [Post-operative management for 86 cases of heart valve replacement surgery patients undergoing transcutaneous electrical acupoint stimulation combined with general anesthesia].

    PubMed

    Zhou, Wen-Xiong; Xu, Jian-Jun; Wu, Yao-Yao; Chi, Hao; Chen, Tong-Yu; Ge, Wen; Zhou, Jia

    2014-02-01

    To summarize post-operative management strategy for heart valve replacement surgery under transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia. From July 2006 to June 2012, a total of 86 cases of open-heart surgery patients experiencing TEAS plus general anesthesia with cardiopulmonary bypass (heart valve replacement surgery without intubation) were recruited in the present summary. Post-operative managements in the Intensive Care Unit (ICU) were administrated with strict hemodynamic monitoring for volume infusion, routine administration of vasoactive drugs (including dopamine and nitroglycerin), oxygen inhalation, and analgesics and monitoring of central nervous system and renal function. All the 86 patients under TEAS + general anesthesia and cardiopulmonary bypass and without intubation experienced successful heart valve replacement surgery. The post-operative pulmonary infection was found in 8 cases (9.30%), the average stay duration in ICU was (28.6 +/- 6.2) hours, and the average draining volume of the interpleural space was (291 +/- 73)mL. The cardia insufficiency was found in 5 cases (5.81%), hypoxia occurred in 8 cases (9.30%), nausea in 8 cases (9.30%), vomiting 5 cases (5.81%) and post-operative gastrointestinal distension 13 cases (15.12%), mild renal insufficiency 3 cases (3.49%), fever (> 38.5 degrees C) 1 case(1. 16%) and severe post-operative pain 7 cases (8.14%). TEAS combined with general anesthesia is safe for patients undergoing heart valve replacement surgery under cardiopulmonary bypass. The key points of treatment in ICU are volume infusion, body temperature maintenance, and pain control.

  17. Ethinylestradiol-chlormadinone acetate combination for the treatment of hirsutism and hormonal alterations of normal-weight women with polycystic ovary syndrome: evaluation of the metabolic impact.

    PubMed

    Guido, Maurizio; Romualdi, Daniela; Campagna, Giuseppe; Ricciardi, Luigi; Bompiani, Alessandro; Lanzone, Antonio

    2010-08-01

    This is the first study evaluating the clinical, metabolic, and hormonal effects of the ethinylestradiol-chlormadinone acetate (EECMA) combination in hirsute women with polycystic ovary syndrome (PCOS). Ultrasonographic pelvic examination, hirsutism score, and hormone profile evaluation were performed at baseline and after 3 and 6 cycles of treatment. Oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, and assessment of lipid profile were carried out at baseline and after 6 cycles of treatment. A significant improvement in hirsutism was evident at the end of treatment. From the third cycle onward, plasma levels of sex hormone binding globulin significantly increased when compared to baseline. Free androgen index, androstenedione, and 17-hydroxyprogesterone significantly decreased after 6 cycles. The treatment did not affect glucose and insulin homeostasis. Total cholesterol, triglycerides, and high-density lipoprotein (HDL) plasma levels remained unvaried, whereas low-density lipoprotein (LDL) concentrations showed a significant reduction. A significant increase in very-low-density lipoprotein (VLDL) levels was seen at the sixth cycle of therapy. In conclusion, EE-CMA combination ameliorates clinical and hormonal features of PCOS women, with no detrimental effects on glucose, insulin, and lipid metabolism.

  18. A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer.

    PubMed

    Carlson, Robert W; O'Neill, Anne; Vidaurre, Tatiana; Gomez, Henry L; Badve, Sunil S; Sledge, George W

    2012-06-01

    EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. The primary endpoint was clinical benefit (complete responses plus partial responses plus stable disease for 6 months or longer). 141 eligible subjects were enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44% [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI 29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus 5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+) versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity.

  19. Gonadectomy and hormone replacement exert region- and enzyme isoform-specific effects on monoamine oxidase and catechol-O-methyltransferase activity in prefrontal cortex and neostriatum of adult male rats.

    PubMed

    Meyers, B; D'Agostino, A; Walker, J; Kritzer, M F

    2010-02-03

    Sex differences and gonadal hormone influences are well known for diverse aspects of forebrain amine and indolamine neurotransmitter systems, the cognitive and affective functions they govern and their malfunction in mental illness. This study explored whether hormone regulation/dysregulation of these systems could be related to gonadal steroid effects on catechol-O-methyltransferase and monoamine oxidase which are principal enzymatic controllers of forebrain dopamine, serotonin and norepinephrine levels. Driven by male over female differences in cortical enzyme activities, by male-specific associations between monoamine oxidase and catechol-O-methyltransferase gene polymorphisms and cognitive and dysfunction in disease and by male-specific consequences of gene knockouts in mice, the question of hormone sensitivity was addressed here using a male rat model where prefrontal dopamine levels and related behaviors are also known to be affected. Specifically, quantitative O-methylation and oxidative deamination assays were used to compare the activities of catechol-O-methyltransferase's soluble and membrane-bound isoforms and of monoamine oxidase's A and B isoforms in the pregenual medial prefrontal cortex and dorsal striatum of male rats that were sham operated, gonadectomized or gonadectomized and supplemented with testosterone propionate or with estradiol for 28 days. These studies revealed significant effects of hormone replacement but not gonadectomy on the soluble but not the membrane-bound isorfom of catechol-O-methyltransferase in both striatum and cortex. A significant, cortex-specific testosterone-but not estradiol-attenuated effect (increase) of gonadectomy on monoamine oxidase's A but not B isoform was also observed. Although none of these actions suggest potential roles in the regulation/dysregulation of prefrontal dopamine, the suppressive effects of testosterone on cortical monoamine oxidase-A that were observed could have bearing on the increased

  20. Digitized assessment of mammographic breast density--effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo.

    PubMed

    Lundström, E; Hirschberg, A L; Söderqvist, G

    2011-12-01

    To determine the effects of continuous combined hormone therapy, tibolone, black cohosh, and placebo on digitized mammographic breast density in postmenopausal women. A prospective, double-blind, placebo-controlled study of 154 postmenopausal women randomized to estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo and a prospective, open, uncontrolled drug safety study, of which 65 postmenopausal women were treated with black cohosh. Mammograms, at baseline and after six months of treatment, were previously classified according to visual quantification scales. Reanalysis of assessable mammograms by digitized quantification of breast density. Treatment groups were comparable at baseline. During treatment, both E2/NETA and tibolone significantly increased breast density (mean increase 14.3%, p<0.001 and 2.3%, p<0.001, respectively), while black cohosh and placebo did not. Twenty-four out of the 43 women on E2/NETA had an increase in density exceeding 10% and 6 women had an increase of 30% or more. In the tibolone group, only one woman had an increase in density of more than 10%. The difference in increase in breast density between E2/NETA on the one hand and tibolone, black cohosh and placebo on the other was highly significant (p<0.0001). Digitized mammographic breast density is a highly sensitive method confirming significant increase in density by standard E2/NETA treatment and to a lesser extent by tibolone, whereas black cohosh does not influence mammographic breast density during six months treatment. Digitized assessment also yields data on individual variation and small increases left undetectable by visual classification. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats

    PubMed Central

    Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

    2013-01-01

    Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method. PMID:23239176

  2. Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats.

    PubMed

    Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

    2013-05-01

    Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method.

  3. Administration of human chorionic gonadotropin to suckled beef cows before ovulation synchronization and fixed-time insemination: replacement of gonadotropin-releasing hormone with human chorionic gonadotropin.

    PubMed

    Marquezini, G H L; Dahlen, C R; Bird, S L; Lamb, G C

    2011-10-01

    Two experiments were conducted to evaluate whether hCG administered 7 d before initiating the CO-Synch + controlled internal drug release (CIDR) ovulation synchronization protocol (Exp. 1 and 2), or replacing GnRH with hCG at the time of AI (Exp. 1), would improve fertility to a fixed-time AI (TAI) in suckled beef cows. In addition, the effects of hCG on follicle dynamics, corpus luteum development, and concentrations of progesterone (P4) were evaluated. In Exp. 1, cows were stratified by days postpartum, age, and parity and assigned randomly to a 2 × 2 factorial arrangement of 4 treatments: 1) cows received 100 µg of GnRH at CIDR insertion (d -7) and 25 mg of PGF(2α) at CIDR removal (d 0), followed in 64 to 68 h by a TAI plus a second injection of GnRH at TAI (CG; n = 29); 2) same as CG but the second injection of GnRH at the time of insemination was replaced by hCG (CH; n = 28); 3) same as CG, but cows received hCG 7 d (d -14) before CIDR insertion (HG; n = 28); and 4) same as HG, but cows received hCG 7 d (d -14) before CIDR insertion (HH; n = 29). Pregnancy rates were 52, 41, 59, and 38% for GG, GH, HG, and HH, respectively. Cows receiving hCG (39%) in place of GnRH at TAI tended (P = 0.06) to have poorer pregnancy rates than those receiving GnRH (56%). Pre-CO-Synch hCG treatment increased (P < 0.05) the percentage of cows with concentrations of P4 >1 ng/mL at d -7, increased (P < 0.02) concentration of P4 on d -7, and decreased (P < 0.001) the size of the dominant follicle on d 0 and 3, compared with cows not treated with hCG on d -14. In Exp. 2, cows were stratified based on days postpartum, BCS, breed type, and calf sex and then assigned to the CG (n = 102) or HG (n = 103) treatments. Overall pregnancy rates were 51%, but no differences in pregnancy rates were detected between treatments. Pre-CO-Synch hCG treatment increased (P < 0.05) the percentage of cows cycling on d -7 and increased (P < 0.05) concentrations of P4 on d -7 compared with pre

  4. Decreasing cardiovascular risk factors in obese individuals using a combination of PGX® meal replacements and PGX® granules in a 12-week clinical weight modification program.

    PubMed

    Reichert, Ronald G; Lyon, Michael R; Kacinik, Veronica; Gahler, Roland J; Manjoo, Priya; Purnama, Monica; Wood, Simon

    2013-05-07

    In this open, clinically based, weight modification program, we determined in six sedentary obese adults (five women; one male; age range 30-62 years) that the combination of a modified calorie diet plus PGX® meal replacement and PGX® supplementation resulted in a significant reduction in several cardiovascular risk factors over a 12-week time period. This included a significant improvement in lipids (-0.98 mmol/l LDL-C), reduction in average weight (-9.2 kg), mean reduction in fat (-4.1%) and an increase in fat-free mass (2.8%).

  5. Effect of thyroid hormone replacement on methionine-stimulated homocysteine levels in patients with subclinical hypothyroidism: a randomized, double-blind, placebo-controlled study.

    PubMed

    Meek, Shon; Smallridge, Robert C

    2006-01-01

    To determine whether treatment of subclinical hypothyroidism with levothyroxine would improve homocysteine metabolism. Twenty-four patients with subclinical hypothyroidism who had thyrotropin (thyroid-stimulating hormone or TSH) levels between 5 and 10 microIU/mL and normal free thyroxine concentrations were recruited from a primary care clinic and were randomized to receive levothyroxine (N = 12) or placebo (N = 12) for a period of 6 months in a double-blind, placebo-controlled study. Homocysteine was measured during fasting and after methionine challenge at the beginning and the end of the study in all patients treated with levothyroxine or placebo. The 12 patients treated with levothyroxine had normal TSH levels at the end of the study, with a median value of 1.8 microIU/mL. The 12 patients receiving placebo had a median TSH of 6.0 microIU/mL after the 6-month study period. The ratio of fasting homocysteine at 6 months in comparison with baseline was 1.16 (95% confidence interval, 0.90 to 1.63) for the levothyroxine-treated group and 1.00 (0.88 to 1.29) for the placebo group (P = 0.95). The ratio of post-methionine homocysteine at 6 months in comparison with baseline was 1.00 (95% confidence interval, 0.92 to 1.35) for the levothyroxine-treated group and 0.89 (0.68 to 1.05) for the placebo group (P = 0.081). In this study, levothyroxine treatment of patients with subclinical hypothyroidism did not alter homocysteine levels in the fasting or post-methionine states.

  6. Sensitive determinations of Cu, Pb, Cd, and Cr elements in aqueous solutions using chemical replacement combined with surface-enhanced laser-induced breakdown spectroscopy.

    PubMed

    Yang, X Y; Hao, Z Q; Li, C M; Li, J M; Yi, R X; Shen, M; Li, K H; Guo, L B; Li, X Y; Lu, Y F; Zeng, X Y

    2016-06-13

    In this study, chemical replacement combined with surface-enhanced laser-induced breakdown spectroscopy (CR-SENLIBS) was for the first time applied to improve the detection sensitivities of trace heavy metal elements in aqueous solutions. Utilizing chemical replacement effect, heavy metal ions in aqueous solution were enriched on the magnesium alloy surface as a solid replacement layer through reacting with the high chemical activity metallic magnesium (Mg) within 1 minute. Unitary and mixed solutions with Cu, Pb, Cd, and Cr elements were prepared to construct calibration curves, respectively. The CR-SENLIBS showed a much better detection sensitivity and accuracy for both unitary and mixed solutions. The coefficients of determination R2 of the calibration curves were above 0.96, and the LoDs were of the same order of magnitude, i.e., in the range of 0.016-0.386 μg/mL for the unitary solution, and in the range of 0.025-0.420 μg/mL for the mixed solution. These results show that CR-SENLIBS is a feasible method for improving the detection sensitivity of trace element in liquid sample, which definitely provides a way for wider application of LIBS in water quality monitoring.

  7. [Combination of exemestane and everolimus may produce toxic side effects: a new treatment option for metastatic hormone-sensitive breast cancer].

    PubMed

    Vincent, Jeroen; de Boer, Maaike; Lobbezoo, Dorien J A; Smeets, Ruud E H; Tjan-Heijnen, Vivianne C G

    2014-01-01

    The combination of exemestane and everolimus is a new treatment option for metastatic hormone-sensitive breast cancer. This treatment is used after progression on non-steroidal aromatase inhibitors. The treatment is generally well tolerated, but sometimes leads to minor or even serious side effects. It is important to be aware of these side effects and to treat them. We describe two patients who had to cope with various forms of toxicity: a 73-year-old woman with aphthous mouth lesions and a 49-year-old woman with pneumonitis. We then discuss the efficacy of the combination exemestane and everolimus and its positioning in the treatment of metastatic hormone-sensitive breast cancer. Finally, some common and some potentially serious side effects will be discussed, along with recommendations for their management and indications for distinguishing side effects from disease progression.

  8. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    SciTech Connect

    Fujita, Tetsuo; Teh, Bin S.; Mai, W.-Y.; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-05-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR{sup +}CD8{sup +} T cells were increased at all timepoints up to 8 months. The mean percentages of DR{sup +}CD4{sup +} T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.

  9. Vein replacement with fresh vital veins: a comparison of transplantation in RT-1-different rat strain combinations.

    PubMed

    Thiede, A; Engemann, R; Korner, H H; Deltz, E; Muller-Ruchholtz, W

    1981-03-01

    Transplantation of the intrathoracic inferior vena cava into the abdominal inferior vena cava of the recipient was performed in inbred rat strains of the following combinations: Syngeneic F344 leads to F344, RT-1-identical allogeneic LEW leads to F344, and RT-1-different allogeneic CAP leads to F344. In the RT-1-different combination subgroups with presensitization (blood, skin) were formed. The transplanted veins were evaluated at different times, macro- and microscopically. To test humoral immunology reactivity, we used a modified hemagglutination test, to analyse cell-mediated reactivity, subsequent skin grafts. The following results were obtained: 1) Aside from sporadic mononuclear cells caused by the operation technique, syngeneic vein grafts do not show any macroscopically visible and microscopically detectable changes. 2) Weakly allogeneic vein grafts do not lead to microscopically detectable changes in the graft. Strongly allogeneic vein grafts cause temporary