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The global increase in life expectancy to 74 years for women, while the median age of the menopause remains at 51 years, means that an increasing number of women will live a significant portion of their adult lives in the menopause. The WHI publications in 2003/4 reported on the dangers of hormone replacement therapy, in particular with respect to breast cancer and dementia risk. This resulted in a dramatic reduction in hormone replacement therapy prescription and use. However, the findings from the WHI studies have been re-appraised, and the new perspective is reflected in the guidance published by NICE in 2015 in which they recommended that more women be offered hormone replacement therapy as the benefits are now perceived to outweigh the risks for most women. However, controversy continues to surround hormone replacement therapy, and there are probably few areas in medicine where the misuse of terminology causes quite as much confusion as in hormone replacement therapy. Commonly used terms such as 'menopausal hormone therapy' and 'hormone replacement therapy' lack specificity and there is an urgent need for correct terminology to accurately describe the hormones replaced.

Background: In recent years there has been a significant increase in the number of trans, gender diverse and non-binary (TGDNB) people accessing healthcare. For many of these individuals the first port of call will be to their local general practitioner (GP). The TGDNB community is a high-priority population with the highest suicide rates of any population group in Australia. There is evidence that mental health outcomes improve significantly when individuals are able to access gender-affirming hormones., Objective: The aim of this article is to provide GPs working in Australia with a practical guide to prescribe gender-affirming hormone therapy to TGDNB patients., Discussion: GPs are ideally placed to provide care for TGDNB patients in the primary care setting. Gender incongruence is no longer viewed as a mental health disorder. In recent years there has been a move away from mandatory psychiatric assessment to more contemporary patient-centred models of care.

Purpose: Ovarian and adrenal aging leads to a progressive decline in androgen levels and deleterious effects on the quality of life. Despite this, specific replacement is not routinely recommended in the management of women with a physiological or pathological decline in their production, mainly due to the lack of long-term follow-up safety data. The purpose of this paper was to meta-analyze and summarize the existing data about hormonal profile changes in menopausal women receiving androgen replacement treatments. Full-text articles published through May 30, 2018 were found via MEDLINE and Embase and selected according to the strict inclusion criteria., Methods: Randomized clinical trials and case-control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. 113 papers fulfilled the inclusion criteria and 56 papers were included in the analysis. Desired data were compiled and extracted by independent observers., Results: Androgen administration increases E1, E2, testosterone, DHEA and DHEAS serum levels, and reduces SHBG. However, the E1 and E2 increase is evident only when DHEA is administered., Conclusions: Whatever androgen formulation we choose in postmenopausal women, the end result is a rise in testosterone serum levels. However, DHEA regimen is also associated with an increased estrogenic availability. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

Purpose: We explored the Medicare database (1999 to 2014) to provide a comprehensive assessment of testosterone therapy patterns in the older U.S. male population., Materials and Methods: We estimated annual age-standardized incidence (new users) and prevalence (existing users) of testosterone therapy according to demographic characteristics, comorbidities and potential indications., Results: There were 392,698 incident testosterone therapy users during 88 million person-years. Testosterone therapy users were predominantly younger, white nonHispanic, and located in South and West U.S. Census regions. On average testosterone therapy use increased dramatically during 2007 to 2014 (average annual percent change 15.5%), despite a decrease in 2014. In 2014 the most common recorded potential indications for any testosterone therapy were hypogonadism (48%), fatigue (18%), erectile dysfunction (15%), depression (4%) and psychosexual dysfunction (1%). Laboratory tests to measure circulating testosterone concentrations for testosterone therapy were infrequent with 35% having had at least 1 testosterone test in the 120 days preceding testosterone therapy, 4% the recommended 2 pre-testosterone therapy tests, and 16% at least 1 pre-testosterone therapy test and at least 1 post-testosterone therapy test., Conclusions: Testosterone therapy remains common in the older U.S. male population, despite a recent decrease. Although testosterone therapy prescriptions are predominantly for hypogonadism, a substantial proportion appear to be for less specific conditions. Testosterone tests among men prescribed testosterone therapy appear to be infrequent.

Objective: To determine the optimal endometrial preparation protocols of frozen-thawed embryo transfer (FET) in young women with regular menstrual cycles., Design: Retrospective cohort study., Setting: Public fertility center., Patient(s): Infertile women with regular menstrual cycles undergoing FET., Intervention(s): Natural cycle (NC) treatment for patients with proven ovulation in previous cycles or who refused medication (n = 308), or hormone treatment (HT) for patients who could not be frequently monitored (n = 1,538)., Main Outcome Measure(s): Live-birth rates., Result(s): The live-birth rates were 61.73% in the NC group and 55.11% in the HT group. The effect size of the endometrial preparation on live-birth rates was evaluated in prespecified and exploratory subgroups in each subgroup, and multivariable logistic regression analysis was used to determine which variables could be independently associated with the live-birth rate. The HT patients had a lower chance of live birth in all subgroups: endometrial thickness on the day of progesterone administration, triple-line endometrial pattern, female age at embryo transfer, fertilization type, and protocol in the fresh cycle. Multivariable analysis showed NC to be associated with an increased likelihood of live birth compared with HT., Conclusion(s): Natural cycle treatment has a higher chance of live birth than HT for endometrial preparation in young women with regular menstrual cycles., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Recommendations for using menopausal hormone therapy (MHT) and bisphosphonates for postmenopausal osteoporosis management have changed over time. After the release of the Women's Health Initiative (WHI) trial results in 2002, new evidence on risks and benefits of MHT became available, and newer guidelines generally specify that MHT should not be prescribed for prevention of chronic disease, including osteoporosis. This raises the question of whether bisphosphonate prescribing changed over time to compensate for the decrease in MHT use. Materials and Methods: We examined trends in dispensed prescriptions in Australia (national) and Canada (province of Manitoba) in relation to prescribing recommendations. Administrative data were used to describe dispensing patterns and changes for persons of all ages from 1996 to 2008, and for women aged 50 to ≥80 years from 2003 to 2008 in Australia and 1996 to 2008 in Canada. Results: In both geographic settings, MHT dispensing increased 1996-2001, peaked in 2001, and declined substantially thereafter (67% reduction in MHT prescriptions for Australia; 64% reduction for Manitoba, Canada to 2008). From 2003 to 2008, the number of MHT prescriptions declined among all age groups in both settings, with the highest declines among women in their 50s. Concurrently, bisphosphonate dispensing increased until 2005 (2001-2005: 260% increase in the number of prescriptions in Australia; 125% increase in Manitoba) and stabilized thereafter, in both settings. Annual bisphosphonate dispensing rates increased 4.1-10.9% for women in their 70s and 80s in Australia and Manitoba during the period studied. Conclusions: Based on dispensed prescriptions data, more recent guidelines for MHT and bisphosphonates use for postmenopausal osteoporosis, which were updated during the study period (and are still consistent with the current guidelines), appear to have been broadly adhered to in both settings.

Background: We assessed whether postmenopausal hormone therapy (HT) was associated with incident heart failure (HF) and its subtypes and examined whether there was a modifying effect of age on the associations., Methods and Results: Postmenopausal women aged 50-79 enrolled in the Women's Health Initiative HT trials were analyzed. The 16,486 women with a uterus were randomized to receive conjugated equine estrogens (CEE 0.625 mg/day) plus medroxyprogesterone acetate (MPA 2.5 mg/day) or placebo, and 10,739 women with prior hysterectomy were randomized to receive CEE (0.625 mg/day) alone or placebo. Incident HF was defined as the first HF hospitalization. HF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) was defined as EF < 50% or ≥ 50%. During the intervention phase, median follow-up was 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial. During the cumulative follow-up of 18.9 years, women randomized to HT vs placebo in the 2 combined trials had incidence rates of 3.90 vs 3.89 per 1000 person-years for total HF; 1.25 vs 1.40 per 1000 person-years for HFrEF, and 1.88 vs 1.79 per 1000 person-years for HFpEF, respectively. There were no significant effects of HT on the risk of total incident HF or its subtypes in either trial, and age at randomization did not significantly modify the results., Conclusions: Postmenopausal HT did not alter the risk of hospitalization for HF or its subtypes during the intervention or cumulative 18.9 years of follow-up, and results did not vary significantly by age at randomization., Trial Registration: clinicaltrials.gov Identifier: NCT0000611 https://clinicaltrials.gov/ct2/show/NCT00000611?cond=women%27s±health±initiative&rank=5., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Both the morbidity and mortality rates from congestive heart failure (CHF) remain elevated despite the medical and non-medical management of the disease, thus suggesting the existence of residual risk factors such as thyroid dysfunction. Particularly, the 15-30% of patients with CHF, especially those with severe ventricular dysfunction, display the so-called low T3 syndrome (LT3S), which seems to negatively affect the cardiovascular prognosis., Objective: Only a few clinical trials have been carried out to verify both the safety and the efficacy of thyroid replacement in the LT3S, aiming to ameliorate the prognosis of CHF, and most of the results were controversial., Methods: Since the aim of the present review was to briefly overview both the indication and contraindication of triiodothyronine replacement in CHF and LT3S, the authors searched PubMed using the medical subject headings (MeSH) related to the following terms: "congestive heart failure" and "low T3 syndrome" or "euthyroid sick syndrome" or "non-thyroidal sick syndrome". The research study only focused on the narrative and systematic reviews, randomized clinical trials and meta-analysis studies which were conducted before June 2019., Results: Studies conducted in both animal models and humans provided controversial information about the effectiveness and safety of the T3 replacement for improving ventricular dysfunction, particularly in the long-term., Conclusion: Further clinical trials are needed to better explore the role of LT3S in patients with CHF and its consequent therapeutic strategy in this clinical setting., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose of Review: Hormonal treatment in trans persons can affect bone health. In this review, recent studies published on this topic in adults are discussed., Recent Findings: Before starting hormonal treatment, trans women were found to have lower bone mineral density than cis men, which seems to be related to lower vitamin D concentrations and lower lean body mass, whereas this was not found in trans men. Short-term and long-term studies show that hormonal treatment does not have detrimental effects on bone mineral density in trans women and trans men. Low estradiol concentrations were associated with a decrease in bone mineral density in trans women., Summary: Based on the reassuring findings in these studies, regularly assessing bone mineral density during hormonal treatment does not seem necessary. This confirms the Endocrine Society Guideline stating that bone mineral density should be measured only when risk factors for osteoporosis exist, especially in people who stop hormonal treatment after gonadectomy. The relationship with estradiol concentrations indicate that hormone supplementation should be adequate and therapy compliance should be stimulated. As vitamin D deficiency frequently occurs, vitamin D supplementation should be considered. Future research should focus on fracture risk and long-term changes in bone geometry.

Migraine is a lifelong condition that disproportionately affects women and, if not effectively managed, can lead to significant disability. It is important for clinicians to have a good understanding of the impact of the hormonal fluctuations that occur throughout a female migraineur's life, so that appropriate, stratified therapies can be implemented. In doing so, whether it is migraine onset at menarche in an adolescent young woman, or migraine worsening in a perimenopausal female migraineur, quality of life can be ensured., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. Turner syndrome is associated with short stature, delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, congenital malformations of the heart, endocrine disorders such as type 1 and type 2 diabetes mellitus, osteoporosis and autoimmune disorders. Morbidity and mortality are increased in women with Turner syndrome compared with the general population and the involvement of multiple organs through all stages of life necessitates a multidisciplinary approach to care. Despite an often conspicuous phenotype, the diagnostic delay can be substantial and the average age at diagnosis is around 15 years of age. However, numerous important clinical advances have been achieved, covering all specialty fields involved in the care of girls and women with Turner syndrome. Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy.

This review summarizes evidence that may enhance and influence clinical practice of women's health. Supporting articles were identified by reviewing high-impact medical and women's health journals published in 2017 and 2018. The chosen articles are pertinent to osteoporosis screening, hormonal contraceptive interactions with antibiotics, hormone replacement therapy in BRCA1 mutation carriers, breast cancer diagnosis using digital tomosynthesis, and risks of hormonal contraception., (Copyright © 2019 Cleveland Clinic.)

Purpose: The purpose of the study is to examine relationships between long-term trends of region- and age-specific rates of mammography, hormone replacement therapy (HRT), and breast cancer incidence and mortality in Canadian women aged 35 years and older., Methods: Population-based complex surveys were used to estimate mammography use in the past 2 years and ever, and HRT use in the past month. National population-based administrative data were used to estimate breast cancer incidence and mortality. Joinpoint analyses were used to estimate trends in rates and years where trend changed., Results: No consistent relationship between mammography use and breast cancer incidence was observed across age groups. Opportunistic screening occurred prior to the establishment of organized screening programs in Canada and prior to substantial declines in breast cancer mortality observed around 1990. Women aged 35-39 years demonstrated a 62.8% relative decrease in breast cancer mortality between 1950 and 2015 despite lower rates of mammography use in the past 2 years (range 9.4-15.9%) reinforcing important treatment advances. A substantial proportion of women in their 40s report mammography use in the past 2 years (range 35.8-42.2%) and regional variation exists reflecting inconsistencies in guidelines across Canada., Conclusion: Rates of mammography use over time do not necessarily reflect national guideline releases or establishment of organized screening programs.

Hormone therapy use has undergone dramatic changes over the past 20 years. Widespread use of hormone therapy in the 1980s and 1990s came to an abrupt halt in the early 2000s after initial findings of the Women's Health Initiative trial were published and the study was terminated. Since then, much has been learned about the characteristics of women most likely to benefit from hormone therapy. There is general agreement that women younger than 60 years or who initiate hormone therapy within 10 years of menopause onset gain short-term benefit in terms of symptomatic relief and long-term benefit in terms of protection from chronic diseases that affect postmenopausal women. Despite accumulating evidence in support of hormone therapy for symptomatic menopausal women, the slow response by the medical community has led to a 'large and unnecessary burden of suffering' by women worldwide. Greater efforts are clearly needed to educate physicians and medical students about the pathophysiology of menopause and the role of hormone therapy in supporting women through the transition. This article provides a brief historical perspective of events that led to the backlash against hormone therapy, explores the current position of guideline groups, and provides practical recommendations to guide first-line management of symptomatic menopausal women.

Major advances in menopause hormone therapy (MHT) hold promise in the future of better and safer care for women at and after the menopause. The principal advances are: (1) the critical window or 'window of opportunity' in the 10 years or so after the menopause, during which the benefits of MHT in healthy women exceed any risks; (2) use of transdermal instead of oral administration of estrogen to reduce the risk of venous thromboembolism; (c) investigation of the use of oral micronized progesterone (MP) and vaginal MP to prevent endometrial hyperplasia and carcinoma without any increased risk of breast cancer and venous thromboembolism in postmenopausal women receiving estrogens; vaginal MP prevents endometrial proliferation in the short term but the long-term effects in MHT remain to be established; (4) investigation into the use of intrauterine levonorgestrel-releasing devices (LNG-IUDs), which are an attractive form of MHT in perimenopausal women, providing contraception and reducing uterine bleeding, although the risk of breast cancer with LNG-IUDs requires clarification. Women in the future can look forward to a symptom-free menopause and to safer and more beneficial MHT.

Objective: This review describes historical development of selective estrogen receptor modulators (SERMs) and their combination with estrogens, termed a tissue selective estrogen complex (TSEC), and considers the potential for future TSEC development., Methods: This narrative review is based on literature identified on PubMed and the TSEC research and development experience of the authors., Results: SERMs have estrogenic and antiestrogenic effects in various tissues; however, no single agent has achieved an optimal balance of agonist and antagonist effects for the treatment of menopausal symptoms. Clinically, a number of SERMs protect against osteoporosis and breast cancer but can exacerbate vasomotor symptoms. Estrogens alleviate menopausal hot flushes and genitourinary symptoms as well as reduce bone loss, but the addition of a progestogen to menopausal hormone therapy to protect against endometrial cancer increases vaginal bleeding risk, breast tenderness, and potentially breast cancer. The search for an effective menopausal therapy with better tolerability led to the investigation of TSECs. Clinical development of a TSEC consisting of conjugated estrogens/bazedoxifene increased understanding of the importance of a careful consideration of the combination's components and their respective doses to balance safety and efficacy. Bazedoxifene is an estrogen receptor agonist in bone but an antagonist/degrader in the endometrium, which has contributed to its success as a TSEC component. Other oral TSEC combinations studied thus far have not demonstrated similar endometrial safety., Conclusions: Choice of SERM, selection of doses, and clinical trial data evaluating safety and efficacy are key to ensuring safety and adequate therapeutic effect of TSECs for addressing menopausal symptoms.

Growth hormone (GH) replacement therapy was recently recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the Pharmaceutical Benefits Scheme for adults with severe GH deficiency and impaired quality of life. This approval was significant for two reasons. First, the application was initiated and coordinated by a health professional working group, who prepared a 'public interest' submission to PBAC. Second, it resulted in a recommendation to subsidise therapy for a rare disease after two prior rejections on the basis of uncertainty about efficacy and cost effectiveness. There are important lessons to learn about the power of professional groups to drive health policy and attain funding for rare diseases., (© 2018 Royal Australasian College of Physicians.)

Over the last decade the use of frozen-thawed embryo transfer has substantially increased, and currently up to one in two embryos transferred has been cryopreserved. To support implantation, endometrial and embryo maturity are required to be synchronized. This can be achieved in various ways. The most commonly applied endometrial preparation methods are the "natural cycle," in which the sequential estrogen and P necessary for endometrial maturation are derived from the developing follicle, and the "artificial" cycle, in which these are sequentially administered. Review of the published data comparing these approaches does not identify a superior approach in terms of clinical outcomes. However, although the "natural cycle" avoids the need for luteal support, the artificial cycle provides more control over timing of ET, and the "modified" natural cycle, in which ovulation is triggered exogenously, may offer both of these advantages. The optimal monitoring strategy for freeze-thaw cycles remains unclear, because only a few studies have addressed this question. Further studies are also required to determine the ideal dosage, method of administration, and duration of estrogen and P supplementation in artificial cycle frozen embryo transfer., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Hormonal interventions are being increasingly used to treat young people with gender dysphoria, but their effects in this population have not been systematically reviewed before., Objective: To review evidence for the physical, psychosocial, and cognitive effects of gonadotropin-releasing hormone analogs (GnRHa), gender-affirming hormones, antiandrogens, and progestins on transgender adolescents., Data Sources: We searched Medline, Embase, and PubMed databases from January 1, 1946, to June 10, 2017., Study Selection: We selected primary studies in which researchers examined the hormonal treatment of transgender adolescents and assessed their psychosocial, cognitive, and/or physical effects., Data Extraction: Two authors independently screened studies for inclusion and extracted data from eligible articles using a standardized recording form., Results: Thirteen studies met our inclusion criteria, in which researchers examined GnRHas ( n = 9), estrogen ( n = 3), testosterone ( n = 5), antiandrogen (cyproterone acetate) ( n = 1), and progestin (lynestrenol) ( n = 1). Most treatments successfully achieved their intended physical effects, with GnRHas and cyproterone acetate suppressing sex hormones and estrogen or testosterone causing feminization or masculinization of secondary sex characteristics. GnRHa treatment was associated with improvement across multiple measures of psychological functioning but not gender dysphoria itself, whereas the psychosocial effects of gender-affirming hormones in transgender youth have not yet been adequately assessed., Limitations: There are few studies in this field and they have all been observational., Conclusions: Low-quality evidence suggests that hormonal treatments for transgender adolescents can achieve their intended physical effects, but evidence regarding their psychosocial and cognitive impact are generally lacking. Future research to address these knowledge gaps and improve understanding of the long-term effects of these treatments is required., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background and Objective: The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit., Methods: Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic)., Results: Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85)., Conclusion: Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background/aim: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment., Methods: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations., Results: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007)., Conclusions: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone., (© 2017 Royal Australasian College of Physicians.)

Background and Purpose: Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of regimens and routes of administration., Methods: A national historical cohort of women aged 51 to 70 years from 1995 to 2010 was established by linking 5 Danish registries. The National Registry of Medicinal Product Statistics provided information on hormone therapy exposure and the National Patient or Cause of Death Registries supplied data regarding stroke diagnoses (ischemic/hemorrhagic/subarachnoid hemorrhage). Multiply adjusted rate ratios with time-varying covariates were fitted in Poisson regression models., Results: Of the 980 003 included women, 20 199 suffered a stroke (78% ischemic, 12% hemorrhagic, and 10% subarachnoid hemorrhage). In total, 36% of women used hormone therapy. Current use conferred a relative rate of 1.16 (95% confidence interval, 1.12-1.22). Compared with never users, the increased rate ratio of all stroke with continuous, cyclic combined estrogen/progestin, and estrogen only oral therapies were 1.29 (95% confidence interval, 1.21-1.37), 1.11 (95% confidence interval, 1.04-1.20), and 1.18 (95% confidence interval, 1.10-1.26), respectively. The increased risk was because of ischemic stroke, but not hemorrhagic stroke. Transdermal application of hormone therapy was not associated with risk of stroke. Vaginal estrogen was associated with a decreased risk of stroke., Conclusions: In a national setting, we found an increased risk of stroke, based on ischemic stroke, with oral hormone therapies that was comparable to findings from randomized studies. We found no risk of stroke with transdermal application and a reduced risk with vaginal estrogen., (© 2017 American Heart Association, Inc.)

Advanced atherosclerotic changes can often resist even to very aggressive treatment. Although basic mechanisms of its origin and development are known, some important steps in this process are still waiting for more detailed explanation. Therefore, in addition to already proved aggressive lowering of LDL cholesterol, appropriate timing of atherosclerosis treatment is of the essence. Revealing different stages of atherosclerotic process, less or more sensitive to treatment is of primary importance; however, its detection is complicated by several facts including not exactly identifiable periods of quiescence and progression of atherosclerotic process. One of populations, study of which could add valuable information regarding this problem, are women in menopausal transition. Previously unsuccessful therapy with hormone replacement therapy is restudied with focus on the time of/after menopause. Now, it is supposed to be favorable in women soon, approximately less than 8 years, after menopause. In addition, the same principle - optimal timing of the intervention of traditional cardiovascular risk factors, especially lipids, could be also of importance. Therefore, menopausal transition could be optimal period for the intervention in women at risk. However, this approach is to be proved by evidence from controlled prospective studies focused on lifestyle and/or pharmacological intervention.

Purpose: Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men., Materials and Methods: This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy., Results: Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001)., Conclusions: In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

For several decades, the role of hormone-replacement therapy (HRT) has been debated. Early observational data on HRT showed many benefits, including a reduction in coronary heart disease (CHD) and mortality. More recently, randomized trials, including the Women's Health Initiative (WHI), studying mostly women many years after the the onset of menopause, showed no such benefit and, indeed, an increased risk of CHD and breast cancer, which led to an abrupt decrease in the use of HRT. Subsequent reanalyzes of data from the WHI with age stratification, newer randomized and observational data and several meta-analyses now consistently show reductions in CHD and mortality when HRT is initiated soon after menopause. HRT also significantly decreases the incidence of various symptoms of menopause and the risk of osteoporotic fractures, and improves quality of life. In younger healthy women (aged 50-60 years), the risk-benefit balance is positive for using HRT, with risks considered rare. As no validated primary prevention strategies are available for younger women (<60 years of age), other than lifestyle management, some consideration might be given to HRT as a prevention strategy as treatment can reduce CHD and all-cause mortality. Although HRT should be primarily oestrogen-based, no particular HRT regimen can be advocated.

Even under established replacement therapy, chronic adrenal insufficiency is associated with an impairment in daily life activities and a higher number of sick-days. In patients with individually adjusted glucocorticoid doses (avoiding over-replacement) the frequency of glucocorticoid side effects is low. Besides the standard treatment with conventional hydrocortisone, new formulas aiming at more adjusted physiological circadian cortisol profiles or improved individual dosing have been evaluated in recent clinical trials. Adrenal crisis is a potential threat for patients with chronic adrenal insufficiency even under established hormone replacement therapy, which is triggered by infectious diseases mostly. Primary adrenal insufficiency, comorbidities and previous adrenal crisis were identified as risk factors. To improve the emergency-management in patients with adrenal insufficiency a nation-wide standardized education program for patients and relatives has been established in Germany. First results show an ongoing improvement of handling their sickness and certitude in patients with chronic adrenal insufficiency., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Objective: The objective of the study was to describe the trends of utilization, supply and prevalence of hormone replacement therapy (HRT) in Spain during the period 2000-2014., Methods: Annual prevalence of HRT use including the 95% CI was calculated for women aged≥40 using individual data from the national population-based database BIFAP. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1,000 inhabitants per day and were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the Spanish National Health System., Results: In the year 2000, overall HRT consumption was 33.12 DDDs/1000 inhabitans/day: 19.81 for oestrogen only, 6.88 for tibolone and 6.44 for combined oestrogen and progestagen. In 2014 overall HRT consumption was 5.32 DDDs/1000 inhabitans/day: 1.08 for oestrogen only, 1.61 for tibolone and 2.62 for combinations of oestrogen and progestagen. The marketed presentations of HRT decreased by 46.9%. Prevalence of HRT use in women aged≥40 in BIFAP was 7.19% (95% CI 6.97-7.40) in 2001 and 0.21% (95% CI 0.20-0.22) in 2014. Women aged 40-45 registered the highest prevalence of use in 2014: 0.71% (95% CI 0.66-0.76)., Conclusions: A sharp decline in the consumption and prevalence of HRT has been observed in Spain since the publication of the Women's Health Initiative and Million Women Study and the regulatory measures taken restricting conditions of use, showing a similar trend to that of other western countries., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Since the first use of cortisone in patients around 65 years ago, the use of synthetic glucocorticoids has made a crucial impact on the treatment of several diseases in medicine. Although significant reductions in morbidity and mortality have occurred in patients suffering from cortisol deficiency, conventional hydrocortisone replacement treatment is still inadequate. A major limitation is that it fails to replace cortisol in a physiological manner. Cortisol has a distinct circadian rhythm and acts as a secondary messenger synchronizing the central to peripheral clocks, hence playing a key role in biological processes and the circadian timing system. Circadian misalignment has been associated with ill-health and so nonphysiological glucocorticoid treatment could explain the increased mortality rate, poor quality of life and metabolic complications in patients suffering from adrenal insufficiency. Attempts at replacing cortisol in a physiological manner have shown significant progress in the past decade with the development of modified-release formulations of hydrocortisone (Chronocort® and Plenadren®) and continuous subcutaneous hydrocortisone infusions. Initial studies investigating the use of these replacement regimens are promising, demonstrating both clinical and biochemical improvement. Larger studies are needed to determine whether this novel approach enhances long-term outcomes in both children and adults with cortisol deficiency. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

The aim of this study was to examine the incidence of adrenal crises (AC) and the prescription of short-acting glucocorticoids (GC) in different geographic areas. To do this we conducted a descriptive study of AC hospitalisations and prescriptions for two GCs (hydrocortisone (HC) and cortisone acetate (CA)), and fludrocortisone acetate (FA), in different geographic areas of Australia between 1999/2000 and 2011/2012, using government databases.There were 2,584 hospital admissions for AC in Australia between 1999/00 and 2011/12 and the corresponding admission rates increased significantly from 7.4 to 11.1/10(6)/year (p<0.001). AC admission rates increased in 5 out of 6 geographic areas. Prescription rates for the combined GCs (HC/CA) increased at an annual rate of between 0.2-2.0% in all areas. All areas had significant (p<0.01) increases in HC prescription rates (4.5% to 13.7% annually) and CA prescription rates decreased in 5 out of the 6 regions (3.5% annual decrease to a 0.5% annual increase). When the geographic areas were combined, there was a significant correlation between the AC admission rates and HC/CA prescription rates (r=0.30, p<0.01). Admissions for AC and GC prescriptions increased significantly in Australia after 1999 and these varied significantly by geographic area. These results suggest that modern recommendations for lower dose, short-acting GC replacement may be of concern and further investigation is warranted., (© Georg Thieme Verlag KG Stuttgart · New York.)

Growth hormone (GH) has been recently approved by the Italian Health Authorities for use in transition patients with childhood onset-growth hormone deficiency (CO-GHD). GH in addition to promote linear growth influences several key metabolic processes. In particular, in the transition period, from late adolescent to early adulthood, GH plays an important role in the achievement of a complete somatic development including body composition, muscle mass maturation, full skeletal mineralization and reproductive maturation, as well as in the prevention of metabolic and cardiovascular risk. Therefore, GH replacement should be restarted if a GH stimulation test at the re-evaluation fulfills established criteria. Endocrinologists experienced in the care of GHD adolescent patients held a workshop in Rome, Italy in July 2012 to review in detail the literature data and compare experiences of five Italian endocrinological centers on the negative consequences of interrupting GH treatment and the positive effects of continued GH replacement on intermediary metabolism, heart, muscle, pubertal development, and bone. The aim of the meeting was to delineate the state of the art on GH therapy in transition age and provide suggestions to pediatric and adult endocrinologists for a smooth transition care.

Purpose: Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD., Methods: Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont., Results: GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development., Conclusions: In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

Unlabelled: The majority of women Veterans using VA (Veterans Administration) care fall in the 45-65 year-old age range. Understanding how menopause is managed in this group is of importance to optimizing their health., Objective: National population estimates showed a prevalence of hormone therapy (HT) use by women over 45 years of 4.7 % (2009-2010). Our study described the frequency of HT use among women Veterans in VA, and examined whether mental health (MH) was predictive of HT use., Design: This was a cross-sectional analysis of national VA administrative data for fiscal year 2009., Participants: Women Veterans over the age of 45 (N = 157,195) accessing VA outpatient care were included in the analysis., Main Measures: Logistic regression analyses using HT use as the dependent variable., Key Results: Mean age was 59.4 years (SD =12.2, range =46-110), and 16,227 (10.3 %) of all women used HT. Hysterectomy (OR 3.99 [3.53, 4.49]) and osteoporosis (1.34 [1.27, 1.42]) were the strongest medical indicators of HT use. A total of 49,557 (31.5 %) women in the sample received at least one primary diagnosis of a MH disorder and were more likely to use HT than women with no MH diagnoses (unadjusted OR 1.56, 95 % CI [1.50, 1.61]). Women Veterans with a mood disorder (depression/bipolar) or anxiety disorder [post-traumatic stress disorder (PTSD), other anxiety diagnoses] were more likely to use HT after controlling for demographics and medical comorbidity., Conclusion: The prevalence of HT use among women Veterans using VA is more than twice that of the general population. Prior work suggested that women Veterans were discontinuing HT at comparable rates, but these data demonstrate that decline in VA HT use has not kept pace with that of civilian medical care. The association of MH diagnosis with HT use suggests that MH plays an important role in VA rates. Further study is needed to understand contributing patient and provider factors.

Introduction: Testosterone treatment has evolved rapidly over the past 25 years as new, more effective and convenient methods have become available. This study reports experience with seven different methods, introduced on the market in the UK., Aim: To establish the symptom response when testosterone treatment was initiated on the basis of clinical features and symptoms of androgen deficiency, and the resulting endocrine, biochemical and physiological responses., Methods: Of 2693 patients attending the 3 Men's Health Centers - The UK Androgen Study (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel), testosterone scrotal cream (Andromen) and scrotal gel (Tostran)., Results: There was no correlation between initial testosterone level, initial symptom score or the success of treatment as defined by adequate resolution of symptoms. Despite the diverse endocrine patterns produced, the testosterone preparations appear equally safe over prolonged periods, with either no change or improvement of cardiovascular risk factors, especially in lowering cholesterol and diastolic blood pressure., Conclusions: It is suggested that because of excessive reliance on laboratory measures of androgens and undue safety concerns, many men who could benefit from symptom relief, improvement in related clinical conditions and given preventive medical benefits remain untreated.

Objective: To provide the first multinational survey of temporal trends in testosterone prescribing, given that anecdotal evidence indicates that it is increasing in some countries, including Australia., Design: Sales data for all testosterone products were obtained for 41 countries for each year from 2000 to 2011. For each testosterone product type (injectable, implantable, oral, transdermal), units sold were converted into defined monthly doses per year, reflecting total testosterone prescribing per product., Main Outcome Measures: National testosterone prescribing rate overall and per product type on a per capita basis., Results: For every region and 37 of 41 countries, there was a major and progressive increase in defined monthly doses per year per capita over the 11 years surveyed. In most countries, the increases were steeper for the last half of the survey period. The proportion of testosterone prescribing represented by transdermal testosterone products, a surrogate measure of prescribing for older men, increased even more than did the total usage of testosterone products., Conclusions: In the absence of any new indications, off-label testosterone prescribing has increased in most countries in 2000-2011, especially over the last half of the period. The increased testosterone prescribing appears to be primarily for older men and driven by clinical guidelines that endorse testosterone prescribing for age-related functional androgen deficiency (andropause). By eliminating the fundamental distinction between pathological and functional androgen deficiency, these guidelines tacitly promote increased testosterone prescribing, bypassing the requirement for high-quality clinical evidence of safety and efficacy and creating dramatic increases in prescription of testosterone products.

Context: Testosterone replacement therapy is the standard treatment for male hypogonadism. There has lately been increased marketing in the medical media promoting testosterone replacement for men with erectile dysfunction or for older men with low serum testosterone, despite the lack of long-term safety and efficacy data. Therefore, we aimed to examine trends in testosterone prescribing in UK primary care over the last 10 years., Methods: Data about the use of testosterone preparations from the Departments of Health Prescription Cost Analysis for community pharmacies 2001-2010, for England, Scotland and Wales, were collated. Community requests for serum total testosterone assay in men to the Biochemistry Department at the Newcastle upon Tyne Hospitals Trust were also examined over the same time period., Results: The number of prescriptions for testosterone preparations increased by nearly 90% from 157 602 to 298 134 dispensed items annually, over a 10-year period. However, due to a particularly significant (fivefold) increase in prescribing of (more expensive) transdermal preparations, the cost to the NHS showed a 267% escalation, from £3·2 to £11·7 million, annually over the same period. Local requests from primary care in the Newcastle and North Tyneside area for serum testosterone measurement in men also increased, from 347 requests in 2000 to 823 requests in 2010, a 137% increase. However, the number of men with likely unequivocal hypogonadism (testosterone less than 6·0 nm) remained constant at 5·2% in 2000 and 6·3% in 2010., Conclusion: Many men in the UK might be receiving testosterone replacement therapy with neither clearly established indications nor robustly diagnosed hypogonadism. A national registry for men treated with testosterone and further evidence to improve current guidance (national and/or international) on the indications for testosterone replacement would be beneficial., (© 2013 John Wiley & Sons Ltd.)

Objective: The results of the Women's Health Initiative studies dramatically altered hormone therapy use around the world. In countries outside the United States, self-use in physicians remained unaltered while prescription use declined, implying that physicians may not concur with the findings. We wished to explore prevailing attitudes among American physicians by examining New York City obstetrician-gynaecologists' self-use and prescription use of hormone therapy., Study Design: All board-certified obstetrician-gynaecologists in New York City were invited to complete and return a detailed, previously validated questionnaire concerning hormone therapy use., Results: Two hundred and nine questionnaires were returned, for a response rate of 12% (209/1797). Gynaecologists agreed with the findings from the Women's Health Initiative studies regarding indications and contraindications to hormone therapy use. Even so, three-quarters of female gynaecologists and female partners of male gynaecologists (74%; 67/91) use or have previously used hormone therapy. However, only 27.3% (21/77) of male gynaecologists and 12.3% (14/114) of female gynaecologists recommend hormone therapy to all menopausal women regardless of contraindications. Gynaecologists remain divided in their attitude toward hormone therapy; 30% of gynaecologists felt that hormone therapy use generally prolonged women's lives, 36% felt it was not useful in prolonging women's lives, and 33% were unsure., Conclusion: Since the publication of the Women's Health Initiative findings, New York City gynaecologists prescribe hormone therapy to fewer patients. However, they continue to self-use hormone therapy at much higher rates, even as they seem to concur with Women's Health Initiative recommendations, contributing to the ongoing controversy surrounding the validity of the Women's Health Initiative findings.

The autoimmune thyroiditis with overt or subclinical primary hypothyroidism is the most common endocrine disease. Although the diagnosis of hypothyroidism is not difficult, the question when a replacement therapy in subclinical hypothyroidism should be initiated is still under discussion. In patients with overt hypothyroidism defined as low FT4 and elevated TSH or TSH > 10 mU/L a replacement with levothyroxine is clearly indicated. In patients with subclinical hypothyroidism defined as a TSH between 4 and 10 mU/L and normal FT4, the treatment with Levothyroxine depends on the underlying disease and symptoms. Levothyroxine is a prohormone with is activated by deiodination in the organs to triiodothyronine. Therefore, levothyroxine for replacement therapy is mainly used. Some patients, however, do not feel well with this treatment and therefore studies with a combination therapy of levothyroxine and triiodothyronine had been performed and it could be shown that this might be related to a polymorphism in type 2 deiodinase in some patients, with the consequence of lower intracellular triodothyronine formation. In women on levothyroxine replacement therapy getting pregnant, the demand of levothyroxine increases up to 25-50 µg, especially in the early weeks of pregnancy. It also has to be considered that the resorption of levothyroxine depends on normal stomach acid and therefore patients on acid blockers or atrophic gastritis require higher dosages of levothyroxine. Only patients after thyroidectomy because of differentiated thyroid carcinoma with higher grad of malignancy need a TSH suppressive therapy, those with occult papillary thyroid carcinoma the TSH should be within the low normal range., (© Georg Thieme Verlag KG Stuttgart · New York.)

Mammography screening and postmenopausal hormone therapy (HT) both influence breast cancer incidence. While breast cancer incidence increased by around 50% during the introduction of screening, a smaller decline in incidence has been reported in several countries after 2002 when the sales of HT started to decline. Data suggest that HT increases the risk of the second most common type of breast cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal carcinoma (IDC). Breast cancer incidences stratified on histological subtypes were obtained from the national cancer registries. HT sales data from drug consumption statistics and information on the county-level introduction of mammography screening were combined, and breast cancer incidence trends were estimated using Poisson regression models, focusing on the period after 2002. From 2002 to 2007 the annual decrease in breast cancer incidence rates for women aged 50-69 was 1.5% (95% CI -2.3% to -0.7%) in Sweden and 0.8% (95% CI -2.8% to 1.2%) in the part of Norway not confounded by prevalence screening. Most of the decline was in the rates of ILC which dropped by 4.7% (95% CI -6.6% to -2.7%) and 7.0% (95% CI -12.8% to -0.9%) per year, respectively. The rates of IDC were stable in this period. Breast cancer incidence has declined in Sweden and Norway since 2002, but the reduction is moderate compared with the large increase that occurred during the introduction of mammography screening. Declining rates of ILC, but not of IDC, support the hypothesis that the drop in breast cancer incidence is associated with reduced HT use., (© 2012 Wiley Periodicals, Inc.)

Objective: The publication of the Women's Health Initiative (WHI) randomized, controlled trial in 2002 resulted in a critical discussion on the risks and benefits of hormone replacement therapy (HRT). The present study aims to evaluate the attitude of German gynecologists regarding changes in the prescription of HRT over recent years. Method A questionnaire was sent to all 9589 German gynecologists in private practice in November 2010., Results: The response rate was 2548 (26.6%). Whereas 82.2% of the responders stated that their advice for primary hormone therapy and alternative agents depended on the severity of symptoms, 9.1% of the responders would recommend HRT in the first place (male: 14.3%; female: 6.1%; p < 0.001). An age limit for hormone prescription was stated by 26.2%, with a mean age limit of 63 ± 5.3 years. An increasing number of patients and becoming more critical about HRT after the WHI was mentioned by 79.8%. Of the responding doctors, 43.9% found that their patients were badly informed by the media, 44.5% stated they were moderately or well (10.1%) informed, whereas only 1% considered their patients to be very well informed. HRT was prescribed for the relief of vasomotor symptoms by 97.4% of responders, making this the primary indication. This percentage decreased slightly to 92.6% between 2003 and 2008 (p < 0.001) and increased again to a similar level at the beginning of 2010 (96.7%, p < 0.05)., Conclusion: German gynecologists generally have a positive attitude towards HRT, but find it important to focus on the evaluation of the risk-benefit ratio. The major barriers to prescription are multiple concerns of the patients resulting from non-objective media.

Objective: To investigate the impact of early hormone replacement therapy (HT) on sperm retrieval rates in patients with Klinefelter syndrome (KS)., Design: A systematic review of the relevant literature using the PubMed NLM database., Result(s): There are no randomized controlled trials evaluating the impact of HT on sperm retrieval or reproductive outcomes in men with KS. On average, surgical sperm retrieval rates in men with KS are around 51%, with a range of 28%-69%. Young patient age is the most consistent positive predictor of sperm retrieval. Lower retrieval rates have been reported in a small subset of KS adults who previously received exogenous T, although the nature, duration, and reason for such therapy in these patient subsets are unknown., Conclusion(s): Early HT is recommended in patients with KS, but its effect on fertility potential has not been definitively studied. Larger studies are needed to better answer this question. Cryopreservation of sperm-containing semen or testicular tissue from a significant proportion of affected adolescents is possible, even when containing very low numbers of spermatozoa, and should be considered to maximize future fertility potential., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic., Evidence Acquisition: We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action., Evidence Synthesis: The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients., Conclusions: Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

The perceptions of menopausal hormone therapy (MHT) have evolved considerably. Observational studies suggested that MHT could relieve vasomotor symptoms and prevent coronary heart disease (CHD). However, randomized controlled trials later showed no reduction in CHD and an increased risk of stroke. Subsequent analyses of these trials have shown that in women younger and closer to menopause, the risks associated with MHT may not be as great as originally thought. Several organizations, including the North American Menopause Society, the International Menopause Society, and the Endocrine Society, have published guidelines and statements that help health care providers translate the research findings into clinical practice. A common theme from these organizations is the need for health care providers to tailor information to their patients so they may make informed treatment decisions (especially considering the media attention MHT has received). It is particularly important to individualize therapy, considering patients' risk factors for atherosclerotic disease, venous thromboembolic disease, osteoporosis, and breast cancer. Ongoing research in women younger than those in prior trials is evaluating lower doses of MHT and directly comparing transdermal and oral formulations. Such research should help define the population of women most likely to benefit from MHT without undue risk of adverse outcomes.

Objective: The aim of this study was to evaluate recent trends and the adoption of practice recommendations for menopausal hormone therapy (MHT) use from 2001 to 2009 by formulation, dose, woman's age, and characteristics of physicians reporting MHT visits., Methods: The IMS Health (Plymouth Meeting PA) National Disease and Therapeutic Index physician survey data from 2001 to 2009 were analyzed for visits in which MHT use was reported by US office-based physicians. Estimated national volume of visits for which MHT use was reported., Results: MHT use declined each year since 2002. Systemic MHT use fell from 16.3 million (M) visits in 2001 to 6.1 M visits in 2009. Declines were greatest for women 60 years or older (64%) but were also substantial for women younger than 50 years (59%) and women 50 to 59 years old (60%). Women 60 years or older accounted for 37% of MHT use. Lower dose product use increased modestly, from 0.7 M (2001) to 1.3 M (2009), as did vaginal MHT use, from 1.8 M (2001) to 2.4 M (2009). Declines in continuing systemic MHT use (65%) were greater than for newly initiated MHT use (51%). Compared with other physicians, obstetrician/gynecologists changed their practices less, thereby increasing their overall share of total MHT visits from 72% (2001) to 82% (2009)., Conclusions: Total MHT use has steadily declined. Increased use of lower dose and vaginal products reflects clinical recommendations. Uptake of these products, however, has been modest, and substantial use of MHT continues in older women., (© 2011 by The North American Menopause Society)

Evidence suggests that initiation of some forms of hormone therapy (HT) early in the perimenopausal or postmenopausal stage might confer benefit to verbal memory and the neural systems underlying memory, whereas late-life initiation confers no benefit or harm. This "critical window hypothesis" remains a topic of debate. Using functional magnetic resonance imaging (fMRI), we examined the long-term impact of perimenopausal HT use on brain function during performance of verbal and figural memory tasks. Participants were 34 postmenopausal women (mean age 60 years) from the Melbourne Women's Midlife Health Project and included 17 early (perimenopausal) and continuous users of HT and 17 never users matched on age, education, and verbal knowledge. Continuous HT use from the perimenopausal stage versus no use was validated with prospective daily diary records and study visit data. The primary outcome was patterns of brain activation in an a priori region of interest in the medial temporal lobe during verbal encoding and recognition of words. Results indicated that perimenopausal HT users performed better than nonusers on the imaging verbal memory task (p<.05). During verbal recognition, perimenopausal HT users showed increased activation in the left hippocampus and decreased activation in the parahippocampal gyrus bilaterally compared with never users. Each of these patterns of activation was associated with better memory performance on the imaging memory task. These results suggest that perimenopausal use of HT might confer long-term benefits to verbal memory and the brain systems underlying verbal memory. More generally, the results support the critical window hypothesis., (Copyright © 2010 Elsevier B.V. All rights reserved.)