Association with menopausal hormone therapy and asymptomatic gallstones in US women in the third National Health and Nutrition Examination Study.

15% of US adults have gallstones, most of which are clinically "silent". Several studies show that menopausal hormone therapy (MHT) increases symptomatic gallstones and cholecystectomy risk. MHT use may be contraindicated in women with gallstones and population studies may be biased by "confounding by contraindication" while the true association between MHT and gallstones remains underestimated. We sought to examine whether MHT use was associated with asymptomatic gallstones using instrumental variable (IV) analysis to account for confounding by contraindication. We used 2018 postmenopausal women from the Third National Health and Nutrition Examination Survey to estimate associations of MHT use with asymptomatic gallstones. A traditional logistic regression analysis was compared to instrumental variable (IV) analysis to account for confounding by contraindication. 12% of women with asymptomatic gallstones and 25% of women without gallstones were current MHT users (P < 0.001). The traditional analysis suggested a decreased odds of asymptomatic gallstones in current versus never users (OR 0.58, 95% CI 0.37, 0.89), but increased odds (OR 1.51, 95% CI 0.44, 5.16) in the IV analysis. The traditional analysis consistently underestimated the odds of asymptomatic gallstones with MHT use compared to the IV analysis. Accounting for confounding by contraindication, we found a suggestive, though imprecise, positive association between MHT use and asymptomatic gallstones among postmenopausal women. Failure to consider contraindication can produce incorrect results.

Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma.

It has been observed that plasmatic concentrations of estrogens, progesterone, or both correlate with symptoms in asthmatic women. Fluctuations in female sex steroid concentrations during menstrual periods are closely related to asthma symptoms, while menopause induces severe physiological changes that might require hormonal replacement therapy (HRT), that could influence asthma symptoms in these women. Late-onset asthma (LOA) has been categorized as a specific asthmatic phenotype that includes menopausal women and novel research regarding therapeutic alternatives that might provide relief to asthmatic women suffering LOA warrants more thorough and comprehensive analysis. Therefore, the present review proposes phytoestrogens as a promising HRT that might provide these females with relief for both their menopause and asthma symptoms. Besides their well-recognized anti-inflammatory and antioxidant capacities, phytoestrogens activate estrogen receptors and promote mild hormone-like responses that benefit postmenopausal women, particularly asthmatics, constituting therefore a very attractive potential therapy largely due to their low toxicity and scarce side effects.

Retrospective study on long-term effects of hormone replacement therapy (HRT) and iron chelation therapy on glucose homeostasis and insulin secretion in female ß- thalassemia major (ß-TM) patients with acquired hypogonadotropic- hypogonadism (AHH).

BACKGROUND AND AIM: Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic ß-cell dysfunction respectively, are the most frequently reported endocrine abnormalities in patients with ß-thalassemia major (ß-TM), also identified as transfusion-dependent thalassemia (TDT). STUDY DESIGN AND PATIENTS: The aim of the present retrospective study was to evaluate the long-term effects of hormone replacement therapy (HRT) on glucose metabolism and insulin secretion/sensitivity during 3-h oral glucose tolerance test (OGTT) in adolescent and young ß-TM women with acquired hypogonadototropic -hypogonadism (AHH).Twelve hypogonadal ß-TM females with AHH on HRT were followed for 8.26 ± 1.49 years. RESULTS: At baseline, 10 patients (83.3%) had normal OGTT, 1 patient presented with impaired glucose tolerance (IGT) and 1 patient had an isolated PG level of 165 mg/dL at 1-h during OGTT (H-NGT). At last evaluation, 7 patients (58.4 %) had normal OGTT, while 5 patients (41.6%) had abnormal OGTT. Reduced insulin sensitivity and impaired first-phase insulin secretion were also documented. Three of 4 ß-TM patients on treatment with estradiol hemihydrate MX 50 patches plus oral medroxyprogesterone acetate (MPA), associated with a very effective iron chelation therapy, maintained normal glucose tolerance from baseline to last evaluation. Significant adverse events due to HRT or additional endocrine complications were not documented in any cases during the follow-up. CONCLUSION: Deterioration of glycemia (dysglycemia) occurred in 45.4% (5/11) of thalassemic females on long-term HRT. Additional studies are needed to elucidate the validity of our preliminary observations.

Hormone Therapy: Aging-Related Hormone Replacement Therapy and Supplementation.

Given their association with aging, growth hormone (GH), dehydroepiandrosterone (DHEA), and melatonin (N-acetyl-5-methoxytryptamine) have been evaluated as potential antiaging treatments. It has been hypothesized that declining endocrine function, specifically the decreases in hormone production and secretion seen with aging, plays a role in development of frailty. This physiologic decrease in hormone levels differs from a pathologic decrease due to a condition or disease. However, the signs and symptoms can be similar. Hormone replacement therapy is a well-established treatment for many conditions, but its role in the healthy aging process remains unclear. Off-label use of these hormones has shown some short-term benefits, such as improved body composition, mood, neurocognition, and sexual function and decreased oxidative stress. However, there are no recommendations for routine measurement of these hormone levels or for hormone replacement therapy because of a lack of high-quality evidence. Long-term studies are needed to evaluate the efficacy and safety of GH, DHEA, and melatonin if they are to be used as antiaging therapies.

Testosterone and aging male, a perspective from a developing country.

PURPOSE: Hypogonadism is associated with a wide range of physical and psychological symptoms that can affect the overall health of men. However, in a developing country, there are several imposing challenges in the diagnosis and treatment of hypogonadism, including a lack of awareness and understanding of the condition among healthcare providers and patients, limited resources and the high cost of treatment. This review aimed to examine the potential benefits and risks of testosterone replacement therapy (TRT) and provides a perspective of a developing country on the topic. MATERIALS AND METHODS: A comprehensive literature review was conducted to gather relevant information on the impact of testosterone deficiency on ageing males and the effectiveness of TRT for treating hypogonadism. Published peer-reviewed articles were analyzed to evaluate the benefits and risks of TRT. Additionally, the unique challenges faced in the diagnosis and treatment of hypogonadism in a developing country were considered. RESULTS: Testosterone replacement therapy has been shown to be an effective treatment for hypogonadism, particularly in symptomatic men with low testosterone levels. It offers potential benefits such as improvements in symptoms and overall quality of life. However, there are associated risks and side effects that need to be considered. In a developing country, challenges such as limited awareness and understanding of hypogonadism, resource constraints, and high treatment costs pose additional barriers to accessing TRT and comprehensive care. CONCLUSION: In conclusion, TRT holds promise as a treatment for hypogonadism, but its implementation and accessibility face significant challenges in a developing country. Addressing these challenges, including raising awareness, allocating resources, and finding cost-effective solutions, is crucial for ensuring that men with hypogonadism in such settings receive appropriate diagnosis and treatment. Further research and efforts are needed to improve the management of hypogonadism in developing countries and optimize the potential benefits of TRT for affected individuals.

Non-pharmacological treatment of reduced quality of life in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is the spontaneous or induced loss of ovarian function in women under the age of 40. POI increases the risk of reduced quality of life. Hormone replacement therapy may be beneficial in POI, but some women have contraindications. Recent studies indicate that exercise, yoga, meditation, acupuncture, and mindfulness may improve quality of life in women with POI. Phyto-oestrogens are not recommended in the treatment of POI since the physiological level of oestrogen cannot be achieved, and phyto-oestrogens should be avoided in women with present or previous breast cancer.

Prescription rules of hormone replacement therapy and its alternative.

Hormone replacement therapy is still the most effective treatment for acute climacteric syndrome and prevention of osteoporosis. When starting treatment within 10 years of menopause, i.e., before the onset of irreversible changes in the vessel wall and nervous tissues, it is a window of opportunity to prevent atherosclerosis and dementia. At a later start, on the contrary, it worsens these processes. To increase the safety of the treatment, especially in affecting the breast tissue, we choose the lowest effective dose of estrogen and give preference to gestagens structurally close to progesterone. For women who, for objective or subjective reasons, prefer non-hormonal treatment, they can choose from an extensive range of complementary and alternative medicines. Unfortunately, it does not always reliable documentation of efficacy and safety from well-performed studies. However, the data for fermented soybean extract DT56a, pollen extract PI82/GC Fem, and some traditional Chinese medicine procedures offer an interesting opportunity. Physical activity cannot be forgotten in a comprehensive approach.

A review of testosterone supplementation and cardiovascular risk.

Testosterone therapy is commonly utilized to treat hypogonadism. After diagnosis with morning serum testosterone level in patients with symptoms of hypogonadism, therapy has been shown to improve symptoms. Research focusing on cardiovascular risks associated with testosterone therapy has produced contradictory statements. We review trials that have investigated the impact of testosterone supplementation on heart failure, coronary artery disease, and myocardial ischemia.

Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

Menopause hormone therapy and complementary alternative medicine, quality of life, and racial/ethnic differences: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: We hypothesized that, among midlife women with vasomotor and/or genitourinary symptoms of menopause, (1) hormone therapy (HT) compared with complementary alternative medicine (CAM) will be associated with higher quality of life (QoL), and (2) race/ethnicity would modify associations of HT and CAM with QoL. METHODS: Cross-sectional and longitudinal analyses of QoL in the Study of Women's Health Across the Nation participants using HT, CAM, or both. Women ( n = 2,514) completed a CAM use questionnaire and QoL assessments at baseline and every 1 to 2 years from 2002 to 2013. Associations between QoL and treatment, adjusted for covariates, and race/ethnicity-by-treatment interactions were analyzed using linear and mixed effects regression models. RESULTS: During 7.8 (SD, 2.9) years of follow-up, 732 women (29%) reported HT of 2.4 (SD, 1.7) years, and 798 women (32%) reported CAM use of 2.1 (SD, 1.4) years. Overall, neither HT nor CAM was associated with QoL. However, the treatment-by-race/ethnicity interaction was significant for self-reported QoL ( P = 0.034 at baseline, P = 0.044 longitudinal). Among White women, self-reported QoL was higher in HT-only users than in those who used neither ( P = 0.030; d = 0.11; 95% confidence interval, 0.01-0.21). In contrast, Black women using HT only had lower self-reported QoL compared with Black women using neither ( P = 0.027; d = -0.21; 95% confidence interval, -0.40 to -0.02). CONCLUSION: Comparisons between treatment type within each racial/ethnic group yielded significant differences in self-reported QoL. Clinicians should be aware of racial/ethnic differences in treatment preferences when counseling patients on treatment options for menopausal symptoms to provide optimal care. VIDEO SUMMARY: http://links.lww.com/MENO/B33 .

Contributions of the Women's Health Initiative to Cardiovascular Research: JACC State-of-the-Art Review.

The WHI (Women's Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.

Ovarian Tissue-Based Hormone Replacement Therapy Recovers Menopause-Related Signs in Mice.

PURPOSE: In women, menopause manifests with a variety of symptoms related to sex-hormone deficiency. Supplementing steroid hormones with pharmacological drugs has been widely practiced. However, considering the possible complications associated with artificial hormone therapy, studies have been conducted to find an alternative to pharmacological hormone replacement therapy. Accordingly, this study aimed to evaluate the efficacy of tissue-based hormone replacement therapy (tHRT) for treating post-menopausal signs and symptoms. MATERIALS AND METHODS: CD-1 mice were ovariectomized, and the ovaries were cryopreserved. Following artificial induction of post-menopausal osteoporosis, cryopreserved ovaries were subcutaneously autografted, and indexes related to bone health were monitored for 12 weeks. Bone mineral density (BMD), bone mineral contents (BMC), total bone volume (BV), and body fat mass were measured by dual energy X-ray absorptiometry. Uterine atrophy was assessed histologically, and bone microstructures were imaged by micro-computed tomography analysis. RESULTS: Regardless of the number of grafted ovaries, the BMC, BMD, and BV values of mice that underwent ovary transplantation were better than those that did not undergo transplantation. The uteruses in these mice were thicker and heavier after auto-transplantation. Furthermore, the bone microstructure recovered after tHRT. CONCLUSION: Recovery of menopause-related bone loss and uterine atrophy was achieved through tHRT. Ovarian tissue cryopreservation and transplantation may be applicable not only in patients wanting to preserve fertility but also in sex hormone-deficient post-menopausal women.

The role for long-term use of dehydroepiandrosterone in adrenal insufficiency.

PURPOSE OF REVIEW: Dehydroepiandrosterone (DHEA) is an androgen produced by the zona reticularis of the adrenal gland. Patients with adrenal insufficiency will have a deficiency of DHEA. Unlike glucocorticoid and mineralocorticoid replacement, DHEA supplementation is not considered essential for life and is therefore not routinely replaced in adrenal failure. DHEA deficiency is associated with morbidity, including adverse impacts on metabolic function, quality of life and sexuality in multiple studies. The role for replacement, however, remains unclear. RECENT FINDINGS: The benefits of DHEA supplementation have been definitively demonstrated in a number of historical studies of patients with primary and secondary adrenal insufficiency. Beneficial impacts on quality of life, body composition, bone health and metabolic markers have been demonstrated. However, published data are inconsistent; controversies persist around the exact role of DHEA replacement and around which patient cohorts are most likely to benefit. There is also a paucity of recent randomized controlled trials in the medical literature to inform on optimal dose and duration of DHEA replacement in adrenal failure. SUMMARY: Here, we review the evidence for DHEA supplementation in patients with adrenal insufficiency. We highlight knowledge gaps in the medical literature and areas that should be prioritized for future research endeavours.

Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society.

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing.

Treating menopause - MHT and beyond.

Every woman who lives past midlife will experience menopause, which, by definition, is complete cessation of ovarian function. This process might occur spontaneously (natural menopause) or be iatrogenic (secondary menopause), and can be further classified as 'early' if it occurs before the age of 45 years and 'premature' if it occurs before the age of 40 years. Globally, the mean age of natural menopause is 48.8 years, with remarkably little geographic variation. A woman's age at menopause influences health outcomes in later life. Early menopause is associated with a reduced risk of breast cancer, but increased risks of premature osteoporosis, cardiovascular disease and premature death. The cardinal symptoms of menopause, and adverse health sequelae, are due to loss of ovarian oestrogen production. Consequently, menopausal hormone therapy (MHT) that includes oestrogen or an oestrogenic compound ameliorates menopausal symptoms, while preventing menopause-associated bone loss and cardiometabolic changes. Importantly, comprehensive care of postmenopausal women involves lifestyle optimization (attention to nutrition and physical activity, reducing alcohol consumption and not smoking) and treating other established chronic disease risk factors. This Review offers a commentary specifically on the contemporary use of MHT and novel pharmaceutical alternatives to manage menopausal symptoms.

Ageing male (part 2): Management of functional hypogonadism in older men, a patient-centric holistic approach.

The diagnosis of functional hypogonadism should prompt a thorough assessment and optimization of general health, including lifestyle changes, weight reduction, care of comorbidities and cessation of offending medications, some of which can lead to meaningful gains in endogenous testosterone (T) concentrations. Having excluded or addressed reversible causes and contra-indications, patients with functional hypogonadism can be offered a trial of testosterone replacement therapy (TRT) after full discussion on the anticipated benefits and potential risks. T treatment improves libido but may be less effective for erectile dysfunction (ED). T treatment can also have modest positive effects on insulin resistance, bone strength, some measures of physical strength, and mild depressive symptoms but the clinical significance of these relatively short-term improvements remain uncertain in terms of longer-term patient-important outcomes. Initiation of TRT is a joint decision between patient and clinician since longer-term benefits and risks have not been adequately defined.

Phytotherapic approach in menopause: light and darkness.

INTRODUCTION: Menopause is a critical period of the woman life, characterized by a peculiar modification in estrogens concentration and accompanied by different signs and symptoms. To prevent and contrast unfavorable consequences of menopause, different therapeutic approaches could be evaluated. The hormone replacement therapy (HRT) is the most known, but it has several contraindications. The increasing interest in phytotherapy introduces the necessity for endocrinologist involved in menopause to suggest different therapeutic approaches, considering the state of health of patient and the real efficacy of the drugs. We aim to outline the main phytotherapy treatments to choose in menopause. EVIDENCE ACQUISITION: This review is based on focused research of the current literature on PubMed and Scopus such as research databases. We selected 4120 papers through these keywords: "MENOPAUSE" AND "phytotherapy," "natural therapy," "phytoterapy drugs." Then, the literature was scanned selecting English papers of last 10 years (last research on October 1, 2021), excluding reviews. Separately, two researchers MGT and CP examined and read 212 full selected papers. We included clinical trials and randomized clinical trials written in English and excluded duplicates, animal studies and studies with lack of group of interest, non-relevant outcomes, inappropriate methodology. Retrospective studies, case reports, case series, original articles, brief communications, and letter to the editor were included in our research. We furthermore completed our research by the examination of every study's bibliography. EVIDENCE SYNTHESIS: Phytotherapy involves the use of plants or plant extracts for the treatment of diseases thanks to the activities of their compounds and metabolites. In particular, many of them have an estrogen-like activity and are identified as phytoestrogens, because thanks to their chemical structure are able to bind the estrogen receptors and carry out biological estrogenic or antiestrogenic activities. The supplementing diet with these compounds can ensure an advantage on various aspects of the climacteric syndrome and some of them also have a beneficial impact on cardiovascular risk, bone health and sleep complaint. These substances can be used with safety due to their good tolerability and low rate of side effects. There are no known serious adverse events associated with their consumption, but as a precaution, its use is not recommended during pregnancy and in association with hormonal therapies or in women with hormone responsive cancers. CONCLUSIONS: Phytotherapy must be considered an interesting tool in the treatment of signs and symptoms in selected menopause woman.

Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.