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Genitourinary syndrome of menopause (GSM) is a chronic and progressive condition with a series of vulvovaginal, sexual, and lower urinary tract discomforts, mainly due to hypoestrogenism. Menopausal hormone therapy (MHT) has generally been considered as the most effective treatment for GSM. In addition, vaginal microbiota is of particular significance to gynecological and reproductive illnesses and potentially has some intimate connections with GSM. Consequently, we sought to evaluate how MHT impacts the composition and structure of vaginal microbiota while alleviating GSM in Chinese menopausal women aged 45–65 years, which has not been investigated previously. 16S rRNA gene sequencing was performed to analyze microbial diversity and composition using vaginal swabs obtained from 100 menopausal women, classified as MHT women who have been taking tibolone regularly (n = 50) and non-treated women who never received any treatment (n = 50). Vaginal Health Index Score (VHIS) and GSM symptoms inquiry were also performed. We found that the vaginal microbial diversity decreased and that the abundance of Lactobacillus increased to be the dominant proportion significantly in the MHT group, in considerable contrast to vaginal microbiota of the non-treated group, which significantly comprised several anaerobic bacteria, namely, Gardnerella , Prevotella , Escherichia-Shigella , Streptococcus , Atopobium , Aerococcus , Anaerotruncus , and Anaerococcus. In this study, women without any MHT had significantly more severe GSM symptoms than those receiving tibolone, especially with regard to vulvovaginal dryness and burning, as well as decreased libido (P < 0.01). However, there was no significant difference in the severity of urological symptoms between the groups (P > 0.05). Furthermore, Lactobacillus was demonstrated to be associated with VHIS positively (r = 0.626, P < 0.001) and with GSM negatively (r = −0.347, P < 0.001). We also identified Chlamydia (r = 0.277, P < 0.01) and Streptococcus (r = 0.270, P < 0.01) as having a prominent association with more serious GSM symptoms. Our study provided an elucidation that MHT could notably alleviate GSM and conspicuously reshape the composition of the vaginal microbiota, which is of extreme importance to clinical practice for the management of GSM. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) is indicated for menopausal symptom relief. However, MHT has also been shown to be beneficial for prevention of long-term estrogen deficiency sequelae including mortality. Based on a comprehensive literature review on MHT and mortality, the authors' recommendations are as follows: in postmenopausal women, MHT appears to confer a (significant) reduction in overall mortality; the benefit especially applies to women who initiate long-term MHT early after menopause; in women with prevalent cardiovascular risk factors (except for diabetes mellitus, where results are mixed), the benefit of MHT on overall mortality is even more pronounced; and, however, study results are difficult to compare due to heterogeneous study designs. [ABSTRACT FROM AUTHOR]

Background: The impact of hormones on the development of breast cancer is despite extensive studies, incompletely understood. Combined estrogen-progestogen treatment augments the risk for breast cancer beyond that of estrogen alone, according to numerous studies. The role of breast cell proliferation as a promoter in the development and growth of breast cancer is well recognized. Materials and methods: Seventy-nine patients from three randomised trials were subject to a re-analysis of breast cell proliferation: (1) 22 women received continuous combined treatment with oral estradiol (E2) 2 mg/norethisterone acetate (NETA) 1 mg once daily for 3 months. (2) Thirty-seven women received 2 months of sequential treatment with oral conjugated equine estrogens (CEE) 0.625 mg daily combined with medroxyprogesterone acetate (MPA) 5 mg for 14/28 days of each cycle. (3) Twenty women received oral estradiol-valerate (E2V) 2 mg daily combined with levonorgestrel (LNG) intrauterine system (IUS), 20 μg/24 h for 2 months. Fine needle aspiration (FNA) (studies 1 and 3) and core needle biopsy (CNB) (study 2) were used for the assessment of breast cell proliferation. Results: There were no baseline proliferation differences, but at the end of treatment there was a highly significant between-group difference for E2V/LNG IUS versus the other two groups (p = 0.0025). E2/NETA and CEE treatments gave a 4–7-old increase in proliferation during treatment (p = 0.04) and (p = 0.007), respectively, which was absent in the E2V/LNG group, showing a significant correlation with insulin-like growth factor binding protein-3 (IGFBP-3) serum levels. Conclusion: E2V in combination with very low serum concentrations of LNG in the IUS gives no increase in proliferation in the normal breast. [ABSTRACT FROM AUTHOR]

The global incidence of breast cancer is increasing, as is the efficacy of treatments. Consequently, increasing survival rates reinforce the importance of survivorship issues, including posttreatment menopausal symptoms, sexual function, and mental health and well-being. Breast cancer patients can experience a range of menopausal symptoms associated with their treatment. Most commonly women may experience vasomotor symptoms, including hot flushes and night sweats. Particularly for women on maintenance tamoxifen therapy, up to 80% will experience hot flushes, with almost one-third of these women reporting severe symptoms. Breast cancer patients may also experience genitourinary symptoms of menopause, which may include vaginal dryness and irritation, dyspareunia, and dysuria. Hormonal therapy has long been established as the most effective treatment for vasomotor symptoms. However, the hormonal nature of breast malignancies renders systemic hormone therapies unsuitable for these patients, posing a unique treatment challenge, which may result in clinicians not feeling confident to manage them. Consequently, this review outlines pharmacological and nonpharmacological options for women with bothersome menopausal symptoms after breast cancer treatment and provides practical, evidence-based guidance for clinicians. [ABSTRACT FROM AUTHOR]

Although menopausal hormone therapy (MHT) seemingly increases the risk of ovarian cancer, evidence is insufficient whether the risk varies between various MHT formulations, regimens and administration modes. With the aim of filling these knowledge gaps, we investigated the effect of different MHT treatment options on the risk of ovarian cancer. This prospective Swedish population‐based matched‐cohort study included all women ≥40 years having used systemic MHT between 2005 and 2012 (288,950 ever‐users), group‐level matched (1:3) to 866,546 nonusers. MHT use was ascertained from the Swedish Prescribed Drug Registry and data was linked to several national health data registries. Multivariable conditional logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for parity, and comorbidities. Current EP‐MHT use was associated with a modestly increased risk of ovarian cancer (OR = 1.38, 95% CI 1.18–1.62), while no consistent risk was found among past users (OR = 1.00, 95% CI 0.84–1.18). Current continuous testosterone derived (OR = 1.50, 95% CI 1.15–1.96) regimens increased the risk whereas progesterone derived (OR = 1.48, 95% CI 1.00–2.21) regimens increased the risk marginally. Nonsignificant positive associations were observed for sequential regimens (OR = 1.87, 95% CI 0.70–5.08; OR = 1.54, 95% CI 0.96–2.47, respectively). An inverse relationship was observed for all E‐MHT use (OR = 0.25, 95% CI 0.22–0.29), but this association might partly be explained by underreporting of oophorectomies or tubal ligations. Current cutaneous EP‐MHT (OR = 1.28, 95% CI 0.81–2.02) suggested a possibly lower risk than oral MHT (OR = 1.48, 95% CI 1.25–1.75). In conclusion EP‐MHT, notably continuous regimens, were associated with a modestly increased risk of ovarian cancer. The role of E‐MHT requires further clarification. What's new? While menopausal hormone therapy (MHT) appears to influence ovarian cancer risk, whether the risk varies between various MHT treatment options remains unknown. In this Swedish population‐based matched‐cohort study, including all MHT receivers during 2005–2012, we found notable differences between MHT regimens. In addition, cutaneous EP‐MHT suggested for less risk than the most commonly prescribed oral MHT. These findings are important for choosing a MHT treatment option, which involves less excess ovarian cancer risk. [ABSTRACT FROM AUTHOR]

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations. What's new? Evidence suggests that sex hormones may influence melanoma risk. As part of a prospective study, the authors of this report found that women who had used oral contraceptives at any time had a moderately increased risk of melanoma, which increased linearly with longer usage. Menopausal hormone therapy (MHT), also increased risk somewhat. Further research is needed, in order to investigate potential confounding or effect‐modification of melanoma risk, for various types and formulations of hormones, and for UV exposure. [ABSTRACT FROM AUTHOR]

A variety of structurally and functionally distinct progestins is used in contraception and menopausal hormone therapy (MHT). Some progestins elicit off-target effects by binding to steroid receptors other than the progesterone receptor, which may impact their therapeutic and side-effect profiles. We directly compared the binding affinities, efficacies and potencies of selected progestins via the mineralocorticoid receptor (MR). We did not detect a significant difference in the affinities of medroxyprogesterone acetate (MPA), norethisterone acetate (NET-A), levonorgestrel (LNG), gestodene (GES), etonogestrel (ETG), nestorone (NES) and nomegestrel acetate (NoMAC) for the MR, while these were significantly lower compared to drospirenone (DRSP). While GES and NoMAC display affinities indistinguishable from progesterone (P 4), the binding affinity of DRSP is significantly greater and all other progestins significantly lower than that of P 4. Dose-response analyses showed that P 4 , GES and ETG display indistinguishable MR antagonist potencies for transactivation to the well-known MR antagonist spironolactone, while LNG, NoMAC and DRSP are significantly more potent than spironolactone and MPA, NET-A and NES are significantly less potent. Similar to our previous findings for NET-A, we show that LNG, GES, ETG and NES dissociate between transactivation and transrepression via the MR. Together our results provide strong evidence for progestin- and promoter-specific transcriptional effects via the MR, which are poorly predicted by relative binding affinities. A comparison of the binding affinities and potencies with reported free serum concentrations of progestins relative to the endogenous mineralocorticoid aldosterone, suggest that all progestins except MPA, NET-A and NES will likely compete with aldosterone for binding to the MR in vivo at doses used in hormonal therapy to elicit physiologically significant off-target effects. • Progestin binding affinities for the MR do not predict their biological activities. • Like P 4 , all progestins except MPA, NET-A and NES are potent MR antagonists. • All progestins and P 4 transrepress via a NFĸB, but not AP-1, promoter reporter gene. • LNG, GES, ETG and NES dissociate between transactivation and transrepression via MR. [ABSTRACT FROM AUTHOR]

Introduction: Dyslipidemias are common and increase the risk of cardiovascular disease. The menopause transition is associated with an atherogenic lipid profile, with an increase in the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (apoB) and potentially lipoprotein (a) [Lp(a)], and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C).Aim: The aim of this clinical guide is to provide an evidence-based approach to management of menopausal symptoms and dyslipidemia in postmenopausal women. The guide evaluates the effects on the lipid profile both of menopausal hormone therapy and of non-estrogen-based treatments for menopausal symptoms.Materials and Methods: Literature review and consensus of expert opinion.Summary Recommendations: Initial management depends on whether the dyslipidemia is primary or secondary. An assessment of the 10-year risk of fatal cardiovascular disease, based on the Systematic Coronary Risk Estimation (SCORE) system, should be used to set the optimal LDL-C target. Dietary changes and pharmacological management of dyslipidemias should be tailored to the type of dyslipidemia, with statins constituting the mainstay of treatment. With regard to menopausal hormone therapy, systemic estrogens induce a dose-dependent reduction in TC, LDL-C and Lp(a), as well as an increase in HDL-C concentrations; these effects are more prominent with oral administration. Transdermal rather than oral estrogens should be used in women with hypertriglyceridemia. Micronized progesterone or dydrogesterone are the preferred progestogens due to their neutral effect on the lipid profile. Tibolone may decrease TC, LDL-C, TG and Lp(a), but also HDL-C concentrations. Low-dose vaginal estrogen and ospemifene exert a favorable effect on the lipid profile, but data are scant regarding dehydroepiandrosterone (DHEA). Non-estrogen-based therapies, such as fluoxetine and citalopram, exert a more favorable effect on the lipid profile than do sertraline, paroxetine and venlafaxine. Non-oral testosterone, used for the treatment of hypoactive sexual desire disorder/dysfunction, has little or no effect on the lipid profile. [ABSTRACT FROM AUTHOR]

Purpose: To compare the influence of Cimicifuga racemosa extract (CR, Ze 450) and menopausal hormone therapy (MHT) on metabolic parameters and body weight in symptomatic menopausal women.Methods: In this monocentric retrospective cohort study, women over 40 years old with a first consultation between 2009 and 2016 were screened. Included in the final analysis were women treated with either MHT or CR and having at least one follow-up consultation. Metabolic serum parameters (lipids, glucose, insulin, and HOMA-IR), body weight, and menopausal symptoms [Menopause Rating Scale (MRS)-II] were the main outcome measures. Statistical analysis by uni- and multi-variable linear mixed-effects regression models assuming a linear effect of time.Results: 174 women were included in the final analysis (CR n = 32, MHT n = 142). There was no difference between the groups regarding baseline characteristics (age, BMI, serum metabolic parameters, hormones, and blood pressure) and total MRS-II score, while reproductive stage differed significantly with more postmenopausal women treated with CR (83%) than MHT (55%) (p = 0.038). Median follow-up time was 12 months. In both groups, metabolic serum parameters and body weight did not change over the follow-up period, while total and MRS-II subscores improved.Conclusion: Menopausal symptoms improved significantly in both groups (MHT and CR), while serum metabolic parameters and body weight did not change in MHT- or CR-treated women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Globally, the total number of people with depression exceeds 300 million, and the incidence rate is 70 % greater in women. The perimenopause is considered to be a time of increased risk for the development of depressive symptoms and major depressive episodes.Aim: The aim of this position statement is to provide a comprehensive model of care for the management of depressive symptoms in perimenopausal and early menopausal women, including diagnosis, treatment and follow-up. The model integrates the care provided by all those involved in the management of mild or moderate depression in midlife women.Materials and Methods: Literature review and consensus of expert opinion.Summary Recommendations: Awareness of depressive symptoms, early detection, standardized diagnostic procedures, personalized treatment and a suitable follow-up schedule need to be integrated into healthcare systems worldwide. Recommended treatment comprises antidepressants, psychosocial therapies and lifestyle changes. Alternative and complementary therapies, although widely used, may help with depression, but a stronger evidence base is needed. Although not approved for this indication, menopausal hormone therapy may improve depressive symptoms in peri- but not in postmenopausal women, especially in those with vasomotor symptoms. [ABSTRACT FROM AUTHOR]

The hormone therapy remains the most effective method for treating of the vasomotor symptoms and genitourinary syndrome in menopause. The evidence available to date suggests that for women younger than 60 and with a postmenopause no more than 10 years without contraindications, the benefits of administering systemic hormone therapy for the treatment of vasomotor symptoms, sleep disorders and prevention of bone loss exceed possible risks. In addition, the data about statistically significant reduction in all-cause mortality in women who initiate hormone therapy before the age of 60 and/or 10 years after the onset of menopause have been obtained. Menopausal hormone therapy (MHT) includes a wide range of hormonal drugs and administration routes that potentially have different risks and benefits, and therefore the term “class effect” is misleading and inappropriate. The risks of menopausal hormone therapy vary depending on the composition, dose and route of administration of hormones, as well as the timing of the onset and duration of use of both estrogens and progesterone. The use of transdermal estrogens in combination with progesterone seems safer for venous thromboembolism, especially in high-risk women. The use of transdermal estrogen drugs in comparison with oral estrogens is associated with a lesser likelihood of developing thrombotic risk, and possibly the risk of developing stroke and coronary heart disease. If progesterone is needed, micronized progesterone is a safer alternative. MHT requires a periodic reassessment of the benefits and risks for deciding whether to continue or stop using it. The use of postmenopausal hormone therapy in women with menopausal disorders should be based on an assessment of all risk factors for cardiovascular disease, age and time from the onset of menopause. The duration of therapy should be motivated by the indications, and the decision should be taken in conjunction with the doctor.

Estrogen deficiencies manifested by vasomotor symptoms, psychological and emotional disorders, urogenital disorders and other complications may be initiated by age-related (physiological) ovarian failure, or a sharp decline in the production of sex steroids in women treated for breast cancer. That results in a significant reduction in the quality of life of women, including general population, and requires treatment. The article tells about the current principles of menopausal hormone therapy based on the provisions of the global consensus, the potential and advancements in herbal medicine, and highlights debatable topics in the management of menopause.

Hormone therapy remains the most effective treatment for menopausal symptoms but decisions are complex, requiring an assessment of benefits and risks and determination of best treatment type, dose, and duration. Benefits exceed risks for most women with bothersome menopausal symptoms or high risk for fracture if initiated under age 60 years or within 10 years since menopause. Long-term mortality and safety data from the Women's Health Initiative is reassuring, with no increase in deaths from cardiovascular disease or cancer compared with placebo after 18 years of follow-up and a trend towards less mortality in those who initiate hormone therapy ages 50 to 59 years. [ABSTRACT FROM AUTHOR]

During menopausal transition, various phenotypical and metabolic changes occur, affecting body weight, adipose tissue distribution and energy expenditure as well as insulin secretion and sensitivity. Taken together, these can predispose women to the development of type 2 diabetes mellitus (T2DM). Many women in midlife experience climacteric symptoms, including hot flashes and night sweats. Menopausal hormone therapy (MHT) is then indicated. MHT has a favourable effect on glucose homeostasis in both women without and with T2DM. T2DM was considered in the past as a cardiovascular disease (CVD) equivalent, which would suggest that women with T2DM should not receive MHT. This notion may still deter many clinicians from prescribing MHT to these patients. However, nowadays there is strong evidence to support an individualised approach after careful evaluation of CVD risk. In older women with T2DM (> 60 years old or > 10 years in menopause), MHT should not be initiated, because it may destabilise mature atherosclerotic plaques, resulting in thrombotic episodes. In obese women with T2DM or in women with moderate CVD risk, transdermal 17β-oestradiol could be used. This route of delivery presents beneficial effects regarding triglyceride concentrations and coagulation factors. In peri- or recently post-menopausal diabetic women with low risk for CVD, oral oestrogens can be used, since they exhibit stronger beneficial effects on glucose and lipid profiles. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as natural progesterone, dydrogesterone or transdermal norethisterone. The goal is to maximise benefits and minimise adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: Clinical practice guidelines (CPGs) are systematically developed statements that guide clinicians to provide appropriate healthcare. The aims of this study were: 1) to systematically evaluate the quality of menopause management CPGs; 2) to identify menopause topics included in the CPGs; 3) to summarize the recommendations regarding either early menopause (EM) or premature ovarian insufficiency (POI) provided by high-scoring CPGs; and 4) to develop EM/POI management algorithms.Study Design: A systematic search for CPGs published between 2012 and 2017 was conducted using Medline, Embase, All EBM, CPG databases and medical websites. Appraisal was conducted by 4 independent reviewers using the Appraisal of Guidelines for Research & Evaluation II instrument (AGREE II). Inter-rater reliability was calculated using the intraclass correlation coefficient. Recommendations regarding EM/POI were extracted from high-scoring CPGs and translated into a management algorithm, which was refined on the basis of feedback from expert clinicians.Results: The systematic search yielded 22 CPGs for review. Only 2 were assessed as high quality, with 10 average and 10 considered low quality. Scope and purpose (73% ± 15%) and clarity of presentation (78% ± 15%) achieved the highest mean scores, while applicability scored the lowest (23% ± 18%). Inter-rater agreement was 0.74 (good) to 0.91 (very good). The most comprehensive CPGs were those developed by the National Institute for Health and Care Excellence (NICE), the International Menopause Society (IMS) and the European Menopause and Andropause Society (EMAS).Conclusions: Most menopause CPGs are poor to average quality and there is variation between them in EM/POI management recommendations. EM/POI management algorithms were developed from high-scoring CPGs. [ABSTRACT FROM AUTHOR]

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen. [ABSTRACT FROM AUTHOR]

Estrogen depletion following menopause predisposes to increased risk of cardiovascular disease (CVD), mainly due to ischemic heart disease. This is mostly evident in cases with premature menopause. The pathophysiological basis for this atherosclerotic process is the accumulation of several risk factors, such as abdominal obesity, atherogenic dyslipidemia, insulin resistance and arterial hypertension. The presence of vasomotor symptoms may further augment this risk, especially in women younger than 60 years. Menopausal hormone therapy (MHT) exerts many beneficial effects on lipid profile and glucose homeostasis as well as direct arterial effects, and may reduce CVD risk if initiated promptly (i.e.,<60 years or within ten years of the final menstrual period). Transdermal estradiol and micronized progesterone or dydrogesterone are the safest regimens in terms of venous thromboembolic events (VTE) and breast cancer risk. In any case, an individualized approach, taking into account the patient's total CVD, VTE and breast cancer risk, is recommended. [ABSTRACT FROM AUTHOR]

Aim. To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. Subjects and methods. From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. Results. 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. Conclusion: By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

The review highlights the role of endo- and exogenous estrogens and androgens in the genesis of cardiometabolic disorders in postmenopausal women and the role of menopausal hormone therapy in their prevention.

Abstract Background Several evaluations of the cost-effectiveness (CE) of menopausal hormone therapy (MHT) have been reported. The aim of this study was to systematically a nd critically review economic evaluations of MHT since 2002, after the Women’s Health Initiative (WHI) trial results on MHT were published. Methods The inclusion criteria for the review were: CE analyses of MHT versus no treatment, published from 2002-2016, in healthy women, which included both symptom relief outcomes and a range of longer term health outcomes (breast cancer, coronary heart disease, stroke, fractures and colorectal cancer). Included economic models had outcomes expressed in cost per quality-adjusted life year or cost per life year saved. MEDLINE, EMBASE, Evidence-Based Medicine Reviews databases and the Cost-Effectiveness Analysis Registry were searched. CE evaluations were assessed in regard to (i) reporting standards using the CHEERS checklist and Drummond checklist; (ii) data sources for the utility of MHT with respect to menopausal symptom relief; (iii) cost derivation; (iv) outcomes considered in the models; and (v) the comprehensiveness of the models with respect to factors related to MHT use that impact long term outcomes, using breast cancer as an example outcome. Results Five studies satisfying the inclusion criteria were identified which modelled cohorts of women aged 50 and older who used combination or estrogen-only MHT for 5-15 years. For women 50-60 years of age, all evaluations found MHT to be cost-effective and below the willingness-to-pay threshold of the country for which the analysis was conducted. However, 3 analyses based the quality of life (QOL) benefit for symptom relief on one small primary study. Examination of costing methods identified a need for further clarity in the methodology used to aggregate costs from sources. Using breast cancer as an example outcome, risks as measured in the WHI were used in the majority of evaluations. Apart from the type and duration of MHT use, other effect modifiers for breast cancer outcomes (for example body mass index) were not considered. Conclusions This systematic review identified issues which could impact the outcome of MHT CE analyses and the generalisability of their results. The estimated CE of MHT is driven largely by estimates of QOL improvements associated with symptom relief but data sources on these utility weights are limited. Future analyses should carefully consider data sources and the evidence on the long term risks of MHT use in terms of chronic disease. Th is review highlights the considerable difficulties in conducting cost-effectiveness analyses in situations where short term benefits of an intervention must be evaluated in the context of long term health outcomes.

The article represents peculiarities of the origination and treatment of surgical menopause at women of reproductive age, principles of monitoring and approaches to the hormonal therapy. In spite of the high efficiency of the therapy of menopausal disorders by estrogen containing substances there are diseases, for which its systemic administration is restricted. The supplement of the local therapy with physicotherapeutic influence in tissues allows to reduce the pain syndrome, to reduce the length of the treatment and to obtain the earlier restoration of the vagina mucous membrane.

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not to MEPT, indicating that melatonin supplementation may reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER2+ breast cancer. Mammary tumor development was similar in EPT and MEPT mice until age 8.6 months, but after 8.6 months, only MEPT continued to suppress cancer development. These data suggest that melatonin supplementation has a negligible effect in young MEPT mice, but is required in older mice to inhibit tumor formation. Since melatonin binding was significantly decreased in older mammary glands, irrespective of treatment, melatonin supplementation may overcome reduced melatonin responsiveness in the aged MEPT mice. Since melatonin levels are known to decline near menopause, nocturnal melatonin supplementation may also be needed in aging women to cooperate with HT to decrease breast cancer risk.

Individual risk assessment for atherosclerotic cardiovascular disease is important for safe menopausal hormone prescription. Besides the traditional risk factors, female-specific risk variables related to pregnancy and gynecologic conditions importantly contribute to a more tailored risk assessment in women at middle age. Of these, prior pre-eclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and early spontaneous menopause (<40 years) seem to be the strongest adverse risk variables. Concomitant inflammatory disorders should also be taken into account. Adding a coronary artery calcium score with a computed tomography scan to risk assessment has a high predictive value for future cardiovascular events. This should be considered to discriminate between low-risk and high-risk women when uncertainty exists. In women at intermediate risk, menopausal hormone therapy can be easily combined with preventive medication if cardiovascular risk factors are present. In women at higher risk who have severe disabling vasomotor symptoms, a lower dosage of hormone therapy can be considered in good collaboration between the gynecologist and the cardiologist/vascular specialist.

Objectives: An increasing number of women living with HIV are transitioning through midlife and menopause. Women living with HIV may experience earlier menopause and a higher symptom burden than women without HIV, but more evidence is needed. Data collection on menopause in women living with HIV is scarce and often not standardized. We sought to assess how menopause data are collected in cohorts and studies of women living with HIV., Methods: This was a literature review conducted within the PubMed database. We included original studies and cohorts assessing menopause and/or menopausal symptoms in women living with HIV. Study characteristics and menopause data collection, including the definition of menopause, symptom assessment tools, and measurement of biomedical parameters, were noted and summarized systematically in data tables., Results: We included 40 articles describing 37 separate studies published between 2000 and 2023; 27 of these were conducted in high-income countries, the majority in the USA (n = 16). Ten studies were from low- and middle-income countries; four of these were conducted in Brazil. In 20 studies, menopause was defined according to the World Health Organization's definition of over 12 months of amenorrhea. Twelve studies used the Menopause Rating Scale to characterize menopausal symptoms, five studies used other specified symptom assessment tools, and 12 studies used a study-specific tool., Conclusions: Menopause data collection in women living with HIV is heterogeneous. We propose that standardized tools should be used to enable comparisons between studies and countries, thereby improving the quality of research and clinical treatment. Further research into the validity of menopausal symptom scoring tools is warranted., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

This systematic review assesses the effect of menopausal hormone therapy (MHT) on cardiovascular outcomes and risk factors in postmenopausal women with cardiovascular disease (CVD). The Medline, Embase and Cochrane databases were searched from inception to December 2022 for randomized controlled trials (RCTs) and observational studies using methodology from a previous Cochrane review. Quality assessment used the Cochrane risk of bias tool and Newcastle-Ottawa scale, respectively. From 5647 studies identified, 29 (23 RCTs and six observational studies) were included. Most studies were conducted in North America or Europe and investigated oral estrogens. Participants were older with varying frequency of cardiac risk factors and underlying CVD. No significant difference was observed between MHT users and controls regarding primary outcomes of non-fatal myocardial infarction, cardiovascular death or stroke. No difference in frequency of angina, heart failure and transient ischemic attacks was observed. Inconsistent effects of MHT on angiographic progression were seen and varied with glycemic status. Estradiol had a positive effect on flow-mediated dilatation. Limited studies identified differing effects of MHT on cardiac risk factors, varying with estrogen preparation. This study confirms no benefit of MHT for secondary CVD prevention, highlighting evidence limitations and the importance of shared decision-making when managing menopausal symptoms in women with CVD.

ABSTRACT Women living with HIV are reaching older age and experiencing menopause and age-related comorbidities. Data suggest that women living with HIV experience earlier menopause and more menopausal symptoms and age-related comorbidities compared to women without HIV. However, there are no guidelines on the screening for and management of age-related comorbidities and events in women living with HIV. Moreover, little is known about provision of care to this population across Europe. We surveyed 121 HIV healthcare providers in 25 World Health Organization European countries to ascertain screening practices for, and management of, menopause, psychosocial and sexual well-being and age-related comorbidities in women with HIV. Most respondents screened for diabetes, cardiovascular disease (CVD) risk factors and poor mental health at least annually. Low bone mineral density (BMD) was regularly checked but less than once a year. Fewer regularly screened for sexual well-being and intimate partner violence. Menstrual pattern and menopausal symptoms in women aged 45-54 were assessed by 67% and 59% of respondents. 44% stated that they were not confident assessing menopausal status and/or symptoms. CVD, diabetes, low BMD and poor mental health were managed mainly within HIV clinics, whereas menopause care was mainly provided by gynaecology or primary care. Most respondents stated a need for HIV and menopause guidelines. In conclusion, we found that whilst metabolic risk factors and poor mental health are regularly screened for, psychosocial and sexual well-being and menopausal symptoms could be improved. This highlights the need for international recommendations and clinician training to ensure the health of this population.

Purpose of Review: Given the potential for exogenous hormones to influence risk and course of MS, this narrative review aims to summarize current knowledge from observational and interventional studies of exogenous hormones in humans with MS., Recent Findings: Large randomized clinical trials for combined oral contraceptives and estriol both show modest effect on inflammatory activity, with the latter showing potential neuroprotective effect. After fertility treatment, large actively treated cohorts have not confirmed any elevated risk of relapse. Preclinical data suggest that androgens, selective estrogen receptor modulators (SERMs), and selective androgen receptor modulators (SARMs) may be neuroprotective but clinical data are lacking. Gender affirming treatment, particularly estrogen in trans-women, could possibly be associated with elevated risk of inflammation. For women with MS entering menopause, hormone therapy appears safe during the appropriate menopausal window, but its long-term effects on neuroprotection are unknown. Exogenous hormones, used in varied doses and for diverse indications, have variable effects on MS risk, inflammatory activity, and neuroprotection. Large randomized trials are needed before it is possible to determine the true effect of exogenous hormones in a condition as complex as MS., (© 2023. The Author(s).)

Purpose: Over the past half century, the annual age-adjusted breast cancer incidence in the USA has fluctuated, potentially influenced by changes in mammography screening, obesity, and menopausal hormone therapy. As the relative contributions of these factors on breast cancer incidence have not been resolved, we assembled reliable sources of year-to-year changes in mammography, obesity, and hormone therapy to graphically display their relationship to breast cancer incidence through 50 years., Methods: Year-to-year trends were assembled: for mammography from the Center for Disease Control National Health Interviews; for hormone therapy from the Collaborative Group on Hormonal Factors in Breast Cancer report; for obesity from the NCD (Non-Communicable Diseases) Risk Factor Collaboration; and for breast cancer for US women 50-64 years of age from Surveillance, Epidemiology, and End Results (SEER) registry findings., Results: Increases in age-adjusted breast cancer incidence trend from about 1982 to 2002 track both mammography and hormone therapy use but not obesity. However, the sudden decrease in breast cancer incidence in 2003, subsequently sustained at a lower incidence level, only tracks the parallel reduction in hormone therapy use., Conclusion: The sustained reduction in hormone therapy use from 2003 provides a plausible explanation for most of the lower breast cancer incidence seen in US postmenopausal women during the last two decades. The strong observational study obesity association with higher breast cancer risk is not reflected in breast cancer incidence trends., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain-specific cognition in later life., Methods: We studied a population-based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing., Results: The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular-related covariates did not attenuate the results., Discussion: Multiple reproductive risk factors are associated with cognitive decline in later life., Highlights: The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain-specific z-scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Aim: Evaluate the cost utility of menopausal hormone therapy for women in China., Materials and Methods: A bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China's Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks., Results: According to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of -7,184$ (-47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China., Conclusion: Contingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E 2 ) intervention developed NAFLD, whereas E 2 supplementation was effective in preventing NAFLD in female rats. The altered pathways and cellular events from both comparison pairs, namely, the OVX vs. sham group and the OVX vs. E 2 group, were assessed using transcriptomic analysis. KEGG pathways enriched by both transcriptomic and metabolomic analyses strongly suggest that oxidative phosphorylation is a vital pathway that changes during the development of NAFLD and remains unchanged when E 2 is applied. Liver tissue from the OVX-induced NAFLD group exhibited increased lipid peroxidation, impaired mitochondria, and downregulated ERα/SIRT1/PGC-1α expression. An in vitro study indicated that the protective effect of E 2 treatment on hepatic steatosis could be abolished when ERα or SIRT1 was selectively inhibited. This damage was accompanied by reduced mitochondrial complex activity and increased lipid peroxidation. The current research indicates that E 2 upregulates the ERα/SIRT1/PGC-1α signaling pathway and protects mitochondrial function to prevent OVX-induced NAFLD.

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

The decision regarding oophorectomy during gynecological surgeries, especially in perimenopausal and postmenopausal women, has historically posed a significant dilemma. Traditionally, it was widely believed that conserving the ovaries held no benefits, leading to a common practice of recommending bilateral salpingo-oophorectomy alongside hysterectomy for benign conditions in women aged 40-45 and above. Given our evolving comprehension of postmenopausal ovarian function and the genetic susceptibility to ovarian epithelial cancers, the decision regarding oophorectomy poses a dilemma. Oophorectomy is recommended for women with a higher risk of ovarian cancer and ovarian conservation is necessary with women with higher risk of co-morbidities. This paper reviews the available literature on these aspects of oophorectomy. Despite a wealth of literature narrating the advantages and disadvantages of oophorectomy, covering various aspects such as ovarian cancer risk, myocardial infarction incidence, and post-oophorectomy peritoneal cancer, there is a notable absence of a comprehensive evaluation system for risk stratification. The objective of the present paper is to address this gap by consolidating existing literature into a risk stratification system. This system will provide treating physicians a tool that facilitates more informed, case-specific decisions in collaboration with patients and their families. While recognizing that the ultimate decision must be tailored to the individual case and agreed upon mutually by the surgeon, patient, and family, the proposed system seeks to streamline risk stratification. This, in turn, should aid in determining the most suitable course of treatment that maximizes benefits for the patient., (© Federation of Obstetric & Gynecological Societies of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law., corrected publication 2023.)

Objective: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature., Methods: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps., Results: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health., Conclusions: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

Objective: We compared the trends of hormone therapy (HT) use among women with and without a history of pre-eclampsia., Methods: This national cohort study consisted of women with a pre-eclamptic pregnancy ( n  = 31,688) or a normotensive pregnancy ( n  = 91,726) (controls) during 1969-1993. The data on their use of HT during 1994-2019 were traced from the National Medicine Reimbursement Register., Results: Both women with a history of pre-eclampsia and controls initiated HT at a mean age of 49.9 years. Cumulative HT™ use during the total follow-up did not differ between the groups (31.1% vs. 30.6%, p  = 0.066). However, HT use in previously pre-eclamptic women was less common in 1994-2006 (20.2% vs. 22.4%, p  < 0.001) and more common in 2007-2019 (22.1% vs. 21.1%, p  < 0.001) than in controls. This trend was also seen in the annual changes of HT starters. Women with a history of pre-eclampsia used HT for a shorter time (6.3 vs. 7.1 years, p  < 0.001)., Conclusions: In contrast to controls, HT use in previously pre-eclamptic women increased during the last half of the follow-up. This may reflect the changes in the international recommendations, the increased awareness of pre-eclampsia-related cardiovascular risk later in life and the aim to diminish this risk with HT.