Search

Menopausal hormone therapy (MHT) has been widely used for the clinical treatment of symptoms associated with menopause in women. However, the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated. The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy, with an elevated risk of breast cancer. The evidence currently available from randomized trials and observational studies is based on data from different populations, drug formulations, and routes of administration. Even though the risks of MHT and breast cancer have received a great deal of attention, information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed. Furthermore, the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied. Therefore, this review aimed to describe the biological effects of estrogen, progesterone, and their metabolites on the proliferation of breast cancer cells, based on relevant basic research and clinical trials, to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.

Aim: to evaluate an impact of menopausal hormone therapy (MHT) on late postmenopausal multimorbid women’s quality of life (QoL).Materials and Methods. 132 late postmenopausal women were enrolled to the study and were divided into two groups: group 1 consisted of 66 subjects with moderate multimorbidity and Charlson Comorbidity Index (CCI) < 3; group 2 (66 patients) had high multimorbidity (CCI ≥ 3). Women receiving or not MHT were subdivided in both groups. SF-36 questionnaire was used to assess QoL, Hospital Anxiety and Depression scale (HADS) – for evaluating emotional status, MMSE test (Mini-Mental State Examination) – for cognition evaluation. Modified Menopausal Index (MMI) was calculated as well.Results. Women with a low level of comorbidity who had previously received MHT have a significantly higher QoL. The median age for subjects was 69 [65; 71] years, median CCI score was 3.5 [2.5; 5.0]. In addition, in group 2 there were found significantly lower physical functioning (p < 0.001), role-physical functioning (p = 0.028), physical health (p = 0.002) domains, as well as more severe persistent menopausal symptoms (p = 0.011) and depression (p = 0.043). History of MHT in group 1 was associated with higher levels of physical functioning (p = 0.033) and role-physical functioning (p = 0.023), whereas in group 2 MHT was associated with better cognition (p = 0.028) and lower depression symptoms compared with those lacking history of MHT.Conclusion. Multimorbidity in late postmenopausal women was associated with impaired QoL physical domains. MHT allows to effectively improve QoL in women with moderate multimorbidity and to protect cognitive state to higher level as well as reduce depression symptoms in women with severe multimorbidity.

OBJECTIVES: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control. METHODS: The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤ 46 years (n = 338) and peri/postmenopausal 47-65 years (n = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months. RESULTS: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 (p

Background Oral postmenopausal hormone therapy (HT) increases the risk of venous thrombosis (VT). We postulated that activated protein C (APC) resistance induced by HT is one of the mechanisms causing VT, and also assessed the role of one of the main determinants of APC resistance, i.e., tissue factor pathway inhibitor (TFPI). Methods We performed a nested case-control study embedded within two Women's Health Initiative (WHI) hormone trials. Women were randomized to hormone therapy or placebo. Biomarkers were measured at baseline and after one-year, in 217 cases and 817 controls. Results Increased APC resistance and decreased TFPI at baseline were associated with VT (OR ranging from 1.20 to 2.06). However, women with such prothrombotic profile at baseline did not have further increased risk of VT when randomized to HT compared with placebo. While there was no change in APC resistance or TFPI in placebo group after one-year, HT group showed prothrombotic changes in the biomarkers, i.e., an increase in APC resistance (mean(sd):0.39 (0.54)) and decrease in TFPI (-0.21(0.50): free TFPI, -0.24(0.22): TFPI activity and -0.22(0.20): total TFPI). However, HT induced prothrombotic change in biomarkers did not increase risk of VT. Conclusion Women with prothrombotic levels of APC resistance and TFPI at baseline were not at increased risk of VT when randomized to HT compared with placebo. This suggests that testing for these biomarkers prior to starting HT is not required. HT led to prothrombotic change in these biomarkers after one year, but this did not relate to increased risk of VT.

Highlights • Melanocytes are known to respond to estrogen stimulation. • Knowledge of estrogen therapy in melanoma tumor behavior is essential to inform accurate patient prognostication. • There is limited evidence to suggest oral contraception and fertility treatments affect melanoma incidence. • The effect of menopausal hormone therapy on melanoma risk requires further investigation with multinational studies., Although primary cutaneous melanoma accounts for approximately 3% of all malignant skin tumors, it has the greatest contribution to skin cancer–related death. Sex-specific differences in melanoma tumor behavior have been described, and melanoma pathogenesis may be hormonally mediated. This review aims to summarize the literature to date regarding the effects of hormone therapy on melanoma in women. Women's exogenous hormone use has changed dramatically over the past few decades. Thus, we focus on studies investigating the associations between oral contraception, fertility treatments, menopausal hormone therapy (MHT), and melanoma. Across hormone therapy types, there does not appear to be a well-established association between exogenous female hormones and melanoma incidence. However, MHT practices and formulations vary significantly across countries. Although MHT does not appear to increase melanoma risk in studies from the United States, conflicting results have been observed in Europe. Unopposed estrogen MHT formulations require further investigation to determine a clear pattern between hormone use and the development of melanoma.

Sex hormones are responsible for multiple physiologic processes by signalling through estrogen (ER) and androgen receptors (AR).(1) ERs and ARs are expressed in liver and biliary tract cells in normal and diseased states in both men and women. Thus, the liver is recognized as a sex hormone responsive organ. In general, estrogen is associated with hepatic "protection" while androgens associate with hepatic "progression".

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Background To examine the relationship between the length of oestrogen exposure and risk of incident stroke. Also, the additive value of each model was compared for assessing oestrogen exposure and stroke risk in postmenopausal women. Study design and setting Prospective study of 5632 post-menopausal women without a prior history of stroke from 1996 through 2016 in Australian Longitudinal Study on Women's Health. Data on surrogate measures of oestrogen exposure were used to derive five indices of oestrogen exposure including reproductive lifespan (RLS) (age at menopause-age at menarche), endogenous oestrogen and total oestrogen exposure (which included menopausal hormone therapy (MHT use)). The relationships between the length of oestrogen exposure (quartiles) and incident stroke events were examined using multivariable adjusted Cox proportional hazard regression and their predictive accuracy were compared using area under the Receiver Operating Characteristic Curve. Results The mean (SD) for RLS was 37.9(4.3) years. A shorter RLS (≤34 years) was associated with a higher risk of incident stroke after adjustment (HR: 1.85, 95%CI: 1.08, 3.15), compared with 38–40 years. There was 7% decrease in risk of stroke per 1-year increase in RLS (HR: 0.93, 95%CI: 0.89, 0.97). Even though the combination of endogenous oestrogen and exogenous hormones aimed to provide more accurate length of oestrogen exposure, the results showed that each model had similar goodness of fit and did not improve the model of just using RLS as a predictor of incident stroke. Conclusions A shorter RLS (≤34 years) was associated with higher risk of incident stroke compared to medium RLS. Endogenous oestrogen and of total oestrogen exposure (which included MHT use) did not improve the model of just using RLS as a predictor of incident stroke.

No abstract available

The article analyzes and presents data for the last 70 years from the PubMed database on endometrial hyperplasia (EH), which is one of the leaders in the structure of gynecological diseases and the main predictor of endometrial cancer (EC). The chronicle of the EH classification is highlighted with a focus on changing the designation and relevance of adenomatous EH. It is shown how the current classification of EH, due to the fact that a large number of synonyms is limited by two options, allows to maximize the reproducibility of the diagnosis, improve the interaction of the obstetrician-gynecologist with the pathologist and reduce the treatment inefficiency. The results of modern studies on the prevalence and risk factors of EH and EC differ from previously accepted ones and destroy the Bohman triad. The risks of EH development with tamoxifen and menopausal hormone therapy are determined. The data of current research methods aimed at the diagnosis of EH and EC are indicated. The differences in etiopathogenesis, prevalence, diagnosis, risk factors for development and progression to the malignant process presented in the review represent two types of EH (without atypia and with atypia) as completely different endometrial diseases included in the same classification.

This study was performed to evaluate serum estradiol level in postmenopausal women using oral menopausal hormone therapy (MHT) with different doses and formulations of estrogens. A total of 344 postmenopausal women who received oral MHT was included in this cross-sectional study. Serum estradiol level was compared according to formulation (estradiol hemihydrate [EH] or valerate [EV], conjugated estrogen [CE]) and dose (estradiol 1 or 2 mg, CE 0.45 or 0.625 mg) of the estrogens. Mean age and years since menopause were 56.9 and 7.9 years, respectively. Mean duration of MHT was 27.4 months. Since serum estradiol levels were not significantly different at either dose, EH and EV at the same dose were combined for comparisons: estradiol 1 mg and 2 mg. The serum estradiol level with estradiol 2 mg (107.6 pg/mL) was significantly higher by 60% than with estradiol 1 mg (65.8 pg/mL) or CE 0.45 mg (60.1 pg/mL), and it was also significantly higher than with CE 0.625 mg (76.8 pg/mL). Our findings suggest that serum estradiol level is not directly proportional to estrogen dose. In terms of serum concentration, CE 0.45 mg is equivalent to estradiol 1 mg.

Administration of menopausal hormone therapy (MHT) in patients with genital endometriosis (GE) is a controversial issue requiring a patient-personalized approach. Current principles for MHT selection and prescription in patients with anamnestic endometriosis are presented, which are based on the guidelines of the International Menopause Society (IMS), The European Menopause and Andropause Society, local and foreign publications retrieved from electronic data bases PubMed, Cyberleninka. The data of our study on observing 724 patients with GE treated with diverse MHT types were presented and analyzed (428 women in perimenopausal period, 296 in postmenopausal period). Patients with endometriosis in perimenopausal and postmenopausal periods showed more prominent manifestations of climacteric and post-ovariectomy syndromes, as well as high risk of reduced bone mineral density (BMD) due to repeated surgery on the ovaries and preceding long-term “antiestrogen therapy”. Custom-compounded MHT based on components combinations, dosage and administration route provides a significantly improved quality of life for patients with endometriosis, prevents loss of BMD and reduces risk of cardiovascular diseases. Using low and ultra-low dose estrogen bioidentical to natural substances in this patient group minimizes a risk of disease recurrence.

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy. Aim. To search a molecular predictive marker of the effectiveness of OS treatment. Materials and methods. The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood. Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy. Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

The review article presents an analysis of the literature over the past 10 years on the relationship of menopausal hormone therapy and the risks of developing malignant diseases in women, including risk factors, such as mutations in the BRCA1/2 genes. The main limiting factor in the appointment of menopausal hormone therapy today remains the question: is there a connection between MHT and the development of oncological pathology, due to the high mortality rates from malignant neoplasms, which occupy the 2nd place after cardiovascular diseases. The main localization of the tumor process, which stops the appointment of MHT, is breast cancer. In the structure of the incidence of malignant neoplasms among the female population in Russia, breast cancer occupies a leading place, and this is the main interest in the effect of MHT. The results of large-scale studies are rather ambiguous and do not answer all the questions. Do not forget about other localizations of the tumor process, which MHT can also influence, and about which, there is also no unequivocal answer to the question about the relationship of MHT and the risks of tumor development. As for any therapy, for MHT there are contraindications, which are also covered in the article. The main modes of taking menopausal hormone therapy and their relationship with the risks of tumor development are also presented. The influence of the main components of menopausal hormone therapy on the processes of neoplastic transformation.

Although estrogen-progestin therapy has traditionally been standard care for postmenopausal women with an intact uterus experiencing bothersome menopausal symptoms, concerns about side effects related to menopausal hormone therapy (MHT) have led to a dramatic decrease in MHT use over recent decades. As many MHT side effects are now believed to be associated with the progestin component of MHT, efforts have been made to develop a progestin-free alternative to conventional MHT. Recently, a tissue-selective estrogen complex (TSEC), a combination of conjugated estrogen and bazedoxifene, was developed as a progestin-free MHT and is now approved and used worldwide for the relief of vasomotor symptoms and the prevention of bone loss in postmenopausal women. Replacement of synthetic progestin with bazedoxifene could allow more favorable safety profiles, such as those for pain or tenderness, mammographic density, and cancer incidence, for the breast. This review examined the effects of the TSEC on breasts and demonstrated evidence from preclinical and clinical studies supporting TSEC use in clinical practice., Graphical Abstract

The loss of estrogen with menopause is associated with an increase in central fat. The objective of this study was to evaluate the effects of menopause hormone therapy (HT) on body composition and metabolic parameters in postmenopausal women. A prospective study was conducted among postmenopausal women from the Climacteric clinic, Universidade Federal de São Paulo. Thirty-two participants, median age 51 years, were included. Sixteen women were eligible to receive a low-dose continuous combined HT, containing 1 mg of E2 plus 0.125 mg of trimegestone for 6 months. The other 16 women remained in the control group. In the HT group, significant decreases from baseline were evident for the total cholesterol (TC) (p

Purpose: The purpose of this study was to determine if the use of menopausal hormone therapy (HT) is related to the development of neovascular (NV) age-related macular degeneration (AMD), geographic atrophy (GA) and/or early/intermediate AMD.Methods: A case-control study was conducted from patients prospectively recruited from July 2014 to June 2019. Cases were females with AMD recruited into a registry and controls were females with age-related cataract and no AMD. Age-related macular degeneration was categorized into NV-AMD, GA, and early/intermediate. Hormone therapy (historic and current) was self-reported by the patient and categorized as ever/never use. Adjusted odds ratios (ORs) from multinomial logistic regressions are presented for each AMD group.Results: Female AMD case patients (n = 409) and controls (n = 132) were included in the analytic database. Almost half (45.5%) of the female AMD patients had NV-AMD, 14.9% had GA, and 39.6% had early/intermediate AMD. Among all study participants, 285 (52.7%) reported historic and/or current use of HT. Controls were significantly more likely to have any HT use (71.2%), compared to 43.0% (p ≤ 0.001) of NV-AMD patients, 47.5% (p = .002) of GA patients, and 50.6% (p ≤ 0.001) of early/intermediate AMD patients. Adjusted for potential confounders of age and Caucasian race, cases were significantly more likely to have lower HT use compared to controls: NV-AMD, OR = 0.31 (95%CI: 0.18-0.54), GA, OR = 0.40 (95%CI: 0.20-0.80), and early/intermediate AMD, OR = 0.36 (95%CI: 0.22-0.61).Conclusion: Our case-control study found that the use of HT was associated with a lower odds of all AMD stages studied: NV-AMD, GA and early/intermediate.

Background The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea. Methods A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002–2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan–Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose–response relationship. Results The median follow-up was 79.6 of months. Kaplan–Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691–0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577–0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605–1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547–0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064). Conclusions The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose–response relationship in a population-based cohort study.

Menopausal hormone therapy (HT) aims to improve a woman's quality of life by treating bothersome menopausal symptoms associated with low estrogen levels. Although HT is prescribed to millions of women worldwide, its breast-related adverse effects have always been a concern. Some of the common adverse effects of HT are breast fullness, increased breast density, and increased breast cancer (BC) risk. Health care professionals need to be aware of the influence of HT on breast tissue to provide appropriate counseling as part of informed decision making. Our review summarizes the influence of HT on breast symptoms, breast density, mammograms, and BC risk.

In this issue of Climacteric, Yoon et al. report results of a clinical trial comparing the use of menopause hormone therapy (MHT) and risedronate for prevention of fracture recurrence in older post...

An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture.Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD).Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

Objective of the Review: To discuss clinical and experimental research data, focused on some non-reproductive effects of estrogens and the role of menopausal hormone therapy (MHT) in ensuring women’s health during aging and preventing age-associated diseases. Key Points: Combination oral MHT is most effective in preventing cardiovascular diseases, metabolic syndrome, and diabetes mellitus, when initiated during the menopause transition. Individually tailored regimens containing the bioidentical estrogen 17β-estradiol and dydrogesterone, a metabolically neutral gestagen, ensure highly safe MHT. Conclusion: Professional medical communities currently have no doubt about the need for early initiation of MHT, taking into account all indications and contraindications, for arresting menopausal disorders and prevention of metabolic and neurodegenerative conditions. Keywords: menopause, combination hormone therapy, cardiovascular diseases, neurodegenerative conditions, metabolic syndrome.

This is the peer reviewed version of the following article: Cervenka, I., Al Rahmoun, M., Mahamat-Saleh, Y., Fournier, A., Boutron-Ruault, M.-C., Severi, G. ... Kvaskoff, M. (2019). Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.32674. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. 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.

The research provided includes analysis of the current state of the problem on the use of oral contraceptives and menopausal hormone therapy. These therapeutic options were evaluated in terms of their importance for the risk of breast cancer. The possibility of using these drugs in a cohort of high-risk patients (women with family history of breast cancer) and in the group of patients with benign pathology was analyzed as well. Modern trends of menopausal hormone therapy prescription in different clinical situations were determined.

The objective: to evaluate the results of a comparative analysis of the clinical efficacy of various compositions, combination and pharmacological effects of drugs (antispasmodic, hormones, of plant origin) for symptoms of the lower urinary tract in women in the premenopausal period. Materials and methods. The efficacy of the treatment of 120 premenopausal women with symptoms of the lower urinary tract was studied. The complaints, uroflow metrics, sociological survey of results to identify the symptoms of menopausal syndrome by the MRS scale, as well as the level of anxiety by the S. Spielberg scale were evaluated as criteria for its assessment in the dynamics before and after 3, 6, 12 months. The data were statistically processed using Student’s and Fisher’s criteria. Results. There have been revealed the frequency and nature of complaints in women aged 40 plus, manifested in the form of urinary disorders, gynecological symptoms of menopausal syndrome. The results of treatment with the use of monotherapy with mirabegron, as well as in combination with menopausal hormone therapy (MHT) and herbal medicine, have been studied. There has been proven clinical advantage in treating women with genitourethral syndrome, using a combination of systemic MHT and symptomatic. Conclusions. Treatment of lower urinary tract symptoms in women of perimenopausal age with the presence of menopausal manifestations requires an integrated approach with the inclusion of systemic menopausal hormone therapy, among which objectively proven advantage of the drug, which includes levonorgestrel, as well as symptomatic therapy.

This article presents the evaluation of efficacy of low-dose dipyridamole used to prevent thrombotic complications during menopausal therapy in women in the early postmenopause.

According to epidemiological studies, about 30% of residents in Russia receive less than 70% of the daily magnesium intake, while magnesium deficiency manifests much more often in women than in men. The prevalence of magnesium deficiency is 1.3 times higher among the female population. Women are more sensitive to magnesium deficiency and normally have higher deposited concentrations of this element. Objective of the study: evaluate the effectiveness of magnesium in the management of menopausal syndrome symptoms. Materials and methods: 30 female patients, aged 47 to 57 years, with various menopausal syndrome symptoms underwent clinical and laboratory examination. In addition to the general clinical examination, all patients underwent atomic absorption spectroscopy to determine serum Mg2+ ions concentrations. All patients received menopausal hormone therapy in combination with magnesium supplement using Magnesium Diasporal 300. Results and discussions: The severe climacteric symptoms relief and an increase in the serum magnesium levels were recorded against the background of the therapy.

Postmenopausal osteoporosis is a frequent health issue in women. Because osteoporosis-related fractures cause a significant increase in mortality and morbidity, it is clinically important to identify as soon as possible women at increased risk for future fracture so that preventive measures can be instituted. At the beginning of menopause, evaluation of the subsequent risk of fracture is not so easy. Most screening tools fail to accurately identify those women who will fracture within the next 10 years. A history of a prior fracture and low bone mineral density are the only major consistently found predictors for the risk of fracture. On the other hand, it is no longer a question whether menopause hormone therapy is efficient not only to prevent postmenopausal bone loss but also the incidence of fragility fracture. Over the last years, utility of menopause hormone therapy for the prevention of osteoporosis has been questioned due to safety concerns. In light of the most recent reports on a more favorable benefit/risk balance than was initially claimed in early postmenopausal women, this needs to be reconsidered. Prevention of bone loss in those women with a moderate or slightly high risk of fracture is likely a strategy to reduce fracture risk in older women. Menopause hormone therapy must be considered as a true primary preventive therapy more than an anti-fracture therapy at an age when the risk of fracture is likely much lower than later in life. Only thereafter should other anti-osteoporotic medications be discussed in women still at high risk for fracture.

Objective:Little is known regarding the progression of preclinical atherosclerosis upon cessation of menopausal hormone therapy (MHT). This study evaluated changes in carotid artery intima-media thickness (CIMT) in a subgroup of participants during 4 years and 3 years after the Kronos Early

Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed againts the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).

ObjectiveTo better understand how to educate patients and providers about study findings relevant to treatment guidelines, we assessed pre- versus post-Women's Health Initiative (WHI) differences in menopausal hormone therapy (MHT) initiation and continuation and their correlates, and in women's reasons for initiation and discontinuation.MethodsWe analyzed survey data from up to 14 approximately annual visits over 17 years (1996-2013) from 3,018 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used logistic regression to compare pre- versus post-WHI associations of covariates with MHT initiation and continuation, and to compare pre- versus post-WHI reasons for initiation and continuation.ResultsMHT initiation dropped from 8.6% pre-WHI to 2.8% post-WHI (P

Physical inactivity, high postmenopausal body mass index, alcohol consumption and use of menopausal hormone therapy are established risk factors for breast cancer. Less is known about whether these factors influence the risk of progression of benign and premalignant breast lesions to invasive breast cancer. This registry-based cohort study was based on women with a precancerous lesion who were followed for breast cancer. The cohort consisted of 11 270 women with a benign lesion, 972 women with hyperplasia with atypia and 2379 women with carcinoma in situ diagnosed and treated after participation in BreastScreen Norway, 2006-2016. Information on breast cancer risk factors was collected by a questionnaire administered with the invitation letter. Cox regression analysis was used to estimate the association between breast cancer and physical activity, body mass index, alcohol consumption, tobacco smoking and menopausal hormone therapy, adjusted for age. During follow-up, 274 women with a benign lesion, 34 women with hyperplasia with atypia and 118 women with carcinoma in situ were diagnosed with invasive breast cancer. We observed an increased risk of breast cancer associated with use of menopausal hormone therapy for women with a benign or premalignant lesion. Alcohol consumption and tobacco smoking showed suggestive increased risk of breast cancer among women with a benign lesion. We were only to a limited degree able to identify associations between modifiable risk factors of breast cancer and the disease among women with a precancerous lesion, and a larger study is needed to confirm or refute associations. The work was funded by The Norwegian Cancer Society (grant no. 5746604).

Colorectal cancer (CRC) is the second most frequently diagnosed cancer in females worldwide. Menopausal hormone therapy (MHT) has been proposed as a potential protective factor for the development of CRC. Yet, the available evidence is controversial. Thus, we aimed at summarizing the current evidence on the effect of MHT on CRC through a systematic review. A systematic literature search identified 1001 potentially relevant articles, out of which 57 original studies and nine meta-analyses were deemed eligible for the final synthesis. The evidence synthesis showed the following: (1) MHT showed a heterogeneity in findings for CRC risk with a slight tendency to a neutral or protective effect; (2) MHT effect was either neutral or protective on colorectal adenoma; (3) MHT had no impact on tumour grade, subsite and histologic types; (4) MHT was not associated with CRC mortality; and (5) MHT showed heterogeneous effects on CRC stage and invasiveness, respectively. In summary, despite some evidence pointing towards a protective effect of MHT on CRC, MHT is currently not recommended for primary CRC prevention by international guidelines due to several important, potentially harmful effects.

Introduction The impact of menopausal hormone therapy (HT) on age‐associated Alzheimer's and neurodegenerative diseases (NDDs) remains unresolved. To determine the effect of HT, formulation, type, and duration on risk of NDDs, a retrospective analysis was performed using a 10‐year Humana claims dataset. Methods Study population included women aged 45 years or older with or without claim records of HT medications. Patients diagnosed with NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) were identified. Relative risk (RR) ratios and 95% confidence intervals (CI) for combined NDDs, or AD, PD, dementia, MS, and ALS were determined. Cumulative hazard ratios were determined to investigate the association between HT and NDDs at different age groups. Results In 379,352 women with or without claim records of HT, use of HT was associated with significantly reduced risk for combined NDDs (RR 0.42, 95% CI 0.40–0.43, P 1 year) on combined NDDs, AD, PD, and dementia was greater compared to short‐term therapy (≤1 year). Discussion HT was associated with reduced risk of all NDDs including AD and dementia, with greater duration of therapy and natural steroid formulations associated with greater efficacy. These findings advance precision HT to prevent NDDs including AD.

Background Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. Methods This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. Results Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44-0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59-0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02-1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06-2.44) in older women, but no association was shown for all-cause mortality. Conclusions Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear.

Background Menopausal hormone therapy (MHT) increases breast cancer (BC) risk, but cohort studies largely consider use only at enrollment. Evidence is limited on how changes in MHT use alter the magnitude of risk, and whether risk varies between invasive and in situ cancer, by histology or by hormone receptor status. Methods We investigated the roles of estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT) on BC risk overall, by histology and estrogen receptor (ER) and progesterone receptor (PR) status, and on incidence of in situ disease, in the NIH-AARP cohort. Participants included 118,760 postmenopausal women (50–71 years), of whom 63.5% (n = 75,398) provided MHT use information at baseline in 1996 and in a follow-up survey in 2004, subsequent to the dissemination in 2002 of the Women’s Health Initiative trial safety concerns regarding EPT. ET analyses included 50,476 women with hysterectomy (31,439 with follow-up data); EPT analyses included 68,284 women with intact uteri (43,959 with follow-up data). Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models using age as the time metric with follow-up through 2011. Results Eight thousand three hundred thirty-three incident BC cases were accrued, 2479 in women with follow-up data. BC risk was not elevated in current ET users at baseline (HR = 1.05, 95% confidence interval [CI] CI = 0.95–1.16) but was higher in women continuing use through 2004 (HR = 1.35, 95% CI = 1.04–1.75). Ever EPT use at baseline was associated with elevated BC risk overall (HR = 1.54 (1.44–1.64), with a doubling in risk for women with 10 or more years of use, for in situ disease, and across subtypes defined by histology and ER/PR status (all p Conclusions ET use was not associated with BC risk in this cohort, although excess risk was suggested in women who continued use through 2004. EPT use was linked to elevated in situ and invasive BC risk, and elevated risk across invasive BC histologic and hormone receptor-defined subtypes, with the highest risk for women who continued use through the 2004 follow-up survey.

Background Age-specific incidence rates of cutaneous Malignant Melanoma (MM) are higher in women during their reproductive years, while the rate of increase slows after menopause, supporting the speculation that hormones might influence the risk of developing cutaneous MM. The aim of our systematic review and meta-analysis is to summarize the evidence on the association between Menopausal Hormone Therapy (MHT) and the risk of MM. Methods Medline and Web of Science were systematically searched for eligible publications until December 2019. Our review and meta-analysis follow the PRISMA guidelines. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using a random effect model. Results The pooled analysis of all 19 studies (9 cohort and 10 case-control) showed a significant positive association of MHT with risk of MM (OR 1.19; 95% CI 1.13-1.26; I2=41.93%, p = 0.029). Excluding Uveal and intraocular MM (3 studies), MHT increased the risk of cutaneous MM (OR 1.19; 95% CI 1.13-1.26; I2=35.73%, p = 0.077). No significant publication bias could be detected. Stratifying by study design, MHT significantly increased the risk of cutaneous MM (OR 1.19; 95% CI 1.12-1.27; I2=42.52%, p = 0.107) in the cohort studies; no significant association was found in case-control studies. Conclusions This meta-analysis of available literature resulted in an increased risk of MM in women used MHT. Further investigations are necessary to increase the reliability of the results and estimate the relationship of other characteristics of MHT, such as type (opposed and unopposed estrogens) and route of administration, with MM. Key messages Menopausal Hormone Therapy (MHT) significantly increases the risk of Malignant Melanoma (MM). Further awareness of clinical practitioners should be raised on the potential association of MHT with MM.

Background: Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years. Methods: Using data from the Nurses' Health Study II, with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed via biennial survey (from 1989), we performed Cox proportional regression models with women contributing person-years from age 36 years. Relevant covariates were assessed at biennial surveys. We considered potential effect modification by race/ethnicity, age at baseline, and period (1989–2002 vs. 2003–2015). Results: Over follow-up, 22,352 of 43,025 women reported initiating MHT use. For example, compared with women with no trauma, the HR for initiating MHT was 1.18 for those with trauma/1–3 PTSD symptoms [95% confidence interval (CI), 1.13–1.22] and 1.31 for those with trauma/4–7 PTSD symptoms (95% CI, 1.25–1.36; P trend < 0.001), adjusting for sociodemographic factors. Associations were maintained when adjusting for reproductive factors and health conditions. We found evidence of effect modification by age at baseline. Conclusions: Trauma and number of PTSD symptoms were associated with greater likelihood of initiating MHT use in a dose–response manner. Impact: MHT may be a pathway linking PTSD to altered chronic disease risk. It is important to understand why women with PTSD initiate MHT use.

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT

Vasomotor symptoms (hot flushes and/or night sweats) affect approximately 80% of women over the menopause transition and can affect quality of life, productivity, and relationships. Vasomotor symptoms are the main reason for seeking treatment during the menopausal transition. Although menopausal hormone therapy (MHT) is effective for symptom management, the majority of symptomatic women do not take MHT. In this article, we review the evidence for non-hormonal treatments for vasomotor symptoms, including pharmacological and non-pharmacological approaches, and provide a clinical algorithm for managing symptomatic women.