EMAS position statement: Vitamin D and menopausal health.

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

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

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

The essential menopause curriculum for healthcare professionals: A European Menopause and Andropause Society (EMAS) position statement.

INTRODUCTION: The menopause, or the cessation of menstruation, is a stage of the life cycle which will occur in all women. Managing perimenopausal and postmenopausal health is a key issue for all areas of healthcare, not just gynecology. AIM: To provide recommendations for the curriculum of education programs for healthcare professionals worldwide, so that all can receive high quality training on menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Training programs for healthcare professionals worldwide should include menopause and postmenopausal health in their curriculum. It should include assessment, diagnosis and evidence-based management strategies.

Global consensus recommendations on menopause in the workplace: A European Menopause and Andropause Society (EMAS) position statement.

INTRODUCTION: Worldwide, there are 657 million women aged 45-59 and around half contribute to the labor force during their menopausal years. There is a diversity of experience of menopause in the workplace. It is shaped not only by menopausal symptoms and context but also by the workplace environment. It affects quality of life, engagement, performance, motivation and relations with employers. AIM: To provide recommendations for employers, managers, healthcare professionals and women to make the workplace environment more menopause supportive, and to improve women's wellbeing and their ability to remain in work. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Workplace health and wellbeing frameworks and policies should incorporate menopausal health as part of the wider context of gender and age equality and reproductive and post-reproductive health. Workplaces should create an open, inclusive and supportive culture regarding menopause, involving, if available, occupational health professionals and human resource managers working together. Women should not be discriminated against, marginalized or dismissed because of menopausal symptoms. Health and allied health professionals should recognize that, for some women, menopausal symptoms can adversely affect the ability to work, which can lead to reduction of working hours, underemployment or unemployment, and consequently financial insecurity in later life.

Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: An EMAS clinical guide.

INTRODUCTION: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. AIM: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term.

Delivery after fetal death in women with earlier cesarean section. A review.

The clinical management of intrauterine fetal demise (IUFD) in women with a previous cesarean delivery presents a dilemma for the obstetrician. With the current reluctance of obstetricians to perform vaginal birth after cesarean (VBAC) and the paucity of data to counsel women regarding maternal risks, management options are limited by physician's clinical experience and biases. In the setting of fetal demise, maternal safety becomes the primary concern. Medicolegal pressures may prevent physicians from attempting a trial of labor in this situation. In this review we will a focus on frequency of birth with IUFD after cesarean section (CS), we discuss the options (VBAC vs CS), different complications, methods for induction of vaginal birth as well as risk factors of vaginal birth and cesarean delivery.

Management of urinary incontinence in postmenopausal women: An EMAS clinical guide.

INTRODUCTION: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. AIM: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered.

Opinion paper: Exercise for healthy aging.

The physical demands of daily life in developed countries have decreased remarkably during the last two centuries. General leisure time has increased and the age at retirement has decreased. General health has improved and life expectancy has increased. Most people can expect to live 20-30 years after retirement. By 2050, one in four people in Europe and North America will be aged 65 or over. Furthermore, women live longer than men. Generally, the physical demands on older women will be low. Thus, their physical fitness will decline, which in turn will affect a variety of organ systems and functions, and so impact on mental health, quality of life and independent living. This opinion paper explores exercise strategies for healthy ageing.

The Mediterranean diet and menopausal health: An EMAS position statement.

INTRODUCTION: Globally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living. AIM: To evaluate the evidence from observational studies and randomized trials on the effects of the Mediterranean diet on short- and long-term menopausal health: estrogen deficiency symptoms, cardiovascular disease, osteoporosis, cognitive and mental health, breast cancer, and all-cause mortality. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: The Mediterranean diet is a non-restrictive dietary pattern common in the olive-growing areas of the Mediterranean basin. It may improve vasomotor symptoms, cardiovascular risk factors such as blood pressure, cholesterol and blood glucose levels, as well as mood and symptoms of depression. Long-term adherence may: improve cardiovascular risk and events, and death; improve bone mineral density; prevent cognitive decline; and reduce the risk of breast cancer and all-cause mortality.

Menopause symptom management in women with dyslipidemias: An EMAS clinical guide.

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.

Management of depressive symptoms in peri- and postmenopausal women: EMAS position statement.

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.

Effects of ospemifene, a novel selective estrogen-receptor modulator, on human breast tissue ex vivo.

OBJECTIVE: Ospemifene (Osp) is a novel selective estrogen-receptor modulator (SERM) accepted for the treatment of dyspareunia, a symptom of postmenopausal vulvovaginal atrophy. We aimed to analyze the effects of Osp on human breast tissue (HBT), in comparison with the clinically established SERMs raloxifene (Ral) and tamoxifen (Tam), using ex vivo explant cultures. METHODS: HBT samples were obtained from postmenopausal women undergoing mammoplasty and cultured with or without Osp, Ral, Tam, or 17ß-estradiol (E2) for 7 and 14 days, and studied for morphology, proliferation, and apoptosis. The expression of epithelial markers, the estrogen-receptor alpha (ERα), the androgen receptor (AR), TFF1, and apolipoprotein D was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The PvuII polymorphism of ERS1 was determined. RESULTS: Osp, similar to Ral and Tam, decreased the number of proliferating cells in a concentration-dependent manner (at 100 nM, P < 0.01) and strongly opposed 10 nM E2-stimulated proliferation (P < 0.001). Corresponding effects were observed in the proportions of cells expressing ERα and TFF1 (P < 0.001). At 14 days apoptosis was increased by 100 nM SERMs (P < 0.01), but, notably, decreased by 1 nM Osp and Ral at day 7 (P < 0.05). The SERMs exerted ER-agonist effects on AR-positive cell populations at 1 nM (P < 0.05), but not at 100 nM concentrations. The effects on proliferation and ERα expressing cell numbers were associated with the ERS1 PvuII genotype. CONCLUSIONS: In summary, Osp inhibited proliferation and opposed E2 stimulation in normal HBT in an efficacious, but less potent way than Ral and Tam. The ESR1 PvuII polymorphisms may influence the responsiveness of HBT to E2 and SERMs.

Climacteric symptoms in middle-aged women with chronic somatic diseases.

OBJECTIVES: Chronic diseases may aggravate or simulate climacteric symptoms. Although acknowledged in clinical practice, there is a lack of research systematically analysing the association between chronic diseases and climacteric symptoms. STUDY DESIGN AND MAIN OUTCOME MEASURES: Our study was a cross-sectional population-based study, which included 3421 women, aged 41-54 years. Climacteric symptoms were evaluated using the Women's Health Questionnaire (WHQ), of which we included seven symptom domains (vasomotor, sleep, depressive, anxiety/fears, cognitive, sexual, and menstrual) and a question concerning whether the women were worried about growing old. The occurrence of various diseases (cardiovascular, neurological, sensory organ, bronchopulmonary, musculoskeletal, gastrointestinal, urological, dermatological, and thyroid disease, diabetes, and cancer) was recorded. The associations between the diseases and symptoms were defined with multivariable analyses, adjusting for various confounding factors. RESULTS: The women with the diseases had more symptoms. Vasomotor symptoms and sleep problems were associated only with gastrointestinal diseases, and lower sexual functioning only with diabetes. The remaining symptoms were associated with several diseases, except being worried about growing old, which was not associated with any. CONCLUSIONS: Many symptoms connected to the climacteric may manifest also due to chronic diseases. Thus, health-care professionals should consider the origin of the symptoms when treating middle-aged women with chronic diseases.

Comparison of the Effects of the Selective Estrogen Receptor Modulators Ospemifene, Raloxifene, and Tamoxifen on Breast Tissue in Ex Vivo Culture.

Explant tissue culture provides a model for studying the direct effects of steroid hormones, their analogs, and novel hormonally active compounds on normal freshly isolated human breast tissues (HBTs). For this purpose, pre- and postmenopausal HBTs can be maintained in this culture system. The results demonstrate that the morphological integrity of HBT explants can be maintained in tissue culture up to 2 weeks and expression of differentiation markers, steroid hormone receptors, proliferation and apoptosis ratios can be evaluated as a response to hormonal stimulation. This chapter describes an ex vivo culture model that we have applied to study the effects of various hormonally active substances, including 17ß-estradiol and selective estrogen receptor modulators (SERMs), on normal human breast tissues.

A population-based survey of quality of life in middle-aged Finnish women.

OBJECTIVE: Factors that cause a decrease in quality of life (QoL) among middle-aged women are contradictory. Given that previous studies have been presumably performed in ethnically heterogeneous populations, we evaluated the impact of socioeconomic and lifestyle factors on QoL in Finnish women because the Finnish population is ethnically homogenous. METHODS: A total of 6,408 women (aged 41-54 y) who were called for municipal screening mammography received a postal survey concerning their health-related issues. A total of 3,421 women returned the questionnaire. QoL was evaluated with the Women's Health Questionnaire, from which we included eight symptom clusters (somatic symptoms, depressive symptoms, cognitive difficulties, anxiety/fears, sexual functioning, vasomotor symptoms, sleep problems, and menstrual symptoms). The effects of variables on QoL were defined with multivariate analysis. RESULTS: Older women had more symptoms. Lower educational level was associated with lower QoL. Retired women had more symptoms than working or unemployed women, and unemployed women had more symptoms than employed women. Increasing body mass index was associated with lower QoL. Women who consumed alcohol occasionally had fewer symptoms, and women who consumed alcohol weekly had more symptoms than abstainers. Women who smoked had more symptoms than nonsmokers. Current hormone therapy users had more symptoms than nonusers, and former hormone therapy users had more symptoms than nonusers or current hormone therapy users. CONCLUSIONS: Higher socioeconomic status and healthier lifestyle are beneficial for good QoL in middle-aged women. Thus, women should be encouraged to continue employment and to avoid behavioral health risks.

Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Vaginal atrophy, the thinning and drying of vaginal mucosa, is associated with menopause. The standard estrogen treatment is not suitable for all women. OBJECTIVE: To investigate the effects of oral sea buckthorn (SB) oil supplementation on vaginal atrophy. METHOD: A total of 116 postmenopausal women experiencing symptoms of vaginal dryness, itching or burning were randomized to this placebo-controlled, double-blind study. Ninety-eight participants completed the intervention of three months, during which they consumed 3g of SB or placebo oil daily. At the beginning and end, factors of vaginal health were scored by a gynecologist, vaginal pH and moisture were measured and vaginal health index was calculated. Symptoms of atrophy and menopause were evaluated at study visits and by daily logbooks. Serum samples were collected for the analysis of circulating lipids, liver enzymes and C-reactive protein. RESULTS: Compared to placebo, there was a significantly better rate of improvement in the integrity of vaginal epithelium in the SB group when both compliant and noncompliant participants were included (odds ratio (OR)=3.1, 95% CI 1.11-8.95). A beneficial trend was observed when only the compliant participants were included (OR=2.9; 95% CI 0.99-8.35). There was a tendency (P=0.08) toward better improvement of vaginal health index from baseline to the end in the SB group [(0.8 (SD 2.8)] compared to placebo [-0.1 (SD 2.0)]. CONCLUSIONS: SB oil showed beneficial effects on vaginal health, indicating it is a potential alternative for mucosal integrity for those women not able to use estrogen treatment for vaginal atrophy.

Androgens inhibit the stimulatory action of 17ß-estradiol on normal human breast tissue in explant cultures.

BACKGROUND: The data concerning the effects and safety of androgen in human breast tissue are conflicting. OBJECTIVE: Our aim was to analyze the effects of androgens on normal human breast tissue (HBT). APPROACH: We cultured explants of HBT (obtained from reduction mammoplasty operations of postmenopausal women) with or without testosterone (T) and 5α-dihydrotestosterone (DHT) or in combination with 17ß-estradiol (E(2)) for 7 and 14 d to study the effects of androgens on proliferation, apoptosis, target gene expression, and steroid receptors. The androgen receptor (AR) and estrogen receptor (ER) dependences of the effects were studied with the antihormones bicalutamide and fulvestrant, respectively. RESULTS: The hormone responsiveness of cultured breast tissue was assessed by assaying apolipoprotein-D and prostate-specific antigen expression increased by androgens and amphiregulin and trefoil factor-1 expression induced by E(2) treatment. T and DHT reduced proliferation and increased apoptosis in breast epithelium, the effects of which were reversed by bicalutamide. In combination with E(2), they suppressed E(2)-stimulated proliferation and cell survival. DHT also inhibited basal (P < 0.05) and E(2)-induced expression of cyclin-D1 mRNA (P < 0.05). Immunohistochemistry showed that T (P < 0.05) and DHT (P < 0.05) increased the relative number of AR-positive cells, whereas ERα-positive (P < 0.001) cell numbers were strongly decreased. The percentage of ERß-positive cells remained unchanged. E(2) treatment increased ERα-positive (P < 0.01) cells, whereas AR- (P < 0.05) and ERß-expressing (P < 0.001) cells diminished. These effects were repressed in combination cultures of E(2) with T and DHT. CONCLUSION: T and DHT inhibited proliferation and increased apoptosis in the epithelium of cultured normal HBT and opposed E(2)-stimulated proliferation and cell survival in an AR-dependent manner. These effects were associated with changes in the proportions of ERα- and AR-positive epithelial cells.