Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: a safety report based on a systematic review and meta-analysis.

IMPORTANCE: Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. OBJECTIVE: This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. EVIDENCE REVIEW: We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). FINDINGS: A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. CONCLUSIONS AND RELEVANCE: Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care.

Associations between Menopausal Hormone Therapy and Colorectal, Lung, or Melanoma Cancer Recurrence and Mortality: A Narrative Review.

Objective: to develop eligibility criteria for use in non-gynecological cancer patients. Methods: We searched all the articles published in peer-reviewed journals up to March 2021. We utilized the PICOS standards and the following selection criteria: menopausal women with a history of non-gynecological and non-breast cancer who underwent hormone replacement therapy (HRT) using various preparations (oestrogens alone or in combination with a progestogen, tibolone, or tissue selective oestrogen complex) and different routes of administration (including oral, transdermal, vaginal, or intra-nasal). We focused on randomized controlled trials as well as relevant extension studies or follow-up reports, specifically examining recurrence and mortality outcomes. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women who are skin melanoma survivors using MHT have a longer survival rate than non-MHT survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rate than those who do not use MHT. Conclusions: MHT is safe for women who have a history of colorectal, lung, or skin melanoma cancers.

Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group.

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms.

Resilience, Perceived Stress, and Depressed Mood in Women Under in Vitro Fertilization Treatment.

It has been suggested that women who display higher resilience levels may have less psychological distress during IVF. The aim of this study was to evaluate how infertile women deal with perceived stress, depressed mood, and sleep disturbances at the first IVF attempt and after one or more negative IVF outcomes depending on their level of resilience. An observational, cross-sectional study was carried out in a sample of 207 infertile women undergoing IVF procedures. The participants completed the short version of the Connor-Davidson Resilience Scale (CD-RISC), the short version of the European Spanish Version of Perceived Stress Scale (PSS-10), the Center of Epidemiologic Studies Depression Scale (CESD-10), and the Jenkins Sleep Scale (JSS). The relationship between CD-RISC scores ranked according to percentiles and mean PSS-10 scores revealed that women with strong resilience had lower perceived stress. After splitting the sample according to CD-RISC percentiles, differences were observed only at the first IVF attempt and the observed protective effect of high resilience scores appears to disappear following a negative IVF outcome. Women with high resilience are less likely to suffer from perceived stress or depressed mood during their first IVF attempt, this protective effect appears to be lost after a negative outcome.

Predictive and criterion validity of the Cervantes-SF menopause quality of life questionnaire.

OBJECTIVES: To determine the predictive and criterion-based validity of the Cervantes-SF scale that measures the impact of menopause on Health-Related Quality of Life. METHODS: We recruited a noninstitutionalized sample of peri/postmenopausal women aged 40 to 65 years, who had their last menstrual cycle 12+ months prior to inclusion in the study of the psychometric validity of the Cervantes-SF scale. Predictive validity of the scale was confirmed for various health outcome measures administered concomitantly (years of disability-free life expectancy, work productivity and impact on daily activities, economic impact arising from loss of work productivity, hours of undisturbed sleep each day, and the utilization of healthcare facilities), whilst criterion validity was determined by the likelihood of identifying a moderate-to-severe vasomotor or genital syndrome requiring specific treatment. RESULTS: A sample of 308 peri/postmenopausal women with a mean age of 55.7 years (SD: 5.3 y) was analyzed in this study. A score >25 points on the dimension of vasomotor problems (or menopausal health) showed values of sensitivity and specificity > 80% for identifying women with moderate-severe vasomotor syndrome requiring pharmacological treatment. Predictive validity was confirmed for menopause-related health outcomes. A change of 6.7 points in the scale score, equivalent to the value of its minimal difference, is indicative of a significant increase in the degree of disability regarding work/day-to-day activities, greater economic loss due to decreased work productivity, fewer years of life expectancy without disability, fewer hours of undisturbed sleep, and more visits to the physician per year due to menopausal symptoms. CONCLUSIONS: These results confirm the criterion and predictive validity of the Cervantes-SF scale in peri/postmenopausal women.

Health-related quality of life and resilience in peri- and postmenopausal women during Covid-19 confinement.

OBJECTIVE: To assess the impact of confinement due to the coronavirus (Covid-19) pandemic on health-related quality of life (HRQoL) and resilience in peri- and postmenopausal women. MATERIAL AND METHODS: We used an online questionnaire which was sent between April 30th and May 13th, 2020 to women aged 40-70 years who were peri- or postmenopausal according to STRAW criteria. We used the 16-item Cervantes short-form scale (Cervantes-SF) to measure HRQoL, and the 14-item Wagnild and Young Resilience Scale (RS-14) to measure resilience. High scores on the Cervantes-SF indicate low HRQoL and high scores on the RS-14 indicate high levels of resilience. Covid-19 status, sociodemographic descriptors, and lifestyle variables were also evaluated. RESULTS: We included 2430 peri- and postmenopausal women with valid questionnaires. All items of the Cervantes-SF were completed in 2151 cases, whilst the RS-14 was completed in 2413 cases. There was a negative correlation between scores on the Cervantes-SF and RS-14 scales (Rho -0.350; p < 0.0001). Multiple linear regression analysis revealed a statistically significant association between Cervantes-SF scores and living with others (ß-coefficient -10.2; p < 0.001), use of antidepressants (ß 9.3; p < 0.001), physical activity (ß -8.6; p < 0.001) and sexual activity (ß -2.7; p < 0.001). Resilience was associated with the use of antidepressants (ß -5.9; p < 0.001), physical activity (ß 3.2; p < 0.001) and sexual activity (ß 1.7; p = 0.005). According to the multivariate analysis, there were no associations between either Covid-19 or menopausal status and HRQoL or resilience scores. CONCLUSIONS: During the period of mandatory Covid-19 confinement, peri- and postmenopausal women who engaged in physical and sexual activity had higher HRQoL and higher levels of resilience, whilst women who were using antidepressants had lower HRQoL and lower levels of resilience. HRQoL was greater in women who lived with others.

Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia.

COVID-19 is associated with a systemic inflammatory response with activation of coagulation in symptomatic patients. The possibility of coagulopathies in peri- and postmenopausal women taking estrogen therapies makes it necessary to consider antithrombotic strategies, such as the use of low molecular weight heparins (LMWH) at specific prophylactic or treatment doses for each individual case, depending on the risk factors that each woman presents. For such reasons, a panel of experts from various Spanish scientific societies has met to develop usage recommendations for managing menopausal women taking menopausal hormone therapy (MHT) or combined hormonal contraception (CHC) during the COVID-19 pandemic.

Arterial palmar arch occlusion in a woman with Raynaud's disease taking oral combined menopausal hormone therapy: A case report.

Patients with surgical menopause often present to their primary care provider with menopausal symptoms. Here we present an unusual case of palmar arch artery occlusion in a 55-year-old woman with primary Raynaud's disease taking oral combined menopausal hormone therapy after surgical menopause for endometriosis. She was successfully treated with intravenous infusion of prostaglandin E1 and nitroglycerin patches over two weeks. Menopausal hormone therapy was stopped and her vasomotor symptoms did not recur.

Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial.

The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.

What do TSECs provide in the menopausal hormone therapy?

Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45 mg/BZA 20 mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women.

Recommendations of the Spanish Menopause Society on the consumption of omega-3 polyunsaturated fatty acids by postmenopausal women.

The consumption of long-chain omega-3 polyunsaturated fatty acids (LCO3-PUFAs) has shown a great variety of beneficial effects, including cardiovascular, metabolic and inflammatory effects, which make them interesting for the postmenopausal woman. Because LCO3-PUFAs could be effective and safe during this period, a panel of experts from the Spanish Menopause Society met to establish a set of recommendations for their use in postmenopausal women based on the best available evidence. The decrease in triglycerides is the most consistent effect observed with LCO3-PUFAs (at doses greater than 3g/day). In addition, LCO3-PUFAs have antiarrhythmic effects, reduce blood pressure, improve depressive and psychotic symptoms, and do not increase the risk of cancer. However, further studies are needed to confirm the benefit of LCO3-PUFAs in the relief of menopause symptoms and osteoporosis.

Benefits of physical exercise in postmenopausal women.

Physical inactivity not only places women's health at risk during menopause, but also increases menopausal problems. Abundant evidence links habitual physical exercise (PE) to a better status on numerous health indicators and better quality of life and to the prevention and treatment of the ailments that typically occur from mid-life onwards. We can infer that PE is something more than a lifestyle: it constitutes a form of therapy in itself. A panel of experts from various Spanish scientific societies related to PE and menopause (Spanish Menopause Society, Spanish Cardiology Society, Spanish Federation of Sports Medicine) met to reach a consensus on these issues and to decide the optimal timing of and methods of exercise, based on the best evidence available.

EMAS position statement: The ten point guide to the integral management of menopausal health.

With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

Spanish consensus on premature menopause.

INTRODUCTION: While we recognise that the term premature menopause is more accepted by most non-specialist health care providers and by the general population, 'primary ovarian insufficiency' (POI) is currently considered the most apposite term to explain the loss of ovarian function, because it better explains the variability of the clinical picture, does not specify definitive failure, and highlights the specific ovarian source. Its pathogenesis involves a congenital reduction in the number of primordial follicles, poor follicle recruitment, or accelerated follicular apoptosis. However, its cause is unknown in most cases. AIM: This guide analyses the factors associated with the diagnosis and treatment of POI and provides recommendations on the most appropriate diagnostic and therapeutic measures for women under 40 years of age who experience POI. METHODOLOGY: A panel of experts from various Spanish scientific societies related to POI (Spanish Menopause Society, Spanish Fertility Society, and Spanish Contraception Society) met to reach a consensus on these issues. RESULTS: Hormonal therapy (HT) is considered the treatment of choice to alleviate the symptoms of hypoestrogenism and to prevent long-term consequences. We suggest that HT should be continued until at least age 51, the average age at natural menopause. The best treatment to achieve pregnancy is oocyte/embryo donation. If a patient is to undergo treatment that will reduce her fertility, she should be informed of this issue and the available techniques to preserve ovarian function, mainly vitrification of oocytes.

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice.

OBJECTIVE: To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility. DESIGN: Experimental. SETTING: University laboratory. ANIMAL(S): Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. INTERVENTION(S): Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. MAIN OUTCOME MEASURE(S): Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. RESULT(S): Plasma insulin and T levels decreased and Homeostatic Index of Insulin Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-α levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. CONCLUSION(S): Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.

Assessment of follicular fluid leptin levels and insulin resistance as outcome predictors in women undergoing in vitro fertilization-intracytoplasmic sperm injection.

OBJECTIVE: To analyze follicular fluid leptin (FFL) levels, abdominal obesity, and insulin resistance as predictors of in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) outcome. DESIGN: Observational study. SETTING: Academic medical center. PATIENT(S): A sample of 130 infertile women aged 26-40 years without polycystic ovary syndrome. INTERVENTION(S): Measurement of FFL levels in controlled ovarian hyperstimulation cycles with an antagonist and agonist protocol for IVF-ICSI. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Mean FFL values were significantly higher in pregnancies not ending in a live birth, even after adjustment for waist circumference and insulin resistance. A multivariable model obtained with the use of logistic binary regression analysis showed that waist circumference and insulin resistance had no influence over IVF-ICSI outcomes, but a higher number of follicles, lower serum progesterone levels on the day before α-hCG administration, and lower FFL concentrations were significantly associated with a higher probability of having a live birth. The multivariate model reached a sensitivity of 87% and a specificity of 71% for predicting the possibility of pregnancy ending in a live birth. CONCLUSION(S): High FFL levels were associated with abdominal obesity, insulin resistance, and a lower live birth rate after IVF-ICSI. Further investigations are warranted to define the precise roles of leptin, obesity, and insulin resistance on IVF-ICSI outcomes.