POESIT recommendations on management of body-identical hormones in menopausal symptoms.

Many women seek treatment to improve menopausal vasomotor symptoms (VMS). The selection of women most likely to benefit from menopause hormone therapy (MHT) is crucial in clinical practice. There is general agreement that women younger than 60 years or who initiate MHT within the first 10 years of menopause, with no contraindications, have greater benefits considering symptomatic relief and additional advantages. This group may have the advantage of protection from osteoporosis and from other chronic diseases that affect postmenopausal women, namely cardiovascular disease (CVD). Cumulating evidence supports MHT for symptomatic women. However, inadequate use according to the needs of symptomatic women led to a burden of suffering worldwide. In recent years, the emergent use of non-regulated body-identical hormones (non-rBHT) can expose patients to potential harms. These hormone preparations are not regulated through the same tests of safety, efficacy or dosing consistency as regulated-BHT (r-BHT). The POESIT (Portugal + Spain + Italy) recommendations highlight the use of 17ß-estradiol (E2) and micronized progesterone (P4) as the real r-BHT. In addition, the group emphasizes as an example the data from the REPLENISH study with 1 mg E2/100 mg P4. The combination of the two hormones in one convenient pill showed a clear reduction or elimination of hot flashes and an improvement in sleep quality and, consequently, quality of life. At the same time, this combination has shown high rates of amenorrhea and no significant impact on lipid, glucose or coagulation parameters. Both the REPLENISH study and a real-life retrospective study pointed to the possibility of a lower risk of venous thromboembolism (VTE) with this formulation than with other combinations.

From couplepause to doublepause: the impact of midlife physical, psychological, and social changes on the sexual life of aging couples.

INTRODUCTION: Midlife men and women are facing frequent sexual problems that affect not only individuals' sexual health but also the sexual health of aging couples. OBJECTIVES: To review the main sexual life challenges faced by midlife couples, to present the concepts of couplepause and doublepause as 2 new paradigms to address the sexual health needs of aging couples, and to discuss key aspects in couple-focused care. METHODS: An online meeting attended by 5 European experts in sexual health was carried out in June 2023 to discuss the topic. The conversation centered on their clinical experience and expert opinion. Additionally, the indexed literature was reviewed to endorse and complement the expert opinions obtained in the aforementioned meeting. RESULTS: Midlife men and women face physical, psychological, and sociocultural changes that affect their sexual activity. These changes may be experienced differently between genders. Both members of a couple may experience age-related changes concurrently or in an unsynchronized manner affecting their sexual health. Communication, sharing expectations, defining sexual dynamics, and couple goals are determinant for the sexual health of a midlife couple. Couplepause and doublepause are 2 new complementary paradigms that effectively address the sexual health needs of aging couples as a unit, considering physical, psychological, cultural, social, and dyadic-related factors. Couple-centered strategies should promote open communication about couple intimacy issues, understanding the diverse expectations according to gender and orientation, communication styles, and goals. The following are identified as crucial aspects to promote couple-focused care: education and training of health care professionals, the provision of information to aging couples, physician involvement in addressing sexual problems, the need for collaboration across medical specialties, and the development of effective tools and strategies. CONCLUSIONS: The sexual problems of aging couples should be managed following couple-centered strategies that effectively address their sexual health needs as a couple.

Obesity and menopause.

Obesity is not a choice or a result of lack of willpower, but a multifactorial, chronic, progressive, and relapsing disease. During menopause, hormonal and body composition changes lead to greater visceral adiposity, that aggravates women's health at a cardiometabolic, mechanic and mental level. Adiposity has been identified as an important modifier of reproductive hormones. During female midlife, obesity has been associated with menstrual cycle alterations (anovulatory cycles ending with abnormal bleedings), menopausal symptoms including hot flashes, poor quality of sleep, aches and joint pain, genitourinary symptoms, and reduced quality of life. However, the relationships between weight, the menopausal process, aging, and hormone levels remain poorly understood. Women with obesity have an increased risk of thromboembolic disease when using menopause hormone therapy (MHT), and it is probably the main medical condition to prescribe or not MHT. However, this risk depends on the route and type of MHT. The use of estrogen-only or combined transdermal MHT does not increase the risk of a thrombotic event in women with obesity.

Efficacy and safety of a device that combines multipolar radiofrequency with pulsed electromagnetic field for the treatment of vulvovaginal atrophy: a randomized, sham-controlled trial.

BACKGROUND: Vulvovaginal atrophy (VVA) negatively affects the sexual well-being and quality of life of postmenopausal women, yet it is underreported and undertreated. AIM: The study sought to investigate the efficacy and safety of a nonablative, noncoagulative multipolar radiofrequency (RF) and pulsed electromagnetic field-based device (PEMF) in treatment of symptoms related to VVA. METHODS: Seventy-six women ≥19 years of age with symptoms associated with VVA were enrolled into this prospective, randomized, sham-controlled, multicenter clinical study. Subjects were randomized to receive 3 RF + PEMF treatments (active group) or sham treatments (sham group) delivered to vaginal tissue at monthly intervals. The Vaginal Health Index (VHI), along with the Female Sexual Function Index (FSFI), subject sexual satisfaction and vaginal laxity (VL) score, treatment-associated pain, and adverse events were assessed at 4 follow-up (FU) visits between 1 and 12 months after treatment. OUTCOMES: Changes from baseline VHI, pH, FSFI, VL, and sexual satisfaction scores between the active and sham groups were compared before and after treatment. RESULTS: Mean VHI scores in the active group were significantly better compared with the sham group after treatment at all but the last FU visit (P < .001). A greater decrease in pH (active over sham) was seen at 1 and 4 months after treatment (P < .05). FSFI improvement was shown in the active group; however, it was not significantly better than sham improvement at all FU visits. Subject sexual satisfaction in the active group showed better improvement over sham at all FU visits (P < .05), while VL evaluations saw greater improvement in the active group at 4, 6, and 12 months posttreatment (P < .05). Treatment satisfaction was greater in the active group and pain was minimal in both groups. No serious adverse effects were reported. CLINICAL IMPLICATIONS: As a noninvasive alternative to traditional surgical and topical procedures, 3 sessions of noninvasive combination RF/PEMF safely demonstrated improvement in symptoms related to VVA. STRENGTHS AND LIMITATIONS: This study was strengthened by the randomized, sham-controlled design; large sample size; and extended FU period. The study assessments were decreased at later FU visits due to the global COVID pandemic, and this was a key limitation to the study. CONCLUSION: Nonablative, noncoagulative multipolar RF/PEMF therapy was safe, improved symptoms associated with VVA, and improved female sexual function while yielding high subject satisfaction.

Combined oral contraceptives: update recommendations of the Latin American contraceptive association.

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'.Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.

Vulvovaginal atrophy in the CRETA study: the healthcare professionals' perception.

OBJECTIVES: The objective is to assess the perception of gynecologists regarding patients' adherence to vulvovaginal atrophy (VVA) treatments, to evaluate the gynecologists' opinions on what their patients think about treatment adherence, and to compare the gynecologists' opinions with the patients' own perceptions within the CRETA study. METHODS: Spanish gynecologists who participated in the CRETA study were asked to fill out an online 41-item questionnaire to evaluate their views on VVA management. RESULTS: From 29 centers across Spain, 44 gynecologists completed the survey. Their mean age was 47.2 years old, two-thirds of them were women, and the average professional experience was over 20 years. According to the gynecologists, the therapy most frequently used by VVA-diagnosed women was vaginal moisturizers (45.5%), followed by local estrogen therapy (36.4%) and ospemifene (18.2%). Nevertheless, ospemifene was viewed as the therapeutic option with the most efficacy, easiest route of administration, shorter time to symptom improvement, lower percentage of dropouts, and higher treatment adherence. CONCLUSIONS: Spanish gynecologists are in general agreement with their patients regarding VVA treatment preferences and the main issues for adherence and effectiveness. However, there is an opportunity for doctor-patient communication improvement. Among the three therapeutic options evaluated, ospemifene is regarded as offering some competitive advantages.

Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

Using advanced analytics to help identify women who are more likely to have a severe subjective experience of vulvovaginal atrophy: a modeling study.

OBJECTIVE: To develop a model to identify women likely to be severely impacted by vulvovaginal atrophy (VVA), based on their experience of symptoms and non-clinical factors. METHODS: Multivariate statistics and machine-learning algorithms were used to develop models using data from a cross-sectional, observational, multinational European survey. A set of independent variables were chosen to assess subjective VVA severity and its impact on daily activities. RESULTS: A final composite model was selected that included three categories of variables: clinical severity, patient demographics/clinical characteristics and Day-to-Day Impact of Vaginal Aging (DIVA) variables related to emotion/mood, impact on lifestyle and frequency of sex. The model accurately classified 71% of women. Three DIVA variables (feeling bad about yourself, desire/interest in sex, physical comfort related to sitting) explained much of the variation in the dependent variable of the model. Over 90% of the impact of VVA relates to certain psychosocial and behavioral aspects that can be identified without the need to consider physical signs/symptoms. CONCLUSION: Non-clinical factors can contribute significantly to the overall VVA burden.Questions used in developing the composite model could form the basis of an instrument to help screen women prior to clinical consultation and improve VVA management.

Miconazole for the treatment of vulvovaginal candidiasis. In vitro, in vivo and clinical results. Review of the literature.

At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in C. albicans, in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.

Impact of vulvovaginal atrophy therapies on postmenopausal women's quality of life in the CRETA study measured by the Cervantes scale.

OBJECTIVE: To assess the correlation of different vulvovaginal atrophy therapeutic options with the quality of life of postmenopausal women. STUDY DESIGN: The CRETA study is a descriptive, observational, cross-sectional, multicenter study designed to measure, besides treatment satisfaction and adherence, the quality of life of postmenopausal women diagnosed with vulvovaginal atrophy in 29 hospitals and centers across Spain. MAIN OUTCOME MEASURES: The study enrolled postmenopausal women currently receiving treatment with vaginal moisturizers, local estrogen therapy or ospemifene. Clinical features and treatment perceptions were collected by self-report questionnaire and quality of life was evaluated using the Cervantes scale. RESULTS: Among the 752 women included, the ospemifene cohort showed a statistically significant lower global score (44.9 ± 21.7) on the Cervantes scale (and therefore, a better quality of life) than the cohorts treated with moisturizers (52.5 ± 21.6, p = 0.003) or local estrogen therapy (49.2 ± 23.8, p = 0.0473). In the analysis by domains, ospemifene-treated women showed statistically significant better scores in menopause & health and psychological status than moisturizers-treated women (p < 0.05). In the domains of sexuality and couple relations, the score for the quality of life of the ospemifene cohort was statistically significantly better than the scores in either of the cohorts treated with moisturizers (p < 0.001) or local estrogen therapy (p < 0.05). CONCLUSIONS: Postmenopausal women diagnosed with vulvovaginal atrophy and treated with ospemifene have better quality of life than women treated with vaginal moisturizers or local estrogen therapy. The improvement observed with ospemifene is more remarkable in those aspects related to sex life and couple relations. CLINCIALTRIALS. GOV NUMBER: NCT04607707.

Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice.

OBJECTIVES: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17ß-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens. STUDY DESIGN: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records. MAIN OUTCOME MEASURES: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA. RESULTS: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92). CONCLUSIONS: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.

The drospirenone (DRSP)-only pill: clinical implications in the daily use.

OBJECTIVES: Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. METHODS: An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. RESULTS: Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30-34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. CONCLUSIONS: This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive.

The 4 mg drospirenone-only pill improves the bleeding profile in comparison to 0.075 mg desogestrel and achieves high contraceptive efficacy even with a 24 h missed pill window.

A randomized trial on the effectiveness and safety of 5 water-based personal lubricants.

BACKGROUND: A range of personal lubricants with different formulations and subsequent properties are available for relief of discomfort associated with vaginal dryness; however, there are limited clinical data to support the efficacy and safety of many commercially available lubricants. AIM: To determine the effectiveness and safety of 5 water-based personal lubricants for the relief of intimate discomfort associated with vaginal dryness in pre- and postmenopausal women: 4 that were formulated to meet the World Health Organization (WHO) guidelines for osmolality and pH and 1 preexisting lubricant of higher osmolality and pH. METHODS: An open-label, parallel-design study was performed in women aged 18 to 65 years with mild-to-moderate vaginal dryness and dyspareunia. Participants were randomized to 1 of 5 lubricants (A-E) from 3 brands (Durex, KY, Queen V). They were instructed to use their allocated lubricants during vaginal intercourse at least once a week over a 4-week period. The Female Sexual Function Index (FSFI) measured sexual functioning after 4 weeks of use as an indicator of lubricant performance. OUTCOMES: The primary outcome was change from baseline in total FSFI score after 4 weeks of product use. RESULTS: A total of 174 women completed the study. The primary end point-a prespecified increase in FSFI ≥4 points from baseline after 4 weeks of use-was met by all 5 lubricants tested. A statistically significant improvement was observed across all 6 domains of the FSFI from baseline to 4 weeks of use with all 5 lubricants (P < .0001 for lubrication and pain reduction and P < .05 for all other domains). No serious adverse events occurred in the study, and the tolerance of all 5 lubricants was good/very good. CLINICAL IMPLICATIONS: The efficacy and safety of the tested lubricants are not compromised when formulated to meet the WHO criterion of osmolality ≤1200 mOsm/kg. The lubricants tested in this investigation can be used not only to relieve symptomatology of vaginal dryness and dyspareunia but also to enhance overall sexual satisfaction. STRENGTHS AND LIMITATIONS: This study provides clinical evidence for the efficacy and safety of 5 lubricants, including those formulated to meet WHO guidelines, in relieving symptoms of vaginal dryness and improving the overall sexual experience. The open-label design may have introduced bias into the study. CONCLUSION: All 5 lubricants, including those formulated to be compliant with guidelines on pH and osmolality, can be considered effective and well tolerated for the relief of discomfort associated with vaginal dryness.

Concentraciones de vitamina D en ginecoobstetras, internistas y médicos generales en tres países latinoamericanos / Vitamin D concentrations in obstetricians, gynecologists, internists, and general practitioners in three Latin American countries

Resumen OBJETIVO: Determinar las concentraciones de 25(OH)D en ginecoobstetras y otros especialistas latinoamericanos y conocer la prevalencia de su deficiencia. MATERIALES Y MÉTODOS: Estudio transversal y observacional efectuado para determinar las concentraciones de 25(OH)D en médicos voluntarios, sobre todo ginecoobstetras, que acudieron a diferentes congresos en distintos países latinoamericanos. RESULTADOS: Se analizaron 643 determinaciones. El 19.4% tenían déficit (media 16.58 ng/mL), 72% insuficiencia (media 24.6 ng/mL) y 36.9% concentraciones normales (media 40.34 ng/mL). Los hombres tuvieron mayor déficit-insuficiencia (62.8%) que las mujeres (59.5%), pero sin diferencias significativas (p < 0.058). Las personas de piel clara tuvieron concentraciones deficitarias e insuficientes, menores que las de piel oscura (p < 0.001). Quienes tomaban suplementos de vitamina D tuvieron menor riesgo de déficit. CONCLUSIONES: El 60% de los ginecoobstetras, médicos internistas y generales de Latinoamérica tienen bajas concentraciones de 25(OH)D. La piel clara puede ser un factor de riesgo de mayor déficit-insuficiencia. En los grupos de médicos estudiados la suplementación con vitamina D parece incrementar las concentraciones de 25(OH)D.

OBJECTIVE: To determine 25(OH)D concentrations in obstetrician-gynecologists and other Latin American specialists and to know the prevalence of its deficiency. MATERIALS AND METHODS: Cross-sectional and observational study to determine 25(OH)D concentrations in volunteer physicians, mainly gynecologists, attending different congresses in different Latin American countries. RESULTS: A total of 643 determinations were analysed. 19.4% had deficiency (mean 16.58 ng/mL), 72% insufficiency (mean 24.6 ng/mL), and 36.9% normal concentrations (mean 40.34 ng/mL). Men had higher deficiency-insufficiency (62.8%) than women (59.5%), but no significant differences (p < 0.058). Light-skinned people had lower insufficiency levels than darker-skinned people (p < 0.001). Those taking vitamin D supplements had a lower risk of deficiency. CONCLUSIONS: Sixty percent of obstetrician-gynecologists, internists, and general practitioners in Latin America have low 25(OH)D concentrations. Caucasian skin may be a risk factor for increased deficiency. Vitamin D supplementation appears to improve 25(OH)D concentrations in the physician groups studied.

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.

Current situation of shared decision making in osteoporosis: A comprehensive literature review of patient decision aids and decision drivers.

Background and Aims: Osteoporosis is a systemic skeletal disease characterized by low bone mass and microstructural deterioration of bone tissues, resulting in bone fragility and increased fracture risk. It is the most common bone-related disease in the population. However, the proportion of patients who start treatment but discontinue it during the first year is very high (around 50%). Endeavors are made to promote patient participation in treatment by implementing patient decision aids (PDA), whose function is to help the patient make disease-related decisions. We aim to summarize the characteristics of the currently available PDA for osteoporosis, as well as deciding factors. Methods: Comprehensive review of the literature. Results: Currently, eleven PDAs can be found for osteoporosis. These PDA have different characteristics or options such as information about treatments tailored to patient needs, graphic information of the results (to facilitate understanding), personal histories (learning), tests to check the knowledge acquired, provision of evidence, clinical practice guidelines or a final summary to share with their doctor. Only five of these PDAs can be considered complete since they provide relevant disease information and therapeutic options to the patient, promote patient's reflection and foment patient-physician discussion. Conclusions: This study provides an update on the current state of decision making on osteoporosis and available PDA, which can help engage the patient through shared decision-making by considering, among other things, patient preferences. Physicians should consider PDA, as it may promote adherence and effectiveness of treatment.

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.

Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.

The human LIPA gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The Drosophila genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that Lipase 3 transcription is highly induced in mutants with defects in peroxisome biogenesis, but the conditions that allow a similar induction in wildtypic flies are not known. Here we show that Lipase 3 is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. We generated a lipase 3 mutant that shows sex-specific starvation resistance and a trend to lifespan extension. Using lipidomics, we demonstrate that Lipase 3 mutants accumulate phosphatidylinositol, but neither triacylglycerol nor diacylglycerol. Our study suggests that, in contrast to its mammalian homolog LIPA, Lipase 3 is a putative phospholipase that is upregulated under extreme conditions like prolonged nutrient deprivation and aging.