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Postmenopause is the 12-month absence of menstrual periods, characterized by decreased estrogen and progesterone levels, leading to physical and psychological alterations such as hot flashes, mood swings, sleep disruptions, and skin changes. Present postmenopausal treatments include hormone replacement therapy, non-hormonal drugs, lifestyle modifications, vaginal estrogen therapy, bone health treatments, and alternative therapies. Advanced drug delivery systems (ADDSs) are essential in managing postmenopausal effects (PMEs), offering targeted and controlled delivery to alleviate symptoms and improve overall health. This review emphasizes such ADDSs for addressing PMEs. Emerging trends such as artificial ovaries are also reviewed. Additionally, the prospects of technologies such as additive manufacturing (3D and 4D printing) and artificial intelligence in further tailoring therapeutic strategies against PMEs are provided. [Display omitted] • Postmenopause involves 12 months without periods, with lower estrogen and progesterone. • Treatments include hormone replacement, non-hormonal drugs, and lifestyle changes. • Advanced drug delivery systems offer significant relief from postmenopausal effects. • Emerging trends for postmenopausal effects include artificial ovaries and 3D/4D printing. • Artificial intelligence holds potential for optimizing drug delivery systems for postmenopausal effects. [ABSTRACT FROM AUTHOR]

Objective: The effects of hormonal therapy, estrogen-based hormone replacement therapy (HRT), and anti-tumor hormone therapy, such as tamoxifen, on the physiological uptake of the endometrium on 2-deoxy-2[18F]fluoro-d-glucose ([18F]F-FDG) positron emission tomography (PET) in postmenopausal women have not been determined. We explored the effect of hormone therapy, particularly HRT, on physiological uptake in the endometrium of postmenopausal women. Materials and methods: Postmenopausal women receiving hormone therapy who underwent cancer screening using PET/computed tomography (CT) between June 2016 and April 2023 were included in the hormone therapy group (n = 21). Postmenopausal women with no history of hormone therapy were included in the control group (n = 49). First, the physiological endometrial uptake at menopausal age and at least 1 year thereafter was compared quantitatively (SUVmax) and qualitatively (4-point scale) in the control group, to assess when the endometrium ceased to show significant physiological [18F]F-FDG uptake after menopause. Endometrial uptake was compared between the hormone therapy and control groups. The association between HRT duration (months) and endometrial uptake (SUVmax) was evaluated. Endometrial thickness, measured using transvaginal ultrasonography, was also compared between the two groups. Results: Endometrial uptake was significantly reduced both qualitatively and quantitatively (P < 0.05) at least 1 year after menopause in control patients, by which time most women (89.8%) no longer had significant endometrial uptake. The hormone therapy group (n = 21) showed higher FDG uptake in the endometrium compared to the control group (median SUVmax: 2.3 vs 1.9, P = 0.0011), as well as a higher visual score (P < 0.0001). HRT duration did not correlate with endometrial uptake (P = 0.097). Endometrial thickness in the hormone therapy group was significantly thicker than in the control group (median: 3.9 mm vs 1.8 mm, P = 0.002). Conclusion: Hormone therapy may affect physiological uptake in the endometrium in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. Methods: The study included postmenopausal women over 40 years from the National Health Insurance Database in South Korea (2011–2014) who either used MHT for over 6 months (MHT group) or never used MHT (non‐MHT group) and were matched 1:1 based on several variables using propensity score matching. Both groups were followed until 2020. Results: The non‐MHT and MHT groups comprised 153 736 women each. In Cox proportional hazard analysis with time‐dependent covariates, MHT was associated with an increased risk of breast cancer (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.15–1.3). Tibolone, estradiol valerate (EV)/medroxyprogesterone acetate (MPA), EV/norethisterone acetate (NETA), conjugated equine estrogen (CEE), EV, estradiol hemihydrate (EH), CEE/micronized progesterone (MP), CEE/MPA, EV/MP, EV/MPA, and EH/MP did not increase the risk of breast cancer compared with the non‐MHT group. However, EH/drospirenone (DRSP) (HR 1.51, 95% CI 1.38–1.66), EH/NETA (HR 1.66, 95% CI 1.34–2.06), EH/dydrogesterone (DYD) (HR 1.37, 95% CI 1.12–1.68), and EV/cyproterone acetate (CPA) (HR 1.74, 95% CI 1.54–1.96) increased the risk of breast cancer compared with the non‐MHT group. Conclusions: MHT was linked to increased breast cancer risk, but not all MHTs. Specific combined therapies (EH/DRSP, EH/DYD, EH/NETA, and EV/CPA) were associated with higher risk, whereas estrogen alone and tibolone were not. Synopsis: Specific progestogens in menopausal hormone therapy were associated with breast cancer risk. [ABSTRACT FROM AUTHOR]

Objective: Menopause is a physiological period characterized by the cessation of ovarian activity. Sequential changes during this transition affect multiple systems, including the brain. Sixty percent of women experience cognitive impairment. The objective of this review is to show the neuroprotective effect of hormone replacement therapy (HRT) through the different scales and whether there is a benefit of this in women. Method: A search was conducted in six databases. Eligibility criteria included women within 10 years of menopause, receiving HRT controlled with placebo, studies lasting more than 6 months and women without a history of chronic underlying pathology. Results: A total of nine randomized controlled trials met the inclusion criteria. Regarding memory, two studies reported better performance of HRT with a significant odds ratio (OR) of 0.67; regarding attention, one study reported potential improvement in women receiving HRT with a significant OR of 0.87; and neuroimaging assessment found an increase in ventricular volume compared to placebo over a 3-year period. Conclusions: The early initiation of menopausal HRT in healthy women appears to yield a positive effect on certain cognitive aspects, such as attention and cortical volume in the central nervous system. These findings should be confirmed through future prospective studies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. Methods: This nested case–control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. Results: Women who started estrogen–progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone – regardless of duration – or EPT or ET for 1–3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1–3 years or ≥5 years than non-users. Conclusion: Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke. [ABSTRACT FROM AUTHOR]

Progesterone is used for hormone replacement therapy through various routes of administration. This study was conducted to (a) evaluate the stability of progesterone in a proprietary anhydrous permeation-enhancing base (APEB) and the efficiency of its skin permeation, and (b) determine the appropriateness of mass spectrometry as a method of analysis for permeated progesterone. Using a proven stability-indicating ultra-performance liquid chromatographic method, the compounded hormone (100 mg progesterone/g APEB gel) was determined to be physically and chemically stable at room temperature for six months. Skin permeation analysis using the Franz skin finite dose model and mass spectrometry imaging showed an optical density of 1699 for the permeated progesterone compounded in APEB and 550 for the permeated progesterone in a water containing VBC, which is a statistically significant different (P = 0.029). The study suggests that APEB can be used as a compounding base for effective skin permeation of progesterone, and mass spectrometry is a reliable method for visualization and quantitative analysis of permeated progesterone. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do women with endometriosis who achieve a live birth (LB) after HRT-frozen embryo transfer (HRT-FET) have different progesterone levels on the day of transfer compared to unaffected women? SUMMARY ANSWER In women achieving a LB after HRT-FET, serum progesterone levels on the day of the transfer did not differ between patients with endometriosis and unaffected patients. WHAT IS KNOWN ALREADY In HRT-FET, several studies have highlighted the correlation between serum progesterone levels at the time of FET and LB rates. In the pathophysiology of endometriosis, progesterone resistance is typically described in the eutopic endometrium. This has led to the hypothesis that women with endometriosis may require higher progesterone levels to achieve a LB, especially in HRT-FET cycles without a corpus luteum. STUDY DESIGN, SIZE, DURATION We conducted an observational cohort study at the university-based reproductive medicine center of our institution, focusing on women who underwent a single autologous frozen blastocyst transfer after HRT using exogenous estradiol and micronized vaginal progesterone for endometrial preparation between January 2019 and December 2021. Women were included only once during the study period. Serum progesterone levels were measured on the morning of the FET by a single laboratory. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were divided into groups based on whether they had endometriosis or not and whether they achieved a LB. The diagnosis of endometriosis was based on published imaging criteria (transvaginal sonography/magnetic resonance imaging) and/or confirmed histology. The primary outcome was progesterone levels on the day of the HRT-FET leading to a LB in patients with endometriosis compared to unaffected women. Subgroup analyses were performed based on the presence of deep infiltrating endometriosis or adenomyosis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1784 patients were included. The mean age of the women was 35.1 ± 4.1 (SD) years. Five hundred and sixty women had endometriosis, while 1224 did not. About 179/560 (32.0%) with endometriosis and 381/1224 (31.2%) without endometriosis achieved a LB. Among women who achieved a LB after HRT-FET, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (13.6 ± 4.3 ng/ml vs 13.2 ± 4.4 ng/ml, respectively; P  = 0.302). In the subgroup of women with deep infiltrating endometriosis (n = 142) and adenomyosis (n = 100), the mean progesterone level was 13.1 ± 4.1 ng/ml and 12.6 ± 3.7 ng/ml, respectively, with no significant difference compared to endometriosis-free patients. After adjusting for BMI, parity, duration of infertility, tobacco use, and geographic origin, neither the presence of endometriosis (coefficient 0.38; 95% CI: −0.63 to 1.40; P  = 0.457) nor the presence of adenomyosis (coefficient 0.97; 95% CI: −0.24 to 2.19; P  = 0.114) was associated with the progesterone level on the day of HRT-FET. Among women who did not conceive, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (P  = 0.709). LIMITATIONS, REASONS FOR CAUTION The primary limitation of our study is associated with its observational design. Extrapolating our results to other laboratories or different routes and/or dosages of administering progesterone also requires validation. WIDER IMPLICATIONS OF THE FINDINGS This study shows that patients diagnosed with endometriosis do not require higher progesterone levels on the day of a frozen blastocyst transfer to achieve a LB in hormonal replacement therapy cycles. STUDY FUNDING/COMPETING INTEREST(S) None declared. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) is an effective treatment for menopause‐related symptoms. Menopause management guidelines recommend a personalized approach to menopause care, including MHT use. Decision‐making around menopause care is a complex, iterative process influenced by multiple factors framed by perspectives from both women and healthcare providers (HCPs). This narrative review aims to summarize evidence around factors affecting decision‐making regarding menopause‐related care. For HCPs, the provision of individualized risk estimates is challenging in practice given the number of potential benefits and risks to consider, and the complexity of the data available, especially within time‐limited consultations. Women seeking menopause care have the difficult task of making sense of the benefit versus risk profiles to make choices in line with their decisional needs influenced by sociocultural/economic, educational, demographic, and personal characteristics. The press, social media, and influential celebrities also impact the perception of menopause and decision‐making around it. Understanding these factors can lead to improved participation in shared decision‐making, satisfaction with the decision and decision‐making process, adherence to treatment, reduced decisional regret, efficient use of resources, and ultimately long‐term satisfaction with care. [ABSTRACT FROM AUTHOR]

Aims: This International Consultation on Incontinence‐Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. Methods: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. Results: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta‐analysis to have a negative effect on LUTS and, therefore are not currently recommended. Conclusions: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing. [ABSTRACT FROM AUTHOR]

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes. [ABSTRACT FROM AUTHOR]

Endometriosis, an inflammatory disease primarily affecting the pelvis and peritoneum, manifests with pelvic pain, dysmenorrhea, dyschezia, dyspareunia, and infertility. Despite its ubiquity, the management of endometriosis is challenging due to its heterogeneous presentation, limitations in diagnostic methods, variable therapeutic responses, and personal and socio-cultural impact on quality of life. This review attempts to consolidate the current literature on endometriosis occurring during and beyond menopause, and to present details regarding management strategies that take into account individual outcomes and goals when managing this condition. The topics included in this review are the clinical features and differential diagnosis of pelvic pain in postmenopausal patients, imaging considerations, serum and laboratory biomarkers, indications for surgery, the principles of hormone replacement therapy, the de novo development of endometriosis after menopause, and malignant transformation. Each topic includes a summary of the current literature, utilizing clinical research, case reports, and expert opinion. Despite a better understanding of the impact of endometriosis beyond menopause, there are many limitations to this condition, specifically with regard to cancer risk and indications for surgery. The existing evidence supports the use of shared decision making and the incorporation of patient preferences in guiding clinical management. Future research endeavors must shed light on the natural history of postmenopausal endometriosis through longitudinal studies in order to foster a deeper understanding of its complicated disease course across women's lifespans. [ABSTRACT FROM AUTHOR]

Background: With the increasing use of hormone replacement therapy (HRT), there is a need to understand its impact on the occurrence of female malignant tumors. This systematic review and meta-analysis aimed to assess the risk of ovarian cancer associated with HRT and its related risk factors. Methods: PUBMED, OVID, Embase, Cochrane, and Web of Science were searched from 1980 to April 2022 to identify studies on the risk of ovarian cancer and hormone replacement therapy. The random-effects model was used to estimate the pooled risk of HRT in ovarian cancer, both in cohort studies and case-control studies. Additionally, the analysis examined the outcomes associated with different types of estrogen plus progesterone regimens. Metaregression and sensitive analysis were performed to evaluate the heterogeneity. Results: 21 cohort studies (involving 15,313 cases and 4,564,785 participants) and 30 case-control studies (including 18,738 cases and 57,747 controls) were analyzed. The pooled risks of ovarian cancer for HRT users were 1.20 (95% confidence interval [CI] 1.01-1.44) from cohort studies and 1.13 (95%CI 1.04-1.22) from case-control studies. However, after restricting the study period to recent decades, the significant results indicating a higher risk disappeared in cohort studies conducted after 2010 and in case-control studies conducted after 2006. Furthermore, the continuous use of estrogen-progesterone replacement therapy (EPRT) was associated with a risk comparable to that of sequential use. Subgroup analysis showed that both estrogen replacement treatment (ERT) and EPRT had minor risks; The risk further increased with prolonged exposure time, particularly for durations exceeding 10 years. Additionally, serous ovarian cancer appeared to be more susceptible than other pathological types. Conclusion: The risk of ovarian cancer associated with HRT has been decreasing over time. However, ERT may increase this risk, particularly when used for an extended period. It is recommended that long-time users consider continuous EPRT as a safer alternative. [ABSTRACT FROM AUTHOR]

Objective: The objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET). Methods: Analyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration. Results: The clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis. Conclusions: This large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to investigate the effectiveness, tolerability and application of estradiol metered-dose transdermal spray (EMDTS) in postmenopausal women during real-world use.This was a prospective, non-interventional, multicenter, observational phase IV cohort study. The Menopause Rating Scale II (MRS II) was used to assess symptoms and clinical response. Safety was assessed by the occurrence of adverse events and adverse drug reactions (ADRs).A total of 451 postmenopausal women were enrolled at 52 gynecological practices across Germany; 383 patients were evaluated for effectiveness and 430 patients for safety. Mean age was 54.3 ± 7.4 years. In total, 228 patients (59.5%) received EMDTS monotherapy and 155 patients (40.5%) received EMDTS plus progestogens. Significant improvements (p < 0.0001) from baseline in symptom severity were recorded for all 11 items of the MRS II at 3, 6 and 12 months of treatment. At 12 months, 81.4% of patients reported improvement in hot flushes/sweating. At final visit, 73% of patients and 77% of physicians were ‘satisfied/very pleased’ with EMDTS. Most common ADRs were headache (n = 6), nausea (n = 4), dizziness (n = 4) and pruritus (n = 3).EMDTS is an effective, well tolerated and easily applied hormone replacement therapy for women experiencing postmenopausal symptoms. [ABSTRACT FROM AUTHOR]

Background: The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a "rescue protocol" for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET). Methods: This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue. Results: Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration = 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902-0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269-0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092-0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth. Conclusions: Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates. [ABSTRACT FROM AUTHOR]

Purpose: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD). Methods: In this retrospective cohort, 119 treatment-naïve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion. Results: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p = 0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p = 0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p = 0.038). Wet AMD started at an earlier age in smokers (p = 0.002). Patients with a better education level presented earlier with better BCVA (p = 0.037). Conclusion: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen’s protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622. [ABSTRACT FROM AUTHOR]

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. Methodology: A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. Results: A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Conclusion: Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12–13 years, taking into consideration the uterus size. Further prospective studies are needed. [ABSTRACT FROM AUTHOR]

In females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERβ)‐Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along‐with this, the association between estrogen, estrogen‐metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD. [ABSTRACT FROM AUTHOR]

Over the last 70 years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI). The reality is probably more nuanced than the conclusions presented by any of these studies. When face to face with a patient, the clinician must negotiate the appropriate decision pathway around the interaction between cardiovascular risk, cardiovascular disease, menopause, and oestrogen +/− progestogen–containing hormone therapy. The metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk, a perception largely led by the Women's Health Initiative study, has shifted the clinician's risk/benefit decision-making away from prescribing menopausal hormone therapy (MHT) for menopausal symptoms. A more nuanced view of the literature and the greater availability of different modes of delivery and formulations of MHT should give the clinician the knowledge and confidence to prescribe appropriate MHT for the greater benefit of midlife health and cardiovascular safety. Image by Bronwyn G. A. Stuckey. [ABSTRACT FROM AUTHOR]

Background: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). Methods: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. Results: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(β) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(β) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). Conclusions: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk. [ABSTRACT FROM AUTHOR]

Background 17α-Hydroxylase deficiency, a rare form of congenital adrenal hyperplasia, presents diagnostic and treatment challenges because of the limited number of cases reported. Case summary This report discusses the case of a 17-year-old Chinese girl who suffered from unexplained dizziness, headaches, and high blood pressure. She had amenorrhoea during puberty and had been diagnosed with ovarian delay. Initially, she was diagnosed with hypertension and received three antihypertensive medications. However, her blood pressure remained poorly controlled. Gene sequencing revealed 17α-hydroxylase deficiency caused by compound heterozygous mutations in CYP17A1. One of the mutation sites, potentially novel, has not been reported previously. Subsequently, dexamethasone therapy was initiated, her blood pressure was controlled, and the symptoms disappeared. During the 1-year follow-up, her blood pressure remained normal, and the symptoms did not recur. Discussion 17α-Hydroxylase deficiency is a rare cause of secondary hypertension. Despite the low prevalence, it should not be overlooked in younger patients. [ABSTRACT FROM AUTHOR]

Fatemah Mohammed AlAhmari,1 Hind Saleh Albahouth,2 Hadeel Ali Almalky,2 Ebtihal Saad Almutairi,2 Muzun Hamoud Alatyan,2 Lama Ali Alotaibi2 1Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia; 2College of Dentistry, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Fatemah Mohammed AlAhmari, King Saud University, Riyadh, Saudi Arabia, Email falahmari@ksu.edu.saObjective: Periodontal diseases are chronic inflammatory disorders influenced by systemic health of the individual. This study aimed to investigate the association between hypothyroidism and periodontal disease in a cohort of adult Saudi population.Methods: This case–control study included 201 adults with hypothyroidism on hormone replacement therapy and 188 healthy controls. The medical files of patients were reviewed to check thyroid stimulation hormone (TSH) and free thyroxine (FT4) levels. Participants completed a questionnaire on demographic and health information, followed by a comprehensive periodontal examination. Pearson chi-square and binary logistic regression analyses determined associations, with a significance set at p ≤ 0.05.Results: Gingivitis was found in 20.9% of cases and 58% of controls. Periodontitis stages I, II, III and IV were in general higher in cases compared to controls (23.4%, 27.9%, 21.9%, 6% in cases versus 13.8%, 17%, 9.6%, 1.6% in controls, respectively). Mean PPD and CAL values were higher in cases (5.54 ± 2.5 and 3.88 ± 3.1) than in controls (4.03 ± 1.6 and 1.72 ± 2.4). Significant associations between periodontal status and hypothyroidism were found (p < 0.0001). The periodontal status in hypothyroid cases correlated significantly with hormone replacement therapy dose and duration (p < 0.0001).Conclusion: The findings of the current study showed that, in a cohort of adult Saudi subjects, patients with hypothyroidism have higher prevalence and more severe periodontal disease symptoms compared to controls, suggesting significant association.Keywords: hypothyroidism, periodontal diseases, hormone replacement therapy, association, case–control study

Abstract Objective The objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET). Methods Analyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration. Results The clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis. Conclusions This large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes.

Introduction: The pathophysiology of idiopathic intracranial hypertension (IIH) is not fully characterized, and less is known about its development in transgender patients. Several cases of IIH in transgender patients have been reported, but fewer cases have been published that identify a cerebrospinal fluid (CSF) leak as a complication of IIH in this population. These patients can serve as an important study population, as an association between exogenous testosterone use in karyotypical females and development of IIH may support a hormonally mediated mechanism of development of this disease. Case Presentation: We describe the case of a 33-year-old obese (BMI: 30.58 kg/m2) female-to-male transgender patient on exogenous testosterone for 15 years who presented with 1 month of acute or chronic headache with profuse rhinorrhea. Fundoscopic exam revealed disk pallor and edema consistent with a Frisen grade 3 papilledema. Nasal secretion was positive for beta-2 transferrin, consistent with CSF. Computed tomography head demonstrated a 5-mm defect in the medial left middle cranial fossa, bilateral optic nerve prominence and tortuosity, and abnormal arachnoid granulations concerning for IIH. After a successful endoscopic endonasal repair of the left lateral sphenoid recess leak, our patient continued to report headaches, was started on acetazolamide, and noted improvement in symptoms. Conclusion: The case described herein further supports the growing body of evidence that implicates a hormonal mechanism of action in the development of IIH. Importantly, it also addresses the need for increased study and conversation about rare neurologic diseases in transgender patients.

Abstract Background The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). Methods Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. Results Longer duration of TT use was associated with increasing degrees of lobular atrophy (p 0.05). Conclusions TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Introduction: Dermatomyositis, systemic and cutaneous lupus erythematosus have a significantly higher prevalence in women than men, emphasizing the relevance of exploring the relationship between sex hormones and autoimmune skin diseases. This review analyzes the interplay between sex hormones and these two skin diseases. Materials and methods: We performed an extensive literature search using the PubMed database from July to August 2023. Search terms included ‘contraceptives’, ‘pregnancy’, ‘hormone replacement’, ‘tamoxifen’, and ‘aromatase inhibitors’. Results and Discussion: This comprehensive literature review shows that there remains considerable debate regarding the use of hormonal contraceptives and hormonal replacement therapy in individuals with autoimmune skin conditions. Nonetheless, it is well established that their use is contraindicated in patients with antiphospholipid syndrome or when antiphospholipid antibodies are positive. Individuals experiencing disease flares and uncontrolled symptoms should also avoid these interventions. Pregnancy planning should be timed to coincide with well-managed disease states to minimize obstetric and neonatal complications. Hormonal breast cancer treatment requires close skin monitoring. Conclusion: Pregnancy, menopause, contraceptive use, hormone replacement therapy, and breast cancer treatment drugs result in substantial shifts in hormone levels. Additionally, hormone levels are altered by aromatase inhibitors and anti-estrogen medications. These fluctuations can modulate mechanisms influencing autoimmune skin abnormalities. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the effects of tibolone versus hormone replacement therapy (HRT) on lower urinary tract symptoms and female sexual function. The current study aimed to compare these treatments. Methods: Women with climacteric symptoms were recruited consecutively and allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg). Patients were followed up at 4 weeks and 12 weeks after treatment. Results: Overall, there were no significance of improvement in the International Prostate Symptoms Score (IPSS) scores in the HRT group. However, nocturia and the IPSS storage score improved after tibolone treatment. In addition, orgasm, satisfaction and pain improved after HRT. However, desire, lubrication, and Female Sexual Function Index (FSFI) total scores improved after tibolone treatment. There was a between-group difference in the change from baseline in the nocturia score after 4 weeks of treatment (0.1 ± 0.9 for HRT vs. −0.4 ± 1.2 for tibolone, p = 0.02). Nonetheless, there were no significant differences of the changes from baseline in the other IPSS and FSFI domains between the tibolone and HRT groups. Conclusion: Despite the limited effect, tibolone seems to have more benefit in nocturia than HRT. In addition, tibolone seems to have benefits on overall low urinary tract storage symptoms; and both tibolone and HRT seem to have beneficial effects on female sexual function, despite there were no significant differences between tibolone and HRT.

Menopause is an inevitable phase in every woman’s life. Women may suffer from unpleasant symptoms during perimenopause. Understanding the health needs of the community during this period will help in developing menopause management programs that can improve quality of life. Aim: To study the symptoms of menopause and perception of women in relation to menopause in order to understand their needs. Settings and Design: A cross-sectional, multi-centric study was undertaken at three institutions (called DH, SJ, and SK) at two cities in India. The study population comprised women between the ages of 40 and 60. Institutional Ethics Committee approval and consent of participants were ensured. Material and Methods: Two instruments, a pilot-tested, peer-reviewed, validated, structured questionnaire and the Menopause Rating Scale (MRS) were utilized for the study. The minimum sample size was calculated to be 385 per site. Statistical analysis was conducted using the IBM Statistical Package for Social Sciences. Results: A total of 1297 forms were analyzed. MRS scores showed psychological symptoms to be most prevalent. Joint and muscular pains were the most common somatic symptoms. Hot flashes and urogenital symptoms were experienced by a lower number. Our MRS scores were significantly higher than those seen in other regions. Urban women, site SJ, those with irregular menstrual cycles, and lower incomes scored higher than their counterparts. Awareness about menopause was patchy, especially regarding medication or support services available. Conclusions: The high MRS scores emphasize the need to institute awareness programs, providing information on choices available for care (hormone replacement therapy, medications, or counseling) and information on where to access services. Primary care physicians can play a vital role in fulfilling this need by ensuring timely knowledge to the community, providing correct diagnosis and treatment. This will help improve the quality of life and sense of well-being of this community.

Purpose: This study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT). Materials and Methods: Database and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta- Analyses extension for Scoping Reviews guidelines. Four databases—PubMed, Cochrane Library, EMBASE, and CINAHL— were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches. Results: A total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty. Conclusions: Further research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40–0.9] and 0.40 [0.16–0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36–0.92] and 0.33 [0.11–1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Aim: To investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole‐body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission. Methods: 22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non‐treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO2peak). Muscle biopsies were obtained at rest and immediately post‐exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity were assessed. Results: HT showed higher absolute mitochondrial respiratory capacity and post‐exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT. Conclusion: Use of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT. [ABSTRACT FROM AUTHOR]

Objective: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all‐cause mortality remains unclear. We conducted a systematic review and dose–response meta‐analysis to determine the effects of HRT on CRC mortality and all‐cause mortality. Methods: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two‐stage random‐effects dose–response meta‐analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality. Results: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all‐cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose–response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose–response analysis showed a nonsignificant decrease in the risk of all‐cause mortality for each additional year of HRT use. Conclusions: This study suggests that the use of HRT is inversely associated with all‐cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association. [ABSTRACT FROM AUTHOR]

Gardner, Laurel, Linda E. Keyes, Caleb Phillips, Elan Small, Tejaswi Adhikari, Nathan Barott, Ken Zafren, Rony Maharjan, and James Marvel. Women at altitude: Menstrual-cycle phase, menopause, and exogenous progesterone are not associated with acute mountain sickness. High Alt Med Biol. 00:000–000, 2024. Background: Elevated progesterone levels in women may protect against acute mountain sickness (AMS). The impact of hormonal contraception (HC) on AMS is unknown. We examined the effect of natural and exogenous progesterone on the occurrence of AMS. Methods: We conducted a prospective observational convenience study of female trekkers in Lobuche (4,940 m) and Manang (3,519 m). We collected data on last menstrual period, use of exogenous hormones, and development of AMS. Results: There were 1,161 trekkers who met inclusion criteria, of whom 307 (26%) had AMS. There was no significant difference in occurrence of AMS between women in the follicular (28%) and the luteal (25%) phases of menstruation (p = 0.48). The proportion of premenopausal (25%) versus postmenopausal women (30%) with AMS did not differ (p = 0.33). The use of HC did not influence the occurrence of AMS (HC 23% vs. no HC 26%, p = 0.47), nor did hormonal replacement therapy (HRT) (HRT 11% vs. no HRT 31%, p = 0.13). Conclusion: We found no relationship between menstrual-cycle phase, menopausal status, or use of exogenous progesterone and the occurrence of AMS in trekkers and conclude that hormonal status is not a risk factor for AMS. Furthermore, women should not be excluded from future AMS studies based on hormonal status. [ABSTRACT FROM AUTHOR]

To study whether midluteal serum estradiol (E2) levels are associated with the live birth rate in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles in patients with optimal midluteal serum progesterone (P4) levels. Observational prospective cohort study. Public fertility clinic. A total of 412 women had an HRT-FET cycle single blastocyst transfer from January 2020 to November 2022. The HRT-FET cycle priming regimen included oral E2 (6mg/24 h) administered in the evening, followed by vaginal P4 (400mg/12 h). Serum E2 and P4 levels were measured using a standardized method, 2–4 hours after the latest P4 administration and 9–14 hours after E4 administration on the day of blastocyst transfer, day 6 of P4 administration. Patients with serum P4 levels (<11 ng/mL [35 nmol/L]) on the day of transfer received additional rectal P4 (400mg/12 h). No additional E2 dose was administered. The primary outcome was the live birth rate (LBR) in relation to E2 levels at blastocyst transfer day. The optimal serum E2 levels correlating with ongoing pregnancy were ≥292 pg/mL and <409 pg/mL (≥1,070 pmol/L and <1,500 pmol/L). The LBR was 59% (60/102) when E2 levels were within this range, whereas a significantly lower LBR of 39% (101/260) was seen in patients when E2 levels were <292 pg/mL (<1,070 pmol/L) and of 28% (14/50) when E2 levels were ≥409 pg/mL (≥1,500 pg/mL). In a logistic regression analysis, adjusting for serum P4 level ≥11 ng/mL or <11 ng/mL (≥35 nmol or <35 nmol/L) on the day of transfer, body mass index, age at oocyte retrieval, day 5 or 6 vitrified blastocysts, and blastocyst score, the adjusted risk difference of live birth was −0.21 (−0.32; −0.10) when the E2 level was <292 pg/mL (<1,070 pmol/L) and −0.31 (−0.45; −0.18) when the E2 level was ≥409 pg/mL (≥1,500 pmol/L) compared with E2 levels ≥292 pg/mL and <409 pg/mL (≥1,070 and <1,500 pmol/L). Importantly, only 25% of patents had optimal levels. The study shows a significant association between serum E2 levels and reproductive outcomes in an HRT-FET cohort in which optimal serum P4 levels were secured. Midluteal serum E2 levels are associated with the LBR in HRT-FET cycles, and E2 levels should neither be too high nor too low. EudraCT No.: 2019-001539-29. [ABSTRACT FROM AUTHOR]

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field. [ABSTRACT FROM AUTHOR]

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers. [ABSTRACT FROM AUTHOR]

Few studies have compared the effects of tibolone versus hormone replacement therapy (HRT) on lower urinary tract symptoms and female sexual function. The current study aimed to compare these treatments. Women with climacteric symptoms were recruited consecutively and allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg). Patients were followed up at 4 weeks and 12 weeks after treatment. Overall, there were no significance of improvement in the International Prostate Symptoms Score (IPSS) scores in the HRT group. However, nocturia and the IPSS storage score improved after tibolone treatment. In addition, orgasm, satisfaction and pain improved after HRT. However, desire, lubrication, and Female Sexual Function Index (FSFI) total scores improved after tibolone treatment. There was a between-group difference in the change from baseline in the nocturia score after 4 weeks of treatment (0.1 ± 0.9 for HRT vs. −0.4 ± 1.2 for tibolone, p = 0.02). Nonetheless, there were no significant differences of the changes from baseline in the other IPSS and FSFI domains between the tibolone and HRT groups. Despite the limited effect, tibolone seems to have more benefit in nocturia than HRT. In addition, tibolone seems to have benefits on overall low urinary tract storage symptoms; and both tibolone and HRT seem to have beneficial effects on female sexual function, despite there were no significant differences between tibolone and HRT. [ABSTRACT FROM AUTHOR]

Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation − all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism. [ABSTRACT FROM AUTHOR]

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups. [ABSTRACT FROM AUTHOR]

Purpose : We performed a retrospective audit of General Practitioners' (GPs) referrals to the specialist Menopause Clinic at Guys and St Thomas's (GSTT) between 2021 and 2022. We aim to establish the indication for the referrals and whether they were compliant with the National Institute for Health and Care Excellence Guidance NICE. Background : GSTT is a teaching hospital in central London that educates gynaecologists in training as well as (GP) for specialist certification in Menopause. The menopause clinic receives approximately 580 GP referrals per month from South East London practices. The current waiting time for an initial appointment is up to 1 year. This delay reflects an increase in demand for menopause care and a deficit in service provision in many areas of the UK. NICE has recommended that GPs refer complicated cases to menopause specialists, with 11 specific criteria. Study Sample and Data Collection : We randomly selected 50 patients referred to the GSTT clinic by a GP between 2021 and 2022. Patient data were collected, including patient demographics, date of referral, indication for referral, date of consultation, waiting time, past medical history, investigations, and treatment instigated during the appointment. Results : The majority of referrals to the GSTT menopause Specialist clinic met the NICE guidelines (76%). One-sixth of the referrals could have been prevented or managed through alternative routes. Finally, although this is a small study, some patient unmet needs (PUNS) and GPs' educational needs have been identified. [ABSTRACT FROM AUTHOR]

Introduction: Natural oestrogen administration as oral or transdermal 17β-estradiol is recommended for pubertal induction in girls with hypogonadism. However, suitable low-dose formulations are not consistently available globally. This questionnaire study aimed to identify the current availability of oestrogen and progesterone preparations worldwide. Methods: Endorsed by the ESPE Turner Syndrome Working Group, the questionnaire targeted paediatric endocrinologists. Questions focused on accessibility of oral/transdermal 17β-estradiol and progestogen preparations. Responses were collected through a SurveyMonkey survey disseminated via ESPE channels, direct outreach, and conferences from June 2020 to December 2022. Results: Participation included 229 healthcare professionals from 45 countries. Oral and transdermal 17β-estradiol in adult dosage was highly accessible (86.5% and 84.3%), with transdermal administration the preferred form (62.8%). Most commonly available estradiol preparations included 50 μg patches (32 countries) and 1 or 2 mg tablets (65.8% and 71.1% countries). However, 0.5 mg 17β-estradiol tablets were available in only 20% of respondents from 8 countries. Patches delivering 14 or 25 μg/day of 17β-estradiol were available in 3 and 20 countries, respectively. Oral progestogen had widespread availability (96.0%) and preference (87.0%), while transdermal usage was limited to 15.2% of respondents. Conclusion: This study highlights global challenges in accessing suitable hormone preparations for female pubertal induction. In most countries, the lowest dose of the estradiol is 50 µg for patches and 2 mg for tablets. Appropriate low-dose 17β-estradiol tablets are much less available than low-dose patches. Our survey underscores the importance of adapting guidelines to local availability, and the need for improved accessibility to address these global disparities. [ABSTRACT FROM AUTHOR]

Objective: Early iatrogenic menopause in gynecological cancer survivors and BRCA mutation (BRCAm) carriers undergoing risk-reducing salpingo-oophorectomy (RRSO) is a major health concern. Hormone replacement therapy (HRT) is the most effective remedy, but remains underused in clinical practice. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group promoted a national survey to investigate the knowledge and attitudes of healthcare professionals regarding the prescription of HRT. Methods: The survey consisted of a self-administered, multiple-choice 45-item questionnaire, available online to all MITO members for 2 months starting from January 2022. Results: A total of 61 participants completed the questionnaire (47 out of 180 MITO centers; compliance: 26.1%). Most respondents were female (73.8%), younger than 50 years (65.6%), and gynecologic oncologists (55.7%), working in public general hospitals (49.2%). An 84.4% of specialists actively discuss HRT with patients and 51.0% of patients ask the specialist for an opinion on HRT. The rate of specialists globally in favor of prescribing HRT was 22.9% for ovarian cancer, 49.1% for cervical cancer, and 8.2% for endometrial cancer patients. Most respondents (70.5%) believe HRT is safe for BRCA-mutated patients after RRSO. Nearly 70% of physicians prescribe systemic HRT, while 23.8% prefer local HRT. Most specialists recommend HRT for as long as there is a benefit and generally for up to 5 years. Conclusion: Real-world data suggest that many healthcare professionals still do not easily prescribe HRT for gynecological cancer survivors and BRCA mutation carriers after RRSO. Further efforts are required to implement the use of HRT in clinical practice and to support both clinicians in recommending HRT and patients in accepting it. [ABSTRACT FROM AUTHOR]

Conflicting evidence exists about the risk of breast cancer in transgender and gender-diverse (TGD) patients treated with testosterone. This review aimed to summarize current knowledge regarding the risk of breast cancer associated with gender-affirming testosterone treatment (GATT). A systematic literature search using the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was conducted in January 2023 through Ovid, Scopus, and Web of Science databases. English-language, peer-reviewed articles evaluating breast cancer in TGD patients after GATT that met the inclusion criteria were included. This review included 22 articles, with 14 case reports, 4 case series, and 4 retrospective cohort studies. The review identified 26 TGD patients who developed breast cancer post-GATT therapy, with inconclusive evidence on the relationship between testosterone and the risk of breast cancer in TGD patients. This uncertainty in part arises from the mechanisms governing testosterone's effects within breast tissue, with contrasting theories proposing both proliferative and antiproliferative impacts. Considering this ambiguity, it is imperative for healthcare providers to engage in informed discussions with patients prior to initiating hormone therapy to discuss potential adverse effects, including the possibility of breast cancer development in TGD individuals. Patient education and shared decision-making are essential components of responsible care in this context. [ABSTRACT FROM AUTHOR]