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Background: The etiology of depression involves many biological and environmental factors, among which the inflammatory process is an important contributor. However, the role of pro-inflammatory cytokines in postmenopausal depression is unclear. Therefore, we aimed to explore the association between the serum concentrations of four pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and depressive symptoms in postmenopausal women who had been receiving menopause hormone therapy (MHT) for at least 6 months and postmenopausal women who had not received MHT. Methods: This study included a total of 136 Chinese postmenopausal women aged 40 to 65 years who visited the gynecology outpatient department between June 2020 and December 2022. They were divided into the POST group (n = 94) and the POST + MHT (n = 42) group. Demographic information was collected, and the Hamilton Rating Scale for Depression (HAMD) was used to assess depression. The circulating levels of IL-1β, IL-6, IL-18, and TNF-α were determined using ELISA kits. Results: According to the HAMD score, 39.36% of the participants in the POST group and 14.29% in the POST + MHT group were considered to have depression. The POST + MHT group had significantly lower serum concentrations of IL-18 and TNF-α than the POST group. Multiple linear regression analysis showed that the serum IL-18 (β = 3.996, 95% CI = 0.508–7.484), and TNF-α levels (β = 4.784, 95% CI = 0.939–8.629) were significant predictors of the HAMD-24 scores in women in the POST group. In addition, age was found to be positively related with the level of depression (β = 0.531, 95% CI = 0.063–0.999). Conclusions: Postmenopausal women who received MHT had a lower HAMD-24 score as well as lower serum TNF-α and IL-18 levels than women who did not receive MHT. Further, the TNF-α and IL-18 level were positively associated with the HAMD-24 score in women who had not received MHT. [ABSTRACT FROM AUTHOR]

Support for a transgender person needs to be holistic, integrating their specific needs and requirements and is therefore personalized. Puberty blockade and/or hormonal transitioning and/or surgical transitioning may be part of this support, to bring body and gender identity into alignment. In this section, we will be looking at how to slow down physiological puberty, at gender affirming hormone treatments, as well as the different options for surgical transitioning. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IDD) can lead to disc herniation and spinal instability, sometimes requiring surgical intervention. Currently, estrogen has a potential protective effect on IDD, and estrogen is associated with an increased risk of some cancers, such as breast and endometrial cancer. Therefore, it is important to identify natural compounds that estrogen analogues treat IDD while reducing the risk of tumor development. Objective: This study aims to explore a natural metabolic treatment strategy by targeting CRISP2 with the natural compound Hesperidin to mimic the protective effects of estrogen on IDD and reduce the risk of tumor development. Methods: Microarray data from healthy volunteers and IDD patients were extracted from the Gene Expression Omnibus (GEO) database, and RNA sequencing and clinical data from various cancer types were analyzed. Differentially expressed genes (DEGs) were identified using the Bioconductor Limma package, followed by principal component analysis, volcano plot, and heatmap visualization. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, CIBERSORT and ssGSEA immune cell infiltration assessments, survival analysis, metabolite enrichment analysis, and molecular docking were performed. Hesperidin's interaction with CRISP2 was further validated through molecular docking and experimental studies. Results: Hesperidin significantly reduced the expression of CRISP2, iNOS, and COX2 in IDD models, decreased reactive oxygen species (ROS) and apoptosis, and diminished inflammatory markers. CIBERSORT and ssGSEA analyses revealed a correlation between CRISP2 and immune cell infiltration. Survival analysis demonstrated that CRISP2 expression levels were associated with patient survival across various cancer types. Hesperidin was found to mimic estrogen's effects on IDD and reduce tumor progression. Cell culture and experimental validation confirmed Hesperidin's protective effects on nucleus pulposus cells (NPCs). Conclusion: Hesperidin, as a potential natural metabolic regulator, not only has therapeutic effects on IDD but may also synergize with estrogen therapy to promote spinal health without increasing cancer risk. This study presents a new clinical approach for IDD treatment and lays the foundation for further drug development and experimental research. [ABSTRACT FROM AUTHOR]

This case report presents a 40-year-old transgender female with a history of gender-affirming hormone therapy who experienced recurrent, medication-resistant arterial thrombi leading to bilateral lower extremity amputations. Despite multiple endovascular and surgical interventions, including bypass grafting and catheter-directed thrombolysis, the patient developed recurrent thrombotic events even while on anticoagulation therapy. Hematologic evaluation for coagulopathy was unremarkable. The case underscores the need for greater understanding of gender-affirming hormone therapy’s long-term cardiovascular effects while highlighting the challenges in managing arterial thrombosis in transgender patients. Further research is required to guide optimal anticoagulation strategies in this population.

Scientific information is incomplete regarding the genitourinary syndrome of menopause. Both the lower genital and urinary tracts are rich in receptors for reproductive hormones and are highly susceptible to waning ovarian hormones at menopause. Symptoms of dryness and pain emerge in late perimenopause, but they can also result earlier from cancer therapies or bilateral oophorectomy. Lower urinary tract symptoms rise in prevalence at midlife and increase further with advancing age. Because ovarian senescence is typically followed by years of aging, some postmenopausal complaints may be attributable to increasing longevity. [ABSTRACT FROM AUTHOR]

Purpose To summarize the current state of knowledge surrounding the impact of testosterone therapy on cardiovascular risk factors in postmenopausal women. Methodology In this scoping review, a comprehensive search of peer-reviewed literature was conducted in adherence to a methodological framework comprising 4 distinct stages: conceptualizing a comprehensive search strategy, screening relevant publications, extracting pertinent data, and organizing and synthesizing the resultant findings. The search used electronic databases, including MEDLINE, Embase, and Google Scholar, to ensure an exhaustive survey of the available literature. Results The database search yielded 150 articles, including systematic reviews, registered trials, and peer-reviewed studies, of which 48 duplicates were removed. Following the title/abstract screening, 36 publications were included in the full-text review. On completion of the full-text review, using the inclusion/exclusion criteria, 29 articles were excluded and 7 remained for data extraction and qualitative synthesis. Main Conclusion Existing research provides promising insights into the benefits of low-dose testosterone therapy, typically combined with estrogen therapy. These benefits may include positive impacts on body composition, functional capacity, insulin sensitivity, inflammatory markers, and cholesterol. However, there remains a substantial lack of knowledge surrounding the effects and mechanisms behind testosterone therapy in postmenopausal women in relation to its impacts on cardiovascular risk. High-quality, evidence-based clinical intervention research is needed to investigate testosterone therapy's potential implication on cardiovascular risk factors in post-menopausal women. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) commonly known as "heart attack" results from the blockage of blood flow to the heart. Postmenopausal women face an elevated risk of MI due to declining estrogen levels, a hormone pivotal in maintaining cardiovascular health. It promotes vasodilation, reduces inflammation, and improves lipid profiles. While estrogen therapy shows promise in mitigating MI risk for postmenopausal women, its efficacy in prevention and recovery remains a subject of debate. This review provides a critical assessment of existing evidence on estrogen therapy's cardioprotective effects for postmenopausal women. It delves into estrogen's role in vascular function enhancement, inflammation reduction, and lipid metabolism modulation. Additionally, it addresses the various forms of estrogen therapy, administration methods, dosage considerations, safety implications, and associated risks. The review highlights the existing controversies and knowledge gaps related to estrogen therapy for MI prevention. It underscores the urgency for in-depth research to decipher the nexus between estrogen therapy and MI risk, especially concerning primary prevention and specific postmenopausal subgroups. Future studies should investigate optimal formulations, doses, and administration routes of estrogen therapy as well as assess treatment timing and duration. Comparative studies and long-term follow-up are necessary to inform clinical decision-making and improve patient care. Addressing these research gaps will empower clinicians to make more judicious choices about estrogen therapy for MI prevention and recovery in postmenopausal women, aiming for enhanced patient outcomes.

Premenopausal women have a lower incidence of cardiovascular disease (CVD) compared with their age-matched male counterparts; however, this discrepancy is abolished following the transition to menopause or during low estrogen states. This, combined with a large amount of basic and preclinical data indicating that estrogen is vasculoprotective, supports the concept that hormone therapy could improve cardiovascular health. However, clinical outcomes in individuals undergoing estrogen treatment have been highly variable, challenging the current paradigm regarding the role of estrogen in the fight against heart disease. Increased risk for CVD correlates with long-term oral contraceptive use, hormone replacement therapy in older, postmenopausal cisgender females, and gender affirmation treatment for transgender females. Vascular endothelial dysfunction serves as a nidus for the development of many cardiovascular diseases and is highly predictive of future CVD risk. Despite preclinical studies indicating that estrogen promotes a quiescent, functional endothelium, it still remains unclear why these observations do not translate to improved CVD outcomes. The goal of this review is to explore our current understanding of the effect of estrogen on the vasculature, with a focus on endothelial health. Following a discussion regarding the influence of estrogen on large and small artery function, critical knowledge gaps are identified. Finally, novel mechanisms and hypotheses are presented that may explain the lack of cardiovascular benefit in unique patient populations. [ABSTRACT FROM AUTHOR]

Purpose: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case–control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment. Methods: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls. Results: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use. Conclusions: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen. [ABSTRACT FROM AUTHOR]

Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are more common near menopause: a phase marked by a decrease in hormone levels, especially estrogen. A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer's disease (AD). Experimental and epidemiological studies suggest that female sex hormones have long-lasting neuroprotective and anti-aging properties. Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging. Menopausal hormone therapy from menopause to the age of 60 years may provide a "window of opportunity" to reduce the risk of mild cognitive impairment (MCI) and AD in later life. Women with earlier menopause should be taken care of by various specialists such as gynecologists, endocrinologists, neurologists, and psychiatrists in order to maintain their mental health at the highest possible level. [ABSTRACT FROM AUTHOR]

Background: Estrogen therapy (ET) plays a key role in maintaining the post-surgical quality of life of patients with endometrial cancer. This study investigated the reality of the use of ET after endometrial cancer surgery in Japan. Methods: Using a healthcare database in Japan, patients who underwent surgery for endometrial cancer between the ages of 40 and 59 years from January 2006 to March 2021 were included. The cumulative prescriptions of ET after endometrial cancer surgeries in patients who had received chemotherapy or radiation therapy (adj-group) and those who did not (non-adj-group) was estimated using the Kaplan–Meier method. Results: Of the 1475 patients, 115 received ET, among whom transdermal estradiol was initiated in 100 (87.0%) individuals. The cumulative proportions of ET prescription 24 months after surgery [95% confidence intervals (CIs)] were 0.088 [0.072, 0.11] in the non-adj-group and 0.058 [0.040, 0.084] in the adj-group. The cumulative proportion [95% CI] of women who received ET at 24 months after surgeries decreased with increasing age, ranging from 0.29 [0.21, 0.38] in the 40‒44 years old to 0.009 [0.002, 0.034] in the 55‒59 years old women in the non-adj-group and from 0.17 [0.094, 0.31] in the 40‒44 years old to 0 in the 55‒59 years old women in the adj-group. Conclusion: The present study shows that ET after endometrial cancer surgery may be underused, even in women who underwent surgery between 40 and 44 years of age and without adjuvant therapy. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women.DesignAs part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression.ResultsOf the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend

ObjectiveTo examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women.DesignAs part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression.ResultsOf the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend

Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods: Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results: Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I (p = 0.414) and 64% of patients in Group II, (p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I (p = 0.68) and 66% of patients in Group II (p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions: Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause. [ABSTRACT FROM AUTHOR]

Adolescents with primary ovarian insufficiency (POI) frequently present with arrested pubertal development or amenorrhea. Early evaluation of menstrual irregularities can avoid a delayed diagnosis. There are various genetic, autoimmune, and iatrogenic causes of POI, although most of the cases will not have an identified cause. Prompt initiation of hormone replacement therapy will restore developmentally appropriate pubertal progression, establishment of menses, and optimization of bone and cardiovascular health. The diagnosis of POI is often unexpected and life-altering for an adolescent and has broad health and psychosocial implications that are best approached with empathy, educational resources, and engagement of multidisciplinary specialists., Competing Interests: Disclosure The authors have nothing to disclose. No funding was received for this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET. NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals. [ABSTRACT FROM AUTHOR]

Objective: To study the trajectories of metabolic parameters after bilateral oophorectomy.Study Design: This population-based cohort study included a random sample of all premenopausal women who underwent bilateral oophorectomy at or before age 45 years from 1988 to 2007 in Olmsted County, Minnesota, and their age-matched (±1 year) referent women who did not undergo bilateral oophorectomy.Main Outcome Measures: The medical records of all women were reviewed to collect the metabolic parameters over a 10-year period. We compared three groups of women: 1) referent women (n = 270), 2) women who underwent bilateral oophorectomy and received estrogen therapy (n = 163), and 3) women who underwent bilateral oophorectomy and did not receive estrogen therapy (n = 107).Results: Over 10 years of follow-up, the three groups had significantly different mean values of diastolic blood pressure, weight, body mass index (BMI), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). However, women with and without bilateral oophorectomy were already different at baseline for hyperlipidemia, systolic blood pressure, weight, and BMI. Nevertheless, the trajectories of change over 10 years were significant for weight (group by time interaction p = 0.03), BMI (p = 0.03), and HDL-C (p = 0.004). The changes occurred primarily in the initial 4-5 years. Women who received estrogen therapy after bilateral oophorectomy were comparable to the referent women with respect to the weight and BMI trends, and they experienced an increase in HDL-C over time.Conclusion: Women who underwent bilateral oophorectomy before menopause experienced unfavorable changes in some metabolic parameters possibly increasing their cardiovascular risk. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemic poses a major global public health threat with more than one million daily new infections and hundreds of deaths. To combat this global pandemic, efficient prevention and management strategies are urgently needed. Together with the main characteristics of COVID-19, impaired coagulation with dysfunctions of the immune response in COVID-19 pathophysiology causes high mortality and morbidity. From recent clinical observations, increased expression of specific types of estrogen appears to protect patients from SARS-CoV-2 infection, thereby, reducing mortality. COVID-19 severity is less common in women than in men, particularly in menopausal women. Furthermore, estrogen levels are negatively correlated with COVID-19 severity and mortality. These findings suggest that estrogen plays a protective role in the pathophysiology of COVID-19. In this review, we discuss the potential roles of estrogen in blocking the SARS-CoV-2 from invading alveolar cells and replicating, and summarize the potential mechanisms of anti-inflammation, immune modulation, reactive oxygen species resistance, anti-thrombosis, vascular dilation, and vascular endothelium protection. Finally, the potential therapeutic effects of estrogen against COVID-19 are reviewed. This review provides insights into the role of estrogen and its use as a potential strategy to reduce the mortality associated with COVID-19, and possibly other viral infections and discusses the possible challenges and pertinent questions. [ABSTRACT FROM AUTHOR]

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Background: Graft-versus-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD in the female genital tract can cause sinusorrhagia, dyspareunia, synechia, and even complete vagina occlusion.Purpose: This prospective study aimed to evaluate the clinical characteristics and effects of preventive and prompt treatment for genital GVHD in females undergoing HSCT (n = 40).Results: Genital GVHD was diagnosed in 11 of 40 patients (27.5%), and the most common complaint was vaginal dryness (54.6%). The majority of patients (63.6%) presented mild genital GVHD (clinical score 1), with interlabial fissures and lichen-like lesions, while a minority of patients (9.1%) presented advanced genital GVHD (clinical score 3) with the fusion of the small and large lips. The median time of onset of genital GVHD signs was 10 months after HSCT, concomitant with GVHD in the skin and oral cavity. Personalized and topical therapy was effective in most cases (81.8%), and no patient required surgical intervention.Conclusion: We confirmed that female genital GVHD affects approximately one-third of females undergoing HSCT, highlighting the importance of periodic gynecological monitoring for early detection and treatment to improve care for these females. [ABSTRACT FROM AUTHOR]

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy--an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population. [ABSTRACT FROM AUTHOR]

Menopause is a universal experience for midlife women. The physiological decline in endogenous estrogen can be associated with vasomotor symptoms or hot flashes, sleep disruption, and mood disorders. Long-term concerns arise with sequelae of estrogen loss such as genitourinary syndrome of menopause and osteoporosis. Although the pendulum has swung widely since the 1942 approval of conjugated equine estrogens, estrogen therapy, now available in an ever-expanding menu of preparations, routes of administration, and dosing, remains the most effective means to collectively address these, and potentially, additional concerns. Refinement of knowledge of risks and benefits facilitates patient selection and counseling. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods: Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results: Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I (p = 0.414) and 64% of patients in Group II, (p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I (p = 0.68) and 66% of patients in Group II (p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions: Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause.

Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson's disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations. Neurologist-confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington State. Final analysis included 137 female cases and 227 controls. Hormone therapy use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin. Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6-1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1-22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6-5.0). The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice.

Zil Goldstein,1 Musaub Khan,2 Tamar Reisman,1 Joshua D Safer11Center for Transgender Medicine and Surgery at Mount Sinai, Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; 2New York Medical College, Valhalla, NY USAIntroduction: Venous thromboembolism (VTE) is a potential risk of estrogen therapy. However, data show an improvement in the quality of life for transgender people who use feminizing hormone therapy. With few transgender-specific data, guidance may be drawn from cisgender (nontransgender) data, with a focus on hormonal birth control and postmenopausal hormone replacement therapy (HRT). The aim of this review is to examine the degree to which routes of administration, patient comorbidities, and type of hormone utilized affect the safety of estrogen therapy.Methods: We identified 6,349 studies by searching PubMed with the terms “transgender”, “estrogen”, “VTE”, and “HRT”. Of these, there were only 13 studies between 1989 and 2018 that investigated the effects of hormone therapy, including types of estrogens used, in transgender women and men.Results: The data suggest that the route of hormone administration, patient demographics, and patient comorbidities all affect estrogen’s link with VTE. For example, avoiding ethinyl estradiol might make the use of hormone therapy in trans feminine individuals safer than oral birth control. Data from both cis and trans groups suggest additional VTE risk associated with the use of progestins. While transdermal estrogens dosed up to 0.1 mg/day or below appear lower risk for VTE than other forms of estrogen, it is unclear whether this is related to the delivery method or a dose effect. Finally, even if the risk from exogenous estrogen use remains significant statistically, the absolute clinical risk remains low.Conclusion: Clinicians should avoid the use of ethinyl estradiol. Additionally, data suggest that progestins should be avoided for transgender individuals. Further study of the relationship between estrogen use and the risk of VTE will serve to inform the safest care strategies for transgender individuals.Keywords: transgender, estrogen therapy, venous thromboembolism

ObjectiveMost girls and women with Turner syndrome (TS) require estrogen replacement therapy (ERT) to initiate or maintain pubertal development. Most likely, the most fundamental effect of ERT in hypogonadism is the promotion of uterine growth. The optimal ERT model is still being discussed. The present study aimed to assess uterine size in girls with TS in the prepubertal state during and after the induction of puberty and compare it to a healthy population.MethodsThe analysis encompassed 40 TS girls. The prepubertal and postpubertal control groups contained 20 healthy girls each. All patients with TS were treated with 17-ß estradiol. Uterine imaging was performed with two-dimensional (2D) transabdominal ultrasound. The uterine volume (UV) and fundocervical antero-posterior ratio (FCR) were calculated in patients with TS before the pubertal induction, after 6-12 months of estrogen replacement therapy (ERT), after ≥ 36 months of ERT or ≥ 12 months after menarche.ResultsThe average age of TS patients at estrogen introduction and at the last control visit, when the uterus was considered mature, was 12.9 years and 16.1 years, respectively. The UV in patients with TS at the beginning of ERT was 1.55 ± 1.22 cm3 and was not significantly different from the UV in the prepubertal controls. The mature UV in patients with TS was 31.04 ± 11.78 cm3 and was significantly smaller than the UV of the postpubertal controls (45.68 ± 12.51 cm3, p

Objective: Most girls and women with Turner syndrome (TS) require estrogen replacement therapy (ERT) to initiate or maintain pubertal development. Most likely, the most fundamental effect of ERT in hypogonadism is the promotion of uterine growth. The optimal ERT model is still being discussed. The present study aimed to assess uterine size in girls with TS in the prepubertal state during and after the induction of puberty and compare it to a healthy population. Methods: The analysis encompassed 40 TS girls. The prepubertal and postpubertal control groups contained 20 healthy girls each. All patients with TS were treated with 17-ß estradiol. Uterine imaging was performed with two-dimensional (2D) transabdominal ultrasound. The uterine volume (UV) and fundocervical antero-posterior ratio (FCR) were calculated in patients with TS before the pubertal induction, after 6-12 months of estrogen replacement therapy (ERT), after ≥ 36 months of ERT or ≥ 12 months after menarche. Results: The average age of TS patients at estrogen introduction and at the last control visit, when the uterus was considered mature, was 12.9 years and 16.1 years, respectively. The UV in patients with TS at the beginning of ERT was 1.55 ± 1.22 cm3 and was not significantly different from the UV in the prepubertal controls. The mature UV in patients with TS was 31.04 ± 11.78 cm3 and was significantly smaller than the UV of the postpubertal controls (45.68 ± 12.51 cm3, p<0.001). The FCR in girls with TS did not differ significantly from that in the prepubertal and postpubertal control groups, respectively. No prognostic factors could be established for the final UV. By the last control visit, thelarche had advanced in most patients to Tanner 4 and 5 (37.5% and 40%, respectively). Conclusions: Before the onset of ERT, patients with TS have a uterus similar in size to that in prepubertal healthy girls. Pubertal induction in patients with TS causes a significant increase in the UV that is detectable after 6-12 months of ERT. The mature uterus is smaller in patients with TS than in the age-matched healthy population. [ABSTRACT FROM AUTHOR]

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ginekologia i Perinatologia Praktyczna is the property of VM Medica-VM Group (Via Medica) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Preoperative estrogen therapy may improve the short-term prognosis of IUAs. • There was no sufficient evidence of the effect on reproductive outcomes. • More well-designed, randomized controlled trials are needed. The aim of this systematic review and meta-analysis was to assess the effect of oestrogen therapy as a preoperative intervention for improving clinical outcomes and fertility outcomes in women with intrauterine adhesions (IUA). A systematic search of PubMed, Embase, The Cochrane Library, clinicaltrials.gov, OVID and Chinese databases was carried out to identify relevant studies published before December 2019. Outcomes were expressed as odds ratios and 95% confidence intervals. Five cohort studies with moderate to high methodological quality were included in the meta-analysis. Preoperative oestrogen therapy was strongly associated with better clinical outcome at second-look hysteroscopy (OR 2.72; 95% CI 1.49 to 4.96; P = 0.001); whereas no significant difference was found in menstruation improvement and conception rate (OR 1.45; 95% CI, 0.95 to 2.23; P = 0.09; and OR 0.96; 95% CI 0.60 to 1.54; P = 0.87, respectively). The overall quality of the evidence ranged from moderate to very low. Preoperative oestrogen therapy may improve the short-term prognosis of IUA at second-look hysteroscopy, whereas the long-term prognosis-fertility outcome was similar to the control group. More strictly designed research studies are needed to assess the effectiveness of oestrogen administration before hysteroscopic adhesiolysis. [ABSTRACT FROM AUTHOR]

The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer's disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-β (Aβ), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOEɛ4 in AD. HSV-1 and APOEɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aβ plaques and neurofibrillary tangles. [ABSTRACT FROM AUTHOR]

In Japan, anabolic steroid hormone (ASH) treatment for Turner syndrome (TS) to promote growth had been provided before GH therapy for TS was approved. ASH effectively improved the adult height (AH) of TS patients without spontaneous puberty but decreased the AH of TS patients with spontaneous puberty. Although GH therapy for TS was approved in 1991, the approved dosage remained 0.5 IU/kg/wk for GH-deficient TS patients and improved AH by approximately 7 cm. However, AH did not reach -2 standard deviations in healthy girls. In 1999, the requirement of GH deficiency was removed and a dose of 1.0 IU/kg/wk was approved. Although an increase in AH was expected, no reports showed significant improvements in AH at a high dose of GH. GH + ASH combination therapy was reevaluated and recommended for TS patients with gonadal failure and an extremely short stature or those who respond poorly to GH therapy. Although early estrogen replacement therapy is recommended to improve psychological quality of life and prevent osteoporosis, it lowered AH even at a low dose of ethinyl estradiol (25 ng/kg/d). The initiation of ethynyl estradiol at an extremely low dose (1-5 ng/kg/d) at a relatively young age successfully improved AH. [ABSTRACT FROM AUTHOR]

In females, endogenous estrogen secretion increases gradually before pubertal development. The benefits of low-dose estrogen therapy in patients with Turner syndrome were originally discussed by Ross et al. and Quigley et al. These seminal studies used ethinyl estradiol (EE2), starting at a dose of 25 ng/kg/d. We hypothesized that the initial dosage of estrogen could be titrated to more closely mimic physiological increments of endogenous estrogen. Therefore, our recent study initiated EE2 treatment at a dosage of 1-2 ng/kg/d, an ultra-low-dose estrogen therapy in pediatric patients with Turner syndrome. The ultra-low-dose estrogen therapy in this syndrome produced a good final height outcome but achieved suboptimal bone mineral density (BMD). In the present review, we have explained our findings to clarify the merits and demerits of this new therapy and to promote further discussion and research. This type of ultra-low-dose estrogen therapy, initiated at an early age, could be ideal for estrogen replacement in female patients with hypogonadism, such as Turner syndrome. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women.DesignAs part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression.ResultsOf the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend or =15 y) users (RR = 0.83; 95% CI, 0.74-0.93 for 15-19 y and RR = 0.87; 95% CI, 0.80-0.94 for 20+ y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (< or =0.625 mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET.ConclusionLong-term ET is associated with lower all-cause mortality in older women.