Menopausal Therapy Research Articles

Hormone replacement therapy in surgical menopause after gynecological malignancies

This review examines hormone replacement therapy (HRT) in cases of surgical menopause following gynecological malignancies. It aims to capture current knowledge, summarize recent findings, and provide recommendations for clinical settings. Unlike natural menopause, surgical menopause occurs abruptly, without an adjustment period, and is associated with a notably higher risk of fractures, arthritis, cognitive decline, dementia, Parkinson’s disease, and various metabolic disorders affecting glucose and lipid levels—all of which contribute to an increased risk of major cardiovascular events. In 2017, The North American Menopause Society recommended that, barring contraindications, HRT should be initiated in women who enter surgical menopause before age 45. If these women do not experience vasomotor symptoms or other issues, HRT should be maintained consistently at least until age 52. This guideline reflects contemporary knowledge and is the result of a multidisciplinary consensus, based on a review of existing literature and several randomized clinical trials focusing on women who have survived gynecological cancers and whose quality of life is significantly impacted by surgical or early menopause. Estrogen supplementation is particularly beneficial, as it is linked to marked improvements in quality of life, including delayed onset of chronic cardiovascular issues, reduced fracture risk, enhanced cognitive function, reduced inflammation, and improved self-esteem, as well as better social and work performance. Clinical implementation of HRT, however, requires a highly individualized approach. This approach must consider the type and stage of malignancy, histopathological characteristics, risk factors for recurrence (such as diet, concurrent medications, medical history, and genetic predispositions), and a thorough assessment of the potential benefits and risks of HRT, as well as the patient’s personal wishes and expectations.

Estrogen receptors and vascular aging

After years of studying cardiovascular diseases (CVD) in men due to their higher incidence compared to women, attention is now being paid to female CVD and their pathophysiology. Even though premenopausal women have a lower incidence of CVD, this disparity progressively diminishes after menopause, highlighting the key role of sex hormones. Many preclinical and fundamental studies have demonstrated protective effects of estrogens on arterial endothelium, suggesting that hormone therapy could improve cardiovascular health in menopausal women. However, disappointing outcomes from a major clinical trial two decades ago questioned the cardiovascular protection by estrogens with age. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens on CVD, with a focus on their impact on endothelial function. Then, we will present abnormalities in the expression and signaling of estrogen receptors (ERs) in the arteries, and the contribution of conventional estrogens to arterial protection during aging. Finally, we will examine how recent advances in the mechanisms of action of ERa could help to optimize hormone therapy for menopause.

Ovarian tissue cryopreservation and transplantation as a natural means to delay menopause.

Ovarian tissue cryopreservation and transplantation (OTCT) offers hope for preserving fertility and endocrine functions in patients undergoing gonadotoxic treatments. Advancements in techniques for the procedure have transformed OTCT from an experimental procedure into a viable option. There is a growing interest in utilizing OTCT to delay menopause and alleviate associated health issues. Menopausal transition affects women globally, leading to symptoms and long- term health risks. OTCT has the potential to restore endocrine functions, reducing menopause-related symptoms while mitigating health consequences such as osteoporosis and cardiovascular diseases. Although the use of OTCT for delaying menopause is not clinically proven, the discussion around shows potential for future utilization. In essence, the remarkable advancements in OTCT have bestowed upon us the ability to safeguard fertility and sustain the delicate endocrine functions of the ovaries. However, it is the tantalizing prospect of utilizing this technique to postpone menopause and alleviate its associated symptoms that truly captivates the imagination. Further research is imperative to substantiate the clinical efficacy of OTCT; nonetheless, its potential in menopausal therapy is both promising and warrants comprehensive exploration. This review highlights advancements and the feasibility of OTCT to postpone menopause as an alternative approach to currently used conventional menopause therapy methods.

Styphnolobium japonicum Fruit and Germinated Soybean Embryo Complex Extract for Postmenopausal-Symptom Relief.

Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms. A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF-GSE complex extract at ratios of 1:1, 1:2, and 2:1. Treatment with the SJF-GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48-72 mg/g sophoricoside and 8-12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles. The SJF-GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.

Homoeopathic Management of Menopause: A Comprehensive Review

Background: Menopause signifies a crucial physiological shift in a woman's journey, denoting the halt of menstrual cycles caused by the gradual decline in ovarian activity. Conventional management options, such as Hormone Replacement Therapy (HRT), are effective but not devoid of risks and limitations. In contrast, homeopathy offers a holistic approach to symptom management, aiming to address the underlying cause of menopausal disturbances. Aim and Objective: By critically analyzing clinical studies, randomized controlled trials, and observational research, this paper seeks to elucidate the role of homeopathy as an alternative and complementary therapy for menopause. The objective is to provide insights into the potential benefits of homeopathy and contribute to the growing body of evidence supporting its use in menopausal care. Methodology: A comprehensive search strategy was done to identify relevant literatures from databases such as PubMed, SCOPUS, and Google Scholar. The selection of eligible studies was conducted according to predefined criteria for inclusion and exclusion. Results: Our findings resulted into nine studies that fulfilled the inclusion criteria, including randomized controlled trials, observational studies, and clinical trials. These studies collectively provided evidence of the efficacy of homeopathic medicines in managing various menopausal symptoms, including hot flushes, mood swings, and sleep disturbances. Conclusion: The reviewed literature suggests that homeopathy offers a promising avenue for managing menopausal symptoms, providing an alternative or complimentary approach to conventional therapies. Individualized treatment strategies tailored to each woman's unique symptomatology appear particularly beneficial. However, further clinical trials are needed to fully elucidate the efficacy and mechanisms of action of homeopathic interventions in menopausal care.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Fraction of cancers attributable to and prevented by reproductive factors and exogenous hormones use in Italy

ObjectiveEndogenous and exogenous hormonal factors have been associated with female breast, genital, and colorectal cancer risk. The aim of the present study is to conduct an evidence-based evaluation of the fraction of cancers attributable to and prevented by exogenous hormonal (i.e., combined oral contraceptives [COC] and combined estrogen-progestogen menopausal therapy [CEPMT]) and reproductive factors (i.e., parity and breastfeeding) in Italy. Study designWe calculated the population attributable and prevented fractions combining relative risks and prevalence of exposure in Italian women. Italian cancer incidence and mortality data were extracted from national sources and used to estimate the number of cancer cases and deaths attributable to reproductive factors and exogenous hormones in Italy in 2020. For long-term effects, a 20-year latency period was considered. ResultsCOC were responsible for 4.4 % of breast and 10.9 % of cervical cancers in women aged 15–44, but also avoided 6.4 % of endometrial, 5.6 % of ovarian, and 2.9 % of colorectal cancers in women of all ages. Overall, COC use prevented 1174 cancer diagnoses and 577 cancer deaths. CEPMT caused 0.4 % of breast cancers at age 45–69. Low parity accounted for 8.1 %, 11.8 % and 15.5 % of breast, endometrial and ovarian cancers, respectively (6267 cases, 1796 deaths). Breastfeeding avoided 6.4 % of breast cancers (3775 cases, 897 deaths). ConclusionsOur analysis quantified the complex effects of hormonal and reproductive factors on cancer burden in Italian women.

(065) ARE CLINICS THAT DO NOT HAVE A MSCP-CERTIFIED PROVIDER MORE LIKELY TO OFFER GUIDELINE-NON-CONCORDANT TREATMENT?

Abstract Introduction Menopausal hormone therapy is the most efficacious option for treating vasomotor symptoms, the genitourinary syndrome of menopause, and to prevent fractures and bone loss. However, publication of contradictory evidence about the risks associated with menopausal hormone therapy and changing recommendations created confusion among patients and providers about how best to manage symptoms. Because providers with varying degrees and specialties may take care of midlife women, and there is no specific certification required to offer menopause treatment, The Menopause Society established its competency exam in 2002 to set the standard for menopause care and assist women in locating clinicians who provide optimal menopause-related care. Objective To identify clinics advertising menopause treatment in Ohio, Michigan, and Pennsylvania and evaluate whether clinics not affiliated with a MSCP-certified provider are more likely to offer guideline-non-concordant treatment compared to clinics affiliated with a MSCP- certified provider. Methods We performed an internet search to identify clinics providing menopause treatment in Ohio, Michigan, and Pennsylvania. From each clinic’s website we abstracted the location, whether the clinic offered guideline-non-concordant treatment (hormone testing, bioidentical “hormone menopause therapy (HRT)”, or compounded HRT), whether the clinic advertised that menopausal hormone therapy(MHT) would promote youthful appearance or weight loss, and whether the clinic accepted insurance. We checked clinic personnel against the Menopause Society directory of practitioners to determine if the clinic was affiliated with a MSCP-certified provider. We used Fisher’s exact test to evaluate association between affiliation with a MSCP provider and guideline-non-concordant care, inaccurate claims about MHT, and accepting insurance. Our primary outcome was odds of offering hormone testing. Results We identified 174 clinics (41% in OH, 28% in PA, and 31% in MI). 13% of clinics were affiliated with a MSCP-certified provider. Clinics with a MSCP-certified provider are significantly more less likely to advertise hormone testing (primary outcome, OR = 0.11, 95% confidence interval: 0.02 to 0.39), compounded hormone therapy (OR = 0.06, 95% confidence interval: 0.001 to 0.41), and bioidentical hormone therapy (OR = 0.07, 95% confidence interval: 0.001 to 0.26), compared to clinics without a MSCP-certified provider. MSCP provider-affiliated clinics are also less likely to advertise that hormone replacement therapy will help maintain youth or help with weight loss (Table). Clinics with a MSCP-certified provider are more likely to accept insurance (OR = 7.55, 95% confidence interval: 1.59 to 72.29). Conclusions Our research has shown that in the states of Ohio, Michigan, and Pennsylvania, MSCP-certified providers were more likely to adhere to the Menopause Society’s guidelines and not advertise for compounded or bioidentical hormones, recommend hormone testing, or advertise hormones for a youthful appearance or weight loss. These clinics were also more likely to accept insurance. Providers who work with midlife women should consider obtaining their MSCP certification to remain current with evidence-based practice and make it easier for patients to locate a provider who is following the most up to date guidelines. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Astellas.

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough.

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.

Pregnancy, Reproductive Factors, and Female Heart Failure Risk and Outcomes.

The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy. Pregnancy-related factors, including hypertensive disorders and gestational diabetes, increase the risk of heart failure in women, while breastfeeding and hormone therapy may offer protection. Hypertensive disorders of pregnancy, gestational diabetes, polycystic ovarian syndrome, placental abruption, younger maternal age at first live birth, younger maternal age at last live birth, number of stillbirths, number of pregnancies, onset of menstruation before 12years of age, shorter reproductive age, ovariectomy, and prolonged absence of ovarian hormones may increase the risk of heart failure in women. Conversely, breastfeeding status and hormone therapy (for menopause or contraception) may serve as protective factors, while fertility treatments have no discernible effect on the risk of heart failure.

Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

Postmenopausal Osteoporosis: Menopause Hormone Therapy and Selective Estrogen Receptor Modulators.

Osteoporosis is a debilitating silent disease with a huge socio-economic impact. Prevention strategies and early detection of osteoporosis need to be carried out in every health care unit to substantially reduce the fracture rates. Indian studies have indicated a knowledge gap on diagnosis and management of osteoporosis amongst medical professionals and consumers. This article reviews the evidences available on searches from PubMed and The National Library of Medicine, author's opinions based on clinical experience. There is a need for escalating the efforts to bridge the knowledge gap regarding various aspects of osteoporosis amongst professionals and consumers. Three indications for postmenopausal hormone therapy (HT), which have constantly withstood the test of time, are symptom relief, urogenital atrophy, and bone health. This article specifically focuses on management of postmenopausal osteoporosis by HT alone or in combinations. Early menopause is within 10years of menopause and late menopause is considered beyond 10years of menopause. HT is a cost-effective therapy in the early post menopause especially in symptomatic women at risk for osteoporosis unless contraindicated. HT prevents all osteoporotic fractures even in low-risk population. All HT preparations including low dose and non-oral routes of estrogen are effective for bone health. The bone protective effect lasts while on HT. Extended use of HT in women after 10years of menopause with reduced bone mass is an option after detailed counselling of the risk benefit analysis compared with the other available therapies for osteoporosis. The primary therapy to prevent bone loss in women with premature menopause and secondary amenorrhea is HT. HT work up and annual follow-up is essential before prescribing HT.

Knowledge of common cancers among new-entry health science students in Japan and Vietnam

BackgroundThe incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions.MethodsThis cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer.ResultsA total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p < 0.001), except for human papillomavirus (HPV) infection awareness. For this understanding, only 14.8% of Japanese students selected the correct answer, which was significantly lower than the 22.4% of Vietnamese students (p = 0.001). Both the Japanese and Vietnamese students had limited knowledge regarding the connection between HPV infection and cancer and the link between estrogen–progestogen menopausal therapy and breast cancer. Additionally, female students had better knowledge about breast, skin, and endometrial cancers than male students.ConclusionsJapanese students generally exhibited higher levels of cancer knowledge than Vietnamese students, except for HPV infection recognition. Both groups had limited knowledge regarding the connection between HPV infection and cancer and the relationship between estrogen–progestogen menopausal therapy and breast cancer.

An Endocrine Perspective on Lynch Syndrome

"Background: A germline mutation of the MisMatch Repairgene that causes a malfunctioning DNA system is the defining feature of the hereditary illness known as Lynch syndrome. This review will discuss the endocrine aspects of LS and highlight current advancements in the area. Methods: We searched the available literature of the last 10 years for terms such as endocrine tumors and LS. Our goal is to provide a summary of the most recent information available on the endocrine perspective in Lynch syndrome. Results: The hormonal chemoprevention methods cited are the use of combined oral contraceptives, the use of progestogen-releasing intrauterine devices, and the use of progesterone-only drugs. In addition, after surgical exclusion of the uterus and ovaries, a method frequently adopted for LS patients, it is necessary to start hormonal menopausal therapy, taking into account certain age-specific features. In addition, numerous LS-associated endocrine tumor types have been described. Conclusions: Many hormonal variants are available that are useful in the chemoprevention involved in the treatment of LS. Menopausal hormone therapy is imperative for LS patients who need it. Clinicians need to be aware of the possible association of certain types of aggressive endocrine cancers associated with LS."

Current insight flavonoid quercetin in epithelial maturation vagina for menopause treatment: a narrative review

Background: Menopause affects all parts of the women's body system, especially in the genitourinary area. The impact on the genitourinary system causes post-menopausal women to complain of menopause-related genitourinary syndrome due to vaginal atrophy, sexual dysfunction, and pelvic organ prolapse in the long term. Various research has been conducted to find alternative therapy, especially flavonoid quercetin, due to its phytoestrogen characteristic. Methods: This review article assembles much literature to highlight the menopause effect on the vagina and the phytoestrogen effect of flavonoid quercetin as a potential alternative therapy. This study aims to develop future experimental studies of quercetin's effect on the vagina. Results: Hypoestrogenic condition affects all vaginal layers. This is due to estrogen receptors distributed in the epithelial lining, lamina propria, and muscular layer of the vagina. In vitro studies showed quercetin induces cell proliferation by activating signal pathway b-catenin/c-Myc/cyclin A2, mediated by estrogen receptor. The signal pathway increases the cell cycle transition to the G1 phase. It also increases keratinocyte proliferation and migration, proliferating cell nuclear antigen, and positive a6 and b1 integrin cells in the basal layer of the epidermis, which causes thickening of the epidermis. Conclusion: Flavonoid quercetin is a promising alternative for menopause therapy in the vagina. Further, in vivo studies are needed to confirm the result of in vitro study and as basic data for comparison with other potent phytoestrogen.

Multidirectional Effects of Red Clover (Trifolium pratense L.) in Support of Menopause Therapy.

Red clover is a raw material of interest primarily due to its isoflavone content. However, other groups of compounds may affect the pleiotropic biological effects of this raw material. It is used to alleviate menopausal symptoms, but the fact that there are many varieties of this plant that can be grown makes it necessary to compare the biological activity and phytochemical composition of this plant. Also of interest are the differences between the leaves and flowers of the plant. The aim of this study was to evaluate the properties of the leaves and flowers of six clover varieties-'Tenia', 'Atlantis', 'Milena', 'Magellan', 'Lemmon' and 'Lucrum'-with respect to their ability to inhibit α-glucosidase, lipase, collagenase and antioxidant activity. Therefore, the contents of polyphenols and the four main isoflavones-genistein, daidzein, biochanin and formononetin-were assessed. The study was complemented by testing for permeability through a model membrane system (PAMPA). Principal component analysis (PCA) identified a relationship between activity and the content of active compounds. It was concluded that antioxidant activity, inhibition of glucosidase, collagenase and lipase are not correlated with isoflavone content. A higher content of total polyphenols (TPC) was determined in the flowers of red clover while a higher content of isoflavones was determined in the leaves of almost every variety. The exception is the 'Lemmon' variety, characterized by high isoflavone content and high activity in the tests conducted.

P-642 Estrogen deprivation and related risks in primary ovarian insufficiency with various hormone therapy initiation time points - evaluating 122,785 Asian women

Abstract Study question Does the initiation time point and/or duration of hormone therapy affect the long-term health consequences in primary ovarian insufficiency (POI)? Summary answer POI women with immediate hormone therapy following their diagnosis showed significantly reduced risk of metabolic syndrome and dyslipidemia, and such effect magnified with aging. What is known already POI women are exposed to extended duration of estrogen deficiency and premature aging, consequently associated with higher risks of cardiovascular, metabolic, osteoporotic and neurodegenerative diseases. The first line of treatment is hormone therapy (HT), preferably until the age of natural menopause. “Timing hypothesis” in terms of hormone replacement therapy (HRT) in menopause has globally changed the treatment protocol, but its evidence in POI is scarce. Study design, size, duration This population-based retrospective cohort study included 122,785 women registered to the National Health Insurance in South Korea from 2009 to 2015. The study group with POI diagnosis contained 24,557 women, determined by the International Classification of Disease, tenth revision (ICD-10) code E283 in the database. Women aged more than 40 years with the E283 code were considered being previously-diagnosed POI. The 1:4 age-matching control group with the systematic random-sampling method included 98,228 women. Participants/materials, setting, methods The participants’ demographic data, diagnosis codes, use of inpatient and outpatient services, pharmacy dispensing claims and mortality data were retrieved and statistically analyzed. According to their use of HT, the study group was further divided into two groups: with (n = 13,240) or without HT (n = 11,317); their routine health check-up data collected in the database were then compared. In all analysis, a p-value &amp;lt;0.05 was considered statistically significant. Main results and the role of chance Compared to the control group, POI women had significantly lower body mass index (BMI), blood pressure, serum total cholesterol and triglyceride (TG), but the incidence rate ratio (IRR) was significantly higher in POI regarding thyroid diseases, type 2 diabetes, dyslipidemia, hypertension, osteoporosis and cardiovascular diseases (IRR with 95% confidence interval (CI) of 1.731[1.691; 1.772], 1.300[1.260; 1.342], 1.499[1.470; 1.529], 1.100[1.071; 1.129], 2.449[2.388;2.513] and 1.468[1.392; 1.547], respectively). Among POI women overall, the HT users had significantly lower BMI, lower systolic blood pressure but similar diastolic blood pressure, and lower serum total cholesterol and TG, compared to the non-users. In terms of IRRs for chronic diseases, the HT users under the age of 40 years did not show any statistically significant difference in comparison to the non-users; however, the HT users aged more than 40 years had significantly lower IRRs for type 2 diabetes, dyslipidemia and hypertension compared to the non-users (0.876[0.822; 0.933], 0.873[0.840; 0.907], 0.849[0.805; 0.896], respectively). Such effect became more statistically vivid when the participants grew older (IRR[95% CI] of 0.849[0.749; 0.963] for thyroid diseases; 0.806[0.708; 0.917] for type 2 diabetes; 0.652[0.592; 0.718] for dyslipidemia; 0.739[0.662; 0.825] for hypertension; 0.835[0.752; 0.928] for osteoporosis; and 0.890[0.728; 1.089] for cardiovascular disease, respectively). Limitations, reasons for caution The current study relied on the health insurance claim data which did not include detailed patient medical record including menstruation pattern and obstetrical/gynecological histories. Also, critical biochemical assay results such as anti-mullerian hormone or pituitary hormones were not available because they were not covered by the national health insurance program. Wider implications of the findings Agreeing with the previous literature, the immediate use of HT is associated with the reduced incidence of chronic diseases in POI women, and its extended use exerts more significant results with aging. If acknowledged early and initiated with HT, previously-inevitable health risks with POI could be conceivably compensated. Trial registration number The current study was supported by Biomedical Research Institute Grant (#202201970001), Pusan National University Hospital.

Care, choice, complexities: The circulations of hormone therapy in early menopause

Navigating whether to prescribe hormone replacement therapy (HRT) requires that health practitioners approach a woman’s individual life circumstances, and early menopause (EM) as a particularly intricate experience and condition. Drawing on qualitative interviews with 16 practitioners in Australia, this article examines the modalities of care that emerge in the nexus of EM and HRT. Early menopause emerges in participants’ narratives as far from a ‘unitary’ medical condition, but rather one that reaches across other embodied changes for women which may be moderated by HRT. Thus, different modes of care and tensions surface, and we suggest that these constitute an oscillation between ‘caring for’ and ‘caring with’ in medical practice. This oscillation combines experimentation with and adjustment of HRT, while contending with responsibility, risk and choice, and shared, knowledgeable care. Our goal is not to neatly split ‘caring for’ from ‘caring with’. Rather, we discuss how ambiguities of care circulate through a complex diagnosis and its treatment options. We argue that care, in this context, manifests as potentiality and as a set of flexible practices that at times cannot be fully disentangled from issues of choice and control, and HRT itself.

Part I: Interactive case: Menopause

Part I: Interactive case: Menopause

Optimizing the pipeline of multipurpose prevention technologies: opportunities across women's reproductive lifespans.

HIV/AIDS and maternal mortality are the two leading causes of death among women of reproductive age in sub-Saharan Africa. A growing body of research investigates opportunities for multipurpose prevention technologies (MPTs) that prevent unintended pregnancy, HIV, and/or other sexually transmitted infections (STIs) with a single product. More than two dozen MPTs are currently in development, most of them combining contraception with HIV pre-exposure prophylaxis, with or without protection from other STIs. If successful, such MPTs could offer women benefits at multiple levels: greater motivation for effective use; lower product administration burden; accelerated integration of HIV, STI, and reproductive health services; and opportunities to circumvent stigma by using contraception as a "fig leaf" for HIV and/or STI prevention. However, even if women find respite from product burden, lack of motivation, and/or stigma in contraceptive-containing MPTs, their use of MPTs will be interrupted, often multiple times, over the reproductive lifecourse due to desire for pregnancy, pregnancy and breastfeeding, menopause, and changes in risk. Interruptions to the benefits of MPTs could be avoided by combining HIV/STI prevention with other life-stage-appropriate reproductive health products. New product concepts could include combining prenatal supplements with HIV and STI prevention, emergency contraception with HIV post-exposure prophylaxis, or hormone replacement therapies for menopause with HIV and STI prevention. Research is needed to optimize the MPT pipeline based on the populations underserved by available options and the capacity of resource-constrained health systems to deliver novel preventative healthcare products.