Menopausal Hormone Therapy Research Articles

The development and evaluation of a fact sheet resource for women managing menopausal-related cognitive complaints.

Cognitive symptoms are frequently reported by women during the menopause transition years. The aim of this research was to codesign and evaluate a fact sheet resource to help women understand and manage cognitive symptoms that may occur during menopause. This study adopted a codesign approach involving women during the menopause transition years as well as professionals to develop and evaluate a fact sheet, with a focus on acceptability and safety. Four phases (discover, define, develop, deliver) were conducted to develop, refine, and evaluate the fact sheet using a mixed-methods approach of focus groups, interviews, and surveys. The discover phase identified a need for online educational resources for women in premenopause, perimenopause, and postmenopause to learn about menopause-related topics. The define and develop phases, relying on focus group sessions with perimenopausal and postmenopausal women, revealed common themes related to the experience of cognitive symptoms and a desire for management tips to optimize cognitive functioning. Structured interviews with professionals highlighted a desire for more concrete examples of cognitive symptoms. The results of the deliver phase found strong acceptability for the fact sheet, alongside requests for additional information on menopausal hormone therapy from premenopausal, perimenopausal, and postmenopausal women. The study reported a wide range of cognitive symptoms among women during the menopause transition years. This study showed broad agreement on the fact sheet's acceptability and safety in addressing menopausal cognitive symptoms. Feedback on menopausal hormone therapy and management tips underscores the demand for more research on effective interventions.

Menopausal Hormone Therapy Use Among Postmenopausal Women

Menopausal hormone therapy (MHT) is the treatment of choice for symptoms of menopause. However, its adoption is hindered by the risk-benefit trade-off in relation to acute and chronic diseases. To evaluate trends in and correlates of MHT use among postmenopausal women in the US from 1999 to March 2020. This serial cross-sectional analysis of MHT use used data from the nationally representative National Health and Nutrition Examination Survey (NHANES). Participants included noninstitutionalized US postmenopausal women from 10 NHANES study cycles (1999-2000 to 2017-March 2020 [pre-COVID-19 pandemic]). Data were analyzed from December 2023 to April 2024. NHANES study cycle. Prevalence of MHT use was extracted from the prescription medication data collected during NHANES household interviews. MHT formulations were determined by hormone type. Data on 13 048 US postmenopausal women (47.1% ≥65 years old) were analyzed. From 1999 to 2020, the prevalence of MHT use decreased among women of all age groups, from 26.9% (95% CI, 22.6%-31.7%) in 1999 to 4.7% (95% CI, 3.4%-6.5%) in 2020. Until 2002, MHT use was highest among women aged 52 to 65 years, but since 2005, MHT use has been highest among women younger than 52 years. MHT use decreased by 23.5% (95% CI, 11.4%-35.6%), 31.4% (95% CI, 23.4%-39.5%), and 10.6% (95% CI, 6.3%-14.8%) for women younger than 52 years, 52 years to younger than 65 years, and 65 years and older, respectively. Prevalence of MHT use decreased from 13.8% (95% CI, 8.5%-21.7%) to 2.6% (95% CI, 1.5%-4.6%) for Hispanic women, 11.9% (95% CI, 8.5%-16.3%) to 0.5% (95% CI, 0.2%-1.1%) for non-Hispanic Black women, and 31.4% (95% CI, 27.1%-36.1%) to 5.8% (95% CI, 4.1%-8.2%) for non-Hispanic White women. Non-Hispanic White women consistently had the highest prevalence of MHT use. Estrogen-only formulation accounted for more than 50% of the MHT for most study periods. The prevalence of MHT use varied by family income-to-poverty ratio, health insurance coverage in all racial and ethnic groups, weight, and smoking status among non-Hispanic White women, as well as by education attainment among non-Hispanic Black and Hispanic women. Results of this cross-sectional study show that over the past 2 decades, MHT use declined among US postmenopausal women of all age and racial and ethnic groups. Women of racial and ethnic minority groups had lower prevalence of MHT use compared to non-Hispanic White women.

Knowledge and Awareness Toward Menopausal Hormone Therapy in a Fourth-Tier City of China.

BACKGROUND Menopausal hormone therapy (MHT) has been receiving increasing attention in developed countries. The purpose of this study was to investigate understanding of menopause and acceptance of MHT in Qinhuangdao, China. MATERIAL AND METHODS We analyzed data from 186 perimenopausal patients on topics including menopausal symptoms and acceptance of and adherence to MHT treatment. We also surveyed 100 medical staff on menopausal-related knowledge. RESULTS Group A consisted of 41 patients treated with MHT for more than 1 cycle, group B consisted of 49 patients who had received MHT but had stopped it for more than 3 months, and group C consisted of 96 patients who never received MHT. There was a significant difference among them in modified Kupermann scores before treatment (P<0.05), but the difference disappeared after MHT (P>0.05). In group C, 32 patients (33%) were unaware of MHT, 60 (62.5%) were worried about the risk of breast/endometrial cancer, 24 (25%) were worried about high costs, and 67 (70%) had no obvious symptoms and did not want MHT. Similarly, in group B, most people stopped MHT for fear of breast or endometrial cancer. A survey targeting 100 medical staff in our hospital found 14 people (14%) knew about and were willing to accept MHT, 44 people (44%) knew about MHT but were afraid to use it, and 42 people (42%) did not know about MHT at all. CONCLUSIONS MHT has not yet been accepted by the majority of people, even medical staff, in Qinhuangdao, China, and much further progress is needed.

Recent Trends in Menopausal Hormone Therapy Use in the US

Recent Trends in Menopausal Hormone Therapy Use in the US

Significance of correcting magnesium deficiency in different groups of women in surgical menopause

Background. In the 21st century, there is a clear trend towards an increase in the proportion of women with climacteric syndrome (CS) and surgical menopause. Medical care for such patients usually includes menopausal hormone therapy (MHT), which often causes changes in magnesium and pyridoxine metabolism and their deficiency, leading to the development of adverse reactions. Therefore, it is necessary to improve rehabilitation programs designed to increаse the quality of life (QoL) for this category of gynecological patients.Objective: to assess the profile of women with CS and surgical menopause receiving and not receiving MHT and to identify the significance of magnesium deficiency (MD) effect on the recovery process.Material and methods. The observational non-interventional study included a total of 9168 women, of which 1528 patiеnts with CS and surgical menopause were taking MHT (Group 1), and 1528 patients with CS and surgical menopause were not taking MHT (Group 2). The Magnesium Deficiency Questionnaire (MDQ) was used to determine the number of participants with MD. A biochemical blood test was also performed, including determination of plasma magnesium concentration. The patients’ profile was analyzed for general somatic pathologies, obstetric and gynecological history, complaints, and MD symptoms using visual analogue scale. To assess QoL before the start of 4-week MD replenishing course and at the end of therapy, the World Health Organization Quality of Life Questionnaire (WHOQL-26) was applied.Results. The MDQ data showed that the prevalence of DM in Group 1 was higher compared to Group 2. In both groups, women with hypomagnesemia had a higher incidence of viral infections, vegetative-vascular dystonia, osteochondrosis and arterial hypertension, more pronounced sleep disorders, irritability, back pain, rapid fatigue, and higher MDQ scores. After completion of the course of therapy with magnesium citrate and pyridoxine combination, the MDQ scores in patients with DM decreased along with an increase in plasma magnesium concentration. Besides, women's satisfaction with their physical, psychological, social wellbeing and microsocial support increased, and self-perception improved. A decrease in the severity of DM and a significant improvement in QoL according to WHOQOL-26 were demonstrated in patients with CS and surgical menopause after therapy.Conclusion. The profile of patients with CS and surgical menopause, regardless of MHT, is often characterized by DM and decreased QoL. It seems reasonable to include blood magnesium level monitoring and DM correction in the comprehensive rehabilitation program for such patients.

Vaginal microbiota, menopause, and the use of menopausal hormone therapy: a cross-sectional, pilot study in Chinese women.

To compare the vaginal microbiota of premenopausal and postmenopausal women and postmenopausal women undergoing menopausal hormone therapy (MHT) and examine the association between vaginal microbiota and genitourinary syndrome of menopause (GSM). This cross-sectional study classified 94 women aged 40 to 60 years into three groups: premenopausal (Pre, n = 32), postmenopausal (Post, n = 30), and postmenopausal women who received MHT orally (Post + MHT, n = 32). Neither the Pre nor the Post group received hormone therapy within the past 6 months. Postmenopausal women who received vaginal MHT were not included. Vaginal swabs were obtained, and microbial composition was characterized by 16S rRNA gene sequencing targeting the V3 to V4 region. Clinical data were collected and serum sex hormones were measured. The most bothersome symptom approach and vaginal health index were used to evaluate GSM. Mann-Whitney U or Kruskal-Wallis ANOVA followed by multiple comparison tests were performed for comparison between or across groups. The correlations between GSM symptom scores and vaginal microbiota were determined using Spearman's correlation analysis. The vaginal community of postmenopausal women was characterized by a decreased abundance of Lactobacillus (Post 18% vs Pre 69%); an increased abundance of several anaerobic bacteria, including Prevotella, Escherichia-Shigella, and Bifidobacterium; and a higher microbial diversity (P < 0.001 for Shannon and Simpson indexes) than those of premenopausal women. The vaginal community of postmenopausal women who received MHT had an increased abundance of Lactobacillus (54%) and lower microbial diversity (P < 0.001 for Shannon and Simpson indexes) than the postmenopausal women. The vaginal microbial community composition of the Pre group shared more similarity with that of the Post + MHT group (Adonis P = 0.051) than with that of the Post group (Adonis P < 0.001). A decreased abundance of Lactobacillus and high diversity in the vaginal community were found in women with moderate to severe GSM symptoms. Among Chinese postmenopausal women, those receiving MHT had higher Lactobacillus abundance but lower abundance of diverse anaerobes and diversity of the vaginal microbial community compared to non-MHT women. MHT in postmenopausal women may potentially contribute to reestablishing vaginal microbiota homeostasis. Findings in this pilot study, however, need to be examined in larger, prospective studies.

Exploring menopausal symptoms, attitudes, and behaviors among menopausal women in China: an online research perspective.

The number of perimenopausal women in China is rising, but the population's concept of menopausal hormone therapy (MHT) is still relatively outdated. In this study, we used the Knowledge-Attitude-Practice (KAP) theory and collected online questionnaires from 1,100 women aged 40 to 60 years nationwide to find out their menopausal symptom profiles; to learn about their perceptions, attitudes, and behaviors toward menopause and MHT; to explore the factors influencing the acceptance of hormone treatments; and to look for better ways to promote the dissemination of menopausal knowledge. The results revealed that among women aged 40 to 60 years, 82.36% experienced possible menopausal symptoms, with hot flushes/sweating, sleep disorders, mood disorders, and fatigue being the most prevalent; 55.90% reported moderate to severe symptoms, but only 46.99% of them sought healthcare services. Among those who sought medical care, 16.00% had their first visit to climacteric clinics/gynecological endocrinology, and 5.66% accepted MHT. Furthermore, 77.82% of participants never heard of MHT or were unaware of its existence. The healthcare-seeking behavior of menopausal women in response to symptoms and their willingness to accept MHT were found to be closely associated with their level of self-care. The prevalence of menopausal symptoms is higher in China than previous research findings, but due to a lack of relevant knowledge, the rate of seeking treatment from the appropriate medical department and accepting MHT is relatively low. Enhancing physicians' knowledge of the menopausal transition and using Internet tools might help improve Chinese women's knowledge of menopause and help them pass through this period smoothly.

Use of menopausal hormone therapy before and after diagnosis and ovarian cancer survival-A prospective cohort study in Australia.

Menopausal hormone therapy (MHT) use before ovarian cancer diagnosis has been associated with improved survival but whether the association varies by type and duration of use is inconclusive; data on MHT use after treatment, particularly the effect on health-related quality of life (HRQOL), are scarce. We investigated survival in women with ovarian cancer according to MHT use before and after diagnosis, and post-treatment MHT use and its association with HRQOL in a prospective nationwide cohort in Australia. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) and propensity scores to reduce confounding by indication. Among 690 women who were peri-/postmenopausal at diagnosis, pre-diagnosis MHT use was associated with a significant 26% improvement in ovarian cancer-specific survival; with a slightly stronger association for high-grade serous carcinoma (HGSC, HR = 0.69, 95%CI 0.54-0.87). The associations did not differ by recency or duration of use. Among women with HGSC who were pre-/perimenopausal or aged ≤55 years at diagnosis (n = 259), MHT use after treatment was not associated with a difference in survival (HR = 1.04, 95%CI 0.48-2.22). Compared to non-users, women who started MHT after treatment reported poorer overall HRQOL before starting MHT and this difference was still seen 1-3 months after starting MHT. In conclusion, pre-diagnosis MHT use was associated with improved survival, particularly in HGSC. Among women ≤55 years, use of MHT following treatment was not associated with poorer survival for HGSC. Further large-scale studies are needed to understand menopause-specific HRQOL issues in ovarian cancer.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Abstract P447: Impact of Altered Receptor Expression On the Cardiovascular Response to Estrogen

Premenopausal women benefit from estrogen's protective effects, including lower arterial stiffness than men of the same age. Despite estrogen's protective role, menopausal hormone therapy showed no cardiovascular benefits in the Women's Health Initiative. One theory is that the response to menopausal hormone therapy is modulated by the presence of pre-existing cardiovascular disease. Estrogen signals through nuclear estrogen receptors ERα and ERβ, and the membrane-bound G protein-coupled estrogen receptor (GPER). Our lab has shown that GPER induces protective cardiovascular effects including decreased blood pressure, protection from renal damage, and attenuation of arterial remodeling. In this study, we hypothesized that GPER deletion would attenuate the protective vascular effects of estrogen after menopause. Female C57Bl/6J wildtype (wt) and global GPER knockout (ko) mice underwent ovariectomy (OVX) at 46 weeks of age and concurrently administered estrogen (E) or vehicle (Veh). Angiotensin II (Ang II; 700 ng/kg/day) infusion was used to induce hypertension either four weeks prior (Ang-E) or at the time of OVX (E-Ang) to evaluate the impact of cardiovascular diseases preceding or coinciding with menopause. Blood pressure was measured by tail-cuff plethysmography and arterial stiffness was assessed by pulse wave velocity (PWV). Statistical analysis was performed using one-way ANOVA. Ang II induced a similar level of hypertension in wt and ko mice and was not impacted by E or timing. In wt mice, PWV was significantly higher in Veh-treated compared with E-treated hypertensive animals, independent of timing (P&lt;0.001). In contrast, PWV was not impacted by E in GPER ko mice (P=0.99). In conclusion, we found that E did not affect the hypertensive response to Ang II in both wt and GPER ko mice. GPER deletion reduced estrogen’s protection from arterial stiffening. Whether Ang II preceded or coincided with menopause did not alter the effects of E. These studies are important for determining whether cardiovascular status should be a factor when considering menopausal hormone therapy.

Is menopausal hormone therapy still a modern social issue? Women's experience in a northern Italian city.

Is menopausal hormone therapy still a modern social issue? Women's experience in a northern Italian city.

The effect of Norethisterone acetate on the uterus of albino rats: histological, histochemical and ultrastructure study

BackgroundNorethisterone acetate (NETA), also known as norethindrone acetate is a progestogens medication that is widely used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders as abnormal uterine bleeding and endometriosis. There is a lack of detailed histological information regarding the effects of NETA on the uterine structure. So, the present study focuses on the uterine histological, histochemical and ultrastructure changes following the exposure to NETA in the albino rats. To do this aim, fourteen adult female albino rats were used. They were randomly divided into two equally groups: Control group and NETA treated group. Albino rats of control group were administered daily food, water and orally distilled water only, while rats of NETA treated group were administered daily orally 20 µg of NETA dissolved in 2 ml distilled water, food, and water. The experiment was continued for three weeks.ResultsThe findings of the present work indicated that the use of NETA has negative effects on the endometrial epithelium (proliferation, autophagy and apoptosis), glands (necrotic, apoptotic or pseudosecretory glands) and stromal and myometrial reactions (granulocytes, connective tissue remodeling, apoptosis, myocytes hypertrophy).ConclusionThis work revealed that NETA has desynchronized progestogenic effect on the uterine tissues of the albino rat and thereby prevent implantation and pregnancy.

Association between type of menopause and mild cognitive impairment: The REDLINC XII study

ObjectiveTo evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). Study designThis study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. MethodWe assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. ResultsThe study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01–2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21–0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14–0.30). ConclusionWhen comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Benefits and Risks of Menopausal Hormone Therapy

Menopausal Hormone Therapy (MHT) (estrogen/progestogen) is used to treat menopausal complaints and to prevent osteoporosis. Additional preventive benefits are reduction of cardiovascular disease, reduction of colon cancer, and perhaps also Alzheimer’s disease, if started within a “window of opportunity”, i.e. in perimenopause or within 6-10 years after menopause. Primary indication for progestogen addition is to avoid the development of estrogen-dependent endometrial cancer, i.e. addition not recommended in hysterectomized women. Two main schedules, sequential- or continuous-combined estrogen/progestogen regimens, are used. For optimizing menstrual regulation detailed recommendations are given

Effect of Menopausal Hormone Therapy on Cellular Immunity Parameters and Cytokine Profile.

A woman's entry into the menopause period is associated with a number of changes in the body, including those related to the immune system. Immune aging is a consequence of age-related changes in the function of immune cells and the composition of their subpopulations. Menopausal hormone therapy (MHT) is thought to partially neutralize the negative effects of aging on the immune system. We aimed to evaluate the effect of oral and transdermal MHT on cellular immunity parameters and cytokine profile in menopausal women. Fifty peri- and early postmenopausal women were included. Immune parameters were assessed by flow cytometry and multiplex analysis. We showed that different routes of MHT administration led to significant changes in monocyte phenotype and a decrease in monocyte chemoattractant protein-1 (MCP-1) level in menopausal patients. In addition, oral MHT resulted in a significant increase in NK and B cells. A significant increase in the number of T-helper cells was observed with transdermal MHT. In addition, oral MHT resulted in a significant decrease in IL-1β level. We have demonstrated for the first time that oral therapy, in contrast to transdermal therapy, has a more pronounced effect on specific immune subpopulations of blood cells in menopausal women. This effect is likely to be responsible for its anti-aging properties in the context of immune aging as well as its protective effects in infectious diseases. Perhaps testing blood immune parameters or assessing immune status before prescribing MHT could become a routine step in clinical practice before choosing a patient management strategy.

Severe menopausal symptoms linked to cognitive impairment: an exploratory study.

To evaluate the association between menopausal symptoms and cognitive decline in postmenopausal women. This was a subanalysis of a cross-sectional, observational study conducted among women attending gynecological consultations across nine Latin American countries. The survey involved late postmenopausal women who were asked to complete a general questionnaire and the Menopause Rating Scale (MRS) to assess menopausal symptoms, with the Montreal Cognitive Assessment used to evaluate cognitive function as an outcome. A Montreal Cognitive Assessment score of less than 21 was used to define women with mild cognitive impairment (MCI). The study included 1,287 postmenopausal women with a mean age of 55.5 years and a mean body mass index of 26.3 kg/m2. On average, participants had 13.8 years of education and 2.3 ± 1.8 children, with 72.8% reporting having a partner. Additionally, 36.7% ever used menopausal hormone therapy. Regarding lifestyle factors, 50.3% engaged in a sedentary lifestyle, whereas 70.5% had never smoked. 15.3% of women had MCI exhibited significantly more intense menopausal symptoms compared with those without MCI (MRS total score 15.24 ± 12.58 vs 10.53 ± 8.84, respectively, P < 0.001). Logistic regression analysis revealed a significant association between severe menopausal symptoms (MRS total score ≥14 points) and MCI (odds ratio [OR], 1.74; 95% CI, 1.25-2.42). Conversely, a lower body mass index (OR, 0.96; 95% CI, 0.95-0.98), sexual activity (OR, 0.70; 95% CI, 0.51-0.96), physical exercise (OR, 0.55; 95% CI, 0.39-0.76), menopausal hormone therapy use (OR, 0.36; 95% CI, 0.24-0.55), and higher educational level (OR, 0.31; 95% CI, 0.21-0.46) were associated with lower odds for MCI. Severe menopausal symptoms in postmenopausal women were associated with cognitive impairment. This study highlights the intricate interplay between hormonal, lifestyle, and sociodemographic factors and cognitive health.

New potential selective estrogen receptor modulators in traditional Chinese medicine for treating menopausal syndrome.

Women go through several predictable conditions and symptoms during menopause that are caused by age, changes in sex hormone levels, and other factors. Conventional menopause hormone therapy has raised serious concerns about the increased risks of cancers, blood clots, depression, etc. Selective estrogen receptor modulators (SERMs) that can be both agonists and antagonists of estrogen receptors in a tissue-specific manner are being developed to reduce the health concerns associated with menopause hormone therapy. Here, we have searched the Chinese national traditional Chinese medicine (TCM) patent database to identify potential SERM-like compounds with reduced health risks. TCM has been widely used for treating complex symptoms associated with menopause syndrome and thus can be a particularly rich source for pharmaceutical alternatives with SERM properties. After extensive literature review and molecular simulation, we conclude that protopanaxatriol, paeoniflorin, astragalin, catalpol, and hyperoside among others may be particularly promising as SERM-like compounds in treating the menopausal syndrome. Compounds in TCM hold promise in yielding comparable outcomes to hormone therapy but with reduced associated risks, thus presenting promising avenues for their clinical applications.

Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential.

Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through invitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.

Prevalence of and risk factors for endometrial polyps among asymptomatic postmenopausal women with uterovaginal prolapse

The prevalence of endometrial polyps among asymptomatic, postmenopausal women is not well defined. There is no clear clinical consensus on how to manage endometrial polyps in this population and whether these polyps truly are cause for clinical concern. To estimate the prevalence of endometrial polyps among asymptomatic (without bleeding), postmenopausal women, and evaluate risk factors associated with their presence. This cross-sectional study assessed the prevalence of endometrial polyps among asymptomatic, postmenopausal women undergoing hysterectomy for uterovaginal prolapse. Patients were excluded if undergoing hysterectomy for other indications including postmenopausal bleeding. Chart review included eligible patients who received care at a single-site in Washington state from 2009 to 2018. The primary outcome was presence of endometrial polyps on pathology. Risk factors associated with polyp prevalence were subsequently assessed using univariate analysis and multivariate regression. Of the 317 eligible women identified, endometrial polyps were identified in 106 women (33.4%). The average polyp size and endometrial thickness was 13 +/- 10mm and 1.4 +/- 1.5mm. Most cases, 78%, had solitary polyps. Premalignant and malignant lesions were found in 2 cases (1.89%); one had endometrial carcinoma and one had endometrial intraepithelial neoplasia. Baseline clinical and demographic characteristics were similar between patients with and without endometrial polyps, including the presence of fibroids, endometriosis and adenomyosis. Multivariate logistic regression showed that presence of polyps was independently associated with high body mass index (OR 1.06, 95%-CI 1.01-1.12, p-value 0.02) and use of menopausal hormone therapy (OR 1.67, 95%-CI 1.02 - 2.72, p-value 0.04). Asymptomatic postmenopausal women undergoing hysterectomy for uterovaginal prolapse exhibit a high prevalence of endometrial polyps. Those with use of menopausal hormone therapy and high body mass index are at a higher risk of developing endometrial polyps. While the malignant risk seems to be low, more investigation is warranted to truly quantify the lifetime risk. For now, expectant management may be a reasonable approach for incidentally found, asymptomatic polyps.

Deciphering the role of classical oestrogen receptor in insulin resistance and type 2 diabetes mellitus: From molecular mechanism to clinical evidence

The biological actions of oestrogen are mediated by the oestrogen receptor α or β (ERα or ERβ), which are members of a broad nuclear receptor superfamily. Numerous in vivo and in vitro studies have demonstrated that loss of circulating oestrogen modulated by classical ERα and ERβ led to rapid changes in pancreatic β-cell and islet function, GLUT4 expression, insulin sensitivity and glucose tolerance, dysfunctional lipid homeostasis, oxidative stress, and inflammatory cascades. Remarkably, 17β-oestradiol (E2) can completely reverse these effects. This review evaluates the current understanding of the protective role of classical ER in critical pathways and molecular mechanisms associated with insulin resistance and type 2 diabetes mellitus (T2DM). It also examines the effectiveness of menopausal hormone therapy (MHT) in reducing the risk of developing T2DM in menopausal women. Clinical trials have shown the protective effects of MHT on glucose metabolism, which may be useful to treat T2DM in perimenopausal women. However, there are concerns about E2's potential side effects of obesity and hyperlipidaemia in menopausal women. Further studies are warranted to gain understanding and find other oestrogen alternatives for treatment of insulin resistance and T2DM in postmenopausal women.