Effect Of Menopausal Hormone Therapy Research Articles

The influence of menopausal hormone therapy on somatic morbidity in postmenopausal women

Menopausal hormone therapy (MHT) which is initiated in women less than 60 years old or within 10 years after the onset of menopause for the relief of menopausal symptoms, treatment of urogenital syndrome or osteoporosis, is currently the only way to reduce the risk of developing cardiovascular diseases, thrombotic and metabolic disorders in healthy middle-aged women. This article presents the results of evaluating the use of hormone therapy in women during the menopausal transition to the state of somatic health in postmenopause by determining its effect on the state of the cardiovascular and bone systems, changes in the lipid profile, as well as on the risk of thrombosis in the postmenopause period.The objective: to determine the effect of MHT on somatic morbidity in postmenopausal women.Materials and methods. An analysis of the anamnesis, anthropometric indicators, results of general clinical and biochemical data of 120 women of menopausal age, who were divided depending on the use of menopausal hormone therapy into a study group (patients used MHT, n=60) and a control group (patients did not use MHT, n=60), is presented.All women were observed on the basis of the communal non-profit enterprise “Kyiv Perinatal Center” in the period from 2013 to 2023. Results. There was no significant difference in the indicators of the metabolic profile (levels of lipid fractions and glucose), as well as in anthropometric parameters (systolic and diastolic blood pressure, body mass index) between women of both groups (p>0.05). The risk of cardiovascular events (especially angina pectoris, hypertension) was higher in women of the control group who did not use hormonal drugs (related risk (RR) 0.5 with a 95% confidence interval (CI) from 0.28 to 0.91; p<0.007). However, it was found that there were significant differences between the groups in bone mineral density (the frequency of women with osteopenia was 43.3% in the control group versus 35% in the study group, and osteoporosis was diagnosed in 15% of women in the group without MHT versus 5% of women from the study group; RR is 0.69 with 95% CI≥0.5 at the confidence level p=0.05) and parameters affecting the risk of thrombotic complications (platelet level was 239.4±28.4×109/l in the control group versus 295.6±28.2×109/l in the study group, p<0.001; the level of fibrinogen was 7.7±1.2 mmol/l in women without MHT versus 8.7±2.0 mmol/l in women with MHT, p=0.001; prothrombin time was 13.2±1.3 sec in the control group versus 15.0±1.1 sec in the study group, p<0.001).Conclusions. Menopausal hormone therapy (MHT) is an effective method of preventing the development of osteopenic and osteoporotic conditions in women during the perimenopause period, but it also reliably significantly affects certain indicators of blood coagulation properties – the level of platelets, fibrinogen and prothrombin time – in the direction of their increase. It was established that the use of hormone replacement therapy the risks of developing adverse cardiovascular events (especially arterial hypertension and angina pectoris) are reduced, but, given the lack of difference between the compared groups of women in indicators of lipid metabolism, glucose, as well as in anthropometric data (which are the main risk factors for the development of cardiovascular diseases), further research is needed to establish the relationships of these parameters in more detail.During the appointment of MHT, one should be guided by the results of an individual risk/benefit assessment for the patient, paying special attention to the study of her anamnestic data.

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.

Relationship between menopausal hormone therapy and incidence of fractures in postmenopausal women

Objective Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. Method This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen–progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. Results EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50–59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. Conclusion In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT.

The effect of vitamin D on the early clinical manifestations of menopausal syndrome and the production of cytokines, involved in bone remodeling

Introduction. The problem of early manifestations of menopausal syndrome is due to the high prevalence among postmenopausal women, a wide range of clinical manifestations, a sharp decrease in the quality of life, not always sufficient effectiveness of menopausal hormone therapy (MHT) in the presence of restrictions on its use.The aim. To evaluate the dynamics of clinical manifestations of menopausal syndrome and to determine the pathogenetic effects of vitamin D preparation when used in combination with menopausal hormone therapy in women of early postmenopausal age with menopausal syndrome.Materials and methods. 154 women were examined, of which 81 were characterized by the presence of clinical manifestations of menopausal syndrome. All women with menopausal syndrome received menopausal hormone therapy with estradiol and didrogesterone drug for 6 months, while 39 women additionally also took the vitamin D drug. Before and after therapy in patients with menopausal syndrome, the prevalence of symptoms of the Green scale was assessed. Concentrations of 25(OH) D, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were determined in the blood serum of all women.Results and discussion. The use of MHT by women with menopausal syndrome leads to a decrease in the frequency of registration of a number of symptoms of the Green scale (p < 0.05). At the same time, a decrease in the frequency of registration of individual complaints is found only in the group of women who, along with MYT, received a vitamin D preparation (p < 0.05). Taking the vitamin D preparation is accompanied by an increase in its initially reduced serum concentrations to normal values (p < 0.001). The addition of cholecalciferol to the complex therapy of menopausal syndrome ensures the normalization of RANKL levels by reducing its production in the dynamics of treatment (p < 0.05) A decrease in the concentration of RANKL in response to the complex intake of a hormonal drug and cholecalciferol caused higher OPG/RANKL index values in the basic group by the end of therapy than in women of the comparison group (p < 0.01).Conclusions. The obtained effects of vitamin D preparation when prescribed in combination with menopausal hormone therapy (reduction of the frequency of symptoms of menopausal syndrome, reduction of initially elevated levels of RANKL) indicate the expediency of its use in the treatment of early manifestations of menopausal syndrome.

Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration

The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.

Menopausal hormone therapy and dementia: nationwide, nested case-control study

ObjectivesTo assess the association between use of menopausal hormone therapy and development of dementia according to type of hormone treatment, duration of use, and age at usage.DesignNationwide, nested case-control study.SettingDenmark...

Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease (25-30% of the global adult general population) with no approved treatment to-date, although its treatment is attractive for the researchers and the pharmaceutical industry. The cessation of ovarian function (natural or iatrogenic menopause, premature ovarian insufficiency) is associated with increased abdominal adipose tissue and changes in carbohydrate and lipid metabolism. These changes lead to a dysmetabolic milieu, characterized by unfavorable lipid profile and the development of NAFLD, which may contribute to the increase in cardiovascular risk observed after menopause. Not only the prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women, but also the rates of advanced types of the disease, i.e., nonalcoholic steatohepatitis and hepatic fibrosis, the latter regarded as the main histological prognostic factor of advanced liver disease and a difficult-to-reverse target. These observations may render menopausal hormone therapy (MHT) an appealing way to retard or even restore NAFLD after menopause. Although there are some experimental data favoring this consideration, there are only a few interventional clinical studies evaluating the effect of MHT on NAFLD, which have provided conflicting results. Some of them showed encouraging effects of MHT on liver function tests and/or lower rates of NAFLD in women receiving as compared with those not receiving MHT. However, other studies showed that MHT may adversely affect NAFLD. Regarding the route of administration of MHT, there are currently not comparative data between per os and transdermal use on NAFLD. Until waiting for the publication of relevant studies, based on the favorable effect of transdermal MHT on triglyceride concentrations and the fact that high triglyceride and low high-density lipoprotein-cholesterol concentrations are associated with the severity of NAFLD, the use of transdermal MHT may be preferred in women with NAFLD after the cessation of ovarian function. Of course, MHT could not be recommended as standard treatment of NAFLD in women, because MHT may be used for a certain time frame in a woman’s life. However, given that NAFLD seems to be common after the pause of ovarian function, any potential effect of MHT on NAFLD may be considered before treatment initiation and during the follow-up of these women.

Principles of cardiovascular risk management in perimenopausal women with type 2 diabetes

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus. It has been established that the period of menopause, associated with an increase in age and a change in the metabolic background, increases the risk of developing cardiovascular diseases in women with diabetes mellitus. Despite tentative expectations, a number of studies have shown conflicting evidence regarding the beneficial effects of menopausal hormone therapy on CV risk markers in diabetes mellitus. In this connection, therapy with hormonal preparations containing estrogen is currently not recommended for the prevention of cardiovascular diseases in the absence of specific indications. At the same time, estrogen therapy can be used in this group to minimize menopausal symptoms. At the same time, the risk of adverse events associated with the use of menopausal hormone therapy can be estimated using calculation methods for determining cardiovascular risk and breast cancer risk using specific calculators, especially in the group of women with type 2 diabetes.The main principles of cardiovascular risk management continue to focus on lifestyle modification and achieving target levels of cardiovascular risk parameters such as lipid levels, glycemia, and blood pressure. The use of pharmacological therapy to address these risk factors, especially some pleiotropic antihyperglycemic drugs, may provide additional options for the prevention of cardiovascular disease.

Effects of menopausal hormone therapy on the risk of ovarian cancer: Health Insurance Database in South Korea-based cohort study.

This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population-based study. This retrospective cohort study used national health checkup and insurance data from January 1, 2002, to December 31, 2019, provided by Korea's National Health Insurance Service. Women older than 40 years who recorded "menopause" in the questionnaire from 2002 to 2011 were included in this study. Menopausal hormone therapy (MHT) preparations were classified into tibolone, combined estrogen plus progestin by the manufacturer, combined estrogen plus progestin by physician, estrogen, and topical estrogen groups. The number of participants recorded as menopausal during the national health examination between 2002 and 2011 was 2,506,271. The MHT and non-MHT groups consisted of 373,271 and 1,382,653 patients, respectively. The hazard ratios (HR) of ovarian cancer according to MHT type, age at inclusion, body mass index, region, socioeconomic status, Charlson comorbidity index, age at menarche, age at menopause, parity, smoking, alcohol consumption, physical exercise, and period from menopause to inclusion were evaluated. The risk of ovarian cancer was reduced in the tibolone group (HR, 0.84; 95% confidence interval, 0.75-0.93; P = 0.003) and in patients in rural areas (HR, 0.90; 95% confidence interval, 0.845-0.98; P = 0.013). The risk of ovarian cancer was not related to the other MHT treatments. Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer.

Cognitive and psychoemotional changes in menopausal transition: The possibility of medical correction

The increasing of older age group in the population determines studying of age related diseases and emergence of new investigations in this area. In Female body, entering the menopausal transition is the start of «aging» of reproductive function and linked with decreasing of sex hormons levels. A direct connection between changes of estrogen, progesterone, androgen ratios and cognitive function of women was revealed. The anatomical localization of sex hormone receptors, the mechanisms of interaction of hormones with these receptors determine the ways of implementing biological effects of steroids on the CNS. Modern theories of «healthy nerve cells» and «eu-estrogenemia» explains the role of additional criteria, such as the absence of neurological diseases history and the duration of hypoestrogenia, to the outcome of menopausal hormone therapy. Additional factors that can affect to MHT action include: the composition of hormone therapy, administration methods, regimens (cyclic, continuous), duration of treatment, history of endocrine diseases, diabetes mellitus, gynecological history (parity, menarche age, COC use), heredity. The sections present the effect of menopausal transition on the development of depression, mood changes, sleep disturbances and mental disabilities. The explanation of negative effects of menopausal hormone therapy to cognitive health is also described by modern point of view. The ambivalent opinions of researchers, the potential of new reading of the results of earlier studies, confirms the necessity of continuing study of this topic.

730 - Effect of menopausal hormone therapy on COVID-19 severe outcomes in women

730 - Effect of menopausal hormone therapy on COVID-19 severe outcomes in women

Menopausal hormone therapy and the risk of cataracts in postmenopausal women in South Korea.

Postmenopausal women have a higher prevalence of cataracts than men of a similar age. This study aimed to evaluate the effects of menopausal hormone therapy (MHT) on lens opacities in postmenopausal women. This retrospective cohort study analysed population-based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N= 2,506,271) were grouped according to post-MHT use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician and topical oestrogen groups. The main outcome measure was the prevalence of cataracts. The control group comprised 463,151 postmenopausal women who had never used MHT after menopause, while the treatment group included 228,033 postmenopausal women who had used MHT continuously for at least 6months. The treatment group had a higher incidence of cataracts than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataracts, and reduced risk of cataracts was associated with living in rural areas and drinking alcohol. Women undergoing post-MHT, including tibolone, had a higher incidence of cataracts. Cataract development should be a concern when examining postmenopausal patients using MHT.

The effect of menopausal hormone therapy on the dermatological status of postmenopausal women or an interdisciplinary approach in anti-age protocols for the integrated management of postmenopausal women

The effect of menopausal hormone therapy on the dermatological status of postmenopausal women or an interdisciplinary approach in anti-age protocols for the integrated management of postmenopausal women

Skin Rejuvenation in Women using Menopausal Hormone Therapy: A Systematic Review and Meta-Analysis.

To evaluate the effect of menopausal hormone therapy (MHT) on skin aging in menopausal women. Studies were identified by searching PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov databases using the key words "hormone replacement therapy" AND "skin" AND "menopausal." Studies that used and compared oral/transdermal MHT with placebo or another type of treatment in menopausal women aged 45-55 years were selected. From 1,526 studies identified, 15 studies comprising 1,589 patients were included in the final analysis. Our meta-analysis aimed to compare skin elasticity (standard [Std] mean difference = 0.28; 95% confidence interval [CI], 0.03-0.54; P = 0.03), skin thickness (Std. mean difference = 1.27; 95% CI, 0.88-1.66; P < 0.00001), collagen content (Std. mean difference = 2.01; 95% CI, 1.42-2.61; P < 0.00001), and skin dryness (Std. mean difference = 0.15; 95% CI, -0.05 to 0.35; P = 0.14). MHT increases elasticity and collagen content in the skin, thereby reducing the severity of wrinkles and increasing skin thickness. Nevertheless, more well-conducted clinical trials are required to answer all questions in an evidence-based manner.

Clinical and genetic aspects of menopausal hormone therapy - a modern paradigm. What changed COVID-19 pandemic?

In the modern paradigm of public health protection, much attention is paid to the health of women in peri- and postmenopause, and a personalized approach prevails. It is generally recognized that the pathogenetic therapy of menopausal disorders is hormone therapy. But the COVID-19 pandemic has made its own adjustments to the routine strategy of choosing menopausal hormone therapy (MHT). The purpose of this review was to analyze studies on the dependence of the effectiveness of MHT on clinical and genetic aspects in the context of the ongoing COVID-19 pandemic. The review highlights the main risks of MHT for thromboembolic diseases and coagulation complications characteristic of COVID-19, discusses genetic predispositions that aggravate the course of the post-COVID period, as well as the effectiveness of estrogens in protecting the vascular endothelium and increasing the number of CD4+ T cells, providing an adequate immune response when infected with SARS-CoV-2. Numerous studies show that the complications characteristic of the severe course of COVID-19 are multifactorial in nature and cannot be unambiguously explained only by genetic predisposition. However, with the development of personalized medicine, special attention should be paid to the study of genetic aspects that can equally contribute to the occurrence of menopausal disorders in healthy women and aggravate the course of the post-pregnancy period. The data presented allow us to conclude that in the context of the ongoing COVID-19 pandemic at the population level, MHT can bring significant benefits to women during menopause due to the beneficial effect of estrogens on vascular walls. Additional study of the relationship between the course of the postcovid period in MHT users and polymorphisms of candidate genes that determine the risks of thrombotic complications and metabolic consequences is required.

Menopausal hormone therapy and the risk of cataract in postmenopausal women in South Korea

AbstractPurpose: Postmenopausal women have a higher prevalence of cataract than similar‐aged men. This study aimed to evaluate the effects of menopausal hormone therapy on lens opacity in postmenopausal women.Methods: This retrospective cohort study analysed population‐based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N = 2 506 271) were grouped according to postmenopausal hormone therapy use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician, and topical oestrogen groups. The main outcome measure was the prevalence of cataract.Results: The control group comprised 463 151 postmenopausal women who had never used menopausal hormone therapy after menopause, while the treatment group included 228 033 postmenopausal women who had used menopausal hormone therapy continuously for at least 6 months. The treatment group had a higher incidence of cataract than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataract, and reduced risk of cataract was associated with living in rural areas and drinking.Conclusions: Women undergoing postmenopausal hormone therapy, including tibolone, had a higher incidence of cataract than those who were not. Old age, low socioeconomic status, and high parity were risk factors for cataract. Our findings may help physicians identify postmenopausal women at a greater risk of developing cataract.

The link between menopause and its treatment with the risk of cardiovascular disease: literature review

Augustina Zaveriuchaitė1 1 Vilnius University, Faculty of Medicine, Vilnius, Lithuania Abstract Background. Cardiovascular disease is the leading cause of death for women and its incidence is increasing after menopause. For women, ischemic heart disease usually develops a few years later than for men. This finding led to the hypothesis that menopausal transition contributes to an increased risk of coronary heart disease. Aim. To review scientific literature about characteristics of menopause and and its hormonal treatment with the risk of cardiovascular disease. Materials and methods. The review of the literature was conducted using the PubMed. The literature research was conducted using predetermined keywords: menopause, perimenopause, cardiovascular disease. 934 articles were ruled out according to their title and abstract non-compliance to the subject. More than 50 articles in English published between 1989 and 2022 have been examined. Results. The menopause transition is the period of significant symptomatic, hormonal, menstrual, and other physiological changes associated with the risk of cardiovascular disease. Prevention of cardiovascular disease in women as well as in men should be started early. Data collected over the last thirty years have shown that hormone therapy for menopause has cardioprotective effects that depend on a woman’s health status and handling characteristics. Conclusions. Assessing menopausal transition characteristics and cardiometabolic changes in chronological aging it was proven, that these factors, which depend on the stages of reproductive aging, are associated with a risk of developing cardiovascular disease. Studies and observations have shown a cardioprotective effect of menopausal hormone therapy. Keywords: menopause, perimenopause, cardiovascular disease.

Effect of menopausal hormone therapy on COVID-19 severe outcomes in women – A population-based study of the US National COVID Cohort Collaborative (N3C) data

Whether menopausal hormone therapy (MHT) lessens the severity of COVID-19 among women is unclear. Leveraging a U.S. national COVID-19 cohort and a cross-sectional analysis, we found MHT use was marginally associated with a lower risk of mortality (odds ratio [OR] 0.73, 95 % CI 0.53–1.01) and significantly associated with a lower risk of prolonged hospital stay (0.7, 0.49–0.99) among inpatient women. When stratifying by MHT type, estrogen-only and estrogen-plus-progestin therapies had a more prominent protective effect than progestin-only therapy, although this difference did not achieve statistical significance. Women with COVID-19 can continue to use MHT. Clinical trials are needed to evaluate MHT's therapeutic effect on COVID-19, especially in terms of severity.

Menopausal hormone therapy does not improve some domains of memory: A systematic review and meta-analysis.

BackgroundAged women appear to be at a higher risk of developing memory impairment than men. Whether menopausal hormone therapy (MHT) could improve memory in postmenopausal women remains unclear. We thus conducted a meta-analysis to investigate the potential effect of MHT on memory, especially verbal memory, in postmenopausal women.MethodsPubMed, Cochrane, Embase, Chinese Biomedical Literature Database, and web of ClinicalTrials.gov were systematically searched for randomized controlled trials comparing MHT versus placebo in postmenopausal women. Our primary outcome of interest is memory function.ResultsWe included 10 studies with 2,818 participants in the final analysis. There was no significant differences in immediate recall (weighted mean difference [WMD] 0.34, 95% confidence interval [CI]: -0.73, 1.40), delayed recall (WMD 0.99, 95% CI: -0.51, 2.48), short-delay (WMD -0.00, 95% CI: -0.37, 0.37), and long-delay (WMD -0.19, 95% CI: -0.69, 0.31) recall between WMT and placebo. WMT was associated with a lower digit span forward (mean reduction -0.20, 95% CI: -0.36, -0.03). In women within 5 years of menopause, MHT did not differ in immediate (0.45, 95% CI: -0.75, 1.65) or delayed recall (1.03, 95% CI: -0.93, 3.00), and digit span forward (-0.11, 95% CI: -0.72, 0.50), when compared with placebo.ConclusionThis meta-analysis suggested that MHT had no effect on verbal memory in postmenopausal women, and may impair some domains of short-term memory. Current available evidence does not support MHT for improving memory in women less than 60 years, even in recently menopausal women.Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021233255.

Effect of menopausal hormone therapy on methylation levels in early and late postmenopausal women

BackgroundCardiovascular disease (CVD) remains the leading cause of death among postmenopausal women but standard primary prevention strategies in women are not as effective as in men. By comparison, the Early versus Late Intervention Trial with Estradiol (ELITE) study demonstrated that hormone therapy (HT) was associated with significant reduction in atherosclerosis progression in women who were within six years of menopause compared to those who were 10 or more years from menopause. These findings are consistent with other studies showing significant reductions in all-cause mortality and CVD with HT, particularly when initiated in women younger than 60 years of age or within 10 years since menopause. To explore the biological mechanisms underlying the age-related atheroprotective effects of HT, we investigated changes in methylation of blood cells of postmenopausal women who participated in ELITE.ResultsWe first validated the epigenetic data generated from blood leukocytes of ELITE participants by replicating previously known associations between smoking and methylation levels at previously identified CpG sites, such as cg05575921 at the AHRR locus. An epigenome-wide association study (EWAS) evaluating changes in methylation through interactions with time-since-menopause and HT revealed two significantly associated CpG sites on chromosomes 12 (cg19552895; p = 1.1 × 10–9) and 19 (cg18515510; p = 2.4 × 10–8). Specifically, HT resulted in modest, but significant, increases in methylation levels at both CpGs but only in women who were 10 or more years since menopause and randomized to HT. Changes in carotid artery intima-media thickness (CIMT) from baseline to 36 months after HT were not significantly correlated with changes in methylation levels at either cg19552895 or cg18515510. Evaluation of other previously identified CpG sites at which methylation levels in either blood or vascular tissue were associated with atherosclerosis also did not reveal any differences in methylation as a function of HT and time-since-menopause or with changes in CIMT.ConclusionsWe identified specific methylation differences in blood in response to HT among women who were 10 or more years since menopause. The functional consequence of these change with respect to atherosclerosis progression and protective effects of HT remains to be determined and will require additional studies.