Randomized Trial Evaluation of the Benefits and Risks of Menopausal Hormone Therapy Among Women 50-59 Years of Age.
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SUBMITTER: Prentice RL
PROVIDER: S-EPMC8086238 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The aim of this study was to assess risks and benefits of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal Chinese women.A retrospective cohort study was undertaken using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women aged 50 to 79 years were classified as exposed to CEE 0.625 mg/day with MPA 5.0 mg/day (estrogen [E] + progestin [P], n = 4,712) or CEE 0.625 mg/day only (E-only, n = 1,208) and were age-matched to unexposed women (n = 10,125). Follow-up was complete in 96% of the participants. The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. The global index summarized risks of primary outcomes, stroke, pulmonary embolism, colon and endometrial cancers, hip fractures, and death. Time-to-event analyses were performed.Median durations of exposure in the E + P and E-only groups were 6.9 and 9 months, respectively. Median follow-up was 110 months. Hazard ratios (95% CI) for E + P exposure were as follows: myocardial infarction, 0.78 (0.51-1.19); CHD death, 1.21 (0.53-2.70); breast cancer, 1.48 (1.20-1.83); global index, 0.79 (0.72-0.87). Hazard ratios for E-only exposure were as follows: myocardial infarction, 0.76 (0.35-1.68); CHD death, 0.57 (0.11-2.80); breast cancer, 1.44 (0.99-2.10); global index, 1.09 (0.92-1.28). Per 10,000 person-years, there were 12 excess breast cancer cases with E + P exposure; there were 39 fewer global index events with E + P exposure. Adjusting for age, statin and aspirin use, hypercholesterolemia, diabetes, and hypertension did not significantly change estimates.In postmenopausal Chinese women, CEE with or without MPA was not associated with increased rates of CHD, but CEE with MPA may be associated with a higher breast cancer rate. E + P exposure conferred lower global index event rates.
| S-EPMC3387327 | biostudies-literature
Project description:Background and objectivesWomen who breastfeed may experience long-term benefits for their health in addition to the more widely appreciated effects on the breastfed child. Breastfeeding may induce long-term effects on biopsychosocial systems implicated in brain health. Also, due to diminished breastfeeding in the postindustrial era, it is important to understand the lifespan implications of breastfeeding for surmising maternal phenotypes in our species' collective past. Here, we assess how women's breastfeeding history relates to postmenopausal cognitive performance.MethodologyA convenience sample of Southern California women age 50+ was recruited via two clinical trials, completed a comprehensive neuropsychological test battery and answered a questionnaire about reproductive life history. General linear models examined whether cognitive domain scores were associated with breastfeeding in depressed and non-depressed women, controlling for age, education and ethnicity.ResultsWomen who breastfed exhibited superior performance in the domains of Learning, Delayed Recall, Executive Functioning and Processing Speed compared to women who did not breastfeed (P-values 0.0003-0.015). These four domains remained significant in analyses limited to non-depressed and parous subsets of the cohort. Among those depressed, only Executive Functioning and Processing Speed were positively associated with breastfeeding.Conclusions and implicationsWe add to the growing list of lifespan health correlates of breastfeeding for women's health, such as the lower risk of type-2 diabetes, cardiovascular disease and breast cancer. We surmise that women's postmenopausal cognitive competence may have been greater in past environments in which breastfeeding was more prevalent, bolstering the possibility that postmenopausal longevity may have been adaptive across human evolutionary history.Lay summaryBreastfeeding may affect women's cognitive performance. Breastfeeding's biological effects and psychosocial effects, such as improved stress regulation, could exert long-term benefits for the mother's brain. We found that women who breastfed performed better on a series of cognitive tests in later life compared to women who did not breastfeed.
| S-EPMC8573189 | biostudies-literature
Project description:The Women's Health Initiative (WHI), a landmark randomized trial of menopausal hormone therapy (HT) for prevention of chronic disease in postmenopausal women aged 50-79, established that such therapy neither prevents coronary heart disease (CHD) nor yields a favorable balance of benefits and risks in such women as a whole. However, a nuanced look at the data from this trial, considered alongside other evidence, suggests that timing of HT initiation affects the relation between such therapy and coronary risk, as well as its overall benefit-risk balance. Estrogen may have a beneficial effect on the heart if started in early menopause, when a woman's arteries are likely to be relatively healthy, but a harmful effect if started in late menopause, when those arteries are more likely to show signs of atherosclerotic disease. However, even if HT-associated relative risks are constant across age or time since menopause onset, the low absolute risk of CHD in younger or recently menopausal women translates into low attributable risks in this group. Thus, HT initiation for relief of moderate to severe vasomotor symptoms in early menopausal patients who have a favorable coronary profile remains a viable option.
| S-EPMC4834454 | biostudies-literature
Project description:ObjectiveAlterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS).MethodsKEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17? estradiol (t-E2, 50?g/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences.ResultsDuring treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments.ConclusionsAlthough OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17?-estradiol. Clinical Trial Registration for KEEPS: NCT00154180.
| S-EPMC5588667 | biostudies-literature
Project description:BackgroundHerpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years.MethodsThis was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination.ResultsThe ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups.ConclusionsIn subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated.Clinical trials registrationNCT00534248.
| S-EPMC4542655 | biostudies-literature
Project description:ObjectiveLimited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF.MethodsThe Women's Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review.ResultsAt baseline, median age was 53 years (IQR 49-60), median menopausal age was 50 years (IQR 46-52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45-49: HR 0.90, 95% CI 0.74 to 1.08; 50-54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events.ConclusionsIn this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women.Clinical trial registrationNCT000000479; Post-results.
| S-EPMC5831356 | biostudies-literature
Project description:OBJECTIVE:Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. METHODS:KEEPS participants were randomized to oral conjugated equine estrogen (n?=?33, oCEE), transdermal 17?-estradiol (n?=?33, tE2), or placebo (n?=?34) for 48 months. Menopausal symptoms (hot flashes, night sweats, insomnia, palpitations) were self-reported before treatment and at 48 months. Estrone (E1), E2, and sulfated conjugates (E1S, E2S) were measured using high-performance liquid chromatography-tandem mass spectrometry. SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) was genotyped using a TaqMan assay. RESULTS:After adjusting for treatment, there was a significant association between the SLCO1B1 rs4149056 TT genotype (encoding normal function transporter) and lower E1S, E1S/E1, and E2S (P?=?0.032, 0.010, and 0.008, respectively) compared with women who were heterozygous (TC) or homozygous (CC) for the reduced function allele. The interactions between genotype, treatment, and E2S concentration were stronger in women assigned to tE2 (P?=?0.013) than the women taking oCEE (P?=?0.056). Among women assigned to active treatment, women with the CT genotype showed a significantly greater decrease in night sweats (P?=?0.041) than those with the TT genotype. CONCLUSIONS:Individual variation in sulfated estrogens is explained, in part, by genetic variation in SLCO1B1. Bioavailability of sulfated estrogens may contribute to relief of night sweats.
| S-EPMC6092108 | biostudies-literature
Project description:Until recently, observational studies suggested a decreased risk of cardiovascular disease, osteoporotic fractures, cognitive decline and colon cancer with the use of hormone replacement therapy (HRT). Recent randomized controlled trials have failed to show a protective effect of HRT in reducing the risk of coronary artery disease and instead have revealed an increased risk of heart disease, stroke, invasive breast cancer and venous thromboembolism, but a decreased risk of colorectal cancer and osteoporotic fractures. In this article we review the current evidence of the risks and benefits of HRT.
| S-EPMC152685 | biostudies-literature
Project description:IMPORTANCE:Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women. OBJECTIVE:To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function. DESIGN:Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999. SETTING:Forty academic research centers. PARTICIPANTS:The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years. INTERVENTION:The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years. MAIN OUTCOMES AND MEASURES:The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory. RESULTS:Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (?0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of ?0.17 (?0.33 to ?0.02) and ?0.25 (?0.42 to ?0.08), respectively; however, this may be a chance finding. CONCLUSIONS AND RELEVANCE:CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01124773.
| S-EPMC3844547 | biostudies-literature
Project description:Understanding factors contributing to variation in 'biological age' is essential to understanding variation in susceptibility to disease and functional decline. One factor that could accelerate biological aging in women is reproduction. Pregnancy is characterized by extensive, energetically-costly changes across numerous physiological systems. These 'costs of reproduction' may accumulate with each pregnancy, accelerating biological aging. Despite evidence for costs of reproduction using molecular and demographic measures, it is unknown whether parity is linked to commonly-used clinical measures of biological aging. We use data collected between 1999 and 2010 from the National Health and Nutrition Examination Survey (n = 4418) to test whether parity (number of live births) predicted four previously-validated composite measures of biological age and system integrity: Levine Method, homeostatic dysregulation, Klemera-Doubal method biological age, and allostatic load. Parity exhibited a U-shaped relationship with accelerated biological aging when controlling for chronological age, lifestyle, health-related, and demographic factors in post-menopausal, but not pre-menopausal, women, with biological age acceleration being lowest among post-menopausal women reporting between three and four live births. Our findings suggest a link between reproductive function and physiological dysregulation, and allude to possible compensatory mechanisms that buffer the effects of reproductive function on physiological dysregulation during a woman's reproductive lifespan. Future work should continue to investigate links between parity, menopausal status, and biological age using targeted physiological measures and longitudinal studies.
| S-EPMC7689483 | biostudies-literature