Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause.
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SUBMITTER: Prentice RL
PROVIDER: S-EPMC2733042 | 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:Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss.Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss.After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend?<?0.001). Compared with women who never used HT, the multivariable-adjusted relative risk of hearing loss among women who used oral HT for 5 to 9.9 years was 1.15 (95% CI 1.06, 1.24) and for 10+ years was 1.21 (95% CI 1.07, 1.37).Older age at menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.
| S-EPMC5570623 | 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:The principal findings are briefly reviewed from the Women's Health Initiative trials of the most commonly used postmenopausal hormone regimens in the United States-conjugated equine estrogens and these same estrogens plus medroxyprogesterone acetate. A more detailed review is presented for three major clinical outcomes: coronary heart disease (CHD), the primary trial outcome for which a major benefit was hypothesized; invasive breast cancer, the primary safety outcome for which some adverse effect was expected; and stroke which surfaced as an important adverse effect with both regimens, and one that is influential in decisions concerning the continued use of postmenopausal estrogens alone. The review for these outcomes includes an update on interactions of treatment effects with study subject characteristics and exposures and with prerandomization biomarker levels. It also includes a focus on timing issues that are important to the understanding of treatment effects. Specifically, with combined estrogen plus progestin, CHD risk was elevated early with the elevation dissipating after a few years of treatment, whereas breast cancer elevations increased during the treatment period, and climbed to about a threefold increase following 5 years of adherence. Importantly, breast cancer risk elevations appear to be higher among women who initiate treatment at the menopause, or soon thereafter, compared with women having a longer gap time. Stroke effects, on the contrary, did not seem to vary appreciably with these timing issues. The adverse effect was evidently localized to ischemic strokes, for which there was an approximate 50% increase with either regimen. The rather limited knowledge concerning the biomarkers and biological pathways that mediate the hormone therapy effects on these diseases is also briefly reviewed.
| S-EPMC4212810 | 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:PurposeTo investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation.Participants and methodsBetween 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference.ResultsAmong recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use (< or = 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated < or = 3 years after menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time.ConclusionOur results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.
| S-EPMC6413836 | biostudies-literature
Project description:Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT.Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n?=?34), transdermal 17?-estradiol (E2) (n?=?33), or placebo (n?=?35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A12), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT.SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P?=?0.014), lower frequency of night sweats (P?=?0.009), and less severe insomnia (P?=?0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P?=?0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/E2 (P?=?0.044).Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.
| S-EPMC4961269 | biostudies-literature
Project description:Estrogen-alone therapy (ET) or estrogen and progestin (EPT) as menopausal hormone therapy (HT) has been commonly used to alleviate menopausal symptoms. Treatments containing > or = 10 days per month of progestin are considered relatively safe with respect to endometrial cancer risk. However, the endometrial safety of long-term EPT regimens is uncertain. We conducted a case-control study of 311 invasive endometrial cancer cases and 570 controls nested within the California Teachers Study cohort. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (95% CI) for the association between long-term HT use and endometrial cancer risk, and to assess the modifying effect of body mass index (BMI). Long-term (> or = 10 years) use of ET, sequential EPT with <10 days per month progestin, and continuous-combined EPT (> or = 25 days/month progestin) were all associated with an elevated risk of endometrial cancer (OR, 4.5; 95% CI, 2.5-8.1; OR, 4.4; 95% CI, 1.7-11.2; and OR, 2.1; 95% CI, 1.3-3.3, respectively; all P(trend) < 0.001). The risk associated with short-term use was elevated only for ET preparations. The association for continuous-combined EPT was confined to thinner women (BMI, <25 kg/m2; P(interaction) = 0.03). Among heavier women (BMI, > or = 25 kg/m2), use of continuous-combined EPT was associated with a statistically nonsignificant reduction in risk. These findings confirm that long-term use of ET, sequential EPT, or, among normal weight women, continuous-combined EPT is associated with increased risk of endometrial cancer.
| S-EPMC2821215 | biostudies-literature
Project description:ImportanceMenopause is associated with biological aging, and hormone therapy (HT) is associated with health outcomes in postmenopausal women.ObjectiveTo evaluate the association between HT use and discrepancies between chronological and biological age in postmenopausal women as well as the potential modifying role of socioeconomic status (SES).Design, setting, and participantsThis population-based, retrospective cohort study included postmenopausal women registered in the UK Biobank. A baseline survey on HT use and biological aging biomarkers was conducted from March 2006 to October 2010. Data analyses were conducted in December 2023.ExposuresInformation regarding HT use, the age at starting HT, and HT duration was collected via a touchscreen questionnaire. SES was evaluated by education, family income, occupation, and the Townsend Deprivation Index.Main outcomes and measuresBiological aging discrepancy was evaluated using validated phenotypic age, which was calculated using chronological age and 9 biomarkers measured at baseline. All-cause and cause-specific mortality were also assessed.ResultsAmong the 117 763 postmenopausal women (mean [SD] age, 60.2 [5.4] years), 47 461 (40.3%) ever used HT. The mean phenotypic age was 52.1 (7.9) years. Ever use of HT was associated with a smaller biological aging discrepancy than never use of HT (β, -0.17 years; 95% CI, -0.23 to -0.10 years). This smaller aging discrepancy was more evident in those who started HT at age 55 years or older (β, -0.32 years; 95% CI, -0.48 to -0.15 years) and in those who used HT for 4 to 8 years (β, -0.25 years; 95% CI, -0.35 to -0.15 years). The association between HT and a smaller aging discrepancy was more evident in women with low SES, with a significant interaction observed for education (higher education: β, -0.08 years [95% CI, -0.17 to 0.01]; other education: β, -0.23 [95% CI, -0.32 to -0.14] years; P for interaction = .02). Phenotypic aging discrepancy mediated 12.7% (95% CI, 6.3% to 23.9%) of the association between HT and all-cause mortality and cause-specific mortality.Conclusions and relevanceIn this study, postmenopausal women with historical HT use were biologically younger than those not receiving HT, with a more evident association observed in those with low SES. The biological aging discrepancy mediated the association between HT and decreased mortality. Promoting HT in postmenopausal women could be important for healthy aging.
| S-EPMC11362863 | biostudies-literature
Project description:ObjectiveOur objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.EvidenceEach expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence.Consensus processA consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors.ConclusionsThe major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.
| S-EPMC6287288 | biostudies-literature