Effect Of Hormone Therapy Use Research Articles

Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have a different role?

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow-up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways.

Menopausal Hormone Therapy Is Associated with Having High Blood Pressure in Postmenopausal Women: Observational Cohort Study

BackgroundThe relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure.Methods and FindingsA total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (<56 years, 56–61 years, 62–70 years and over 71 years) and adjusted for demographic and lifestyle factors. MHT use was associated with higher odds of having high blood pressure: past menopausal hormone therapy use: <56 years (adjusted odds ratio 1.59, 99% confidence interval 1.15 to 2.20); 56–61 years (1.58, 1.31 to 1.90); 62–70 years (1.26, 1.10 to 1.44). Increased duration of hormone use was associated with higher odds of having high blood pressure, with the effect of hormone therapy use diminishing with increasing age.ConclusionsMenopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use.

Timing of hormone therapy, type of menopause, and coronary disease in women: data from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation.

The aim of this study was to assess the relationship of the timing of hormone therapy (HT) use with angiographic coronary artery disease (CAD) and cardiovascular disease (CVD) events in women with natural versus surgical menopause. We studied 654 postmenopausal women undergoing coronary angiography for the evaluation of suspected ischemia. Timing and type of menopause, HT use, and quantitative angiographic evaluations were obtained at baseline, and the women were followed for a median of 6 years for CVD events. Ever users of HT had a significantly lower prevalence of obstructive CAD compared with never users (age-adjusted odds ratio, 0.41 [0.28-0.60]). Women with natural menopause initiating HT before age 55 years had lower CAD severity compared with never users (age-adjusted β [SE] = -6.23 [1.50], P < 0.0001), whereas those initiating HT at age 55 years or more did not differ statistically from never users (-3.34 [2.13], P = 0.12). HT use remained a significant predictor of obstructive CAD when adjusted for a "healthy user" model (odds ratio, 0.44 [0.30-0.73]; P = 0.002). An association between HT and fewer CVD events was observed only in the natural menopause group (hazard ratio [95% CI], 0.60 [0.41-0.88]; P = 0.009) but became nonsignificant when adjusted for the presence or severity of obstructive CAD. Using the quantitative measurements of the timing and type of menopause and HT use, earlier initiation of HT was associated with less angiographic CAD in women with natural but not surgical menopause. Our data suggest that the effect of HT use on reduced cardiovascular event rates is mediated by the presence or absence of angiographic obstructive atherosclerosis.

Age-specific effects of hormone therapy use on overall mortality and ischemic heart disease mortality among women in the California Teachers Study

Although the Women's Health Initiative trial suggested that menopausal hormone therapy (HT) does not reduce coronary heart disease mortality overall, subsequent results have suggested that there may be a benefit in younger women. The California Teachers Study questionnaire and mortality data were used to examine whether age modified the association between HT and the relative risk of overall mortality and ischemic heart disease deaths. Participants from the California Teachers Study were 71,237 postmenopausal women (mean age, 63 y; range, 36-94 y) followed prospectively for mortality and other outcomes from 1995-1996 through 2004. Age at baseline was a much more important modifier of HT effects than was age at start of therapy. Risks for all-cause mortality (n = 8,399) were lower for younger current HT users at baseline than for never users (for women ≤ 0 y: hazard ratio, 0.54; 95% CI, 0.46-0.62). These risk reductions greatly diminished, in a roughly linear fashion, with increasing baseline age (for women 85-94 y: hazard ratio, 0.94; 95% CI, 0.81-1.10 for all-cause mortality). Similar results were seen for ischemic heart disease deaths (n = 1,464). No additional significant modifying effects of age at first use, duration of use, or formulation were apparent. These results provide evidence that reduced risks of mortality associated with HT use are observed among younger users but not for older postmenopausal women, even those starting therapy close to their time of menopause.

Timing of hormone therapy and dementia: The critical window theory revisited

Although previous research has shown that initiation of postmenopausal estrogen hormone therapy (HT) in late life increases risk of dementia, animal studies and some observational studies have suggested that midlife use of HT may be beneficial; however, this has not been rigorously investigated in large population-based studies. Our objective was to compare HT use in midlife with that in late life on risk of dementia among 5,504 postmenopausal female members of an integrated healthcare delivery system. HT use was determined at midlife (mean age, 48.7 years) from a survey in 1964 and in late life (mean age, 76 years) using pharmacy databases from 1994 to 1998. Risk of dementia diagnosis was evaluated with inpatient and outpatient diagnoses made in Neurology, Neuropsychology, and Internal Medicine from 1999 to 2008. Cox proportional hazard models were used to examine effects of HT use at different times on dementia risk with adjustment for age, education, race, body mass index, number of children, and comorbidities. A total of 1,524 women (27%) were diagnosed with dementia during the follow-up period. Compared to women never on HT, those taking HT only at midlife had a 26% decreased risk (multivariate adjusted hazards ratio [aHR], 0.74; 95% confidence interval [CI], 0.58-0.94 ), whereas those taking HT only in late life had a 48% increased risk (aHR, 1.48; 95% CI, 1.10-1.98), and women taking HT at both mid and late life had a similar risk of dementia (aHR, 1.02; 95% CI, 0.78-1.34 ). These findings suggest that use of HT in midlife only may protect against cognitive impairment, whereas HT initiation in late life could have deleterious effects.

The rise and fall in menopausal hormone therapy and breast cancer incidence

Studies conducted in different areas of North America and Europe showed a 5–10% decline in the incidence of breast cancer following reductions up to 70% in menopause hormone therapy (HT) use after 2002. The observation that the decline was larger in (or limited to) women aged ≥50 years weighs in favour of an effect of reduced HT use on breast cancer incidence. However, changes in screening are also likely to play a role in the decreasing incidence of breast cancer observed in several countries. In particular, the technical improvements and the increased effectiveness of breast cancer screening and detection during the 1990s led to a decreased number of pre-clinical cases found by screening in subsequent years. Further, disentangling the effects of HT use and screening is difficult, as women who stop using HT may also undergo mammography screening less frequently. Thus, the reasons of the falls in incidence remain open to discussion.

Hormone Therapy and Risk of Lung Cancer: A Meta-Analysis

The association between hormone therapy (HT) use and lung cancer risk is inconsistent in epidemiological studies. This meta-analysis was conducted to examine the association between HT and lung cancer risk. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in April 2008. All articles searched were independently reviewed and selected by two evaluators according to predetermined inclusion and exclusion criteria. We included a total of 11 studies (8 case-control studies and 3 prospective cohort studies), involving a total of 220,599 participants. When all studies were pooled, the odds ratio (OR) of HT use for lung cancer risk was 0.87 (95% confidence interval (CI) 0.74-1.02). In subgroup meta-analyses, there was no association among cohort studies (relative risk (RR) 1.01; 95% CI 0.74-1.38), while there was a significant association between HT use and lung cancer risk among case-control studies (OR 0.81; 95% CI 0.68-0.97) based on a random-effects model. No significant association between HT use and lung cancer risk was observed in most of the subgroup meta-analyses by methodological quality of study, type of HT use, duration of HT use, and histology of lung cancer, while significant protective effects were observed among former and never smokers except for current smokers. However, cumulative meta-analyses based on year of publication showed a distinct trend toward a protective effect of HT use on lung cancer risk in the recent studies. Overall, the findings of this meta-analysis do not support the hypothesis that there is a link between HT use and lung cancer risk. Our findings should be evaluated in further prospective cohort studies.

Lipoprotein-Associated Phospholipase A 2 , Hormone Use, and the Risk of Ischemic Stroke in Postmenopausal Women

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2).

Influence of Estrogen Receptor α and Progesterone Receptor Polymorphisms on the Effects of Hormone Therapy on Mammographic Density

Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPIC-Norfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P < 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P < 0.01), but not in those with the XX genotype (-0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P < 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density.

Cognitive function across the life course and the menopausal transition in a British birth cohort

Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.

Menopausal hormone therapy after breast cancer: a meta-analysis and critical appraisal of the evidence

IntroductionMenopausal hormone therapy (HT) is typically withheld from breast cancer survivors because of concerns about risk for recurrence. Our objectives were to estimate the effects of HT on recurrence in breast cancer survivors and to examine the reliability of these estimates.MethodsIn a systematic review of the literature we identified all reports of HT use in breast cancer survivors that included comparison groups. Study design features that might affect selection of participants, detection of recurrence, and manuscript publication were assessed. The relative risks for breast cancer recurrence associated with HT were combined with random effects models.ResultsTwo randomized and eight observational studies included 1,316 breast cancer survivors who used HT and 2,839 nonusers. In the observational studies, HT users were younger and more commonly node negative; only two reported balanced restaging for HT and control groups. Randomized trials suggest that HT increased the risk for recurrence (relative risk 3.41, 95% confidence interval 1.59–7.33), whereas observational studies suggest that HT decreased this risk (relative risk 0.64, 95% confidence interval 0.50–0.82).ConclusionResults from observational studies of HT conducted in breast cancer survivors are discrepant with results from randomized trials. Observational studies of HT use in breast cancer survivors have design limitations that cannot be controlled for using standard statistical methods. Therefore, the randomized clinical trial data provide the only reliable estimates of the effect of HT use on recurrence risks in breast cancer survivors.

Health behaviors and other characteristics of women on hormone therapy: results from the Third National Health and Nutrition Examination Survey, 1988-1994.

To examine the prevalence of hormone therapy (HT) use and compare demographic characteristics, health behaviors, and health indicators between current HT users and never-users in a nationally representative sample of postmenopausal women. The Third National Health and Nutrition Examination Survey was a cross-sectional survey conducted between 1988 and 1994, including 3,673 postmenopausal women aged 40 years and older. Overall, 419 (11.4%) of the women reported current HT use, 857 (23.3%) reported past use, and 2,397 (65.3%) were never-users. Non-Hispanic black women and women aged 70 years or older were less likely to be current users. Higher socioeconomic status (education and income) and surgical menopause were associated with increased odds of current hormone use. After adjusting for the above variables, women who reported being inactive during leisure time and obese women (body mass index >or= 30) were less likely to be current users. Women who had 5 to 29 alcoholic drinks per month, perceived their health status as "good," took a multiple vitamin, were aware of having high blood cholesterol, and had a clinic for regular medical care were more likely to be current users. Smoking habits were not significantly different between the groups. Current HT users have different demographic profiles and may lead healthier lives than never-users. This is important to take into account when studying the effects of HT, and it may partly explain differences in findings regarding the health effects of HT use in observational studies compared with randomized clinical trials.