Use Of Postmenopausal Hormone Therapy Research Articles

A case–control study of reproductive factors, female hormone use, and risk of pancreatic cancer

Findings from several previous studies that have assessed the relation of reproductive factors and female hormone use to the risk of pancreatic cancer are inconclusive. The authors examined the association between reproductive factors and the use of oral contraceptives and postmenopausal hormone therapy to the risk of pancreatic cancer among 284 patients with pancreatic cancer and 1,096 controls using data from the hospital-based Case-Control Surveillance Study. Older age at first pregnancy and long-duration oral contraceptive use were associated with an increased risk of pancreatic cancer: the odds ratio was 2.0 (95% CI: 1.1-3.3) for first birth at age 30 or older compared with before age 20 (p for trend = 0.042) and 2.0 (95% CI: 1.0-4.0) for ten or more years of use of oral contraceptive use relative to no-use (p for trend < 0.01). Risk of pancreatic cancer risk was not associated with postmenopausal female hormone use. The findings suggest that increased exposure to estrogen during the reproductive years may play a role in the development of pancreatic cancer in women. Further studies are needed to confirm the findings.

Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer.

Breast cancer concern is a major reason for the recent marked reduction in use of postmenopausal hormone therapy, although equally effective means of controlling menopausal symptoms are lacking. Single nucleotide polymorphisms (SNP) in the fibroblast growth factor receptor 2 (FGFR2) gene are substantially associated with postmenopausal breast cancer risk and could influence hormone therapy effects. We interrogated eight SNPs in intron 2 of the FGFR2 gene for 2,166 invasive breast cancer cases from the Women's Health Initiative clinical trial and one-to-one matched controls to confirm an association with breast cancer risk. We used case-only analyses to examine the dependence of estrogen plus progestin and estrogen-alone odds ratios on SNP genotype. Seven FGFR2 SNPs, including six in a single linkage disequilibrium region, were found to associate strongly (P < 10(-7)) with breast cancer risk. SNP rs3750817 (minor allele T with frequency 0.39) had an estimated per-minor-allele odds ratio of 0.78, and was not in such strong linkage disequilibrium with the other SNPs. The genotype of this SNP related significantly (P < 0.05) to hormone therapy odds ratios. For estrogen plus progestin, the odds ratios (95% confidence intervals) at 0, 1, and 2 minor SNP alleles were 1.52 (1.14-2.02), 1.33 (1.01-1.75), and 0.69 (0.41-1.17), whereas the corresponding values for estrogen alone were 0.74 (0.51-1.09), 0.99 (0.68-1.44), and 0.34 (0.15-0.76). Postmenopausal women having TT genotype for SNP rs3750817 have a reduced breast cancer risk and seem to experience comparatively favorable effects of postmenopausal hormone therapy.

Screening mammography intervals among postmenopausal hormone therapy users and nonusers

The recent decline in US breast cancer incidence rates has been attributed to the marked reduction in use of postmenopausal hormone therapy (HT). An alternative explanation is that women who are not routinely seeking medical care to renew HT prescriptions may be less adherent to recommendations for mammographic screening. To investigate the latter possibility, we compared mammographic intervals according to HT use. Using data (1995-2007) from the New Hampshire Mammography Network (NHMN), a state-based mammography registry, we assessed mammographic intervals corresponding to HT use or nonuse among postmenopausal women. We used linear mixed effects models to assess whether the length of screening mammogram intervals differed according to HT use. A total of 310,185 mammograms, representing 76,192 postmenopausal women and 319,353 person-years of screening, were included in the analysis. The median screening interval corresponding to HT use overall was 13.0 months (interquartile range: 12.4-15.1) and for nonuse was 13.1 (interquartile range: 12.4-15.8). Virtually, all screening mammograms occurred within a 2-year interval regardless of HT use or nonuse (98.5 and 98.1%, respectively). Our findings indicate that screening mammography intervals are similar whether or not women are using HT. Thus, reduced utilization of screening mammography is unlikely to account for the decrease in breast cancer incidence seen soon after the WHI report.

Total Estrogen Time and Obstructive Coronary Disease in Women: Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)

It has been suggested that both endogenous reproductive hormones and hormone therapy may play a protective role against coronary artery disease (CAD). However, recent clinical trials have failed to demonstrate the benefit of a variety of forms of hormone therapy. The observational data on the role of endogenous reproductive hormones, using surrogate measures such as number of birth, age at menarche, and age at menopause are inconsistent. In addition, the longer-term associations have not been evaluated. The aim of this study was to evaluate the relationships between detailed measurements of endogenous and exogenous estrogen exposure time with angiographic CAD and major adverse cardiovascular events. We assessed total estrogen exposure time, quantitative CAD by a core angiography laboratory, and prospectively measured major adverse cardiovascular events in 646 postmenopausal women undergoing coronary angiography for evaluation for suspected ischemia in the Women's Ischemia Syndrome Evaluation (WISE) study. Timing of postmenopausal exogenous hormone therapy (HT) use was associated with reduced CAD. Two summarized total estrogen time scores (TET and sTET) were not related to angiographic CAD after accounting for HT use. In addition, these scores were not related to cardiovascular events over a median of 6.0 years of follow-up. There was no independent relation of estrogen exposure time to angiographic CAD or major adverse cardiovascular events in a contemporary cohort of postmenopausal women evaluated for suspected ischemia. Our results suggest that the paradigm of estrogen protection from CAD in women may be more complex than estrogen exposure duration alone.

Postmenopausal Hormone Use and Symptoms of Gastroesophageal Reflux

The association of elevated levels of estrogen and progesterone with increased gastroesophageal reflux (GERD) has been reported in a number of studies. Observations supporting this association include decreases found in lower esophageal sphincter (LES) pressures during pregnancy and with the use of sequential oral contraceptives, and data showing that postmenopausal hormone (PMH) therapy may increase the risk of GERD symptoms in overweight and obese women. This prospective cohort study evaluated the risk of GERD among postmenopausal women using PMH therapy, selective estrogen receptor modulators (SERMs), or over-the-counter (OTC) hormone preparations. The study subjects were female nurses with GERD symptoms among a cohort of 51,637 postmenopausal women enrolled in the Nurse’s Health Study who provided information biennially on use of PMH therapy since 1976 and on GERD symptoms, current use of SERMS or OTC hormone preparations since 2002. Of the 51,637 women in the total cohort, 12,018 women (23%) reported GERD symptoms. Multivariate logistic regression analysis showed that compared with women who never used PMH, the odds ratio (OR) for the risk of GERD symptoms was 1.46 (95% confidence interval [CI], 1.36–1.56) for past users of PMH, 1.66 (95% CI, 1.54–1.79) for current users of estrogens only, and 1.41 (95% CI, 1.29–1.54) for current users of combined estrogen and progesterone. The associations persisted after controlling for potential confounders: age-adjusted, age- and body mass index adjusted, and multivariate models. The risk of GERD symptoms associated with PMH use was significantly greater with both increasing dosage and duration of estrogen use (P value for trends <.001). Compared with women who never used PMH or SERMs, women currently using a SERM had an OR for GERD symptoms of 1.39 with a 95% CI of 1.22–1.59. Women currently using OTC hormone preparations had an OR for GERD symptoms of 1.37 with a 95% CI of 1.16–1.62) compared with nonusers. These findings show that postmenopausal use of estrogens, SERMs, or OTC hormone preparations is associated with increased risk of GERD symptoms.

Postmenopausal hormone therapy with estradiol and norethisterone acetate and mammographic density: findings from a cross-sectional study among Norwegian women

Background Although a number of studies have evaluated the associations between use of postmenopausal hormone therapy (HT) and mammographic density, few have assessed the effects of the medications containing estradiol (E2) plus norethisterone acetate (NETA). In particular, there are few data on the effects of the low-dose E2/NETA regimen.Methods We included data from 724 women, aged 50–70 years, residing in south-east Norway, who participated in a cross-sectional study conducted within the Norwegian Breast Cancer Screening Program. We assessed mammographic density using a previously validated computer-assisted method.Results After adjusting for age at screening, number of children and body mass index, women who currently used HT had 6.0% higher percent mammographic density than never-users, p < 0.0001. Women who used either low- or high-dose continuous combined E2/NETA regimens had 7.7% (p < 0.0001) and 8.8% (p < 0.0001) higher percent mammographic density than never-users, respectively.Conclusion Our study suggests that the effect of E2/NETA regimens on mammographic density could be at least as detrimental to the breast tissue as several other estrogen + progestin regimens. Our results suggest that both low- and high-dose E2/NETA influence mammographic density, but there were some indications in our analyses that the effect of low-dose E2/NETA could be slightly lower than that of the older high-dose regimen.

Postmenopausal hormone therapy and incident urinary incontinence in middle-aged women

The objective of the study was to examine the association of hormone therapy with incident urinary incontinence (UI) in postmenopausal women aged 37-54 years in the Nurses' Health Study II. Participants reported use of hormone therapy, including hormone type, on biennial questionnaires from 1989 to 2001. Among 7341 postmenopausal women reporting no UI in 2001, we identified 1026 women who developed UI at least monthly between 2001 and 2003. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Women currently using hormone therapy had 1.39-fold (95% CI, 1.16-1.67) increased odds of incident UI, compared with women who never used hormone therapy. ORs were similar in current users of oral estrogen alone (OR, 1.35, 95% CI, 1.03-1.78) and oral estrogen with progestin (OR, 1.37, 95% CI, 1.13-1.67). These findings suggest an increased risk of UI associated with use of postmenopausal hormone therapy in younger postmenopausal women.

Postmenopausal hormone drugs and breast and colon cancer: Nordic countries 1995–2005

ObjectivesThe purpose of this study was to utilize the variation in the level and timing of the change in postmenopausal hormone therapy (HT) use between the Nordic countries to assess the population-level impact of decline in HT use on the breast and colon cancer incidences. MethodsNationwide HT-sales data in defined daily doses (DDDs) per 1000 inhabitant in 1995–2005 in Finland, Iceland, Norway and Sweden were obtained from drug control authorities. Breast and colon cancer incidence data by 5-year age-groups were obtained from the National Cancer Registers. By time series analysis we estimated in each age-group and country how much a change in HT-sales changes cancer incidence. ResultsThe decline of HT-sales varied; the decline from the highest sales was 61% in Sweden, 51% in Norway, 43% in Iceland and 25% in Finland. With the exception of Finland, the breast cancer incidence increased from 1995 to the year following the year with maximum HT-sales and decreased after that year. In the model combining countries and years, changes in HT-sales predicted the change in breast cancer incidence, an average 7% for each 10 DDD units of HT-sales. No clear association between HT-sales and colon cancer incidence was found. ConclusionsThe time and country specific data suggest, that on the population level, a notable drop from high level of HT use somewhat decreases breast cancer incidence or breaks its increasing trends. The suggested protective effect of HT for colon cancer was not seen.

Reproductive history, hormonal factors and the incidence of hip and knee replacement for osteoarthritis in middle-aged women

Objectives:To examine the effect of reproductive history and use of hormonal therapies on the risk of hip and knee joint replacement for osteoarthritis.Methods:A prospective study of 1.3 million women aged...

Postmenopausal Hormone Use and Symptoms of Gastroesophageal Reflux

Previous studies suggest that elevated levels of estrogen and progesterone, either through endogenous or exogenous sources, increase gastroesophageal reflux. To evaluate the relationship between symptoms of gastroesophageal reflux disease (GERD) and postmenopausal hormone (PMH) therapy, including the use of selective estrogen receptor modulators and over-the-counter (OTC) hormone preparations, we performed a prospective cohort study of 51,637 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PMH therapy biennially since 1976, and information about symptoms of GERD in 2002. Among eligible participants, 12 018 women (23%) reported GERD symptoms. Compared with women who never used PMHs, the multivariate odds ratio (OR) for the risk of GERD symptoms was 1.46 (95% confidence interval [CI], 1.36-1.56) for past hormone users, 1.66 (95% CI, 1.54-1.79) for current users of estrogen only, and 1.41 (95% CI, 1.29-1.54) for current users of combined estrogen and progesterone. The risk of GERD symptoms increased significantly with increasing estrogen dosage (P < .001) and increasing duration of estrogen use (P < .001). Moreover, current selective estrogen receptor modulator users experienced an OR of 1.39 (95% CI, 1.22-1.59) for GERD symptoms, and women currently using OTC hormone preparations had an OR of 1.37 (95% CI, 1.16-1.62). Postmenopausal use of estrogens, selective estrogen receptor modulators, or OTC hormone preparations is associated with a greater likelihood of symptoms of GERD. This suggests a hormonal component to the pathophysiologic characteristics of GERD in women.

Conjugated Equine Estrogens and Breast Cancer Risk in the Women's Health Initiative Clinical Trial and Observational Study

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Response: Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Response: Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population

Bone mineral density at menopause does not predict breast cancer incidence

In this prospective study in 2,137 perimenopausal and early postmenopausal women who were followed over a 13.1-year period of time, we observed no association between bone mineral density measured at the beginning of menopause and the subsequent risk of breast cancer. This study aimed to investigate the relationship between BMD and the risk of breast cancer (BC) in young postmenopausal women. As part of a clinical research program, 2,137 women who were perimenopausal or within their 5 first postmenopausal years were scanned between 1988-1990 and reviewed on average 13.1 years after their initial examination. Ninety-eight incident BC cases were recorded throughout the follow-up. Women with incident BC significantly differed from those who had never had BC with regard to age at menarche, age of birth of 1st child, familial history of BC and postmenopausal hormone therapy (PHT) use. There was no significant difference between the two groups for baseline DXA of the spine. There was a trend for BC cases for having lower femoral neck BMD compared to women without BC. However, women with low BMD were more likely to have taken PHT by the end of the study. In Cox multivariate analyses the relationship between BC risk and femoral neck BMD no longer existed. There was no relationship between BMD measured within the first postmenopausal years and the risk of BC, which makes unlikely the possibility of using BMD as a predictor factor for BC in early postmenopausal women.

Estrogen Plus Progestin Therapy and Breast Cancer in Recently Postmenopausal Women

The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.

Estrogen Receptor Alpha and Matrix Metalloproteinase 2 Polymorphisms and Age-related Maculopathy in Older Women

In this study, the authors sought to determine whether single nucleotide polymorphisms in the estrogen receptor alpha (ESR1) and matrix metalloproteinase 2 (MMP2) genes are associated with age-related maculopathy (ARM) in older women. Subjects comprised a random sample of Caucasian women aged > or =74 years participating in the Study of Osteoporotic Fractures year 10 follow-up (n = 906) in 1997-1998. Fundus photographs were graded for ARM using a modification of the Wisconsin Age-Related Maculopathy Grading System. The prevalences of early ARM and late ARM were 46% and 4%, respectively. The MMP2 rs2287074 single nucleotide polymorphism (G-->A) was associated with ARM. The A allele was present in 47%, 43%, and 30% of subjects with no, early, and late ARM, respectively (p = 0.01), and was associated with lower odds of any ARM (for AG vs. GG, odds ratio = 0.80, 95% confidence interval: 0.65, 0.99; for AA vs. GG, odds ratio = 0.64, 95% confidence interval: 0.42, 0.98). An interaction with use of postmenopausal hormone therapy was significant (p = 0.02). The MMP2 rs2287074 A allele may be associated with a lower likelihood of ARM in older Caucasian women, particularly those who have never used hormone therapy. The role of MMP2 rs2287074 in ARM should be further elucidated.

Postmenopausal Hormone Therapy and Lung Cancer Risk in the Cancer Prevention Study II Nutrition Cohort

Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status. We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR). During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected. These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality.

Body Mass and Endometrial Cancer Risk by Hormone Replacement Therapy and Cancer Subtype

Epidemiologic studies unequivocally show that greater body mass increases the risk of endometrial cancer, but whether risk varies by use of postmenopausal hormone therapy (HT), location of fat deposition, or cancer subtype is still unclear. We examined these associations among 33,436 postmenopausal women in the Cancer Prevention Study II Nutrition Cohort, who completed questionnaires on diet, lifestyle, and medical history at baseline in 1992. A total of 318 cases were eligible through June 2003. Cox-proportional hazards analyses were used to estimate multivariate-adjusted rate ratios (RR). As expected, adult body mass index (BMI) was a strong predictor of risk [RR, 4.70; 95% confidence interval (CI), 3.12-7.07 for BMI 35+ versus 22.5-25.0, P trend < 0.0001]. Use of estrogen plus progestin postmenopausal HT modified the association. Among never-users, risk was significantly linear across the entire range of BMI examined (RR, 0.51; 95% CI, 0.29-0.92 for <22.5 versus 22.5-25.0; RR, 4.41; 95% CI, 2.70-7.20 for > or =35 versus 22.5-25.0, P trend < 0.0001), but among ever estrogen plus progestin users, the association was not significant (P trend = 1.0; P interaction < 0.0001). We observed no difference in risk according to tendency for central versus peripheral fat deposition. Greater BMI (> or =30 versus <25.0) increased risk of both "type I" (classic estrogen pathway, RR, 4.22; 95% CI, 3.07-5.81) and "type II" (serous, clear cell, and all other high grade) cancers (RR, 2.87; 95% CI, 1.59-5.16). The increased risk of endometrial cancer across the range of BMI in women who never used postmenopausal HT stresses the need to prevent both overweight and obesity in women.

Postmenopausal Hormone Therapy and Age-Related Maculopathy in Older Women

Purpose: To examine the association between postmenopausal hormone therapy and Age-Related Maculopathy (ARM) in older women and to determine if these associations vary by smoking status. Methods: A cross-sectional analysis of 1065 women of European origin aged ≥ 74 years attending the year-10 examination of the Study of Osteoporotic Fractures was performed. Fundus photographs were graded for ARM using a modification of the Wisconsin Age-Related Maculopathy Grading System used in NHANES III. Multiple imputation methods were used to examine the associations of type and duration of postmenopausal hormone therapy use with early and late ARM as well as interactions with smoking history. Results: Compared to never users, Neither estrogen alone (E), Estrogen plus progestin (E+P), nor duration of use was significantly associated with early ARM [odds ratio (OR) E = 1.01, 95% confidence interval (CI) 0.77–1.34; OR E+P = 0.85, 95% CI 0.55–1.35; OR ≤ 3 years use = 1.04, 95% CI 0.74–1.47; OR > 3–12 years use = 0.93, 95% CI 0.64–1.35; OR > 12 years use = 0.95, 95% CI 0.65–1.37] or late ARM (OR any E/E+P = 0.59, 95% CI 0.29–1.19; OR ≤ 3 years use = 0.73, 95% CI 0.30–1.77; OR > 3 years of use = 0.51, 95% CI 0.22–1.17), though power for late ARM was limited. Tests for smoking interactions were not significant. Conclusions: This study found no evidence to support an association between use of E, E+P, or duration of use and ARM risk.