Current Hormone Therapy Users Research Articles

Relationship between the subgingival microbiome and menopausal hormone therapy use: The Buffalo OsteoPeriostudy.

This study investigated the association between menopausal hormone therapy (HT) use and the subgingival microbiome, for which published information is limited. This cross-sectional study included 1270 postmenopausal women, aged 53-81 years, who completed clinical examinations. Detailed information on HT use (type, delivery mode, duration) was obtained from questionnaires. HT use was categorized into three groups (never, former, current). 16S rRNA sequencing was performed on subgingival plaque samples obtained during dental examinations. Operational taxonomic units were centered log2-ratio (CLR) transformed to account for the compositional data structure. Analysis of variance was used to compare mean microbial relative abundances across HT categories with Benjamini-Hochberg correction. Significantly higher alpha diversity (Shannon Index) and beta diversity (Aitchison distance) was observed in never compared with current HT users (p<0.05, each). Of the total 245 microbial taxa identified, 18 taxa differed significantly among the three HT groups, 11 of which were higher in current users and seven of which were lower in current users as compared with never users (p<0.05, each). Differences in relative abundance between never and current HT users were materially unchanged after adjustment for age, body mass index, and oral hygiene. Relative abundance of several subgingival bacteria differed significantly between never and current HT users in a cohort of postmenopausal women. Additional studies are needed to determine the extent that these relationships might account for the previously reported inverse association between HT use and periodontal disease in older women.

Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study.

Background and purposeSex differences in multiple sclerosis (MS) prevalence and disease course are thought to be driven by hormones. Exogenous exposure to estrogens may affect MS disease course. Thus, our aim was to investigate the association between hormone therapy (HT) and disease activity and disability accrual among women with MS.MethodsA register‐based cohort study was conducted with prospectively enrolled cases from the Danish MS registry. Information on hormone exposure was retrieved from the National Prescription Registry. Outcomes were relapse rate, relapse rate ratio, recurrent relapses, 6‐month confirmed and sustained Expanded Disability Status Scale (EDSS) milestones 4 and 6, and recurrent EDSS worsening.ResultsIn all, 3325 women were eligible for analyses, of whom 333 (10%) were ever on HT at some time during follow‐up. We found no association between HT and disability accrual, although a trend for increasing risk with increasing length of use was seen. The risk of reaching 6‐month confirmed and sustained EDSS 4 among users was 0.6 (95% confidence interval [CI] = 0.3–1.2) after <1 year of use and 1.4 (95% CI = 0.9–2.2) after >5 years of HT compared to never use. The risk of recurrent relapse was increased by 20% (95% CI = 1.0–1.4) among current users of HT compared to nonusers. However, the risk of recurrent relapses was driven by the first calendar period (1996–2005) before the introduction of high‐efficacy disease‐modifying therapy.ConclusionsOur findings from this nationwide MS population suggest that HT does not affect disability accrual in women with MS, especially if used for <5 years.

Oral postmenopausal hormone therapy and genetic risk on venous thromboembolism: gene-hormone interaction results from a large prospective cohort study.

Oral postmenopausal hormone therapy (HT) has been shown to be associated with venous thromboembolism (VTE), but whether this association is modified by VTE-associated genetic susceptibility is unknown. We examined interactions between oral HT use and a genetic risk score (GRS) of VTE. Eligible women were postmenopausal women who had data on oral HT use, VTE incidence between 1990 and 2012, and genetic data in the Nurses' Health Study. We built a GRS aggregating 16 VTE-related genetic variants. We used Cox regression to estimate associations of HT use with incident VTE and assessed interactions between HT use and VTE GRS. We also estimated incidence of VTE between age 50 and 79 years for groups of women defined by HT use and VTE GRS. We identified 432 incident VTE cases. Current HT users were at higher risk of VTE than never users (HR: 1.9, 95% CI: 1.5-2.6), with slightly higher risk for estrogen plus progestin HT than estrogen only (HR: 2.4 vs 1.9). The GRS was associated with VTE risk (HR comparing 4th quartile to 1st: 2.0, 95% CI: 1.2-3.4). We did not observe significant multiplicative interactions between HT use and GRS. The estimated VTE risk difference (per 10,000 person-years) comparing 50-year-old current HT users to never users was 22.5 for women in the highest GRS quartile and 9.8 for women in the lowest GRS quartile. The VTE GRS might inform clinical guidance regarding the balance of risks and benefits of HT use, especially among younger women.

Abstract MP46: Metabolomic Response to Randomized Treatment With Estrogen and Estrogen Plus Progestin Therapy in Postmenopausal Women

Introduction: Hormone therapy (HT) has been linked to chronic disease risk in postmenopausal women, but the effect of HT on the metabolome is unclear. Hypothesis: Randomized HT is associated with perturbations in the metabolome. Methods: The discovery set, from the Women’s Health Initiative (WHI), included 288 women in the conjugated equine estrogens-alone (CEE) trial (139 active; 149 placebo) and 244 women in the CEE + medroxyprogesterone acetate (CEE+MPA) trial (133 active; 111 placebo). Blood samples were collected 1 year after intervention. The validation set included 494 women from the Nurses’ Health Study (NHS) and NHS2 (264 non-users, 158 estrogen-alone users, and 72 estrogen + progestogen users). Plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry; 478 known metabolites were used in analyses. We used elastic net regressions to develop metabolomic signatures for CEE and CEE+MPA in the WHI, adjusting for age and race. We applied the signature models to NHS/NHS2 and compared the signatures of current HT users to those of non-users. Pathway analysis was done using MetaboAnalyst. Results: In the WHI, we identified a CEE metabolomic signature comprised of 42 metabolites and a CEE+MPA signature comprised of 34 metabolites ( Fig. A ). The two signatures shared 8 metabolites (4 amino acids, 2 glycerophospholipids, and 2 quaternary amines). In NHS/NHS2, CEE and CEE+MPA signatures were highly correlated ( r =0.85) and both significantly higher in current HT users than non-users ( P ≤2.7х10 -15 ) ( Fig. B ). The CEE+MPA signature metabolites were enriched in 3 pathways (glycerophospholipid metabolism; aminoacyl-tRNA biosynthesis; and glycine, serine and threonine metabolism); no pathway enrichment was found for the CEE signature. Conclusions: We identified and validated metabolomic signatures for CEE and CEE+MPA use in postmenopausal women from WHI and NHS/NHS2. Whether alterations in lipid or amino acid metabolism mediate associations of HT use with chronic disease needs future investigation.

Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women.

Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Physical Activity, Hormone Therapy Use, and Stroke Risk among Women in the California Teachers Study Cohort

Background: Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. Methods: Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430–432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995–1996] and 10-year follow-up [2005–2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. Results: Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use: HR_baseline 1.28 (95% CI 1.13–1.44); HR_{10-year follow-up} 1.17 (95% CI 0.91–1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995–1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08–1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005–2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80–1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. Conclusion: Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use.

Perspectives and decision-making about menopausal therapies in women who had bilateral oophorectomy.

The aim of the study was to explore the process of decision-making about menopausal treatments in women who have had surgical menopause as a result of bilateral oophorectomy (≤50 y). We used a descriptive qualitative research design. Women who had a surgical menopause were purposefully selected from the Edmonton Menopause Clinics. Focus groups were held, each with six to nine participants. All sessions were audio-recorded and transcribed verbatim. Data were analyzed using qualitative content analysis. We conducted five focus groups from June 30 to July 21, 2016 (N = 37). One-third of the women had the surgery within the last 5 years. Almost all women had a concurrent hysterectomy (97%) and were current users of hormone therapy (70%). Four main themes identified were "perceptions of surgical menopause," "perceptions of received support," "being my own advocate," and "concept of adequate support." Women shared that the experience was worse than their expectations and did not believe they were given adequate support to prepare them to make therapy decisions. Women had to "be their own advocates" and seek support from within the healthcare system and outside to cope with their health issues. To make an informed decision about treatments postsurgery, women expressed a need to learn more about the symptoms of surgical menopause, treatment options, resources, avenues for support, and stories of similar experiences, preferably before the surgery. We identified several modifiable deterrents to decision-making in early surgical menopause which can help inform the development of a patient decision aid for this context.

Associations of coffee consumption and caffeine intake with mammographic breast density.

Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. We investigated the association of coffee and caffeine intake with mammographic breast density by woman's menopausal status and, in postmenopausal women, by hormone therapy (HT). This study included 4130 cancer-free women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD) was measured from digitized film mammograms using a computer-assisted thresholding technique and square root-transformed for the analysis. Average cumulative coffee/caffeine consumption was calculated using data from all food frequency questionnaires preceding the mammogram date. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of regular, decaffeinated, and total coffee, and energy-adjusted caffeine intake with percent density. In multivariable analyses, decaffeinated coffee was positively associated with PD in premenopausal women (2+cups/day: β=0.23, p trend=0.03). In postmenopausal women, decaffeinated and total coffee were inversely associated with PD (decaffeinated 2+cups/day: β=-0.24, p trend=0.04; total 4+cups/day: β=-0.16, p trend=0.02). Interaction of decaffeinated coffee with menopausal status was significant (p-interaction<0.001). Among current HT users, regular coffee and caffeine were inversely associated with PD (regular coffee 4+cups/day: β=-0.29, p trend=0.01; caffeine 4th vs. 1st quartile: β=-0.32, p trend=0.01). Among past users, decaffeinated coffee was inversely associated with PD (2+cups/day β=-0.70, p trend=0.02). Associations of decaffeinated coffee with percent density differ by woman's menopausal status. Associations of regular coffee and caffeine with percent density may differ by HT status.

Abstract 4255: Associations of coffee consumption and caffeine intake with mammographic breast density

Abstract Purpose: Previous studies suggest that coffee consumption and caffeine intake may be associated with reduced breast cancer risk which may result from stimulating effect of coffee on estrogen metabolism enzymes and subsequent changes in bioavailable estrogen. We investigated the association of coffee consumption and caffeine intake with mammographic density by woman’s menopausal status and, in postmenopausal women, by hormone therapy (HT). Methods: This study included 4,130 cancer-free women within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percent breast density (PD), absolute dense and non-dense areas were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square-root transformed for the analysis to improve normality. Diet was assessed with a food frequency questionnaire; average cumulative coffee/caffeine consumption was calculated using data available from all the questionnaires preceding the mammogram date. Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations between exposures and breast density measures, adjusted for potential confounders. Associations were examined separately for regular coffee, decaffeinated coffee, total coffee, and energy-adjusted caffeine intake. Results: In multivariable analyses, decaffeinated coffee was positively associated with PD in premenopausal women (2+ cups/day: β=0.23, p-trend=0.03). In postmenopausal women, decaffeinated and total coffee were inversely associated with PD (decaffeinated coffee 2+ cups/day: β=-0.24, p-trend=0.04; total coffee 4+ cups/day: β=-0.17). These associations appeared to be driven by the inverse associations of these exposures with absolute dense area. Among current HT users (n=980), regular coffee and caffeine intake were inversely associated with PD (regular coffee 4+ cups/day: β=-0.29, p-trend&amp;lt;0.01; caffeine 4th vs. 1st quartile: β=-0.32, p-trend&amp;lt;0.01). Among past users (n=430), decaffeinated coffee was inversely associated with PD (2+ cups/day β=-0.70, p-trend=0.02). Conclusions: Our findings suggest that among current HT users, regular coffee and caffeine are inversely associated with mammographic percent breast density. Citation Format: Lusine Yaghjyan, Graham Colditz, Bernard Rosner, Aleksandra Gasparova, Rulla Tamimi. Associations of coffee consumption and caffeine intake with mammographic breast density [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4255. doi:10.1158/1538-7445.AM2017-4255

A population-based survey of quality of life in middle-aged Finnish women.

Factors that cause a decrease in quality of life (QoL) among middle-aged women are contradictory. Given that previous studies have been presumably performed in ethnically heterogeneous populations, we evaluated the impact of socioeconomic and lifestyle factors on QoL in Finnish women because the Finnish population is ethnically homogenous. A total of 6,408 women (aged 41-54 y) who were called for municipal screening mammography received a postal survey concerning their health-related issues. A total of 3,421 women returned the questionnaire. QoL was evaluated with the Women's Health Questionnaire, from which we included eight symptom clusters (somatic symptoms, depressive symptoms, cognitive difficulties, anxiety/fears, sexual functioning, vasomotor symptoms, sleep problems, and menstrual symptoms). The effects of variables on QoL were defined with multivariate analysis. Older women had more symptoms. Lower educational level was associated with lower QoL. Retired women had more symptoms than working or unemployed women, and unemployed women had more symptoms than employed women. Increasing body mass index was associated with lower QoL. Women who consumed alcohol occasionally had fewer symptoms, and women who consumed alcohol weekly had more symptoms than abstainers. Women who smoked had more symptoms than nonsmokers. Current hormone therapy users had more symptoms than nonusers, and former hormone therapy users had more symptoms than nonusers or current hormone therapy users. Higher socioeconomic status and healthier lifestyle are beneficial for good QoL in middle-aged women. Thus, women should be encouraged to continue employment and to avoid behavioral health risks.

Use of hormone therapy in Swedish women aged 80 years or older

Menopausal symptoms such as hot flashes and night sweats may persist for 10 to 20 years or even longer. Information about the extent to which older women use hormone therapy is limited. The aim of this study was to determine the use of hormone therapy in Swedish women aged 80 years or older. The study is based on national register data on dispensed drug prescriptions (ie, prescribed therapy that has been provided to individuals by pharmacies) for hormone therapy and local low-dose estrogens. Of 310,923 Swedish women who were aged at least 80 years, 609 (0.2%) were new users of hormone therapy. A total of 2,361 women (0.8%) were current users of hormone therapy. The median duration of hormone therapy use in new users was 257 days (25th to 75th percentiles, 611-120 d). About one in six women aged 80 years or older had used local vaginal estrogen therapy for at least four 3-month periods. The drugs were mainly prescribed by gynecologists and general practitioners. Our results show that a number of women aged 80 years or older still use hormone therapy and that most women who started a new treatment period had only one or two dispensations despite the median duration of treatment being more than half a year. Because at least some of the women aged 80 years or older who used hormone therapy probably did so owing to persistent climacteric symptoms, vasomotor symptoms and hormone therapy are still relevant issues that need to be discussed when counseling women around and after age 80.

Abstract P377: Oral Estrogen Hormone Therapy Use after Incident Venous Thrombosis and the Risk of Recurrence

Background: Oral estrogen hormone therapy (HT) is associated with a 2-fold increased risk of incident venous thrombosis (VT). Patterns of HT use following an incident VT and the association between HT use and recurrence are poorly characterized. Objectives: We aimed: (1) to characterize the use of oral estrogen HT in the 5 months following a first VT event; and (2) to evaluate whether the use of HT following an incident VT is associated with VT recurrence. Methods: In Group Health Cooperative (GHC), an integrated health care system, we identified an inception cohort of women aged 40-89 who experienced an incident VT from 2002 to 2010 (n=1,121). Using medical record review, we followed participants for VT recurrence, defined by physician diagnosis &gt;2 weeks after the incident VT with clinical and/or imaging evidence of a new or expanded clot. HT use at 80% compliance was defined using GHC computerized pharmacy data. Characterization of HT use was restricted to women who survived for ≥5 months. Cox proportional hazards models were used to evaluate the association between time-varying current HT use and risk of recurrent VT, adjusting for race, baseline age, BMI, idiopathic incident VT, diabetes status, and the following time-varying covariates: cancer, CVD, and current anticoagulation use. In primary analyses, time was defined as days since incident event and censoring occurred at last follow-up or death. To evaluate the influence of possible HT misclassification soon after the incident event, we conducted 2 sensitivity analyses in which women entered the risk set after 30 and 60 days post-incident VT. Additional secondary Cox analyses were restricted to current HT users at the time of incident VT. Results: Of women who survived ≥5 months post-incident VT (n=993), 12% used oral estrogen HT at time of the incident event (n=123); among these, 90 (73%) discontinued use whereas 33 (27%) continued to fill ≥1 HT prescription within the next 5 months. Compared with users who stopped HT, persistent users were on average older (70 vs. 65 years), had a lower BMI (29 vs. 32 kg/m 2 ), and were less likely to have experienced an incident PE as part of their first VT event (27% vs. 61%). Over an average follow-up of 3.4 years, we identified 164 recurrent VTs among 1,121 women. We found no evidence of an association between HT use after incident VT and VT recurrence risk, adjusted for confounders (HR=0.73; 95% CI: 0.26-1.99; p=0.53); no evidence of an association was found in sensitivity or secondary analyses. Conclusions: In this population of GHC enrollees, over one-quarter of oral estrogen HT users at VT incidence continued use and filled subsequent HT prescriptions in the 5 months following the incident event. We found no evidence of an association between post-event HT use and the risk of VT recurrence, however, the number of HT users in our population was small.

Association of ischemic stroke, hormone therapy, and right to left shunt in postmenopausal women

Postmenopausal hormone therapy (HT) increases the risk of venous thrombosis and ischemic stroke. We postulated that HT might increase the risk of ischemic stroke by promoting venous clots that travel to the brain through a right to left shunt (RLS). A total of 2,389 records were studied. After eliminating the premenopausal patients, and those with TIAs and non-ischemic strokes, the medical records of 1846 postmenopausal women hospitalized at four institutions for ischemic stroke were reviewed to identify those who had undergone an adequate study to assess for RLS. The proportion of women with a shunt in users and non-users of HT was compared in stroke patients and in a reference population consisting of postmenopausal women undergoing elective cardiac catheterization. There were 363 (20%) records that had complete data and were included in the analysis. A shunt was more prevalent in patients with a cryptogenic stroke than in patients with a stroke of known cause (55/88 (63%) vs. 53/275 (19%), P < 0.001). In patients with a stroke of known cause, the frequency of a shunt was similar to that in reference women 31/136 (23%), and the proportion of women with a shunt was similar in non-users and current users of HT (14% vs. 20%, P = 0.40). However, among patients with a cryptogenic stroke, the prevalence of a shunt was 1.5 times higher in current users than non-users of HT (82% vs. 56%, P = 0.04). Approximately 23% of older women have a RLS. HT in these women may increase the risk of ischemic stroke by promoting paradoxical embolism.

Abstract T MP67: Physical Activity Reduces Stroke Risk Among Women in the California Teachers Study Cohort

Background: Major modifiable stroke risk factors are well-established, yet strategies for effective prevention remain challenging. Developing stroke prevention strategies for women is critical due to: (i) the higher fatality and disability rate that women suffer compared to men, (ii) the unique risks to women such as from post-menopausal hormone therapy use, and (iiii) the aging female population. We evaluated three important modifiable stroke risk factors- obesity, hormone therapy, and physical activity, in the California Teachers Study cohort to identify potential stroke prevention strategies. Methods: The California Teachers Study comprises 133,479 women who enrolled in 1995 and have since been continuously followed. Using linked California state hospitalization data from 1996-2010, 3126 stroke events were defined as ischemic (N=2416; ICD-9 433, 434, 436) or hemorrhagic (N=710; ICD-9 430-432, excluding 432.1) and were validated by medical record review. Information about obesity, physical activity, hormone therapy, and medical history was collected at baseline and in follow-up questionnaires. Multivariable-adjusted hazards ratios and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2010. Results: Consistent with previous reports, current post-menopausal hormone therapy use was associated with a 1.3-fold increased risk for stroke (95% CI=1.03-4.85). Moderate to strenuous physical activity in the 3 years before enrollment (but not lifetime activity) decreased stroke risk by 20% (HR=0.79, 95% CI=0.71-0.98). This decreased risk among physically active women was similar among current hormone therapy users, and appears to counteract the increased risk observed with current hormone therapy use. We found no association between obesity and stroke that was independent of diabetes. Conclusions: Recent physical activity reduces stroke risk and appears to counteract the increased risk associated with post-menopausal hormone therapy use.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study

Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk. A total of 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). During 3.3 million years of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years after last reporting HT use. RRs in current vs. never users at last reporting varied by HT formulation: the risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91 [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first 2 years after starting HT than later (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate. The risk of VTE varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate.

Alcohol consumption and breast cancer risk among postmenopausal women following the cessation of hormone therapy use: the California Teachers Study.

Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today. Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users [RR, 1.60; 95% confidence interval (CI), 1.13-2.26 and RR, 2.11; 95% CI, 1.41-3.15 for <20 and ≥20 g/d of alcohol], with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3 to 4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for estrogen receptor positive (ER+) and ER+PR+ progesterone receptors positive (PR+) tumors; while power was limited, no increase in risk was observed for ER- tumors. Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a nonsignificant increased risk was observed among women who never used HT. Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced.

Abstract 2503: Plasma Estradiol and Testosterone Levels and Risk of Ischemic Stroke in Postmenopausal Women

Background: Large randomized trials have shown that use of exogenous estrogens with or without progestin increase the risk of ischemic stroke among women. Current data on the association between endogenous sex hormones and ischemic stroke are very limited. Data are also lacking on the association with endogenous androgens, which, through aromatization, are the primary source of endogenous estrogen in postmenopausal women. Thus, we evaluated plasma estradiol and testosterone levels and risk for ischemic stroke among women in the Nurses’ Health Study (NHS). Methods: Among 32,826 participants in the NHS who provided blood samples in 1989-1990, 405 postmenopausal women (209 never/past users and 196 current users of hormone therapy) had a confirmed diagnosis of ischemic stroke through 2006. An equal number of controls who were free of stroke during follow-up were matched for age, use of postmenopausal hormones, and smoking status. Estradiol and testosterone levels were measured by mass spectroscopy. Conditional logistic regression was used to evaluate the association of log-transformed levels of estradiol and testosterone with stroke risk, within strata of hormone therapy use. Results: Circulating estradiol was not associated with stroke risk among never/past users; the relative risk (RR) (95% confidence interval) for highest to lowest estradiol quartiles was 1.27 (0.74-2.19), when adjusted for matching factors (p trend=0.75). However, there was a nonsignificantly increased risk of stroke among current users with higher estradiol levels; conditional on matching factors, the RRs were 2.28 (1.20-4.33), 1.55 (0.81-2.96), and 1.90 (0.96-3.79), for quartiles 2-4, respectively (p for trend=0.56). No association was observed between total testosterone levels and stroke risk in either group; the RRs for highest to lowest quartiles were 0.86 (0.50-1.49) and 1.06 (0.60-1.87) in never/past and current users, respectively (p for trends ≥0.39). The associations with free sex hormone levels were similar to those observed with total circulating levels. Additional adjustment for body mass index, aspirin use, alcohol consumption, and history of diabetes, elevated cholesterol, hypertension, or coronary heart disease, as well as levels of c-reactive protein (CRP) and the total/HDL cholesterol ratio did not materially change the associations. No association was observed between total and free testosterone levels and stroke risk in either never/past or current users (p for trends ≥0.39). These associations did not vary across levels of aspirin use smoking status, or CRP (p for interactions &gt;0.05). Conclusions: Estradiol and testosterone levels were not associated with risk of ischemic stroke in this cohort of postmenopausal women.

Common Carotid Artery Diameter and Cardiovascular Risk Factors in Overweight or Obese Postmenopausal Women

Arterial diameter is an underutilized indicator of vascular health. We hypothesized that interadventitial and lumen diameter of the common carotid artery would be better indicators of vascular health than carotid plaque or intima media thickness (IMT). Participants were 491 overweight or obese, postmenopausal women who were former or current hormone therapy (HT) users, 52–62 years, with waist circumference >80 cm. We evaluated cross-sectional associations of cardiovascular risk factors with carotid measures, by HT status. Former HT users had a worse cardiovascular profile than current HT users: larger adventitial (6.94 mm versus 6.79 mm) and lumen diameter (5.44 mm versus 5.31 mm, both P < 0.01) independent of cardiovascular risk factors; IMT and plaque were similar. Larger diameters were best explained by former HT use, higher pulse pressure, and greater weight. Independent of potential confounders, overweight and obese postmenopausal former HT users had larger carotid diameters than current HT users. Carotid diameter should be considered in studies of HT.

Hormone therapy use and mammographic density in postmenopausal Norwegian women

While studies have shown that use of postmenopausal hormone therapy with estrogen and progestogen (EPT) increases mammographic density, aspects of this association remain unclear. We examined whether mammographic density differed by type of hormone therapy (HT) used, dose, duration of use, time since last use, and whether the effects are modified by age and body mass index (BMI). Using a cross-sectional design, we recruited 2,424 postmenopausal women aged 50-69 years participating in the Norwegian Breast Cancer Screening Program. Mammographic density was assessed with a computer-assisted method, and we estimated mean absolute and percent mammographic density through multiple linear regression, and adjusting for possible confounders. Mammographic density was higher among current HT users (percent density: 22.6%; 95% CI: 22.1-23.2%) than among former (17.7%; 17.2-18.2%) or never users (16.3%; 15.7-16.8%). The highest density was seen in current EPT users of high-dose norethisterone acetate (NETA) regimens who had a percent density of 26.2% (24.3-28.1%). Results differed when considering the combined effect of age and BMI. The effect of EPT on mammographic density was modified by age and BMI, with no apparent association among the youngest women (aged 50-55) with the highest BMI (BMI ≥ 26). A higher mammographic density was found in EPT users compared to never HT users, particularly in women using high-dose NETA regimens. Age and BMI modified the association between EPT use and mammographic density.

The association between caffeine intake and forearm bone mineral density in postmenopausal women: The Oslo Health Study

-