Past Hormone Therapy Research Articles

Natural premature menopause relates to higher risk of mild cognitive impairment and Alzheimer’s disease and related dementias in APOE‐ε4 carriers only

AbstractBackgroundOverall risk of Alzheimer’s disease (AD) and APOE‐ε4‐related risk for AD is higher among women than men, but the sex‐specific biological underpinnings of these sex differences are unknown. Earlier age at menopause has been associated with higher risk of AD and related dementias (ADRD); however, it is unclear whether this relationship holds among naturally menopausal (versus surgically menopausal) women only or whether it is impacted by APOE‐ε4 genetic risk. We examined the association of natural premature (occurring ≤40 years of age) menopause with MCI and ADRD risk among older women and whether this relationship was moderated by APOE‐ε4 genotype.MethodThis study included 3,557 older women (age range: 65‐79 years at baseline; all White; 5.3% premature menopause; 25.5% APOE‐ε4 carriers) from the Women’s Health Initiative Memory Study (WHIMS) who experienced menopause spontaneously and not as a result of hysterectomy or bilateral oophorectomy. All participants had data on reproductive history, APOE genotype and longitudinal cognitive evaluations, and were cognitively unimpaired at baseline (follow‐up time: range = 0.92‐24.19, mean = 9.92 years). Incident MCI and ADRD were determined with a comprehensive neuropsychological battery and centrally adjudicated by a panel of specialists with expertise in dementia diagnosis. A set of Cox regression models was applied to determine whether premature menopause and its interaction with APOE‐ε4 carrier status was associated with risk of MCI or ADRD, adjusting for age, education, cardiovascular risk factors, parity, age at menarche, past contraceptive use and current or past hormone therapy use and the timing of initiation relative to menopause.ResultThe APOE‐ε4 X premature menopause interaction was significant (p = .04). Among APOE‐ε4 allele carriers, premature (vs. non‐premature) menopause was associated with an approximate two‐fold increased risk of MCI/ADRD (HR = 2.05, 95%CI: 1.22‐3.44). No such association was present among women without an APOE‐ε4 allele (HR = 1.16, 95%CI: 0.72‐1.86).ConclusionNatural premature vs non‐premature menopause was associated with two‐fold higher risk of MCI/ADRD but only among APOE‐ε4 carriers. Results suggest interactive effects of premature menopause and the APOE‐ε4 genotype. Future studies are needed to determine whether the menopause and APOE‐ε4 pathophysiological mechanisms of dyslipidemia, inflammation and brain metabolism deficiencies may explain this association.

Associations of reproductive factors with postmenopausal follicle stimulating hormone

PurposeRecent studies have suggested that higher postmenopausal follicle stimulating hormone (FSH) may be associated with lower risk of diabetes. However, relatively little is known about postmenopausal FSH levels, including the level of variation between women and whether reproductive factors are associated with this variation.MethodsWe assessed the relationship of multiple reproductive factors with FSH levels among 588 postmenopausal women in the Kuopio Ischaemic Heart Disease Risk Factor Study. Participants were aged 53 to 73 years and not using hormone therapy at study enrollment (1998–2001) when reproductive factors were assessed and FSH was measured.ResultsAfter adjustment for age, menopause timing, sex steroid levels, adiposity and behavioral factors, we observed numbers of pregnancies and age at first birth were each inversely associated with FSH levels. For example, women with ≥ 3 births and an age at first birth ≥ 25 years had mean FSH levels that were 7.8 IU/L lower than those of women with 1–2 births and an age at first birth ≤ 24 years (P = 0.003). Number of miscarriages was inversely associated with FSH levels (-2.7 IU/L per miscarriage; P = 0.02). Women reporting 4 or more years of past hormone therapy use had significantly higher mean FSH levels than women who had never used hormone therapy (P for trend = 0.006).ConclusionMultiple reproductive factors were associated with postmenopausal FSH, independent of estradiol, adiposity and other confounders. These findings warrant replication and further exploration of potential underlying mechanism.

Progestins and the Risk of Breast Cancer.

The present paper aims to investigate the effects of both progesterone and progestin treatment mainly related to the occurrence of breast cancer in women. Extensive systematic bibliographic review of Greek and International articles was conducted through the electronic databases Pubmed, Cinahl, Uptodate, and Google Scholar for the identification of articles related to progesterone, progestins and breast cancer treatment. Hormone therapy with the use of estrogen alone presents a small increased risk or does not present at all an increased risk of breast cancer. With ORs in some studies below 1.0 in current users for 3 plus years and safe option until 7 years, while in other studies the risk was increased with the ORs 1.29. However, the use of estrogen in combination with progestogens, depending on the type of progestogens, shows an increased risk of breast cancer, with the ORs to vary between 1.14- 2.38 from 3 to 5 years and is inversely proportional to the time of its use. This risk varies depending on the combination of the preparations. Other factors that are associated with breast cancer risk when receiving hormone therapy are the years that hormone therapy is taken, directly proportional to the risk. At higher risk are older women, women with low body mass index in menopause (BMI <25kg/m2) and women with increased mammographic breast density. Continued use of hormone therapy is associated with an increased risk for breast cancer compared to sequential. The risk became visible sooner to women who used in the past hormone therapy and were using it again. Starting hormone therapy in the immediate postmenopausal period also increased the risk for breast cancer. Hormone therapy was associated with tumors with positive estrogen and progesterone receptors, and also the lobular histological type was associated with its use. Tibolone use was associated with an increased risk.

Interactions of alcohol and postmenopausal hormone use in regards to mammographic breast density

We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status. This study included 2,100 cancer-free postmenopausal women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0, < 5, and ≥ 5g/day). Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to examine associations between alcohol and breast density measures in women with no HT history, current, and past HT users. In multivariable analyses, we found no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend = 0.53) and an inverse association with NDA (β = - 0.41, 95% CI - 0.73, - 0.09 for ≥ 5g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol was not associated with PD in any of the strata. We found a significant inverse association of alcohol with NDA among past HT users (β = - 0.79, 95% CI - 1.51, - 0.07 for ≥ 5g/day, p trend = 0.02). There were no significant interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction = 0.19, 0.42, and 0.43, respectively). Our findings suggest that associations of alcohol with breast density do not vary by HT status.

Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway

ObjectivesWith the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC).SettingCohort study based on the linkage of Norwegian population-based registries.ParticipantsWe...

Pelvic organ prolapse: does hormone therapy use matter?

To determine the effect of hormone therapy (HT) use on pelvic organ support. A retrospective observational study involving postmenopausal women with pelvic floor dysfunction attending a tertiary urogynecology center between January 2012 and March 2015. All underwent a clinical examination including International Continence Society Pelvic Organ Prolapse Quantification and 4D translabial ultrasound imaging. Information on current or former use of systemic HT and current local estrogen use was collected. Main outcome measure was pelvic organ support. One thousand four hundred forty-three women were seen during the study period. On univariate analysis, current HT was significantly associated with sonographically determined descent of the rectal ampulla (β [95% confidence interval] 3.4 mm [0.4-6.5], P = 0.03) and Gh + Pb (-0.45 mm [-0.8 to -0.1], P = 0.005). Past HT use, duration of HT use, or current vaginal estrogen use was not associated with pelvic organ support. On multivariate analysis controlling for age, parity, body mass index, history of forceps delivery, and avulsion, the association between current HT on the one hand and Gh + Pb as well as increased descent of the rectal ampulla on ultrasound, remained significant (P = 0.008 and P = 0.012, respectively). HT may have a minor negative effect on pelvic organ support; however, the effect is likely too small to be clinically relevant.

Use of hormone therapy and isoflavones and mammographic density in Spain.

The use of some forms of hormone therapy (HT) is associated with an increase in mammographic density-a major risk factor for breast cancer. The role of isoflavones, however, is unclear. Here, we quantify the prevalence of HT and isoflavone use among postmenopausal Spanish women, determine associated risk factors, and explore the relationship between these therapies and mammographic density. This cross-sectional study included 2,754 postmenopausal women who underwent breast cancer screening in seven geographical areas. Mammographic density was evaluated using Boyd's semiquantitative scale. Multinomial logistic regression models were adjusted to assess risk factors associated with both therapies. Ordinal regression models were fitted to study the association between HT and isoflavone consumption with mammographic density. The prevalence of ever-use of HT was 12%, whereas that of the current use was 2.3%. Isoflavone lifetime prevalence was 3.7%, and current use was 1.7%. The most common HT types were tibolone and estrogens. Surgical menopause, oral contraceptive use, educational level, population density, and years since menopause were positively associated with HT, whereas body mass index and parity were inversely associated. Mammographic density was not associated with current or past HT use. However, women who reported having consumed isoflavones in the past and those who started their use after menopause had a higher mammographic density when compared with never-users (odds ratio 1.98, 95% CI 1.21-3.25, P = 0.007; and odds ratio 1.60, 95% CI 1.01-2.53, P = 0.045 respectively). Our results show a low prevalence of HT and isoflavone use in postmenopausal Spanish women. In this population, HT use was not associated with mammographic density, whereas some categories of isoflavone users had higher density.

Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.

This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints. One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses. Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10). Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET.

Past hormone therapy in older women

Women transitioning into menopause, particularly those who experience hot flashes, face the challenging decision about whether or not to initiate hormone therapy (HT). Those who choose to take HT must also decide how long to continue treatment. The Women's Health Initiative Memory Study (WHIMS), the only randomized controlled trial of the effects of HT on incident dementia, found that conjugated equine estrogen (CEE), when combined with medroxyprogesterone acetate, doubled the risk of dementia in women who initiated treatment at age 65 years and later.1 Unopposed CEE (i.e., without medroxyprogesterone acetate) did not increase the incidence of dementia, but a pooled analysis of both treatment arms revealed a 76% increased incidence of dementia.2

Do hormone treatments for prostate cancer cause anxiety and depression?

To investigate the relationship between hormone therapy (HT) and incidence of anxiety and depression among prostate cancer patients (PCa). 526 PCa patients completed a survey about their cancer status, treatment received, anxiety, and depression status. Total scores on anxiety and depression inventories, plus symptom profiles that discriminated between patients with current HT, past HT, and never having received HT, were compiled for analysis. Patients who were currently receiving HT had significantly higher total anxiety and depression scores than patients who had previously received HT or who had never received HT. Analysis of the symptoms of anxiety and depression which distinguished between these groups of patients suggested that patients who had never received HT had significantly lower scores than current or past HT patients. Although several symptoms could be directly allocated to PCa and/or HT, symptom profiles were indicative of clinically significant anxiety and/or depression in patients who were currently receiving, or who had previously received, HT. Current HT may lead to symptoms of anxiety and/or depression which require clinical attention. These effects seem to decrease after completion of HT.

Costs, Evidence, and Value in the Medicare Program

Costs, Evidence, and Value in the Medicare Program

Estrogen metabolism and mammographic density in postmenopausal women: a cross-sectional study.

Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD. Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm(2)) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use. Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm(2) (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI. In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD. Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD.

Prevalence, frequency and problem rating of hot flushes persist in older postmenopausal women: impact of age, body mass index, hysterectomy, hormone therapy use, lifestyle and mood in a cross‐sectional cohort study of 10 418 British women aged 54–65

Hot flushes and night sweats (HFs/NSs) are the main menopausal symptoms, but few studies have been adequately powered to examine the dimensions or predictors of experiencing HFs/NSs. We report on these variables in a large UK cohort of postmenopausal women. Cross-sectional cohort study. UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) cohort. A cohort of 202,638 postmenopausal women, aged 50-74 years, without oophorectomy, recruited to UKCTOCS between 2001 and 2005. Women completed a follow-up questionnaire, and those aged 54-65 years were mailed a survey in July 2008. Hot flush prevalence and hot flush rating scale. Of the 15,000 women mailed, 10,418 returned completed questionnaires; 90% had previously had HFs/NSs. Despite being on average 10 years postmenopausal, 54% experienced HFs/NSs (frequency of 33 per week with mean problem rating 4/10) that persisted across the age range. Past hysterectomy (OR 1.50, 95% CI 1.19-1.86), ever having smoked (OR 1.27, 95% CI 1.11-1.46) and alcohol consumption (current units) (OR 1.05, 95% CI 1.01-1.09) predicted ever having had HFs/NSs. Anxiety (OR 3.09, 95% CI 2.57-3.72), hysterectomy (OR 2.74, 95% CI 2.32-3.25), depressed mood (OR 1.57, 95% CI 1.24-1.99), years since last menstrual period (OR 0.95, 95% CI 0.94-0.96) and education (above and below 18 years) (OR 0.98, 95% CI 0.97-0.99) predicted the current prevalence of HFs/NSs. Few predictors of frequency were identified, but problem rating was associated with depressed mood, hysterectomy, skirt size increase and frequency of HFs/NSs. Past hormone therapy users who had discontinued treatment were more likely to have HFs/NSs that were more frequent and problematic. To date, this is the largest UK study of the experience of HFs/NSs amongst older postmenopausal women. HFs/NSs are more prevalent in this age band than has previously been assumed. These findings and the associations of smoking, hysterectomy, anxiety, depressed mood and hormone therapy use with the experience of HFs/NSs have implications for prevention and symptom management.

Postmenopausal hormone use impact on emotion processing circuitry

Despite considerable evidence for potential effects of estrogen on emotional processing, several studies of postmenopausal women who began hormone therapy (HT) remote from menopause report no effects of HT on emotional measures. As early HT initiation may preserve brain mechanisms, we examined effects of HT on emotional processing in postmenopausal women who started HT early after menopause. We performed a cross-sectional comparison of 52 postmenopausal women 66 ± 5 years old, including 15 users of conjugated equine estrogen, 20 users of conjugated equine estrogen plus medroxyprogesterone acetate, and 17 who never used hormones (NT). All hormone users started therapy within two years of menopause, and received at least 10 years of continuous therapy. Outcomes were fMRI-detected brain activity and behavioral measures during an emotional processing picture rating task. During processing of positive pictures, NT women had greater activation than estrogen treated women in medial prefrontal cortex extending to the anterior cingulate, and more activation than estrogen plus progestin treated women in the insula. During processing of negative pictures, estrogen treated women had higher activation than NT women in the entorhinal cortex. Current compared to past HT users showed greater activation in the hippocampus and higher emotion recognition accuracy of neutral stimuli. Estrogen plus progestin treated women had slower response time than NT women when rating all pictures. In conclusion, hormone use was associated with differences in brain functional responses during emotional processing. These fMRI effects were more prominent than those observed for behavioral measures and involved brain regions implicated in cognitive-emotional integration.

Past use of hormone therapy and breast cancer risk.

1502 Background: Although current use of hormone therapy (HT) is clearly associated with breast cancer risk, most studies have not seen an increased risk among past users of HT. However, the effects of longer term past use of HT have not been well quantified. Methods: We examined the relationship between past HT use and invasive breast cancer risk within the Nurses’ Health Study, a prospective cohort of 121,700 registered nurses aged 30-55 in 1976 who update information on cancer risk factors and outcomes through biennial questionnaires. For this analysis, the follow-up period was 1980 through 2006 and only included person-time for postmenopausal women. Status of HT use (never, past, or current), type of HT (oral unopposed estrogen (E alone) or combination oral estrogen + progesterone (E+P)), and duration of HT use were assessed every 2 years and defined prospectively. Proportional hazards models controlled for age, body mass index, parity, age at first birth, family history of breast cancer, benign breast disease, alcohol consumption, type of menopause, and ages at menarche and menopause. Results: During 1,458,952 person-years of follow-up among postmenopausal women, invasive breast cancer was diagnosed among 1653 women who had never used HRT, 365 past users of E+P and 532 past users of E alone. Regardless of duration of use, past use of E alone was not associated with breast cancer risk. Although past use of E+P for less than 10 years was not associated with breast cancer risk (RR (95% CI) 0.91 (0.77-1.06) for < 5 years and 1.06 (0.88-1.27) for 5-9.9 years), past use of E+P for greater than 10 years was associated with an increased risk of breast cancer (RR 1.37 (1.06-2.77) for 10-14.9 years and 1.46 (0.97-2.21) for 15-19.9 years, p for trend=0.004). Results were similar regardless of time since last use, but stronger for hormone-receptor positive tumors. Conclusions: Although shorter-term past use of E+P was not associated with breast cancer risk, past use of E+P for greater than 10 years was associated with persistenly increased breast cancer risk even after HT discontinuation.

Does hormone therapy counter the beneficial effects of physical activity on breast cancer risk in postmenopausal women?

Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Women's Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P (trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.

Depressive Symptoms and Incidence of Mild Cognitive Impairment and Probable Dementia in Elderly Women: The Women's Health Initiative Memory Study

To examine whether significant depressive symptoms in postmenopausal women increases the risk of subsequent mild cognitive impairment (MCI) and dementia. Prospective cohort study. Thirty nine of the 40 Women's Health Initiative (WHI) clinical centers that participated in a randomized clinical trial of hormone therapy. Six thousand three hundred seventy-six postmenopausal women without cognitive impairment aged 65 to 79 at baseline. Depressive disorders were assessed using an eight-item Burnam algorithm and followed annually for a mean period of 5.4 years. A central adjudication committee classified the presence of MCI and probable dementia based on an extensive neuropsychiatric examination. Eight percent of postmenopausal women in this sample reported depressive symptoms above a 0.06 cut point on the Burnam algorithm. Depressive disorder at baseline was associated with greater risk of incident MCI (hazard ratio (HR)=1.98, 95% confidence interval (CI)=1.33-2.94), probable dementia (HR=2.03, 95% CI=1.15-3.60), and MCI or probable dementia (HR=1.92, 95% CI=1.35-2.73) after controlling for sociodemographic characteristics, lifestyle and vascular risk factors, cardiovascular and cerebrovascular disease, antidepressant use, and current and past hormone therapy status. Assignment to hormone therapy and baseline cognitive function did not affect these relationships. Women without depression who endorsed a remote history of depression had a higher risk of developing dementia. Clinically significant depressive symptoms in women aged 65 and older are independently associated with greater incidence of MCI and probable dementia.

Postmenopausal hormone therapy, timing of initiation, APOE and cognitive decline

Associations between postmenopausal hormone therapy (HT) and cognitive decline may depend on apolipoprotein E (APOE) status or timing of initiation. We included 16,514 Nurses' Health Study participants aged 70–81 years who were followed since 1976 and completed up to 3 telephone cognitive assessments (2 years apart), between 1995 and 2006. The tests assessed general cognition (Telephone Interview of Cognitive Status; TICS), verbal memory, and category fluency. We used longitudinal analyses to estimate differences in cognitive decline across hormone groups. APOE genotype was available in 3697 participants. Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was −0.04 (95% confidence interval, −0.07 to −0.004); for current estrogen + progestin users, the mean difference was −0.05 (95% confidence interval, −0.10 to −0.002). These differences were equivalent to those observed in women who are 1–2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p interaction, 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users. Regardless of timing of initiation, HT may be associated with worse rates of decline in general cognition, especially among those with an APOE e4 allele.

Synergistic Effect of Statins and Postmenopausal Hormone Therapy in the Prevention of Skeletal Fractures in Elderly Women

To examine the role of concurrent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis-related fractures. Case-control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. Postmenopausal hormone therapy use was classified as "current" (12 mo before index date) or "never or past." The risk of fractures was ascertained among continuous (> or = 80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid-lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. Concurrent statin use and hormone therapy may have a synergistic protective effect on skeletal fractures beyond the additive effect of each individual therapy.

Postmenopausal hormones and sleep quality in the elderly: a population based study

BackgroundSleep disturbance and insomnia are commonly reported by postmenopausal women. However, the relationship between hormone therapy (HT) and sleep disturbances in postmenopausal community-dwelling adults is understudied. Using data from the multicenter Study of Osteoporotic Fractures (SOF), we tested the relationship between HT and sleep-wake estimated from actigraphy.MethodsSleep-wake was ascertained by wrist actigraphy in 3,123 women aged 84 ± 4 years (range 77-99) from the Study of Osteoporotic Fractures (SOF). This sample represents 30% of the original SOF study and 64% of participants seen at this visit. Data were collected for a mean of 4 consecutive 24-hour periods. Sleep parameters measured objectively included total sleep time, sleep efficiency (SE), sleep latency, wake after sleep onset (WASO), and nap time. All analyses were adjusted for potential confounders (age, clinic site, race, BMI, cognitive function, physical activity, depression, anxiety, education, marital status, age at menopause, alcohol use, prior hysterectomy, and medical conditions).ResultsActigraphy measurements were available for 424 current, 1,289 past, and 1,410 never users of HT. Women currently using HT had a shorter WASO time (76 vs. 82 minutes, P = 0.03) and fewer long-wake (≥ 5 minutes) episodes (6.5 vs. 7.1, P = 0.004) than never users. Past HT users had longer total sleep time than never users (413 vs. 403 minutes, P = 0.002). Women who never used HT had elevated odds of SE <70% (OR,1.37;95%CI,0.98-1.92) and significantly higher odds of WASO ≥ 90 minutes (OR,1.37;95%CI,1.02-1.83) and ≥ 8 long-wake episodes (OR,1.58;95%CI,1.18-2.12) when compared to current HT users.ConclusionsPostmenopausal women currently using HT had improved sleep quality for two out of five objective measures: shorter WASO and fewer long-wake episodes. The mechanism behind these associations is not clear. For postmenopausal women, starting HT use should be considered carefully in balance with other risks since the vascular side-effects of hormone replacement may exceed its beneficial effects on sleep.