Estrogen Users Research Articles

Alzheimer’s Disease in Man and Transgenic Mice: Females at Higher Risk

The major risk factors for Alzheimer’s disease (AD) are aging, Down’s syndrome, genetics, and a positive family history. Most, but not all, studies also find that aging women have a higher risk of developing AD than men. 1-4 Female apolipoprotein E4 (ApoE4) carriers are also at higher risk than males. 5-8 Together with the greater life expectancy of women in developed societies, this means that the majority of patients who live and die with AD are women. The etiology of the higher risk of AD in females is unknown. Perhaps because cognitive functions tend to be more distributed and bilateral in females compared to males, the neuronal disconnections associated with AD may affect women more profoundly. A role for estrogen, by influencing brain development (pre- or postmenarche) or senescence (postmenopause), is a leading hypothesis. In agreement with this notion, some studies suggest a protective effect of estrogen replacement therapy in the risk of developing AD. For example, the risk of developing AD among self-reported estrogen users is about one-third less than among non-users (odds ratio 0.65), and the risk decreases with increased duration and dosage of conjugated equine estrogen, the major form of estrogen replacement in clinical use. 9,10 Women who begin menstruation at later, rather than earlier, ages have a higher risk of developing AD. 9 A protective effect of estrogen is also found in a cohort of elderly women in Manhattan. In this study, estrogen use decreases the risk of developing AD by about half (odds ratios 0.40 and 0.50 after adjustment for education) and is independent of ApoE genotype. 11 Other studies, however, find no protective benefit of estrogen replacement therapy 12,13 and suggest that artifactual variables, such as higher socioeconomic status, more education, or better access to medical care among women who are prescribed estrogen, mediate this difference. A subsequent meta-analysis of ten studies, including eight case control and two prospective studies, found a risk reduction of 29% in postmenopausal women taking estrogen replacement therapy compared to untreated women. 14 Two more recent case-control studies also demonstrate a risk reduction of 58 to 72%. 15,16 Finally, a recent review of 15 case-control studies published since 1990 suggests that estrogen replacement decreases the risk of developing AD by half. 17 Given this epidemiological evidence, as well as positive results from brief, small, open trials of estrogen replacement in AD, 14 three large double-blind placebo-controlled clinical trials of patients with probable AD have now been published—all three with disappointing results. 18-20 With this information, estrogen replacement therapy cannot currently be recommended as a treatment for AD. Furthermore, the risk of developing AD should not factor into the difficult clinical and personal decision to use estrogen replacement, balancing its beneficial effects on osteoporosis, cardiovascular disease, and other conditions with its carcinogenic potential. The debate now centers on whether the gender effect of AD risk is in fact mediated by postmenopausal estrogen decline and, if so, whether treatment of patients diagnosed with probable AD is too little, too late. Perhaps estrogen must be given in preclinical stages of AD, such as in higher-risk subjects with isolated memory impairment or minimal cognitive impairment, as a preventive therapy. Testing of this hypothesis is underway in 5- and 10-year AD prevention trials, the results of which will be available in 2003 and 2008. Furthermore, the correct estrogen preparation, dosage, and duration, with or without progestins, route of administration (transcutaneous versus oral), and use of drug holidays may all influence the outcome of clinical trials.

Carotid Vascular Resistance in Long-Term Estrogen Users

Carotid Vascular Resistance in Long-Term Estrogen Users

Carotid vascular resistance in long-term estrogen users

Objective: To compare carotid vascular resistance in long-term estrogen users with that of age-matched nonusers. Methods: Pairwise comparisons between 18 long-term users of 17β-estradiol (E2) implants (mean age 67.8 years, mean duration of treatment 18.8 years, range 5.8–33.9 years) and 18 age-matched (± 2 years) nonusers. We used color Doppler ultrasound to assess pulsatility index (PI) and resistance index (RI) in common, external, and internal carotid arteries. Results: Estrogen users compared with age-matched nonusers had significantly lower mean values for common carotid RI, −4%; −0.04 (95% confidence interval [CI] −0.07, −0.03, P = .036) and marginally significant for PI, −12%; −0.25 (95% CI −0.54, 0.04, P = .087). Differences in external and internal carotids were smaller and insignificant. Age was a determinant of internal carotid vascular resistance in estrogen users and nonusers. Increasing pairwise differences in external carotid vascular resistance with advancing age ( r = 0.55; P = .02), with magnitudes of mean group differences indicate a modest but true effect of long-term estrogen therapy on vascular resistance in common carotids, less in external, and negligible in internal carotid arteries. The study had an 80% power to detect a 10% mean difference (0.08 units) in common carotid RI at the 5% level. The standard deviation was considerably lower for estimates of RI than for PI. Conclusion: Long-term estrogen therapy was associated with minor reduction of vascular resistance in common carotid, less in external, and negligible in internal carotid arteries. Effects on carotid vascular resistance do not seem to be a major mechanism in the long-term protective effect of estrogen therapy on cardiovascular risk.

Effect of body mass on the association between estrogen replacement therapy and mortality among elderly US women.

In observational studies, estrogen replacement therapy is associated with decreased cardiovascular disease rates and increased breast cancer rates. Recent evidence suggests that the impact of estrogen use on disease outcomes may vary by body mass. In a prospective study of 290,827 postmenopausal US women with no history of cancer or cardiovascular disease at enrollment in 1982, the authors examined the association between postmenopausal estrogen use and all-cause, coronary heart disease, stroke, all-cancer, and breast cancer death rates and whether these associations differed by body mass. After 12 years of follow-up, results from Cox proportional hazards models showed that all-cause death rates were lower among baseline estrogen users than never users (rate ratio (RR) = 0.82, 95% confidence interval (CI): 0.78, 0.87). The lowest relative risk was found for coronary heart disease (RR = 0.66, 95% CI: 0.58, 0.77). The inverse association between estrogen use and coronary heart disease mortality was strongest for thin women (body mass index <22 kg/m2) (RR = 0.49, p for interaction = 0.02). Breast cancer mortality did not increase with estrogen use overall, and no increased risk was observed for thin or heavy women. In this population, the reduction in coronary heart disease mortality among estrogen users was greatest for thinner women. Additional studies are needed to confirm or refute these results.

Association of Circulating Cellular Adhesion Molecules with Menopausal Status and Hormone Replacement Therapy: Time-Dependent Change in Transdermal, but not Oral Estrogen Users

The incidence of coronary heart disease is lower in premenopausal than in postmenopausal women, and estrogen use may be cardioprotective among postmenopausal women. Cellular adhesion molecules (CAM) are involved in the early stage of atherosclerosis, and short-term administration of oral estrogen decreased plasma concentrations of their soluble forms in postmenopausal women. However, data evaluating transdermal estrogen are sparse and long-term effect of hormone replacement therapy (HRT) on CAM is unknown. Therefore, we have investigated the association of circulating CAM (cCAM) with menopausal status and long-term HRT. Plasma levels of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), P-selectin, E-selectin, C-reactive protein (CRP), and fibrinogen were measured in 74 premenopausal women, 60 postmenopausal women not using HRT, 30 postmenopausal women using opposed oral estrogen therapy, and 30 postmenopausal women using opposed transdermal estrogen therapy. All women were apparently healthy and aged between 45 and 54 years. Duration of HRT ranged from 3 to 96 months. Postmenopausal women not receiving HRT had 24% higher mean levels of cICAM-1 than premenopausal women (318 vs. 255 ng/ml, P<.001). In postmenopausal women, users of oral estrogen had 16% lower, and users of transdermal estrogen had 17% lower mean levels of cICAM-1 than non-users (268 and 264 vs. 318 ng/ml, P=.001 for both comparisons). Furthermore, in users of transdermal route, the lowering effect of estrogen on cICAM-1 was dependent on treatment duration, while no time-dependent effect was seen in oral estrogen users. Users of transdermal estrogen had lower cVCAM-1 and P-selectin levels than postmenopausal non-users (327 vs. 364 ng/ml ( P=.05) and 18 vs. 23 ng/ml ( P=.05). There was no difference in CRP and E-selectin levels between the groups. Adjustment for age and body mass index (BMI) made no substantial change in the results. These data suggest that oral and transdermal estrogen may play a long-term cardioprotective role through favourable changes in endothelial function.

Estrogen replacement therapy: determinants of persistence with treatment

Objective: To evaluate the persistence rate for estrogen therapy and to identify its determinants. Methods: From the Quebec health insurance database we chose a cohort of 4527 women 35 years and older who received social assistance and were new users of estrogen between January 1989 and December 1997. Incident use was defined by the absence of any dispensed prescription of estrogen in the 3 years before the index date (date of first dispensed prescription). We estimated the cumulative persistence rate of treatment by Kaplan–Meier failure time analysis and identified its determinants with the Cox proportional hazards model. Results: From the initial cohort, 3395 women (75%) renewed their first dispensed prescription and 905 (20%) continued treatment after 4 years. The determinants measured at the index date and significantly associated with a better persistence rate (relative risk [RR]) were younger than 60 years (RR 1.15, 95% confidence interval [CI] 1.01, 1.30), low dosage (RR 1.49, 95% CI 1.32, 1.70), continuous progestin combination (RR 1.40, 95% CI 1.27, 1.54), and a gynecologist as the first prescribing physician (RR 1.15, 95% CI 1.03, 1.21). Also, coronary heart disease or at least one risk factor for it in the year before the index date was associated with a better persistence rate for estrogen replacement therapy (RR 1.15, 95% CI 1.05, 1.22). Conclusions: The persistence rate for estrogen therapy is poor, implying that few women take it long enough to benefit from it.

Comparison of soft tissue body composition in postmenopausal women with or without hormone replacement therapy considering the influence of reproductive history and lifestyle

OBJECTIVES: To examine long-term effects of at least 5 years' conventional hormone replacement therapy (HRT), reproductive history and lifestyle on fat mass and muscle mass in postmenopausal women. RESEARCH DESIGN AND METHODS: A cross-sectional retrospective approach was used, including 64 healthy women (56-69 years, mean age 63.4 years). Hormone users were compared with age-matched non-users with respect to (a) type of HRT used (oestrogen vs oestrogen plus gestagen vs no hormones), (b) categories of oestrogens used (oestradiol-based oestrogens vs conjugated equine oestrogens vs no oestrogens) and (c) categories of gestagens used (testosterone derivatives vs progesterone derivatives vs no gestagens). Data on hormone use, reproductive history (age at menarche, age at menopause, number of years postmenopausal, number of children) and lifestyle (physical activity level, alcohol consumption, smoking habits) were collected by questionnaires. Body composition was analysed by multiple-frequency bioelectrical impedance analysis, estimating fat mass, fat-free mass and body cell mass as absolute values (FM, FFM, BCM, respectively) and percentages of body weight (% FM, % FFM, % BCM). RESULTS: Analysis of covariance, adjusting body composition variables for body mass index, showed that (a) unopposed oestrogen users, oestrogen plus gestagen users and non-users did not differ significantly in body composition variables, (b) users of oestradiol-based oestrogens had significantly more BCM than oestrogen abstainers (p < 0.05), (c) users of testosterone-based gestagens had more BCM than gestagen abstainers (p = 0.05). Stepwise multiple regression analyses, including HRT-related, reproductive and lifestyle variables, indicated that the duration of HRT (p < 0.05) and physical activity level (p = 0.01) were significant positive predictors of % BCM, whereas the number of children significantly positively predicted FM and % FM (each p < 0.05). No significant associations between fat-free mass and HRT were found. CONCLUSIONS: The results suggest that conventional doses of oestrogens and gestagens used in HRT might be a factor in preserving muscle mass after long-term administration. It is recommended that BCM is used instead of FFM as an indicator of muscle mass. Studies relating muscle mass to HRT in postmenopausal women should consider physical activity as a possible confounding variable.

The association of dietary fat and plant foods with endometrial cancer (United States).

To examine the associations of dietary fat and selected plant foods with endometrial cancer in a population-based case-control study. Six hundred and seventy-nine incident cases of endometrial cancer diagnosed between 1985 and 1991, and 944 population-based controls completed a 98-item semi-quantitative food-frequency questionnaire and a detailed in-person interview which collected information on endometrial cancer risk factors. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of endometrial cancer, adjusted for age, county, energy intake, hormone use, smoking and, in separate models, for body mass index (BMI: kg/m2). Percent energy from fat was associated with an increased risk of endometrial cancer (highest quintile cf. lowest: OR = 1.8, 95% CI 1.3-2.6), with saturated and monounsaturated fats being the main contributors of risk. There was a stronger association between dietary fat and endometrial cancer among groups with higher circulating estrogen levels (i.e. women with higher BMI, users of unopposed estrogens, non-smokers, and younger age at menarche). Consumption of fruits or vegetables was inversely associated with endometrial cancer risk (highest quintile cf. lowest: OR = 0.65, 95% CI 0.46-0.93 and OR = 0.61, 95% CI 0.43-0.88, respectively). Further adjustment for BMI resulted in little or no attenuation of the ORs and associated CIs. These results provide support for the theory that a low-fat, high-fruit and high-vegetable diet may reduce the risk of endometrial cancer, and that these dietary factors may act independently of the effect of BMI.

Vitamin C supplement use and bone mineral density in postmenopausal women.

Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with bone mineral density (BMD) have been conflicting, probably because of the well-known limitations of dietary nutrient assessment questionnaires. The purpose of this study was to evaluate the independent relation of daily vitamin C supplement use with BMD in a population-based sample of postmenopausal women. Subjects were 994 women from a community-based cohort of whom 277 women were regular vitamin C supplement users. Vitamin C supplement use was validated. Daily vitamin C supplement intake ranged from 100 to 5,000 mg; the mean daily dose was 745 mg. Average duration of use was 12.4 years; 85% had taken vitamin C supplements for more than 3 years. BMD levels were measured at the ultradistal and midshaft radii, hip, and lumbar spine. After adjusting for age, body mass index (BMI), and total calcium intake, vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip (p < 0.05). In a fully adjusted model, significant differences remained at the femoral neck (p < 0.02) and marginal significance was observed at the total hip (p < 0.06). Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Among current estrogen users, those also taking vitamin C had higher BMD levels at all sites, with marginal significance achieved at the ultradistal radius (p < 0.07), femoral neck (p < 0.07), and total hip (p < 0.09). Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck (p = 0.001), total hip (p = 0.05), ultradistal radius (p = 0.02), and lumbar spine. Vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.

Risk of breast cancer in users of combined oestrogen-progestogen HRT compared with users of oestrogen alone

Risk of breast cancer in users of combined oestrogen-progestogen HRT compared with users of oestrogen alone

A Beneficial Effect of Estrogen on Working Memory in Postmenopausal Women Taking Hormone Replacement Therapy

Recent neurophysiological data suggest that the prefrontal cortex (PFC) may be susceptible to modulation by estrogen. In humans, the PFC mediates a number of cognitive processes that contribute to memory function, particularly working memory. The present study examined whether memory tasks that recruit PFC-dependent information processing might exhibit estrogen sensitivity in women. Performance on several memory tasks, including measures of working memory, was evaluated in three groups of postmenopausal women: (1) women who were tested when taking estrogen only (n = 38, Mage = 55.1 years), (2) women who were tested when taking estrogen and a progestin concurrently (n = 23, Mage = 55.9 years), and (3) women who were not taking hormone replacement therapy (n = 35, Mage = 56.0 years). Estrogen users exhibited significantly better performance on a verbal task and on a spatial task, each with a prominent working memory component, but did not differ from nonusers on control tasks involving simple passive recall. These findings are consistent with the hypothesis that estrogen is active within PFC and is capable of influencing functions dependent on this region. The results of this study raise the possibility that estrogen may play a role in maintaining certain frontal lobe functions in women.

Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa.

Anorexia nervosa is highly prevalent among young women. To determine prevalence and predictive factors for regional bone loss. Prospective cohort analysis. University hospital. 130 women with anorexia nervosa. Dual-energy x-ray absorptiometry. The prevalence of osteopenia (-1.0 SD >/= T-score > -2.5 SD) and osteoporosis (T-score </= -2.5 SD) was 50% and 13% for the anterior-posterior spine, 57% and 24% for the lateral spine, and 47% and 16% for the total hip, respectively. Bone mineral density (BMD) was reduced by at least 1.0 SD at one or more skeletal sites in 92% of patients and by at least 2.5 SD in 38% of patients. Weight was the most consistent predictor of BMD at all skeletal sites. Twenty-three percent of patients were current estrogen users, and 58% were previous estrogen users. Bone mineral density did not differ by history of estrogen use at any site. Bone mineral density is reduced at several skeletal sites in most women with anorexia nervosa. Weight, but not estrogen use, is a significant predictor of BMD in this population at all skeletal sites.

Prevalence and clustering of menopausal symptoms in older women by hysterectomy and oophorectomy status.

This study examines the association of hysterectomy and oophorectomy with the prevalence and clustering of menopausal symptoms in a large population-based sample of older women. Subjects were 1121 women aged 50-89 from the Rancho Bernardo Study. Information on menopause, hysterectomy, oophorectomy, estrogen use, and other covariates was obtained in 1984-1987. A 1989 mailed survey obtained information on menopausal symptoms. In this sample, 22.1% reported hysterectomy with bilateral oophorectomy, and 25.3% reported hysterectomy with ovarian conservation. Mean time since hysterectomy was 26 (+/-12) years. Overall, 37% reported current estrogen use, and 40% reported past use. The duration of estrogen use was longer for women who had a hysterectomy (p < 0.001). Age-adjusted comparisons indicated that more women who had a hysterectomy, with or without bilateral oophorectomy, reported greater energy after menopause (p = 0.003 and p = 0.001, respectively), and more women with bilateral oophorectomy reported greater interest in sex (p = 0.007) and that life was getting better (p = 0.012) than women with natural menopause. Principal components factor analysis of the symptom data for all women yielded four factors: psychological, vasomotor, positive feelings, and self-image. Analyses performed within each group of women yielded similar factors and loadings. Adjusted comparisons of factor scores indicated that positive feelings were significantly higher in women who had a hysterectomy, with or without bilateral oophorectomy (p < 0.01) than in women with natural menopause. This difference was limited to current estrogen users. Vasomotor symptoms, psychological symptoms, and negative self-image did not differ by hysterectomy or oophorectomy status before or after stratification for estrogen use (p > 0.10). This study found after a hysterectomy, women are more likely to recall positive feelings about their menopause than women with natural menopause. Relief from symptoms leading to hysterectomy and use of replacement estrogen may be partly responsible. Results do not support the thesis that surgical menopause is associated with a sustained increased prevalence of vasomotor, psychological, or other symptoms.

Postmenopausal estrogen therapy and depressive symptoms in older women.

Evidence regarding the effect of postmenopausal estrogen therapy on mood is limited. To determine whether postmenopausal estrogen therapy is associated with fewer depressive symptoms in elderly women, we conducted a cross-sectional study of 6, 602 white women ages 71 years or older who were recruited from population-based listings in Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley, Pa. Use of estrogen and progestin was determined by interview. Participants completed the Geriatric Depression Scale short form (GDS) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. A total of 6.3% (72/1,150) of current estrogen users, 7.2% (142/1,964) of past estrogen users, and 9.0% (313/3,488) of never users reported 6 or more symptoms of depression (P =.004). Current estrogen users had a decreased risk of reporting 6 or more depressive symptoms, compared with not current (past or never) users of estrogen (odds ratio [OR], 0.7; 95% CI, 0.5 to 0.9; P =.01], adjusted for living alone, bilateral oophorectomy, current smoking, physical activity, social network, self-perceived health, cognitive function, functional status, and antidepressant use. However, excluding women who use estrogen or progestin alone, we were unable to find an association between current use of combined estrogen plus progestin therapy and depressive symptoms (adjusted OR, 0.8; 95% CI, 0.5 to 1.4; P =.5). This cross-sectional study found that current use of unopposed estrogen was associated with a decreased risk of depressive symptoms in older women. Additional studies are needed to understand the effect of combined estrogen and progestin therapy on the prevalence of depressive symptoms in older women.

Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies

OBJECTIVESThis study sought to evaluate the effects of postmenopausal estrogen use on mortality in aging women with congestive heart failure (CHF).BACKGROUNDThe age-related increase in CHF mortality in women may be related to a menopause-associated increased incidence of coronary artery disease. In addition to inhibiting coronary atherosclerosis, estrogen may also have protective effects on cardiac myocytes independent of the coronary vasculature. We hypothesized that estrogen use is associated with improved survival in elderly women with CHF.METHODSAssociations between survival, estrogen use and patient characteristics were assessed in 1,134 women who were at least 50 years of age, had CHF and left ventricular ejection fraction (EF) ≤30% and were enrolled in one of three clinical trials of vesnarinone.RESULTSAll-cause 12-month mortality was 15.0% among the 237 estrogen users versus 27.1% among the 897 estrogen nonusers (p = 0.004 for unadjusted comparison of survival). Similar results were observed for cardiac mortality. Regression analysis demonstrated that estrogen use was independently associated with improved survival (relative risk of mortality = 0.68, 95% confidence interval 0.48 to 0.96, p = 0.03). Advanced age, low EF, New York Heart Association class IV CHF, Caucasian race and abnormal serum creatinine, sodium, potassium and transaminase were independently associated with increased mortality.CONCLUSIONSEstrogen use among older women with CHF is associated with decreased overall and cardiac mortality.

Oestrogens and Alzheimer's disease

In the last decade, several reports suggest that oestrogen replacement therapy (ORT=ERT=estrogen replacement therapy) might prevent or delay Alzheimer's disease. Oestrogens influence and modulate brain structure and brain function. There are substantial arguments that the postmenopausal oestrogen loss might, together with other factors, accelerate the appearance of Alzheimer's disease. The evidence is suggestive, but not compelling, that ORT can reduce the relative risk to suffer from Alzheimer's disease. Furthermore, recent findings are consistent with the hypothesis that oestrogens might ameliorate the symptomatology in early stages of Alzheimer's disease. However, it has to be remembered that in most clinical trials the number of oestrogen users was quite small, and, usually, oestrogen use was not randomised. The aim of the present review is to discuss the data available today in view of their clinical relevance. Copyright © 2000 John Wiley & Sons, Ltd.

Oestrogen and cognitive function throughout the female lifespan.

Evidence that oestrogen helps to maintain verbal memory in women comes from several sources. Studies that have tested cognitive functioning at different phases of the menstrual cycle have found few differences, perhaps because oestrogen levels are sufficiently high, albeit variable, during all cycle phases. Experimental studies in postmenopausal women have generally found a protective effect of oestrogen, specifically on verbal memory. Results of several large, longitudinal studies that have become available recently have also demonstrated that women who were oestrogen users performed better on certain tests of cognitive function than non-users of similar age. On the basis of this body of evidence, it is possible to conclude that oestrogen may attenuate or prevent the decline in aspects of memory that occur with normal ageing in women.

Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.

APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline. - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke. Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

Estrogen therapy in women undergoing coronary artery bypass grafting: effect on surgical complications

Objective: To determine whether estrogen therapy at the time of coronary artery bypass grafting affects postoperative complications. Methods: Consecutive postmenopausal women who had coronary artery bypass grafting between 1992 and 1997 were identified and their medical records were reviewed. Outcome measures included mortality, perioperative cardiac morbidity, and early and late postoperative complications. Results: Estrogen therapy was noted in 13.9% of 734 women. Those using estrogen replacement were younger (63.9 ± 0.27 versus 68.8 ± 0.64 years) and had higher ejection fractions (2.8 ± 0.11 versus 3.1 ± 0.04) and fewer vessels bypassed. Mortality rates were 2.9% for estrogen users and 7.4% for nonusers (odds ratio [OR] 0.38; confidence interval [CI] 0.07, 1.21). Perioperative cardiac morbidity rates were 5.8% for estrogen users and 11% for nonusers (OR 0.52; CI 0.23, 1.7). Early complication rates were 0.98% for estrogen users and 1.11% for nonusers. Late inpatient complications were noted in 6.8% of treated women and 14.8% of those untreated (OR 0.42; CI 0.16, 0.96). Stepwise logistic regression confirmed age, New York Heart Association angina classification, and ejection fraction as significant variables for mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy did not influence mortality, perioperative cardiac morbidity, or early or late complications. Conclusion: Age, ejection fraction, and New York Heart Association angina classification predicted mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy at the time of admission for coronary artery bypass grafting did not influence surgical mortality, perioperative cardiac morbidity, or early or late complications.

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.