Current Estrogen Users Research Articles

The interaction of age and hormone replacement therapy on colon adenoma risk

Background: Several studies have identified a possible interaction between age and hormone replacement therapy on colon neoplasm risk. We re-evaluated this interaction and determined if this interaction may be explained by the longer duration of estrogen use in older, rather than younger, women. Methods: Included in the case-control study were 755 women (169 cases and 586 controls.) who were recruited from patients with no prior history of colorectal neoplasm and undergoing an elective colonoscopy examination. Results: There was a significant interaction between age and hormone replacement therapy use ( P = 0.03) with current estrogen users who were over 56 years of age having a reduced odds of colon adenoma (OR, 0.40; 95% CI, 0.16–0.98) when compared to never users. Both older women who had used hormone replacement therapy for 3 or less years (OR, 0.07; 95% CI, 0.006–0.81) and those reporting greater than 10 years of use (OR, 0.27; 95% CI, 0.09–0.80) had a reduced adjusted odds for adenomas when compared to non-users. No apparent association with estrogen replacement therapy was found among younger women (<56 years). Conclusions: Duration of use is not likely to explain the stronger association of hormone replacement therapy use with colon neoplasm in older women. Additional work is needed to better characterize the underlying mechanisms associated with this interaction.

Combined Estrogen and Testosterone Use and Risk of Breast Cancer in Postmenopausal Women

The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer. We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1 359 323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires. Among women with a natural menopause, the risk of breast cancer was nearly 2.5-fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53-4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosterone therapy was significantly greater compared with estrogen-only therapy (P for heterogeneity, .007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use. Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer.

Menopausal estrogen therapy predicts better nocturnal oxyhemoglobin saturation

Objectives The respiratory responses in the few previous studies evaluating the effects of short-term unopposed estrogen therapy on breathing in postmenopausal women have been inconsistent. We performed a study to investigate whether long-term estrogen therapy would prevent age-related decline in nocturnal arterial oxyhemoglobin saturation and whether higher serum estradiol concentration is associated with better arterial oxyhemoglobin saturation. Methods Sixty-four healthy postmenopausal women were followed-up for 5 years in a 5-year prospective open follow-up study. The women were users or non-users of estrogen therapy according to their personal preference. Results Mean overnight arterial oxyhemoglobin saturation was similar at baseline (94.3 ± 1.1%) and after follow-up (94.5 ± 1.6%). Present estrogen users had higher mean arterial oxyhemoglobin saturation (95.2 ± 1.4%) than present non-users (94.0 ± 1.5%), when adjusted for age and body mass index ( p = 0.042). The change in mean arterial oxyhemoglobin saturation during follow-up was not associated with serum estradiol concentration at baseline but associated with estradiol at follow-up ( p = 0.042), when adjusted for age and body mass index. At follow-up, women with higher serum estradiol concentration had also higher mean nocturnal arterial oxyhemoglobin saturation (Pearson r = 0.29, p = 0.019) and lower apnea-hypopnea index (Spearman r = −0.28, p = 0.031). The pooled current estrogen users spent proportionally less time with SaO 2 below 90% than non-users (ANCOVA adjusted for age and BMI, p = 0.017). Conclusions Estrogen use and especially high serum estradiol concentration predict higher mean overnight arterial oxyhemoglobin saturation. The present data suggest that estrogen therapy has favorable respiratory effects.

Hormone therapy and coronary artery calcification in asymptomatic postmenopausal women: the Rancho Bernardo Study

To determine (1) whether past or current hormone therapy (HT) in postmenopausal women is associated with subclinical coronary artery plaque burden, (2) whether any association is independent of age, body size, blood pressure, lipids, fasting plasma glucose, cigarette smoking, leisure time physical activity, alcohol intake, use of lipid-lowering medications, and socioeconomic status, and (3) whether any association varies by duration of HT or by the use of combined versus unopposed HT. An observational study, with HT validated and coronary heart disease risk factors determined between 1997 and 1999 in a research clinic, and coronary artery calcium score (CACS) evaluated by electron beam computed tomography in 2001 through 2002. Participants were 204 community-dwelling postmenopausal women from the Rancho Bernardo cohort aged 55 to 78 years with no history of heart disease. The odds of severe CACS in current estrogen users (n = 127) was 0.40 (95% CI 0.19, 0.82), controlling for all covariates. Past users (n = 40) had intermediate odds (multiply adjusted OR = 0.66, 95% CI = 0.28, 1.58). In subgroup analyses, age-adjusted associations did not differ between the 68 women using unopposed estrogen versus the 59 using an estrogen-progestin regimen. Women who had used HT for at least 10 years (n = 86) had significantly less (P = 0.01) plaque burden than shorter term users (n = 41). Both the strong association and the duration of use effect independent of lifestyle and social class suggest an antiatherogenic effect of postmenopausal estrogen. Only a clinical trial can completely exclude confounding by social class, lifestyle, and unmeasured covariates.

Prospective study of postmenopausal hormone use and newly diagnosed asthma and chronic obstructive pulmonary disease.

Female reproductive hormones appear to influence asthma, although data are conflicting, and may modulate development of chronic obstructive pulmonary disease (COPD). Therefore, in a prospective cohort study, we evaluated whether postmenopausal hormone use was associated with an increased rate of newly diagnosed asthma and, separately, newly diagnosed COPD. Postmenopausal hormone use was assessed by questionnaire biennially from 1976 onward. New physician diagnoses of asthma or COPD were reported on questionnaires from 1988 to 1996 and confirmed in 1998 using supplementary questionnaires. Grades of diagnostic certainty were established from reports of medication use and pulmonary function using validated definitions. During 546259 person-years of follow-up, current use of estrogen alone was associated with an increased rate of asthma (multivariate rate ratio, 2.29; 95% confidence interval [CI], 1.59-3.29) compared with those who never used hormones. Current users of estrogen plus progestin had a similarly increased rate of newly diagnosed asthma. Rate ratios increased with certainty of diagnosis of asthma. In contrast, rates of newly diagnosed COPD were the same among hormone users and nonusers (multivariate rate ratio, 1.05; 95% CI, 0.80-1.37). Postmenopausal hormone use was associated with an increased rate of newly diagnosed asthma but not newly diagnosed COPD. Female reproductive hormones may contribute to the onset of asthma among adult women, but do not appear to hasten the development of COPD.

Evaluation of dietary, medical and lifestyle risk factors for incident kidney cancer in postmenopausal women.

Kidney cancer incidence rates in the United States have been increasing and are not fully accounted for by better diagnostic techniques. Risk factors in women are incompletely described. A total of 34,637 Iowan women initially free of cancer completed a mailed questionnaire in 1986. Kidney cancer incidence was identified over 15 years of follow-up (n = 124) through linkage to a statewide cancer registry. Adjusted for age and other risk factors, kidney cancer was associated positively with maximum adult weight (p for trend = 0.02) and current waist-to-hip ratio (p for trend = 0.002). Compared to nondrinkers, consumers of alcohol of 3.0 or more grams per day had a relative risk (RR) of 0.52 (95% CI = 0.29-0.92). Total vitamin C intake was associated positively with risk of kidney cancer (p for trend = 0.04), whereas total vitamin E intake was associated negatively with risk (p for trend = 0.002). The few women who used copper supplements had a 6.52-fold increase in risk of kidney cancer (95% CI = 1.95-21.8). Compared to never users, women who were former users of estrogen had an increased risk of kidney cancer (RR = 1.62; 95% CI = 1.11-2.36), but current users of estrogen were not at a higher risk. Women who were nulliparous or had more than 2 live births were also at increased risk of kidney cancer compared with women who had 1 or 2 live births. In conclusion, in these postmenopausal women, overweight, particularly central adiposity, was an important risk factor for kidney cancer. Potential risk factors that warrant further exploration were low intake of alcohol and vitamin E, higher intake of vitamin C, nulli- or multiparity and use of copper supplements.

Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction

AbstractWe hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction = .03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy. (Blood. 2003;102:25-30)

Predictors of sensitivity of clinical breast examination (CBE).

Clinical breast examination (CBE) is one of the most common breast cancer screening modalities, but factors that affect its sensitivity are not well understood. We examined the association between CBE sensitivity and tumor, breast and personal characteristics among members of a managed care organization's Breast Cancer Screening Program (BCSP). The study population was 468 screened women 40 years and older diagnosed with invasive breast cancer between 1988 and 1994 within 1 year of a screening CBE. Logistic regression was used to evaluate the likelihood of a true positive versus a false negative CBE result, after adjustment for age, body weight and tumor size. CBE sensitivity increased with larger tumor size (17% for tumors < or = 0.5 cm and 58% for tumors > or = 2.1 cm, adjusted p for trend < 0.001) and decreased with higher body weight (48 and 23% for the lowest and highest quartiles, adjusted p for trend < 0.001). CBE was more sensitive in Asian women compared to white women (88% v.s. 35%, adjusted p = 0.04) and in current users of estrogen and progesterone combination therapy compared to never/former users (52% v.s. 33%, adjusted p = 0.08). There was an inverted U-shaped association between age and CBE sensitivity (40-49: 26%, 50-59: 48%, 60-69: 36%, 70-79: 33%, 80+: 18%, significant for oldest and youngest groups v.s. age 50-59 years). These findings suggest certain groups of women, for example, obese women and younger women, receive less benefit from CBE.

Postmenopausal hormone replacement therapy: scientific review.

Although postmenopausal hormone replacement therapy (HRT) is widely used in the United States, new evidence about its benefits and harms requires reconsideration of its use for the primary prevention of chronic conditions. To assess the benefits and harms of HRT for the primary prevention of cardiovascular disease, thromboembolism, osteoporosis, cancer, dementia, and cholecystitis by reviewing the literature, conducting meta-analyses, and calculating outcome rates. All relevant English-language studies were identified in MEDLINE (1966-2001), HealthSTAR (1975-2001), Cochrane Library databases, and reference lists of key articles. Recent results of the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) are included for reported outcomes. We used all published studies of HRT if they contained a comparison group of HRT nonusers and reported data relating to HRT use and clinical outcomes of interest. Studies were excluded if the population was selected according to prior events or presence of conditions associated with higher risks for targeted outcomes. Meta-analyses of observational studies indicated summary relative risks (RRs) for coronary heart disease (CHD) incidence and mortality that were significantly reduced among current HRT users only, although risk for incidence was not reduced when only studies that controlled for socioeconomic status were included. The WHI reported increased CHD events (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.02-1.63). Stroke incidence but not mortality was significantly increased among HRT users in the meta-analysis and the WHI. The meta-analysis indicated that risk was significantly elevated for thromboembolic stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral stroke. Risk of venous thromboembolism among current HRT users was increased overall (RR, 2.14; 95% CI, 1.64-2.81) and was highest during the first year of use (RR, 3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies. Protection against osteoporotic fractures is supported by a meta-analysis of 22 estrogen trials, cohort studies, results of the WHI, and trials with bone density outcomes. Current estrogen users have an increased risk of breast cancer that increases with duration of use. Endometrial cancer incidence, but not mortality, is increased with unopposed estrogen use but not with estrogen with progestin. A meta-analysis of 18 observational studies showed a 20% reduction in colon cancer incidence among women who had ever used HRT (RR, 0.80; 95% CI, 0.74-0.86), a finding supported by the WHI. Women symptomatic from menopause had improvement in certain aspects of cognition. Current studies of estrogen and dementia are not definitive. In a cohort study, current HRT users had an age-adjusted RR for cholecystitis of 1.8 (95% CI, 1.6-2.0), increasing to 2.5 (95% CI, 2.0-2.9) after 5 years of use. Benefits of HRT include prevention of osteoporotic fractures and colorectal cancer, while prevention of dementia is uncertain. Harms include CHD, stroke, thromboembolic events, breast cancer with 5 or more years of use, and cholecystitis.

Use of low potency estrogens does not reduce the risk of hip fracture

High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50–81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67–1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58–1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61–1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49–0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.

"Doctor, are you trying to kill me?": ambivalence about the patient package insert for estrogen.

In 1976, the U.S. Food and Drug Administration proposed new requirements for patient labeling for estrogens prescribed for menopausal and postmenopausal women. This paper explores the variety of responses to this proposal from women and their husbands, feminist and consumer activists, physicians, pharmacists, and pharmaceutical manufacturers, as represented in letters written to the FDA. The drug industry and the medical profession opposed patient labeling on the grounds of cost and a resentment of governmental intrusion. Feminists and consumer advocates were in favor of the idea, but the response from current estrogen users was mixed: most women wished to be better informed, but many expressed concern that estrogen would be removed from the market. This ambivalence suggests unresolved tensions regarding conceptions of female aging, the medical management of menopause and aging, informed consent in medicine, and governmental regulation of medical practice. The debate thus represents an important moment in the history of women's health care.

Hysterectomy, oophorectomy, and cognitive function in older women.

It has been proposed that estrogen deficiency is a cause of memory loss in postmenopausal women. Bilateral oophorectomy leads to an abrupt decrease in gonadal hormone levels including testosterone. Hysterectomy with ovarian conservation may also lead to a decline in ovarian hormones. This study examines the effects of hysterectomy and oophorectomy on cognitive function in a large sample of older, postmenopausal women with and without current estrogen replacement therapy. Cross-sectional. Community-based sample in Southern California. Subjects were 885 postmenopausal women aged 60 to 89 who were initially enrolled in the Rancho Bernardo Study between 1972 and 1974 and had a follow-up clinic visit in 1988-91. All were Caucasian, middle to upper-middle class, relatively well educated, and ambulatory. Participants completed 12 standardized tests of cognitive function in 1988-91. Hysterectomy and oophorectomy status were assessed and use of estrogen therapy was also ascertained and validated. Of the 885 women, whose mean age +/- standard deviation was 74.3 +/- 7.5, 225 reported having had a hysterectomy with conservation of one or both ovaries and 190 reported having a hysterectomy with bilateral oophorectomy. Current estrogen use was reported by 35.4%. Among women not using estrogen, there were no significant differences on mean cognitive function scores by hysterectomy and oophorectomy status. Among current estrogen users, after adjustment for age, education, age at menopause, and past estrogen use, those with a hysterectomy and bilateral oophorectomy performed significantly less well on serial sevens and Trails B. These differences, although statistically significant, were small and unlikely to be of clinical significance. No differences in cognitive function were observed between women who had a hysterectomy with ovarian conservation and intact women. The present study suggests that, overall, there are no long-term effects of hysterectomy and bilateral oophorectomy on cognitive function and does not support the thesis that estrogen deficiency is associated with poor cognitive function in postmenopausal women.

Postmenopausal hormone use and lens opacities

purpose Women are at higher risk for age-related cataract than men, and it has been hypothesized that this difference is due in part to gender-related hormonal differences. methods We investigated the association between postmenopausal hormone use and lens opacities in a population of 480 postmenopausal women from the Nurses' Health Study for whom we had prospectively collected exposure data. Participants received standardized eye exams; the Lens Opacity Classification System III (LOCS III) was used to measure the degree of opacification. results A total of 342 women had some opacity in one or both eyes. Overall, we did not observe a significant association between current hormone use and presence of any type of opacity (compared to never users, multivariate relative risk: 0.85; 95% confidence interval (CI): 0.54–1.34). In ordinal logistic regression compared to never users, current hormone users had multivariate relative risks of cortical opacities of 0.80 (95% CI: 0.54–1.19) and for past users the relative risk was 0.76 (95% CI: 0.48–1.22). For nuclear opacities, the comparable relative risk for current use of hormones was 0.77 (95% CI: 0.52–1.13), and for past use the relative risk was 1.48 (95% CI: 0.92–2.34). Current use of estrogen-only preparations was associated with a 49% decreased risk of nuclear opacities compared to never use (multivariate relative risk 0.51, 95% CI: 0.29–0.89). conclusions While the overall findings are null, they do not exclude the possibility of a protective effect, particularly among current estrogen users.

Hormone Replacement Therapy and Cardiovascular Disease

In Canada, cardiovascular diseases (CVD) are the leading cause of mortality. In 1998, CVD were responsible for 39,447 deaths among Canadian women (almost 38% of all deaths in women), which is greater than the number of deaths for women due to all cancers combined. The proportion of deaths due to CVD in women increases significantly after menopause and continues to increase with advancing age. It remains unclear, however, whether this increase in incidence of CVD in middle-aged and elderly women is caused by lower estrogen levels or is an overall manifestation of advancing age. The use of hormone replacement therapy (HRT), especially estrogen, has been advocated as a means to reduce the risk of CVD. Menopause is associated with adverse effects on blood lipids including an increase in total cholesterol, LDL cholesterol, and triglycerides, and a decrease in HDL cholesterol. Reduced estrogen levels after menopause can also lead to adverse changes in blood pressure, obesity, body fat distribution, blood clotting factors, glucose metabolism and diabetes, all of which increase the risk of coronary heart disease. Laboratory studies have found evidence for both beneficial and adverse effects of estrogen. Oral estrogen has been shown to lower LDL cholesterol, lipoprotein (a), and increase HDL cholesterol. There is accumulating evidence that estrogen improves endothelial function, thus enhancing vasodilatation. In addition, estrogen replacement is associated with reduced blood levels of fibrinogen and plasminogen activator inhibitor-1, and may thus have anti-thrombotic and pro-fibrinolytic effects. However, other effects may be pro-inflammatory (increased C-reactive protein) and pro-coagulant and therefore detrimental to the overall cardiovascular risk profile. As estrogen is usually prescribed with progestin in those women with a uterus in order to protect against endometrial cancer, some of the beneficial cardiovascular effects may be attenuated by the addition of progestin (such as a lesser effect on HDL cholesterol). Other routes of administration of estrogen may have less favourable effects on plasma lipoproteins, but may be beneficial in other ways. Selective estrogen receptor modulators (SERMs) are also being studied because these may result in direct cardiovascular effects. The evidence for a protective effect of estrogen on coronary heart disease is based on over 30 observational epidemiologic studies conducted over the last two decades. These studies have shown a 40% reduction in the risk of coronary heart disease for current users of estrogen or estrogen and progestin compared to women who have never used these hormones. Recent updates have confirmed this conclusion, even with lower doses of estrogen, and have also found no effect of HRT on stroke. However, these types of studies are hampered by an inability to control completely for confounding factors, including the fact that women who are compliant with HRT

Back problems among postmenopausal women taking estrogen replacement therapy: the study of osteoporotic fractures.

Cross-sectional and prospective. To investigate the association between estrogen replacement therapy use, back pain, and back function in a large cohort of elderly women. Several studies have suggested that women who use estrogen replacement therapy may be more likely to experience back pain than those who do not. However, the relationships between estrogen replacement therapy, back pain, and impaired back function have not been clearly delineated. At baseline information on estrogen replacement therapy use, functional status, back pain and function, and general lifestyle variables was obtained from 7209 elderly white women (mean age 71 years)enrolled in the Study of Osteoporotic Fractures. Lateral radiographs of the lumbar and thoracic spine were taken at baseline and at the third clinic visit, an average of 3.7 years after the baseline visit. Bone mineral density at the hip and spine was measured approximately 2 years after baseline. Follow-up information on back pain and function was also obtained at the third clinic visit. A total of 1039 (14.4%) women were using estrogen replacement therapy at baseline, 2016(28.0%) reported former use, and 4154 (57.6%) had never used estrogen replacement therapy. Compared with never-users, a statistically significant higher percentage of current estrogen users reported clinical back pain (52.7% vs. 43.4%) and back impairment (12.3% vs. 9.2%) at baseline and at the follow-up visit (pain 50.8% vs. 41%; impairment 16.0% vs. 12.1%). This occurred despite a higher prevalence of vertebral fractures in never-users of estrogen at the baseline visit. Current and former estrogen users without vertebral fractures had statistically significant higher likelihoods of having back pain and back dysfunction at both the baseline and third follow-up visit. The increased likelihood of back pain and back impairment in current and former estrogen users remained despite statistical adjustment for age, vertebral fracture, body mass index,smoking history, parity, exercise, arthritis, and diabetes in multivariate models. The relative risk (95%confidence interval) for impaired back function in former and current users at follow-up was 1.1 (0.9, 1.3) and 1.6 (1.3, 2.0), respectively. Our results indicate that postmenopausal estrogen use is associated with an increased likelihood of back pain and impaired back function in elderly white women.

Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease.

Previous studies have examined the relation between postmenopausal estrogen replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings have been inconsistent, since some studies have been interpreted as showing a protective effect while others have reported no effect. To determine whether exposure to ERT is associated with a reduced risk of AD. Population-based nested case-control study. The United Kingdom-based General Practice Research Database. The base cohort consisted of women who were recipients of ERT (n = 112 481) and a similar cohort of women who did not use estrogens (n = 108 925). The 2 cohorts were restricted to women born on or before January 1, 1950. From the 2 cohorts, we identified and verified 59 newly diagnosed cases of AD and 221 matched control subjects. Prior and current use of ERT in cases compared with controls. Among the 59 newly diagnosed cases of AD, 15 (25%) were current estrogen users, while among the controls, 53 (24%) were current users. The adjusted odds ratio comparing all current estrogen recipients with nonrecipients was 1.18 (95% confidence interval, 0.59-2.37). In estrogen users who took the drug for 5 years or longer compared with nonusers, the odds ratio was 1.05 (95% confidence interval, 0.32-3.44). Odds ratios were similar for estrogen recipients who received estrogens alone and recipients who received combined estrogen-progestin treatment. The use of ERT in women after the onset of menopause was not associated with a reduced risk of developing AD.

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.

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.