Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Longitudinal study of hormone levels and depression among women transitioning through menopause.

OBJECTIVE: To address the association between depression and absolute levels of estradiol, and change in estradiol, among women during the menopausal transition. METHODS: This was a prospective, observational study conducted in Massachusetts, USA. Analyses reported here are based on the first three interviews following baseline (T1-T3). The participants were 309 women aged initially 43-53 years, who contributed a total of 728 observations (mean number of observations per subject 2.36). The main outcome measure was depression as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. RESULTS: CES-D score was not significantly associated with menopause status categories, nor was it associated with annual change in estradiol level (E2) (p = 0.19). The unadjusted association between log E2 and CES-D was negative (odds ratio 0.69) and statistically significant (p = 0.03). Upon adjustment for symptoms, however, the association remained negative but was no longer statistically significant (p = 0.26). Hot flushes/night sweats were positively associated with CES-D (p = 0.04), and trouble sleeping was strongly positively related to CES-D (p < 0.001). CONCLUSIONS: Results provide strong support for the domino or symptom hypothesis, which posits that depressed mood is caused by vasomotor symptoms associated with changing estrogen levels. Estradiol did not have a direct effect, independent of symptoms. This study adds to the body of literature suggesting that any association found between menopause and depression is most likely to be explained by other factors, such as symptoms and sleep problems. Findings also highlight the importance of studying the complex relationship between hormone levels, sleep problems and vasomotor symptoms during the menopausal transition.

Metabolism of orally administered androstenedione in young men.

Androstenedione is a steroid hormone and the major precursor to testosterone. It is available without prescription and taken with the expectation that it will be converted to testosterone endogenously and increase strength and athletic performance. The metabolism of orally administered testosterone has not been well studied. We randomly assigned 37 healthy men to receive 0, 100, or 300 mg oral androstenedione in a single daily dose for 7 d. Single 8-h urine collections were performed on the day before the start of the androstenedione administration and on d 1 and 7 to assess excretion rates of free and glucuronide- conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone. Serum testosterone glucuronide concentrations were measured by frequent blood sampling over 8 h on d 1 in 16 subjects (5 each in the 0 and 100 mg group and 6 in the 300 mg group). In the control group, mean (+/-SE) d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 3 +/- 1, 215 +/- 26, 175 +/- 26, and 0.4 +/- 0.1 microg/h, respectively. In the 100 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 47 +/- 11, 3,836 +/- 458, 4,306 +/- 458, and 1.6 +/- 0.2 microg/h, respectively. In the 300 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 115 +/- 39, 8,142 +/- 1,362, 10,070 +/- 1,999, and 7.7 +/- 1.5 microg/h, respectively. Urinary excretion rates of all metabolites were greater in both the 100 and 300 mg groups than in controls (P < 0.0001). Urinary excretion rates of testosterone (P = 0.007), androsterone (P = 0.009), etiocholanolone (P = 0.0005), and dihydrotestosterone (P < 0.0001) were greater in the subjects who received 300 mg androstenedione than in those who received 100 mg. In the treated groups, excretion of free testosterone accounted for less than 0.1% of the total excreted testosterone measured. Serum testosterone glucuronide levels increased significantly during frequent blood sampling in both the 100 and 300 mg groups compared with controls (P = 0.0005 for the 100 mg group; P < 0.0001 for the 300 mg group). The net mean changes in area under the curve for serum testosterone glucuronide were -18 +/- 25%, 579 +/- 572%, and 1267 +/- 1675% in the groups receiving 0, 100, and 300 mg/d androstenedione, respectively. We conclude that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than the changes observed in serum total testosterone concentrations. These findings demonstrate that orally administered androstenedione is largely metabolized to testosterone glucuronide and other androgen metabolites before release into the general circulation.

Regulation of sex hormone-binding globulin secretion in human hepatoma G2 cells.

Our purpose was to examine the roles of natural (estradiol (E2) and estrone (E1)) and synthetic estrogens (ethinyl estradiol (EE), moxestrol (MOX), and tamoxifene (TAM)) in regulating production of sex hormone-binding globulin (SHBG) by human hepatoma G2 (Hep G2) cells, the rationale being that synthetic estrogens are less rapidly metabolized than natural estrogens and, thus, may alter SHBG levels more readily. In Hep G2 cells, E2, E1, and EE at 10(-7) M did not result in significantly greater SHBG secretion compared to control cells. The synthetic estrogens, MOX and TAM, caused significant, P < 0.001, increases of 30% and 51% in SHBG secretion at 10(-7) M compared to controls. However, when TAM and E2 were added together, each at 10(-7) M, no increase in SHBG secretion was noted. We conclude that natural estrogens at physiologic concentrations do not increase SHBG secretion by Hep G2 cells, but the increase of SHBG secretion caused by MOX and TAM suggests that the lack of effect of E2 and E1 may, in part, be due to their rapid metabolism. In addition, TAM stimulates SHBG secretion by interaction with the genome that is different, in certain respects, from that of E2.

Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study.

OBJECTIVES: To determine whether prediagnostic serum hormones are predictive of prostate cancer risk in a sample of men 40 to 70 years old at baseline. METHODS: Seventeen serum hormones, including androgens, estrogens, and adrenal and pituitary hormones, were measured at baseline (1987 to 1989) and used to predict incident prostate cancer by follow-up (1995 to 1997) using data from the Massachusetts Male Aging Study, a prospective, population-based random sample. RESULTS: Seventy men (4%) of 1576 were diagnosed with prostate cancer between the baseline and follow-up periods (approximately 8 years). None of the hormones were associated with prostate cancer risk except for androstanediol glucuronide (AAG), which exhibited a nonlinear, inverse relationship with prostate cancer (P <0.003) when age, body mass index, alcohol use, dihydrotestosterone, and total prostate-specific antigen were controlled for. Men in the second, third, and fourth quartiles of AAG relative to the first were less likely to be diagnosed with prostate cancer, although only the comparison of the second versus the first achieved statistical significance (odds ratio 0.2, 99% confidence interval 0.04 to 0.6). No dose-response relationships were observed. CONCLUSIONS: The lack of association with most hormones and the nonlinear association with AAG calls into question whether serum hormones collected during midlife are risk factors for prostate cancer.

Sources of elevated serum androgens in postmenopausal women who develop breast cancer.

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (Delta4A). 11beta-Hydroxyandrostenedione (11betaOHA) is elevated, and the Delta4A:11betaOHA ratio is depressed when the adrenals are the primary source of elevated Delta4A in women. Conversely, Delta4A:11betaOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11betaOHA and Delta4A:11betaOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Delta4A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta4A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However, neither 11betaOHA concentration nor Delta4A:11betaOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11betaOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta4A:11betaOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta4A in postmenopausal women who develop breast cancer, but rather both may contribute.

Macronutrient intake and estrogen metabolism in healthy postmenopausal women.

The purpose of this study was to determine if dietary factors could bias estimates of the relationships between estrogen metabolites and breast cancer risk factors. A lower ratio of urinary 2-hydroxyestrone/16alpha-hydroxyestrone (2/16) has been associated with breast cancer diagnosis. However, both estrogen metabolism and breast cancer risk have been associated with dietary intake, and breast cancer patients may have different dietary patterns than healthy controls. An association between urinary 2/16 levels and breast cancer risk may be due to transitory dietary change after diagnosis, or due to other breast cancer risk factors which have been associated to steroid hormone metabolism. Thirty-seven healthy postmenopausal women provided two 24-h urine samples at a two-week interval. Six 24-h diet recalls were administered in this same time period. In linear regression analysis, dietary fat-to-fiber ratio (fat/fiber) and the saturated fat/soluble fiber ratio was inversely associated with urinary 2/16 values (b = -0.22, 95% CI (-0.43, -0.01); b= -0.26, 95% CI (-0.43, -0.09), respectively). The effects of these dietary factors on 2/16 were independent of body mass index or other breast cancer risk factors. These study results suggest that some of the variation in estrogen metabolite levels among postmenopausal Caucasian women may be due to dietary intake, and that dietary factors should be carefully measured and evaluated when investigating the relationship between estrogen metabolites and breast cancer risk.

Endocrine function of the postmenopausal ovary.

The ovaries of postmenopausal women are smaller than those of premenopausal women and consist primarily of stromal cells. These cells have receptors for, and respond to, gonadotropins and secrete testosterone and lesser amounts of other androgens and estrogens. The ovaries of some postmenopausal women contain P-450 aromatase and secrete estradiol. There is little evidence that inhibins A or B are secreted by postmenopausal ovaries.

Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.

Sex hormone levels in premenopausal African-American women with upper and lower body fat phenotypes.

Body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. This cross-sectional study of 106 healthy premenopausal African-American (AA) women compared the midfollicular phase sex hormone and sex hormone-binding globulin levels in upper body fat (UBF) and lower body fat (LBF) phenotype and obese and nonobese women. Multivariate regression analyses were used to control for various confounders, including dietary factors. UBF phenotype women had 37% (P = 0.02), 50% (P = 0.01), 52% (P = 0.007), and 50% (P = 0.009) higher levels of estradiol (E2), free E2, testosterone (T), and free T, respectively, than LBF phenotype women. Only %free T was higher in obese than in nonobese women (P = 0.02). The levels of E2, free E2, %free E2, T, and free T were higher [by 42% (P = 0.01), 68% (P = 0.001), 18% (P = 0.04), 36% (P = 0.04), and 61% (P = 0.01), respectively] and the level of sex hormone-binding globulin was lower [by 28% (P = 0.04)] in obese UBF than in nonobese LBF phenotype women. These findings support the hypothesis that body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. Obese UBF phenotype AA women, in particular, have a high-risk hormonal profile. Future breast cancer studies might consider controlling for measures of obesity and body fat distribution to minimize confounding.

Is there an association between menopause status and sexual functioning?

OBJECTIVE: The purpose of this study was to address whether: (1) there is an association between menopause status and various aspects of sexual functioning, and (2) the relative contributions of menopause status and other variables to various aspects of sexual functioning. DESIGN: Analyses are based on 200 women from the Massachusetts Women's Health Study II, a population-based sample of women transitioning through the menopause who were not HRT users, who had not had a surgical menopause, and who had partners. The women were classified as pre-, peri-, or postmenopausal according to menstrual cycle characteristics. Estradiol, estrone, and follicle-stimulating hormone were also measured. Sexual functioning was measured in terms of satisfaction, desire, frequency of sexual intercourse, belief that interest declines with age, arousal compared with a younger age, difficulty reaching orgasm, and pain. Predictor variables included sociodemographics, health, vasomotor symptoms, psychological variables, partner variables, and lifestyle behaviors. RESULTS: Menopause status was significantly related to lower sexual desire, a belief that interest in sexual activity declines with age, and women's reports of decreased arousal compared with when in their 40s. Menopause status was unrelated to other aspects of sexual functioning in either unadjusted or multiple regression analyses. In analyses in which log estradiol (E2) was included in addition to menopause status, log E2 was only related to pain. In multiple regression analyses, other factors such as health, marital status (or new partner), mental health, and smoking had a greater impact on women's sexual functioning than menopause status. CONCLUSIONS: Menopause status, but not E2, is related to some, but not all, aspects of sexual functioning. This may be due to menopause per se or other factors associated with menopause and aging (e.g., increased sexual dysfunction among aging men). Menopause status has a smaller impact on sexual functioning than health or other factors.

Brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women.

Previous studies suggest that the estrogen metabolite 16alpha-hydroxyestrone acts as a breast tumor promoter. The alternative product of estrogen metabolism, 2-hydroxyestrone, does not exhibit estrogenic properties in breast tissue, and lower values of the ratio 2-hydroxyestrone:16alpha-hydroxyestrone (2:16) in urine may be an endocrine biomarker for greater breast cancer risk. Vegetables of the Brassica genus, such as broccoli, contain a phytochemical, which may shift estrogen metabolism and increase the 2:16 ratio. Adding 500 g/day of broccoli to a standard diet shifts 2:16 values upward in humans; however, it is unknown as to whether healthy women are able to consume a sufficient quantity of Brassica to affect breast cancer risk through this mechanism. In this study, 34 healthy postmenopausal women participated in an intensive intervention designed to facilitate the addition of Brassica to the daily diet. The diet was measured by repeated 24-h recall, and estrogen metabolites were measured by enzyme immunoassay in 24-h urine samples. In a crude analysis, there was a nonsignificant increase in the urinary 2:16 ratio associated with greater Brassica consumption. With adjustment for other dietary parameters, Brassica vegetable consumption was associated with a statistically significant increase in 2:16 values, such that for each 10-g/day increase in Brassica consumption, there was an increase in the 2:16 ratio of 0.08 (95% confidence interval, 0.02-0.15). To the extent that the 2:16 ratio, as measured in urine, is associated with breast cancer risk, future research should consider Brassica vegetable consumption as a potentially effective and acceptable dietary strategy to prevent breast cancer.

Oral androstenedione administration and serum testosterone concentrations in young men.

CONTEXT: Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. OBJECTIVE: To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. DESIGN: Open-label randomized controlled trial conducted between October 1998 and April 1999. SETTING: General clinical research center of a tertiary-care, university-affiliated hospital. PARTICIPANTS: Forty-two healthy men aged 20 to 40 years. INTERVENTION: Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. MAIN OUTCOME MEASURES: Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. RESULTS: Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. CONCLUSIONS: Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.

Diet and sex hormone-binding globulin.

The serum concentration of sex hormone-binding globulin (SHBG) is inversely related to weight and in animal studies is inversely related to protein intake. As SHBG can affect the biological activity of testosterone and estradiol, we wished to determine the role of protein intake on SHBG levels in men. Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men (aged 40-70 yr) for whom these factors were known. Analyzed by multiple regression, controlling for testosterone and estradiol levels, age (P<0.001) and fiber intake (P = 0.02) were positively correlated to SHBG concentration, whereas body mass index (P<0.001) and protein intake (P<0.03) were negatively correlated to SHBG concentration. The intakes of calories, fat (animal or vegetable), and carbohydrate were not related to SHBG concentration. We conclude that age and body mass index are major determinants of SHBG concentrations in older men, and fiber and protein intake are also significant contributors to SHBG levels, but total caloric intake and the intake of carbohydrate or fat are not significant. Thus, diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity. The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass, and contribute to the loss of bone density.

Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women.

BACKGROUND: In animal studies, prolactin has been found to be important for mammary epithelial development and its administration has been shown consistently to increase the rate of mammary tumor formation. Previous epidemiologic studies of prolactin and breast cancer risk in postmenopausal women have been limited in size, and the results have been inconsistent. We conducted a nested case-control study within the prospective Nurses' Health Study cohort to better determine the relationship between plasma prolactin levels and postmenopausal breast cancer risk. METHODS: Blood samples were collected from cohort members during the period from 1989 through 1990. Prolactin levels were measured by use of a microparticle enzyme immunoassay. Included in this analysis were 306 postmenopausal women who were diagnosed with breast cancer after blood donation but before June 1994. One or two postmenopausal control subjects were matched per case subject on the basis of age, postmenopausal hormone use, and time of day and month of blood collection; the study included a total of 448 control subjects. RESULTS: In conditional logistic regression analyses, a significant positive association was observed between plasma level of prolactin and postmenopausal breast cancer risk (highest versus lowest quartile, multivariate relative risk = 2.03; 95% confidence interval = 1.24-3.31; two-sided P for trend = .01). The relationship was independent of plasma sex steroid hormone levels and was similar after excluding case subjects diagnosed in the first 2 years after blood collection. CONCLUSIONS: These prospective data suggest that higher plasma prolactin levels are associated with an increased risk of breast cancer in postmenopausal women.

Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women's Health Study.

Low circulating levels of the adrenal steroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are thought to be associated with increased risk of cardiovascular disease (CVD) in men. In women, either a positive or null association with CVD has been found. The nature of the relation between DHEAS and CVD risk factors in women is unclear and is based on cross-sectional data. We present results from a longitudinal investigation of serum DHEA and DHEAS and cardiovascular disease risk factors in 236 women, initially 50-60 years old, from a population-based prospective (1986-1995) study of the menopausal transition. We used generalized estimating equations to model the relation of serum DHEA and DHEAS to systolic and diastolic blood pressure and serum levels of total cholesterol, high density lipoprotein cholesterol, and apolipoproteins A and B, adjusting for other factors related to CVD. Both DHEA and DHEAS were positively related to diastolic and systolic blood pressure, and DHEAS was negatively related to apolipoprotein A. DHEA and DHEAS were also positively related to smoking, alcohol use, estrone, and estradiol levels, and inversely related to age. Our results suggest that higher levels of DHEA and DHEAS in middle-aged women may indicate increased CVD risk.

Plasma steroid hormones, surgery for benign prostatic hyperplasia, and severe lower urinary tract symptoms.

Because benign prostatic hyperplasia (BPH) may be influenced by plasma steroid hormones, we examined their relation in the Health Professionals Follow-up Study. In 1993-1995, 18,000 cohort members provided blood. We selected as cases men who had had surgery for BPH (n=174) or who scored 20-35 points (n=126) on the American Urological Association index of severity of lower urinary tract symptoms. Cases were matched by age to men who scored