Metabolism of dehydroepiandrosterone.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C Longcope
Publications and source records attributed to C Longcope.
Serum gonadotropins and steroid hormones and the development of ovarian cancer.
OBJECTIVE: To prospectively examine the association between endogenous hormones and development of ovarian cancer. DESIGN: Nested case-control study. SETTING: A population-based serum bank in Washington County, Maryland. PARTICIPANTS: Serum samples were collected in 1974 from 20305 county residents and stored at -70 degrees C. From 1975 through 1989, a total of 31 cases of ovarian cancer were identified in women who were not taking hormones at the time of blood collection. These cases were matched to 62 controls on age, menopausal status, and, for premenopausal women, number of days from the beginning of the last menstrual period. MAIN OUTCOME MEASURE: Prediagnostic endogenous hormone levels of cases and controls were compared. RESULTS: Mean follicle-stimulating hormone levels were lower among cases (43.3 IU/L) compared with controls (54.4 IU/L) (P = .04), and increasing levels were associated with significantly lower risk (P for trend = .01), particularly among postmenopausal women. Luteinizing hormone levels were 9% lower among cases than controls, but the difference was not statistically significant (P = .39). Compared with controls, cases had higher androstenedione levels (4.5 nmol/L vs 3.3 nmol; P = .03) and higher dehydroepiandrosterone (DHEA) levels (15.9 nmol/L vs 9.7 nmol/L; P = .02). The risk of ovarian cancer increased with higher levels of androstenedione and DHEA sulfate (P for trend = .008 and .11, respectively). These associations were not materially different between premenopausal and postmenopausal women. CONCLUSION: The results suggest that women with low serum gonadotropin levels or high androgen levels have an increased risk of ovarian cancer. These findings do not support the hypothesis that pituitary gonadotropins increase the risk of ovarian cancer. Replication of the study in other populations is highly desirable.
Adult↗
Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women.
BACKGROUND: Alcohol use, height, and postmenopausal adiposity have each been positively associated with postmenopausal breast cancer risk in most epidemiologic studies. The mechanism underlying these associations is unclear, although an effect of these factors on hormone levels has been hypothesized. Few previous studies have evaluated the relationship of either alcohol consumption or height with plasma hormone levels. A positive association between adiposity and plasma estrogen levels in postmenopausal women has been reported consistently. PURPOSE: Using archived frozen plasma samples and corresponding data from participants in the Nurses' Health Study, we determined plasma hormone levels and assessed these levels in relation to alcohol consumption, height, and adiposity among postmenopausal women. METHODS: Blood samples were collected from a subset of participants in the Nurses' Health Study in 1989 and 1990, then stored in liquid nitrogen. Hormone concentrations in 217 archived plasma samples (from healthy postmenopausal women) were analyzed in 1993. Spearman correlation coefficients were calculated to assess the linear association between alcohol consumption during the previous year (mean daily intake in grams per day ascertained from semiquantitative food-frequency questionnaires completed in 1990 or 1991), height, and adiposity (as measured by body mass index [BMI] in kg/m2, with weight reported at time of blood collection), and plasma hormone levels. Two-sided P values were also calculated. RESULTS: After controlling for age, height, smoking status, and BMI, alcohol consumption was positively associated with estrone sulfate concentrations (r = .17; P = .02); no statistically significant association was noted for the other plasma hormones measured. Mean plasma estrone sulfate levels were 159 pg/mL in women who reported no alcohol use versus 211 pg/mL in women consuming 30 g or more of alcohol per day. After adjusting for the other covariates, we observed a strong positive correlation between BMI and plasma estrogens (r ranging from .37 for estrone and estrone sulfate to .63 for bioavailable estradiol, with all P values < or = .01; prolactin was the only hormone unassociated with BMI, r = -.01). Height was unrelated to either plasma estrogens or prolactin. CONCLUSIONS: BMI and alcohol use were positively associated with postmenopausal plasma estrogen and estrone sulfate levels, respectively. IMPLICATIONS: The association of alcohol consumption and postmenopausal obesity with subsequent breast cancer risk might be mediated, at least in part, through an influence on postmenopausal plasma estrogen levels. Additional studies are needed to further quantify the relationship between alcohol consumption and plasma hormone levels and to elucidate the physiologic basis for this association.
Adult↗
A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia.
We assessed the relation of plasma hormone levels and nonhormonal factors with subsequent occurrence of surgical treatment for benign prostatic hyperplasia (BPH) among participants in the Physicians' Health Study. Frozen plasma samples, collected at the study onset, were available for 320 men who developed surgically treated BPH up to 9 years later and for 320 age-matched controls. Plasma testosterone (T), dihydrotestosterone (DHT), androstenedione, estradiol (E2), and estrone (E1) were measured for each case-control pair. In unadjusted analyses, none of the hormones or hormone ratios were associated with BPH; for example, for T and E2 the odds ratios (OR) comparing the highest quintile (Q5) with the lowest (Q1) were 0.74 (95% CI = 0.42, 1.30) and 1.07 (95% CI = 0.51, 2.22), respectively. However, in multivariate analyses controlling diastolic blood pressure, exercise, alcohol, E1, and DHT:T ratio, we observed a strong trend for increasing risk across quintiles for E2 (Q5 vs. Q1 OR = 3.56, P trend = 0.009), and a weak inverse trend for E1 (Q5 vs Q1 OR = 0.51, P trend = 0.07). The excess risk associated with E2 was confined to men with relatively low androgen levels. Three nonhormonal factors previously suspected as risk factors were independently associated with surgical BPH in these data. The OR for a 1-mm Hg difference in diastolic blood pressure was 1.04 (95% CI = 1.01, 1.07). Alcohol use and infrequent exercise were inversely associated with risk of BPH surgery; however, risk estimates were not consistent across categories of exercise and alcohol frequency. Our results indicate that normal variation in circulating androgen levels does not influence development of BPH, but that variation in estrogen levels might be important.
Adult↗
The relation of body size to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States).
We analyzed data from a cross-sectional study of 107 premenopausal women to evaluate the relations of height, weight, and body mass index (BMI) with plasma hormone levels. Participants were 20- to 40-year old women residing in Maryland (United States), whose reported menstrual cycle lengths were not more than 35 days and whose measured weights for height were 85 to 130 percent of 'desirable' based on 1983 Metropolitan Life Insurance tables. Fasting blood specimens were collected on each of days 5-7, 12-15, and 21-23 of every participant's menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Adjusted for age, taller women had significantly higher follicular-phase plasma-estradiol levels (percent difference/cm = 1.5, 95 percent confidence interval [CI] = 0.3-2.7, and heavier women had significantly lower plasma sex-hormone binding globulin (SHBG) levels averaged across the menstrual cycle phases (percent difference/kg = -1.2; CI = -1.9-(-0.6). Body weight within the range studied, however, was not related significantly to the concentration of SHBG-bound estradiol during any phase of the menstrual cycle. The results of this cross-sectional study suggest a possible mechanism by which height may influence breast cancer risk.
Adult↗
Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses' Health Study (United States).
Parity, age at first birth, age at menarche, and a family history of breast cancer have each been associated consistently with breast cancer risk. Whether this increase in risk is mediated, at least in part, through changes in endogenous hormone levels is unclear. We conducted a cross-sectional study of the relationships between these factors and plasma hormone levels in 216 healthy postmenopausal women in the Nurses' Health Study (United States). The hormones evaluated were estradiol, percent and total free estradiol, percent and total bioavailable estradiol, estrone, estrone sulfate, and prolactin. After controlling for age, body mass index (weight/height2), and alcohol use, we observed inverse associations between estrone sulfate and parity (r = -0.15, P = 0.03) and between percent bioavailable estradiol and age at first birth (r = -0.17, P = 0.02). Although women with a family history of breast cancer tended to have higher estrogen levels compared with women without such history, the differences were not statistically significant. Age at menarche was not related significantly to any of the hormones. These data provide some additional evidence that the inverse relationship observed between parity and breast cancer risk may be mediated, at least in part, through decreased estrogen levels. Our data do not support a substantial influence of either family history of breast cancer or age at menarche on postmenopausal estrogen or prolactin levels.
Adult↗
Binding of 17-alpha-methyltestosterone in vitro to human sex hormone binding globulin and rat ventral prostate androgen receptors.
We measured the relative binding affinity (RBA) of 17-alpha-methyltestosterone (MET) for the rat prostate androgen receptor and human sex hormone-binding globulin (SHBG) in vitro. The reference compound in both instances was dihydrotestosterone (DHT), the RBA of which was set at 100%. The RBA of methyltestosterone was 44% for the androgen receptor, but 11% for SHBG. The androgen receptor, therefore, would appear to recognize a different part of an androgen compared to the recognition site on SHBG. The difference in RBAs may amplify the biologic action of methyltestosterone.
Animals↗
Relationships of age and reproductive characteristics with plasma estrogens and androgens in premenopausal women.
We used data from a cross-sectional study of 107 premenopausal women to evaluate the relation of age, menarcheal age, parity, and age at first live birth with plasma estrogen and androgen levels in premenopausal women. Fasting blood specimens were collected on each of days 5-7, 12-15, and 21-23 of menstrual cycles of the participants and pooled to create follicular, midcycle, and luteal phase samples, respectively, for each woman. Age was associated significantly and positively with plasma estradiol levels during the follicular phase [percentage difference/year = 2.6; 95% confidence interval (CI) = 1.0-4.2] and midcycle (percentage difference/year = 2.7; 95% CI = 0.9-4.7) but not the luteal phase (percentage difference/year = -0.4; 95% CI = -1.9-1.3) of the menstrual cycle. The relation of age to plasma estradiol varied by parity, with significant interactions during midcycle and luteal phase. Among nulliparous women, plasma estradiol levels increased with age midcycle and during the luteal phase, but among parous women estradiol levels decreased with age during these phases of the menstrual cycle. Plasma estrone increased with age in all women during the follicular phase of the menstrual cycle (percentage difference/year = 1.5; 95% CI = 0.2-2.8). During the luteal phase there was a significant interaction with parity; estrone levels in nulliparous women varied only slightly with age, but levels in parous women decreased significantly as age increased. The androgens, androstenedione and dehydroepiandrosterone sulfate decreased, and sex hormone-binding globulin increased as age increased. The results of this cross-sectional study suggest that pregnancy may modify age-related changes in plasma estrogen levels.
Adult↗
Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period.
We evaluated the reproducibility of plasma hormone levels over time in 79 healthy postmenopausal women, ages 51-69 years at baseline, who were not using postmenopausal hormones. Three blood samples were collected between 1989 and 1992 from each of these women. We assessed plasma levels of estradiol, free estradiol, percentage of free estradiol, bioavailable estradiol, percentage of bioavailable estradiol, estrone, estrone sulfate, sex hormone-binding globulin (SHBG), androstenedione, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin at each of three sample collections. The means and SD for each of the plasma estrogens, SHBG, and prolactin were similar at each collection. For the androgens, plasma levels tended to decrease over time consistent with an aging effect; decreases with increasing age were statistically significant for androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Intraclass correlation coefficients (ICCs) ranged from 0.92 (95% confidence interval = 0.89-0.95) for SHBG to 0.53 (95% confidence interval = 0.43-0.69) for prolactin. Most correlations were at least 0.70. The ICCs did not vary by age or time since menopause. Women who changed weight over the course of the study tended to have lower ICCs for a number of the hormones, although these differences were not statistically significant. These data indicate that, for most of these plasma hormones, a single measurement can reliably categorize average levels over at least a 3-year period in postmenopausal women.
Age Distribution↗
The effect of dietary fat and fiber on serum estrogen concentrations in premenopausal women under controlled dietary conditions.
The effect of dietary fiber and fat on serum sex hormones was studied in premenopausal women. After an initial control period during which the diet was high in fat (40% of calories as fat) and low in fiber (12 g/day), the amounts of fat and fiber were varied in the setting of a metabolic kitchen and carefully monitored meals. Forty-eight women completed 58 protocols. When the diet was changed to low-fat (20-25% calories as fat) and high fiber (40 g/day), there were significant decreases in serum concentrations of estrone, estrone sulfate, testosterone, androstenedione, and sex hormone binding globulin (SHBG) and near significant decreases in estradiol and free estradiol. When independent effects were examined, high fiber alone caused a decrease in estradiol and SHBG, whereas fat and fiber caused the observed decrease in estrone sulfate. Dietary fat independently influenced the serum concentration of androstenedione. Increased dietary fiber caused a lengthening of the menstrual cycle by 0.72 day and a lengthening of the follicular phase by 0.85 day.
Adult↗
The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States).
We undertook a cross-sectional study in 107 premenopausal women in Maryland (United States) of alcohol intake and hormonal status in order to evaluate whether plasma hormone levels might mediate the reported positive relation between alcohol ingestion and breast cancer risk. Alcohol ingestion was estimated using a drinking pattern questionnaire, a food frequency questionnaire, and seven-day food records. Fasting blood specimens were collected on days 5-7, 12-15, and 21-23 of each participant's menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Estrone, estrone sulfate, estradiol, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) in plasma were measured by radioimmunoassay, and sex-hormone binding globulin (SHBG) was measured by an immunoradiometric assay. After adjusting for age, weight, and total energy intake, alcohol ingestion was not associated with plasma estrogens in the follicular, midcycle, or luteal phases of the menstrual cycle, nor with the level of SHBG or DHEAS in plasma averaged from the three phases of the cycle. Alcohol, however, was significantly positively associated with the average level of plasma androstenedione. Based on these cross-sectional findings among premenopausal women, the increased risk of breast cancer related to alcohol ingestion does not appear to be mediated by elevated plasma estrogen levels. Androstenedione, however, may mediate the alcohol/breast cancer-association.
Adult↗
Feminization as a result of both peripheral conversion of androgens and direct estrogen production from an adrenocortical carcinoma.
A 45-year-old man presented with gynecomastia, hypertension and a large left adrenal mass. Further evaluation revealed elevated serum concentrations of estrogen, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, deoxycorticosterone, and aldosterone and increased 24-hour urinary 17-ketosteroid and free cortisol excretion. Removal of a 10 kg adrenocortical carcinoma led to normalization of the hormone concentrations and partial resolution of the gynecomastia. There was no clinical evidence of metastases. Incubation of tumor slices demonstrated that the tumor had an active aromatase and sulfotransferase. We estimated that about half the serum estrone arose from peripheral conversion of androstenedione. Feminizing adrenocortical carcinomas are rare and this case is unusual given the lack of clinical metastases and the probable dual source of estrogen from tumor as well as from the peripheral conversion of tumor-derived androgens.
Adrenal Cortex Neoplasms↗
The metabolism of estrone sulfate in the female rhesus monkey.
In order to study the metabolism of estrone sulfate in the adult female rhesus monkey, we gave four monkeys a pulse injection of [3H]estrone sulfate and obtained blood samples at 15, 30, 60, 120, 300, and 1,440 minutes after the pulse. All blood samples were analyzed for [3H]estrone sulfate. The mean +/- SE for the initial volume of distribution was 4.6 +/- 0.9 L. The mean metabolic clearance rate (MCR) was 42.0 +/- 2.9 L/day. In addition, 2 monkeys were infused for 240 minutes with [3H]estrone sulfate and 5 monkeys were infused for 240 minutes with [3H]estrone sulfate/[14C]estrone. Three blood samples were obtained during the last hour of the infusions and analyzed for radioactivity as estrone sulfate, estrone, and estradiol, and MCRs, conversion ratios, and [rho]BB values were calculated. The mean +/- SE for the MCR was 67.5 +/- 8.3 L/day, and for the conversion ratio, estradiol to estrone sulfate was 0.054 +/- 0.016. The mean [rho]BB value for estrone sulfate conversion to estrone was 43.6 +/- 3.4% and for estrone conversion to estrone sulfate was 33.5 +/- 6.6%. Thus estrone sulfate is cleared slowly and is converted to both estrone and estradiol. The hydrolysis of estrone sulfate to estrone is not significantly different than the conversion of estrone to estrone sulfate.
Animals↗
The effects of ovariectomy and progesterone on peripheral aromatization in the female rhesus monkey.
We investigated the acute effects of surgery, i.e. ovariectomy, the long-term effects of ovariectomy, and the effects of progesterone on the peripheral aromatization of androstenedione in rhesus monkeys (Macaca mulatta). For the acute effects of surgery, 7 rhesus monkeys were given a pulse of [3H]androstenedione/[14C]estrone 2 weeks before and immediately after ovariectomy. In each case all urine was collected for 4 days and analyzed for radioactivity as estrone glucuronide and the peripheral aromatization calculated from the isotope ratios. Similarly, 5 monkeys were studied before and 18 months after ovariectomy. The acute effects of surgery resulted in a significant decrease in the peripheral aromatization of androstenedione to estrone from a mean +/- SE of 0.94 +/- 0.26 to 0.61 +/- 0.19%, P = 0.0452. Conversely, the long-term effects of ovariectomy resulted in a significant increase in peripheral aromatization from 0.38 +/- 0.06 to 0.67 +/- 0.12%, P = 0.0207. In 7 monkeys the peripheral aromatization was measured before and 10 days after the administration of progesterone, 100 mg in oil. There was no difference in peripheral aromatization before, 0.62 +/- 0.04% and after progesterone, 0.58 +/- 0.05%, P = 0.10. We conclude that the acute stress of ovariectomy, or possibly the loss of ovarian aromatizing tissue, results in a decline in peripheral aromatization, but ovariectomy will have the long-term effect of an increase in aromatization, and that the presence or absence of progesterone does not play a role.
Androstenedione↗
Body composition and gonadal steroids in older white and black women.
Obesity offers protection against osteoporosis in older women. The mechanisms are not well understood, but relate in part to increased aromatization of adrenal androgens to estrone in peripheral fat and muscle tissue. Two hundred and one white and 77 black women previously reported to be free of skeletal disease and to have normal bone mass had measurements of total body bone mineral (TBBM), fat mass (TBFM), and lean mass (TBLM) performed by dual energy x-ray absorptiometry. Serum estrone, androstenedione, and dihydroepiandrostenedione sulfate were measured on the same day. Body weight, body mass index, TBFM, and TBLM were all significantly higher in the black women. However, proportionately, there were no differences in body composition between the two groups. This suggests that the black women were not more obese despite their greater body mass index, and that future studies on the health impact of obesity in older black women should take this into consideration. Despite the greater TBFM and TBLM in the black women and no difference in serum androstenedione levels, the serum estrone level was not higher in the black women, and the higher bone mass in blacks was not related to serum estrone. In both ethnic groups, TBBM was significantly related to body weight (white, r = 0.80; black, r = 0.85; P < 0.001 for both). Both TBFM and TBLM were significantly related to TBBM in both ethnic groups. Serum estrone was significantly related to all measures of body mass in the white women, but to no measures of body mass in the black women, indicating apparent differences in the metabolism of estrone between older white and black women.
Adipose Tissue↗
The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.
The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake.
Adrenal Glands↗
A prospective study of endogenous hormones and breast cancer.
To examine the association prospectively between endogenous hormones and breast cancer, a population-based, nested case-control study was conducted using serum collected in 1974. Serum hormone levels among 51 women, who subsequently developed breast cancer, were compared with controls matched on age and time since last menstrual period. The levels of estrogens, progesterone, sex-hormone binding globulin, and androstenedione were compared between cases and controls. No statistically significant differences in endogenous hormones levels were observed between women who subsequently developed breast cancer and controls. Despite the fact that risk factors for breast cancer implicated endogenous hormones, especially estrogen, in the etiology of this disease, our study failed to demonstrate a statistically significant association between endogenous hormones and the risk of breast cancer. If there is an association between endogenous hormones and breast cancer, the magnitude of the effect is weak.
Adult↗
Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women.
BACKGROUND: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. PURPOSE: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. METHODS: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. RESULTS: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1% (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. CONCLUSION: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. IMPLICATION: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation.
Adult↗