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PURPOSE: The comparability between serum, plasma, and urinary measurements of estrogen metabolites via liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not been largely explored, and it is unclear if urinary LC-MS/MS measurements are suitable surrogates of circulating levels. METHODS: Serum, plasma (EDTA and heparin), and urinary estrogen/estrogen metabolite levels were measured via LC-MS/MS in paired samples from 64 healthy volunteers (18 men, 20 premenopausal women, 26 postmenopausal women). Geometric means and Spearman correlation coefficients were used to compare individual and combined pathway levels of estrogens/estrogen metabolites across biologic matrices by sex/menopausal status. RESULTS: Measured concentrations of estrogens/estrogen metabolites across blood matrices were almost identical (percent differences

Mechanistic and observational data together support a role for prolactin in breast cancer development. Determinants of prolactin in Asian populations have not been meaningfully explored, despite the lower risk of breast cancer in Asian populations. Determinants of plasma prolactin were evaluated in 442 postmenopausal women enrolled in the Singapore Chinese Health Study, a population-based prospective cohort study. At baseline all cohort members completed an in-person interview that elicited information on diet, menstrual and reproductive history, and lifestyle factors. One year after cohort initiation we began collecting blood samples. Quantified were plasma concentrations of prolactin, estrone, estradiol, testosterone, androstenedione, and sex hormone-binding globulin (SHBG). Analysis of covariance method was used for statistical analyses with age at blood draw, time since last meal, and time at blood draw as covariates. Mean prolactin levels were 25.1% lower with older age at menarche (p value = 0.001), and 27.6% higher with greater years between menarche and menopause (p value = 0.009). Prolactin levels were also positively associated with increased sleep duration (p value = 0.005). The independent determinants of prolactin were years from menarche to menopause, hours of sleep, and the plasma hormones estrone and SHBG (all p values

Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3α-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason7) or high-grade (Gleason 7-10) PCA.Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.

Objective To identify factors that mediate or moderate the effects of exercise on postmenopausal sex hormone concentrations. Methods Postmenopausal women were randomized to 12 months of aerobic exercise for 200 min/week (n = 160) or to a control group (n = 160). Intention-to-treat analyses were performed using general linear models with sex hormone concentrations at 6 and 12 months as the outcome. Mediation by adiposity and insulin was investigated by examining changes in effect estimates after adjustment for changes in these factors over 12 months. Moderation was studied as the interaction between group assignment and eight baseline characteristics. Results Intervention effects on sex hormone–binding globulin (SHBG) and estradiol changes were attenuated with adjustment for change in overall body fat, while there was less attenuation adjusting for intra-abdominal fat change. Intervention effects on SHBG levels were unaffected by adjustment for insulin change. Significant interactions were identified between treatment and physical fitness (for SHBG and testosterone) and age (for testosterone), implying subgroup differences in intervention effect. Conclusions Our data suggest that overall fat loss partially mediated exercise-induced changes in estradiol and SHBG concentrations. No previous RCT in postmenopausal women has studied moderators of exercise-induced sex hormone changes; therefore, future studies are needed to corroborate our results.

Objective Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. Methods These questions were investigated in a case–control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. Results Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score

Blood and urine concentrations of hormones are implicated in the etiology of some cancers. Small studies have assessed relationships between production of the daidzein metabolites equol and O-desmethylangolensin (ODMA) and hormones, but findings are unclear. We evaluated relationships between daidzein-metabolizing phenotypes and follicular phase concentrations of estrogens, androgens, sex hormone binding globulin (SHBG), and urinary estrogen metabolites in premenopausal women.Two-hundred women collected a first-void urine sample after a 3-day soy challenge, and 191 and 193 provided fasting blood and spot urine samples, respectively, during days 5-9 of their menstrual cycle. Soy challenge urines were analyzed for isoflavones; serum was analyzed for estrogens, androgens, and SHBG; spot urines were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. Data were log-transformed and multiple regression analyses were conducted to assess relationships between daidzein-metabolizing phenotypes and hormones and SHBG. Data from 187 and 189 women were included in analyses of serum and urine hormones, respectively.55 (27.5%) and 182 (91%) of the 200 women who provided a soy challenge urine sample were equol- and ODMA-producers (87.5 ng/ml urine), respectively. In unadjusted analyses, equol-producers (n = 52) had lower free testosterone than equol non-producers (n = 137, p = 0.02). In adjusted analyses, there were no differences between producers and non-producers of either daidzein metabolite.In the absence of a soy intervention, we found no difference in serum or urine hormone concentrations between producers and non-producers of equol or ODMA.