Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known

Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

Background: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1), and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk.\ud \ud Methods: In this nested case–control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls.\ud \ud Results: Median posttreatment changes in concentrations of 3α-dG, T, E1, and E2 were −73.8%, +10.1%, +11.2%, and +7.5% (all P < 0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99–1.93) Ptrend = 0.03; 0.64 (0.43–0.93) Ptrend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09–2.17) Ptrend = 0.03; 1.49 (1.07–2.07) Ptrend = 0.02, respectively].\ud \ud Conclusions: Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered.\ud \ud Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer