Impact of Male Hormonal Contraception on Prostate Androgens and Androgen Action in Healthy Men: A Randomized, Controlled Trial.

Publication Type:

Journal Article

Source:

The Journal of clinical endocrinology and metabolism (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, Human Biology Division, June 2012, Public Health Sciences Division

Abstract:

Context:Male hormonal contraception (MHC) combines hypothalamic-pituitary-gonadal axis blockade with exogenous androgen delivery to maintain extragonadal androgen end-organ effects. Concern exists that MHC may adversely impact prostate health.Objective:The objective of the study was to determine the molecular impact of MHC on intraprostatic androgen concentrations and androgen action.Design:This was a single-blind, randomized, placebo-controlled study.Setting:The study was conducted at an academic medical center.Participants:32 healthy men aged 25-55 yr participated in the study.Intervention:Interventions included placebo, daily transdermal testosterone (T) (T-gel), T-gel + depomedroxyprogesterone acetate (T+DMPA), or T-gel + dutasteride daily (T+D) for 12 wk, and prostate biopsy during treatment wk 10.Main Outcome Measures:Serum and prostate androgen concentrations and prostate epithelial-cell gene expression were measured.Results:Thirty men completed the study. Serum T levels were significantly increased in T-gel and T+D groups compared with baseline (P < 0.05) but were decreased with the addition of DMPA. Intraprostatic androgens were no different from placebo with T-gel treatment. Addition of DMPA to T resulted in 40% lower intraprostatic dihydrotestosterone (DHT) concentration (P = 0.0273 vs. placebo), whereas combining dutasteride with T resulted in a 90% decrease in intraprostatic DHT (P = 0.0012), 11-fold increased intraprostatic T (P = 0.0011), and 7-fold increased intraprostatic androstenedione (P = 0.0011). Significant differences in global or androgen-regulated prostate epithelial-cell gene expression were not observed. Androgen-regulated gene expression correlated with epithelial-cell androgen receptor and prostatic DHT in placebo, T-gel, and T+DMPA arms and with T and androstenedione levels in the T+D arm.Conclusions:MHC regimens do not markedly alter gene expression in benign prostate epithelium, suggesting they may not alter risk of prostate disease. Longer-term studies examining the impact of MHC on prostate health are needed.