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

• Published in: The journal of clinical endocrinology and metabolism 2012-08, Vol.97 (8), p.2809-2817
• Main Authors: Mostaghel, Elahe A, Lin, Daniel W, Amory, John K, Wright, Jonathan L, Marck, Brett T, Nelson, Peter S, Matsumoto, Alvin M, Bremner, William J, Page, Stephanie T
• Format: Article
• Language: English
• Subjects: Adult; Androgens - adverse effects; Androgens - analysis; Biological and medical sciences; Contraception; Endocrine Research; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Humans; Hypothalamo-Hypophyseal System - drug effects; Luteinizing Hormone - blood; Male; Medical sciences; Middle Aged; Prostate - drug effects; Prostate - metabolism; Receptors, Androgen - analysis; Single-Blind Method; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2012-1536

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.