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.
Written by:
Mostaghel EA, Lin DW, Amory JK, Wright JL, Marck BT, Nelson PS, Matsumoto AM, Bremner WJ, Page ST Are you the author?
Divisions of Human Biology and Clinical Research (E.A.M., P.S.N.) and Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Departments of Medicine (E.A.M., J.K.A., P.S.N., A.M.M., W.J.B., S.T.P.) and Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; and Geriatric Research, Education, and Clinical Center and Department of Medicine (B.T.M., A.M.M.), Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108
Reference: J Clin Endocrinol Metab. 2012 Jun 1
doi: 10.1210/jc.2012-1536
PubMed Abstract
PMID: 22659250