Impact of Male Hormonal Contraception on Prostate Androgens and Androgen Action in Healthy Men: A Randomized, Controlled Trial
Year: 2012
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
DOI: 10.1210/jc.2012-1536
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Prostate Cancer Foundation, Damon Runyon Cancer Research Foundation, GlaxoSmithKline, University of Washington, National Institutes of Health, Genentech, National Institute on Aging, National Cancer Institute, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Dose-response relationship between circulating and prostatic androgens in men, G1278948098, G1964883604, Male Contraception Research Center Grant, G4202529541, Hormonal and molecular consequences of androgen replacement on the prostate, G4831154717, G5037531216, In Vivo Efficacy of Multi-Targeted Androgen Inhibition as Prostate Cancer Therapy, G9000099545, G9000103237, The Pacific Northwest Prostate Cancer SPORE
OpenAlex ID: W2003543953