Impact of male hormonal contraception on prostate androgens and androgen action in healthy men: a randomized, controlled trial.
BACKGROUND
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.


METHODS
This was a single-blind, randomized, placebo-controlled study.


METHODS
The study was conducted at an academic medical center.


METHODS
32 healthy men aged 25-55 yr participated in the study.


METHODS
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.


METHODS
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.
Division of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Elahe A
EA
Mostaghel
Daniel W
DW
Lin
John K
JK
Amory
Jonathan L
JL
Wright
Brett T
BT
Marck
Peter S
PS
Nelson
Alvin M
AM
Matsumoto
William J
WJ
Bremner
Stephanie T
ST
Page
D000328:Adult; D000728:Androgens / Q000009:adverse effects* / Q000032:analysis; D003267:Contraception; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011944:Receptors, Androgen / Q000032:analysis; D016037:Single-Blind Method
C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; D007986:Luteinizing Hormone