Dataset Information

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

SUBMITTER: Mostaghel EA

PROVIDER: S-EPMC3410271 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Mostaghel Elahe A EA Lin Daniel W DW Amory John K JK Wright Jonathan L JL Marck Brett T BT Nelson Peter S PS Matsumoto Alvin M AM Bremner William J WJ Page Stephanie T ST

The Journal of clinical endocrinology and metabolism 20120601 8

<h4>Context</h4>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.<h4>Objective</h4>The objective of the study was to determine the molecular impact of MHC on intraprostatic androgen concentrations and androgen action.<h4>Design</h4>This was a single-blind, randomized, placebo-controlled study.<h4>Setting</h4>The ...[more]

PMID: 22659250

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Project description:Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland that is frequently found in aging men. Androgens are essential for the development and differentiated function of the prostate, as well as for proliferation and survival of prostatic cells. In man, dog and rodent, there are age-related decreases in serum testosterone. Despite the lower serum testosterone levels, benign prostatic hyperplasia increases with age in men and dogs, while age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes of the rat prostate. The possible mechanisms that lead to prostate hyperplasia have been extensively studied over many years. It is clear that androgens, estrogens and growth factors contribute to the condition, but the exact etiology remains unknown. Prostate cancer (CaP) represents a significant cause of death among males worldwide. As is the case of BPH, it is clear that androgens (testosterone and dihydrotestosterone) and their metabolites play important roles in the disease, but cause-effect relationships have not been established. Androgen deprivation therapy has been used for decades, primarily in the metastatic stage, to inhibit androgen-dependent prostate cancer cell growth. Androgen deprivation, which can be achieved by targeting hormone biosynthesis or androgen receptor activation, results in symptom amelioration. However, most patients will develop hormone refractory cancer or castration-resistant prostate cancer (CRPC). Prostatic epithelial cells demonstrate enormous plasticity in response to androgen ablation. This characteristic of prostatic epithelial cells may give rise to different populations of cells, some of which may not be dependent on androgen. Consequently, androgen receptor positive and negative cells might co-exist within CRPC. A clear understanding of this possible cellular heterogeneity and plasticity of prostate epithelial cells is necessary to develop an optimal strategy to treat or prevent CRPC.

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Dataset Information

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

Context

Objective

Design

Setting

Participants

Intervention

Main outcome measures

Results

Conclusions

Publications

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

Similar Datasets

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