Hormonal contraception and testicular function in man

$0U54FY2002HDNIH

University Of Washington, Seattle WA

Investigators

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Abstract

DESCRIPTION (provided by applicant): The general objective of this work is to obtain knowledge that will aid in the development of safe effective and reversible hormonal contraceptives for men. In particular, we are concerned with the gonadotropin and steroid environment necessary to suppress human spermatogenesis. We will be experimentally manipulating the hormonal environment of the testis in normal men and determining the resultant effects on steroidogenesis, spermatogenesis and overall health and well-being. More specifically, the objectives of this work are to answer questions in three areas pertaining to the efficacy, reversibility and long-term safety of male hormonal contraception: 1) Will a regimen of a gonadotropin-releasing hormone (GnRH) antagonist plus long-acting testosterone (T) plus a progestin prove more effective as a potential male contraceptive in normal men than a regimen using a GnRH antagonist long-acting T alone? If so, is this due to more complete suppression of circulating FSH or intratesticular T levels? 2) What is the role of physiological levels of dihydrotestosterone (DHT) in regulating spermatogenesis in normal men and what are its effects on body composition, lipids and prostate growth? 3) Does suppression of circulating FSH levels lead to defects in both spermiation and spermatogoniai development in men? Might a combination of a GnRH antagonist plus exogenous T more completely suppress circulating FSH levels and lead to more severe spermiation defects and, therefore, more rapid onset of the contraceptive effect than exogenous T alone? This work will make use of new compounds including newer, long-acting preparations of GnRH antagonists, androgens, and progestins as well as a 5-a-reductase inhibitor to explore human testicular function and physiology. These studies are directly relevant to the development of safe, effective reversible methods of human male contraception.

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