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This version published online on February 26, 2008
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-2768
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Submitted on December 17, 2007
Accepted on February 20, 2008

Determinants of the Rate and Extent of Spermatogenic Suppression during Hormonal Male Contraception: An Integrated Analysis

Peter Y. Liu*, Ronald S. Swerdloff, Bradley D. Anawalt, Richard A. Anderson, William J. Bremner, Joerg Elliesen, Yi-Qun Gu, Wendy M. Kersemaekers, Robert. I. McLachlan, M. Cristina Meriggiola, Eberhard Nieschlag, Regine Sitruk-Ware, Kirsten Vogelsong, Xing-Hai Wang, Frederick C. W. Wu, Michael Zitzmann, David J. Handelsman, and Christina Wang*

* To whom correspondence should be addressed. E-mail: pliu{at}mail.usyd.edu.au or wang{at}labiomed.org.

Context: Male hormonal contraceptive methods require effective suppression of sperm output.

Objective: To define the covariables that influence the rate and extent of suppression of spermatogenesis to a level shown in previous WHO sponsored studies to be sufficient for contraceptive purposes (≤ 1 million/mL).

Design: An integrated analysis of all published male hormonal contraceptive studies of at least 3 months treatment duration.

Setting: De-identified individual subject data provided by investigators of 30 studies published between 1990–2006.

Participants: 1756 healthy (by physical, blood and semen exam) men aged 18–51 years of predominately Caucasian (two-thirds) or Asian (one-third) descent. This represents about 85% of all the published data.

Intervention(s): Men were treated with different preparations of testosterone, with or without various progestins.

Main Outcome Measure: Semen analysis.

Results: Progestin coadministration increased both the rate and extent of suppression. Caucasian men suppressed sperm output faster initially but ultimately to a less complete extent than did non-Caucasians. Younger age and lower initial blood testosterone or sperm concentration were also associated with faster suppression, but the independent effect sizes for age and baseline testicular function were relatively small.

Conclusion: Male hormonal contraceptives can be practically applied to a wide range of men, but require coadministration of an androgen with a second agent (i.e progestin) for earlier and more complete suppression of sperm output. While considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required.
Key words: Contraception • male • suppression • semen • androgen




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