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

Department of Andrology (P.Y.L., D.J.H.), ANZAC Research Institute and Concord Hospital, Concord 2139, Australia; Division of Endocrinology (R.S.S.), Department of Medicine, LABiomed and Harbor-UCLA Medical Center, Torrance, California 90509; Department of Medicine (B.D.A.), Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington 98195; Division of Reproductive and Developmental Sciences (R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Department of Medicine (W.J.B.), University of Washington, Seattle, Washington 98195; Bayer Schering Pharma AG (J.E.), 93 HRB 283 Berlin, Germany; Department of Endocrinology (Y.-Q.G.), National Research Institute for Family Planning, Beijing 100081, China; Translational Medicine Department (W.M.K.), N.V. Organon, a part of Schering-Plough Corporation, Oss NL-5340 BH, The Netherlands; Prince Henry's Institute and Monash Medical Centre (R.I.M.), Monash University, Clayton 3168, Australia; Departments of Obstetrics and Gynecology (M.C.M.), S. Orsola-Malpighi Hospital and University of Bologna, 40138 Bologna, Italy; Institute of Reproductive Medicine (E.N., M.Z.), University Hospital, D-48149 Münster, Germany; Center for Biomedical Research (R.S.-W.), Population Council, and Rockefeller University, New York, New York 10021; The United Nations Development Programme/United Nations Fund for Population Activities/World Health Organization/World Bank Special Programme of Research (K.V.), Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, 1211 Geneva 27, Switzerland; Jiangsu Family Planning Research Institute (X.-H.W.), Jiangsu 210029, China; Department of Endocrinology (F.C.W.W.), Manchester Royal Infirmary, University of Manchester, Manchester M13 9WL, United Kingdom; and General Clinical Research Center (C.W.), LABiomed and Harbor-UCLA Medical Center, Torrance, California 90509

Address all correspondence and requests for reprints to: Peter Y. Liu, M.B.B.S., Ph.D., Department of Andrology, ANZAC Research Institute, University of Sydney and Concord Hospital, Concord, New South Wales 2139, Australia. E-mail: pliu{at}mail.usyd.edu.au; or Christina Wang, M.D., General Clinical Research Center, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, 1000 West Carson Street, Torrance, California 90509. E-mail: wang{at}labiomed.org.

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

Objective: The objective of the study was to define the covariables that influence the rate and extent of suppression of spermatogenesis to a level shown in previous World Health Organization-sponsored studies to be sufficient for contraceptive purposes (1 million/ml).

Design: This was an integrated analysis of all published male hormonal contraceptive studies of at least 3 months' treatment duration.

Setting: Deidentified individual subject data were provided by investigators of 30 studies published between 1990 and 2006.

Participants: A total of 1756 healthy men (by physical, blood, and semen exam) aged 18–51 yr of predominantly Caucasian (two thirds) or Asian (one third) descent were studied. 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 was the main measure.

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. Whereas considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required.