This Article Full Text (PDF) All Versions of this Article: 28/3/362    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Related articles in Journal of Andrology Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aaltonen, P. Articles by Zitzmann, M. Search for Related Content PubMed PubMed Citation Articles by Aaltonen, P. Articles by Zitzmann, M.

Recommendations

10^th Summit Meeting Consensus: Recommendations for Regulatory Approval for Hormonal Male Contraception

JOHN K. AMORY

RICHARD A. ANDERSON

HERMANN M. BEHRE

GABRIEL BIALY

DIANA BLITHE

WILHELM BONE

WILLIAM J. BREMNER

DOUG COLVARD

TREVOR G. COOPER

JöRG ELLIESEN

HENRY L GABELNICK

YI-QUN GU

DAVID J. HANDELSMAN

ELOF A. B. JOHANSSON

WENDY KERSEMAEKERS

PETER LIU

TRENT MACKAY

STEPHEN MATLIN

MICHAEL MBIZVO

ROBERT I. MCLACHLAN

MARIA CRISTINA MERIGGIOLA

STEPHAN MLETZKO

ELLEN MOMMERS

HILDE MUERMANS

EBERHARD NIESCHLAG

VIVECA ODLIND

STEPHANIE T. PAGE

ALBERT RADLMAIER

REGINE SITRUK-WARE

RONALD SWERDLOFF

CHRISTINA WANG

FREDERICK WU

MICHAEL ZITZMANN

Schering AG, Berlin, Germany

University of Washington, Seattle, Wash

Centre for Reproductive Biology, University of Edinburgh, United Kingdom

Martin-Luther-University, Halle, Germany

Center for Population Research, NIH, Bethesda, Md

NICHD, NIH, Bethesda, Md

Schering AG, Berlin, Germany

University of Washington, Seattle, Wash

CONRAD, Arlington, Va

University of Münster, Münster, Germany

Schering AG, Berlin, Germany

CONRAD, Arlington, Va

National Research Institute for Family Planning, Beijing, P.R. China

ANZAC Research Institute, University of Sydney, Australia

Population Council, New York, NY

NV Organon, Oss, The Netherlands

ANZAC Research Institute, Sydney, Australia

NICH/HD, Bethesda, Md

Global Forum for Health Research, Geneva, Switzerland

WHO, Geneva, Switzerland

Prince Henry's Institute, Melbourne, Australia

University of Bologna, Bologna, Italy

Schering AG, Berlin, Germany

NV Organon, Oss, The Netherlands

NV Organon, Oss, The Netherlands

University of Münster, Münster, Germany

University of Uppsala and Medical Products Agency, Uppsala, Sweden

University of Washington, Seattle, Wash

Schering AG, Berlin, Germany

Population Council and Rockefeller University, New York, NY

Harbor-UCLA Medical Center Los Angeles, Biomedical Research Institute, Torrance, Calif

Harbor-UCLA Medical Center Los Angeles, Biomedical Research Institute, Torrance, Calif

University of Manchester, Manchester, United Kingdom

University of Münster, Münster, Germany

At the Ninth Summit Meeting on Hormonal Contraception, Nyon, Switzerland, held on October 9–11, 2005, the group of experts reviewed the status of clinical development projects for male hormonal contraception and discussed the need to update the recommendations

The following revised recommendations are the result of this discussion and present the consensus statement confirmed at the 10th Summit Meeting, New York, NY, October 22–23, 2006.

It is stressed that the following recommendations are valid exclusively for hormonal methods for which the mechanism of action is based on the inhibition of sperm production. Methods with a different mode of action are outside the scope of these recommendations.

The goal of hormonal male contraception is the reversible suppression of spermatogenesis to a level compatible with infertility. In principle, this can be achieved with the use of an androgen alone or an androgen in combination with a gestagen or a GnRH-antagonist. The success of this principle in terms of lowering sperm counts in semen to azoospermia or to severe oligozoospermia has been demonstrated in multiple studies. Some trials demonstrated the contraceptive efficacy of this approach when couples used no other method of contraception. Investigators agree that information gained from preliminary studies on male contraception have reached a stage that hormonal contraceptive products for men should now be proposed for development for general use.

To bring a hormonal method to the market, large-scale clinical trials are required. Because no pharmacological method for male contraception is currently available, this represents a novel effort requiring new recommendations for testing and regulatory approval.

The investigators agreed that the following criteria should be fulfilled:

• In phase II dose-finding studies, the suppression of spermatogenesis can be used as the main parameter. As the surrogate parameter, sperm concentrations, measured according to World Health Organization recommended methods, can be used, and the goal should be 1 million/mL.
  
• After cessation of treatment, each participant should be followed until reversibility of sperm production to criteria that are compatible with normal fertility has been shown. Usually, return to sperm concentrations of at least 20 million/mL provides sufficient evidence of fertility. These figures could be revised, probably downward, as new data on fertility parameters emerge.
  
• Currently, only men with sperm concentrations 20 million/mL should be included. This threshold could be revised, probably downward, in the future as new data on fertility parameters emerge. Participants with known or suspected infertility should not be enrolled in clinical efficacy studies.
  
• Open-label, noncomparative contraceptive efficacy studies are acceptable if the primary endpoint is not susceptible to bias (eg, pregnancy rate).
  
• For contraceptive efficacy, 2 independent phase III trials for 1 year beginning when the male volunteer has suppressed to 1 million sperm/mL should be completed by 200 men or couples per trial.
  
• For safety assurance for a new chemical entity, trials are required to involve at least 300–600 men for 6 months at the intended combination and dose, 100 men exposed for 1 year, and a total of 1500 men in phase I–III studies at the minimum.
  
• Long-term safety will be monitored by postmarketing surveillance.
  
• The necessary laboratory investigations, especially semen analysis, need to be made under strict quality control.
  

These recommendations were drafted and approved by the participants in the 10th Summit Meeting on Male Contraception. This statement reflects the opinion of the individuals, but not necessarily the institution with which they are affiliated.

Related articles in Journal of Andrology:

Autologous Tunica Vaginalis and Subcapsular Orchiectomy: A Hormonal Therapy for Prostate Cancer

Martyn A. Vickers, Jr, Donald P. Lamontagne, Khurshid A. Guru, Ramgopal K. Satyanarayana, Kristin E. Vickers, and Mani Menon
Journal of Andrology 2004 25: 375-381. [Abstract] [Full Text]  

This article has been cited by other articles:

				P. Y. Liu and R. I. McLachlan Male Hormonal Contraception: So Near and Yet So Far J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2474 - 2476. [Full Text] [PDF]

				S. T. Page, J. K. Amory, and W. J. Bremner Advances in Male Contraception Endocr. Rev., June 1, 2008; 29(4): 465 - 493. [Abstract] [Full Text] [PDF]

				D. J. Handelsman Update in Andrology J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4505 - 4511. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) All Versions of this Article: 28/3/362    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Related articles in Journal of Andrology Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aaltonen, P. Articles by Zitzmann, M. Search for Related Content PubMed PubMed Citation Articles by Aaltonen, P. Articles by Zitzmann, M.