Gonadotropin Suppression Predicts Suppression of Spermatogenesis in Men Applying Transdermal Testosterone and Nestorone TM Gels for Male Hormonal Contraception

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 524-553-Male Reproductive Endocrinology
Bench to Bedside
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-549
Mara Yvonne Roth*1, Niloufar Ilani2, Christina CL Wang3, Stephanie T Page1, Jean Jacques S Nya-Ngatchou1, William J Bremner1, Ronald S. Swerdloff2, Clint Dart4, Regine Sitruk-Ware5, Narender Kumar5, Diana Lynn Blithe6, Jason Woo6 and John Kenneth Amory1
1University of Washington, Seattle, WA, 2Harbor - UCLA Med Ctr and Los Angeles Biomedical Research Institute, Torrance, CA, 3Harbor - UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, 4Health Decisions, Durham, NC, 5The Population Council, New York, NY, 6Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
Context: Development of a safe, effective male hormonal contraceptive has been challenging due to the 5-10% of men who fail to suppress spermatogenesis to levels compatible with effective contraception. 

Objective: To determine if serum hormones and/or gonadotropin measurements in men, after receiving 4 weeks of a gel-based male hormonal contraceptive regimen, can predict the suppression of sperm concentrations to <1 million/ml at 24 weeks.

Methods: Analysis of serum hormone and gonadotropin concentrations in 99 healthy men enrolled in a randomized, double-blind, clinical trial conducted at two academic medical centers.

Intervention: Subjects were randomized to one of three groups for 24 weeks of daily application with either:  1%Testosterone gel 10 gm + placebo gel, 1% Testosterone gel 10 gm + NestoroneTM gel 8 mg, 1% Testosterone gel 10 gm + NestoroneTM gel 12 mg.

Analysis: Analysis included data pooled from all 3 study groups and groups specifically receiving active NestoroneTM gel. Logistic and linear regression models were used to identify significant early predictors of failure to adequately suppress spermatogenesis after 24 weeks of treatment.

Results: A luteinizing hormone (LH) or follicle-stimulating hormone (FSH) of greater than 1 IU/L after 4 weeks of transdermal testosterone/NestoroneTM treatment was 97% sensitive for failure to suppress spermatogenesis after 24 weeks of treatment.  However, LH and FSH concentrations of <1 IU/L at 4 weeks are not highly specific for suppression of spermatogenesis.  Serum testosterone concentrations were not significantly associated with suppression of spermatogenesis, but serum NestoroneTM concentrations above a threshold limit were significantly associated with suppression at every time point.

Conclusion:  After 4 weeks of treatment with a transdermal androgen/progestin male hormonal contraceptive regimen, serum gonadotropin concentrations > 1 IU/ml were highly sensitive for failure to achieve suppression of spermatogenesis at week 24. Compliance of the user may be a significant factor in failure to suppress. Early suppression of gonadotropins is predictive of, but does not ensure, adequate suppression of spermatogenesis.  In addition, serum NestoroneTM concentrations above a minimum threshold level were associated with suppression of spermatogenesis.  This information may be useful in the development of male hormonal contraceptive regimens to consider altering the participation of men whose serum gonadotropins are not suppressed after 4 weeks of treatment.

Nothing to Disclose: MYR, NI, CCW, STP, JJSN, WJB, RSS, CD, RS, NK, DLB, JW, JKA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development contracts HHSN 2752004033691 and HHSN 2751008060044U, and the Population Council.  The University of Washington site was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreement U54 HD-42454 as part of the Cooperative Contraceptive Research Centers Program and through K12 HD053984 and the National Institute of Diabetes and Digestive and Kidney Diseases training grant T32 DK007247-35.  The Los Angeles Center was supported by the Endocrinology, Metabolism and Nutrition training Grant T32 DK007571, and the General Clinical Research Center MO1 RR00425 and the UCLA Clinical and Translational Science Institute 1UL1-RR033176 at Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute.