This Article Full Text Full Text (PDF) All Versions of this Article: 90/1/91    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matthiesson, K. L. Articles by Bremner, W. J. Search for Related Content PubMed PubMed Citation Articles by Matthiesson, K. L. Articles by Bremner, W. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LEVONORGESTREL TESTOSTERONE Related Collections Male Endocrinology Neuroendocrinology and Pituitary

Novel Male Hormonal Contraceptive Combinations: The Hormonal and Spermatogenic Effects of Testosterone and Levonorgestrel Combined with a 5-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist

Prince Henry’s Institute of Medical Research and Department of Obstetrics and Gynaecology (K.L.M., R.I.M.), Monash University, Monash Medical Centre, Clayton, Victoria 3168, Australia; The Center for Research in Reproduction and Contraception (J.K.A., R.B., W.J.B.), University of Washington, Seattle, Washington 98195; and School of Physiotherapy (A.U.), University of Melbourne, Parkville, Victoria 3010, Australia

Address all correspondence and requests for reprints to: Kati Matthiesson, M.B.B.S., F.R.A.C.P., Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: kati.matthiesson{at}phimr.monash.edu.au.

We postulated that the addition of a combined types I and II, 5-reductase inhibitor (dutasteride) or long-acting GnRH antagonist (acyline) to combination testosterone plus levonorgestrel treatment may be advantageous in the suppression of spermatogenesis for male contraception. This study aimed to examine effects of novel combination contraceptive regimens on serum gonadotropins and androgens and sperm concentration.

This study was divided into three phases: screening (2 wk), treatment (8 wk), and recovery (4 wk). Twenty-two men (n = 5–6/group) received 8 wk of treatment with testosterone enanthate (TE, 100 mg im weekly) combined with one of the following: 1) levonorgestrel (LNG) 125 µg orally daily; 2) LNG 125 µg plus dutasteride 0.5 mg orally daily; 3) acyline 300 µg/kg sc every 2 wk (as a comparator for any additional progestin effects); or 4) LNG 125 µg orally daily plus acyline 300 µg/kg sc every 2 wk.

Serum gonadotropin levels were similarly suppressed by all treatments, falling to a nadir between 1.2 and 3.4% and 0.5 and 0.8% baseline for FSH and LH, respectively (P < 0.05). Serum dihydrotestosterone levels were significantly (P < 0.05) decreased in the dutasteride group throughout the treatment period to a nadir of 31% baseline (wk 7). No significant differences in sperm concentrations among treatment groups were seen. Severe oligospermia (0.1–3 million/ml) or azoospermia was seen in none of five and four of five in TE + LNG; two of six and four of six in TE + LNG + dutasteride; two of six and four of six in TE + acyline; and one of five and three of five in TE + LNG + acyline groups, respectively. There was one nonresponder in each of the TE + LNG and TE + LNG + acyline groups.

We conclude that the addition of a combined types I and II, 5-reductase inhibitor or long-acting GnRH antagonist to a testosterone plus LNG regimen provides no additional suppression of gonadotropins or sperm concentration over an 8-wk treatment period. However, further evaluation of the effects of these regimens on the testis (including testicular steroid levels and germ cell maturation) and the treatment of larger numbers of men (and for longer periods) may provide data to support their place in contraceptive development.

This article has been cited by other articles:

				C. Wang, Y.-G. Cui, X.-H. Wang, Y. Jia, A. Sinha Hikim, Y.-H. Lue, J.-S. Tong, L.-X. Qian, J.-H. Sha, Z.-M. Zhou, et al. Transient Scrotal Hyperthermia and Levonorgestrel Enhance Testosterone-Induced Spermatogenesis Suppression in Men through Increased Germ Cell Apoptosis J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3292 - 3304. [Abstract] [Full Text] [PDF]

				J. K. Amory, C. Wang, R. S. Swerdloff, B. D. Anawalt, A. M. Matsumoto, W. J. Bremner, S. E. Walker, L. J. Haberer, and R. V. Clark The Effect of 5{alpha}-Reductase Inhibition with Dutasteride and Finasteride on Semen Parameters and Serum Hormones in Healthy Men J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1659 - 1665. [Abstract] [Full Text] [PDF]

				S. T. Page, J. K. Amory, B. D. Anawalt, M. S. Irwig, A. T. Brockenbrough, A. M. Matsumoto, and W. J. Bremner Testosterone Gel Combined with Depomedroxyprogesterone Acetate Is an Effective Male Hormonal Contraceptive Regimen and Is Not Enhanced by the Addition of a GnRH Antagonist J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4374 - 4380. [Abstract] [Full Text] [PDF]

				M. J. Walton, R. A. L. Bayne, I. Wallace, D. T. Baird, and R. A. Anderson Direct Effect of Progestogen on Gene Expression in the Testis during Gonadotropin Withdrawal and Early Suppression of Spermatogenesis J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2526 - 2533. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson and R. I. McLachlan Male hormonal contraception: concept proven, product in sight? Hum. Reprod. Update, July 1, 2006; 12(4): 463 - 482. [Abstract] [Full Text] [PDF]

				D. S. JOHNSTON, J. WOOTERS, G. S. KOPF, Y. QIU, and K. P. ROBERTS Analysis of the Human Sperm Proteome Ann. N.Y. Acad. Sci., December 1, 2005; 1061(1): 190 - 202. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, P. G. Stanton, L. O'Donnell, S. J. Meachem, J. K. Amory, R. Berger, W. J. Bremner, and R. I. McLachlan Effects of Testosterone and Levonorgestrel Combined with a 5{alpha}-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist on Spermatogenesis and Intratesticular Steroid Levels in Normal Men J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5647 - 5655. [Abstract] [Full Text] [PDF]