This Article Full Text Full Text (PDF) All Versions of this Article: 28/5/734    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Page, S. T. Articles by Amory, J. K. Search for Related Content PubMed PubMed Citation Articles by Page, S. T. Articles by Amory, J. K.

Intratesticular Androgens and Spermatogenesis During Severe Gonadotropin Suppression Induced by Male Hormonal Contraceptive Treatment

THOMAS F. KALHORN

BRADLEY D. ANAWALT^*,

ALVIN M. MATSUMOTO^*,,

From the ^* Department of Medicine and Department of Medicinal Chemistry, University of Washington, Seattle, Washington; Department of Medicine, Veterans Affairs Puget Sound Health Care System; and Geriatric Research, Education and Clinical Center, Seattle, Washington.

Correspondence to: Dr Stephanie T. Page, Box 357138, 1959 NE Pacific, Seattle, WA 98195 (e-mail: page{at}u.washington.edu).

Male hormonal contraceptive regimens function by suppressing gonadotropin secretion, resulting in a dramatic decrease in testicular androgen biosynthesis and spermatogenesis. Animal studies suggest that persistent intratesticular (iT)–androgen production has a stimulatory effect on spermatogenesis in the setting of gonadotropin suppression. We hypothesized that men with incompletely suppressed spermatogenesis (>1 000 000 sperm/mL) during male hormonal contraceptive treatment would have higher iT-androgen concentrations than men who achieved severe oligospermia (1 000 000 sperm/mL). Twenty healthy men ages 18–55 years enrolled in a 6-month male contraceptive study of transdermal testosterone (T) gel (100 mg/d) plus depomedroxyprogesterone acetate (300 mg intramuscularly every 12 weeks) with or without the gonadotropin releasing hormone (GnRH) antagonist acyline (300 µg/kg subcutaneously every 2 weeks for 12 weeks) were studied. During the 24th week of treatment, subjects underwent fine needle aspirations of the testes and iT-T and iT-dihydrotestosterone (iT-DHT) were measured in testicular fluid by liquid chromatography–tandem mass spectrometry. All men dramatically suppressed spermatogenesis; 15 of 20 men were severely oligospermic, and 5 of 20 suppressed to 1.5 million–3.2 million sperm per milliliter. In all subjects, mean iT-T and iT-DHT concentrations were 35 ± 8 and 5.1 ± 0.8 nmol/L. IT-androgen concentrations did not significantly differ in men who did and did not achieve severe oligospermia (P = .41 for iT-T; P = .18 for iT-DHT). Furthermore, there was no significant correlation between iT-T or iT-DHT and sperm concentration after 24 weeks of treatment. In this study of prolonged gonadotropin suppression induced by male hormonal contraceptive treatment, differences in iT-androgens did not explain differences in spermatogenesis. Additional studies to identify factors involved in persistent spermatogenesis despite gonadotropin suppression are warranted.

     Key words: Testosterone, dihydrotestosterone, INSL3, LH, FSH

This article has been cited by other articles:

				E. A. Mostaghel, B. T. Marck, S. R. Plymate, R. L. Vessella, S. Balk, A. M. Matsumoto, P. S. Nelson, and R. B. Montgomery Resistance to CYP17A1 Inhibition with Abiraterone in Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants Clin. Cancer Res., September 15, 2011; 17(18): 5913 - 5925. [Abstract] [Full Text] [PDF]

				B. J. Attardi, J. A. Engbring, D. Gropp, and S. A. Hild Development of Dimethandrolone 17{beta}-Undecanoate (DMAU) as an Oral Male Hormonal Contraceptive: Induction of Infertility and Recovery of Fertility in Adult Male Rabbits J Androl, September 1, 2011; 32(5): 530 - 540. [Abstract] [Full Text] [PDF]

				M. Y. Roth, S. T. Page, K. Lin, B. D. Anawalt, A. M. Matsumoto, B. Marck, W. J. Bremner, and J. K. Amory The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men J. Clin. Endocrinol. Metab., April 1, 2011; 96(4): 1175 - 1181. [Abstract] [Full Text] [PDF]

				J. K. Amory, C. H. Muller, J. A. Shimshoni, N. Isoherranen, J. Paik, J. S. Moreb, D. W. Amory Sr, R. Evanoff, A. S. Goldstein, and M. D. Griswold Suppression of Spermatogenesis by Bisdichloroacetyldiamines Is Mediated by Inhibition of Testicular Retinoic Acid Biosynthesis J Androl, January 1, 2011; 32(1): 111 - 119. [Abstract] [Full Text] [PDF]

				M. Y. Roth, S. T. Page, K. Lin, B. D. Anawalt, A. M. Matsumoto, C. N. Snyder, B. T. Marck, W. J. Bremner, and J. K. Amory Dose-Dependent Increase in Intratesticular Testosterone by Very Low-Dose Human Chorionic Gonadotropin in Normal Men with Experimental Gonadotropin Deficiency J. Clin. Endocrinol. Metab., August 1, 2010; 95(8): 3806 - 3813. [Abstract] [Full Text] [PDF]

				M. Y. Roth, K. Lin, J. K. Amory, A. M. Matsumoto, B. D. Anawalt, C. N. Snyder, T. F. Kalhorn, W. J. Bremner, and S. T. Page Serum LH Correlates Highly With Intratesticular Steroid Levels in Normal Men J Androl, March 1, 2010; 31(2): 138 - 145. [Abstract] [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]

				R. B. Montgomery, E. A. Mostaghel, R. Vessella, D. L. Hess, T. F. Kalhorn, C. S. Higano, L. D. True, and P. S. Nelson Maintenance of Intratumoral Androgens in Metastatic Prostate Cancer: A Mechanism for Castration-Resistant Tumor Growth Cancer Res., June 1, 2008; 68(11): 4447 - 4454. [Abstract] [Full Text] [PDF]