94 IS THERE A ROLE FOR GONADOTROPIN-RELEASING HORMONE ANTAGONISTS IN MALE HORMONAL CONTRACEPTION?

• Published in: Journal of investigative medicine 2006-01, Vol.54 (1), p.S95-S96
• Main Authors: Page, S. T., Amory, J. K., Anawalt, B. D., Matsumoto, A. M., Brockenbrough, A. T., Irwig, M. S., Bremner, W. J.
• Format: Article
• Language: English
• ISSN: 1081-5589; 1708-8267
• DOI: 10.2310/6650.2005.X0004.93

Gonadotropin-releasing hormone (GnRH) is the hypothalamic decapeptide that stimulates LH and FSH secretion from the pituitary and thereby controls reproduction. GnRH antagonists potently suppress gonadotropin production at the pituitary within hours of administration and have the potential to improve the degree and/or rapidity of sperm suppression in male hormonal contraceptive regimens. The long-acting GnRH antagonist Acyline suppresses gonadotropin levels for 2 weeks after a single dose. We are currently conducting a trial to determine the suppressive effects of 12 weeks of acyline on spermatogenesis and pituitary gonadotropin secretion when administered in combination with testosterone (T) in a transdermal gel form and the progestin depot-medroxyprogesterone acetate (DMPA). Forty-four men, ages 18-55, in good health and with normal spermatogenesis and hormonal status have been randomized to T gel (100 mg daily) + DMPA (300 mg IM q 3 months) or T gel + DMPA + acyline (300 μg/kg SQ q 2 weeks × 12 weeks). Six men did not complete the drug exposure period. To date, 37 men have completed the 24-week treatment protocol with the following sperm concentrations:  The T/DMPA/Acyline combination exhibited a trend towards more rapid suppression of sperm concentrations to less than 1 million sperm/mL (the primary end point) after 12 weeks of administration compared with T gel + DMPA alone. There were no significant differences in sperm concentrations between groups after 24 weeks of treatment. There were no serious adverse effects of treatment. Acyline induced transient itching in most subjects that lasted for less than 24 hours. The addition of 12 weeks of the potent GnRH antagonist Acyline may accelerate and enhance the suppression of spermatogenesis by testosterone-progestogen male hormonal contraceptive regimens in men.