Induction of azoospermia in normal men with combined Nal-Glu gonadotropin-releasing hormone antagonist and testosterone enanthate.

Abstract

The effects of a combined GnRH antagonist and testosterone (T) replacement regimen on gonadotropins and spermatogenesis were examined to assess its potential as a male contraceptive regimen. The potent Nal-Glu GnRH antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5, D4-p-methoxybenzoyl-2-amino butyric acid6,D-Ala10]GnRH) was administered daily (7.5 mg, sc) to eight normal men for 16 weeks. T enanthate was given im starting at week 2 and every 2 weeks thereafter through week 14 of the treatment phase. Serum LH, FSH, T, and estradiol concentrations were measured frequently during the 5-week control period, the 16-week treatment phase, and the 14-week recovery phase. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. Seven of eight subjects became azoospermic by 6-10 weeks of treatment; the eighth subject, who failed to achieve azoospermia, suppressed his sperm count to 7 million/mL by week 14 (from a mean baseline of 42 million/mL) before treatment was prematurely terminated because of localized swelling at each of his injection sites. Sperm counts returned to baseline 10-14 weeks after the end of Nal-Glu administration. Seven of the eight subjects showed suppression of LH to the limit of assay detection (less than 0.2 U/L), whereas the eighth subject showed incomplete suppression. Serum bioactive and immunoreactive LH concentrations showed concordant responses. Mean serum FSH concentrations were also markedly suppressed. Serum T and estradiol concentrations declined dramatically during the first 2 weeks of Nal-Glu GnRH treatment, but returned to the normal physiological range after T enanthate replacement was initiated. Libido and sexual potency were maintained. No systemic side-effects, other than erythema and induration at injection sites, were observed. These data demonstrate that combined GnRH antagonist plus T treatment can predictably and reversibly induce azoospermia in most men and has potential as a male contraceptive regimen.

• Authors: L Tom, S Bhasin, W Salameh, B Steiner, M Peterson, R Z Sokol, J Rivier, W Vale, R S Swerdloff
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 75 Issue 2 Pg. 476-83 (Aug 1992) ISSN: 0021-972X [Print] United States
• PMID: 1639948 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Contraceptive Agents, Male
• Hormones
• LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-
• Gonadotropin-Releasing Hormone
• Testosterone
• testosterone enanthate

Topics

• Adult
• Contraceptive Agents, Male (pharmacology)
• Gonadotropin-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Hormones (blood)
• Humans
• Male
• Middle Aged
• Oligospermia (chemically induced)
• Reference Values
• Sexual Behavior (drug effects)
• Sperm Count (drug effects)
• Spermatozoa (drug effects, physiology)
• Testosterone (analogs & derivatives, pharmacology)