Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.
Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.
Bebb
R A
RA
Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
Anawalt
B D
BD
Christensen
R B
RB
Paulsen
C A
CA
Bremner
W J
WJ
Matsumoto
A M
AM
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010919:Placebos; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D015430:Weight Gain
D008076:Cholesterol, HDL; D003272:Contraceptive Agents, Male; D010919:Placebos; D013739:Testosterone; D016912:Levonorgestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone