Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach

Abstract

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.

PIP: In Washington State, 36 men aged 20-42 years were randomly allocated to either the group receiving intramuscular injection of 100 mg/week testosterone (T) enanthate alone or to the group receiving the same dose T plus oral 500 mcg/day levonorgestrel (LNG). This 6-month, placebo-controlled, single blind trial aimed to compare the effectiveness of both regimes in suppressing sperm production. The combination of T plus LNG was more likely than T alone to achieve severe oligospermia or azoospermia in 6 months (94% vs. 61%; p .05). It also achieved azoospermia more quickly than T alone (9.9 vs. 15.3 weeks; p .05). Men in the T plus LNG group experienced greater reduction in serum high density lipoprotein than those in the T alone group (21.7% vs. 1.8%; p .05). They also gained more weight than those in the T alone group (5.3 vs. 2.3 kg; p .05). The two groups experienced a similar rate for acne and increase in hemoglobin. The increase in hemoglobin was significant for both groups. In conclusion, T plus LNG treatment over a 6-month period is a more effective and quicker acting method than T alone for suppressing sperm production to levels low enough to prevent pregnancy.