A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations
Bd. Anawalt et al., A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations, J ANDROLOGY, 20(3), 1999, pp. 407-414
Studies using exogenous high-dosage testosterone (T) or a combination regim
en of physiologic T plus high-dosage levonorgestrel (LNG) administration in
normal men have shown that oligoazoospermia (<3 million/mL) or azoospermia
can be achieved in the majority of the men. However, these hormonal regime
ns have been associated with significant weight gain and suppression of ser
um high-density lipoprotein (HDL) cholesterol levels. We hypothesized that
a combination of physiologic exogenous testosterone and lower dosage LNG wo
uld result in uniform severe oligoazoospermia or azoospermia in normal men
but would cause fewer adverse metabolic side effects. We conducted a random
ized, placebo-controlled, single-blind trial comparing 6 months of T enanth
ate (100 mg IM, weekly) plus LNG, 125 mu g by mouth, daily (LNG 125; n = 18
) or LNG, 250 mu g by mouth, daily (LNG 250; n = 18) and compared these reg
imens with our previous study of the same dosage of T enanthate combined wi
th placebo LNG (LNG 0; n = 18) or with 500 mg of LNG (LNG = 500; n = 18). A
ll three combination regimens of T enanthate and LNG suppressed spermatogen
esis more rapidly and resulted in significantly more uniform severe oligoaz
oospermia (<1 million/mL) than the T-alone regimen. Severe oligoazoospermia
was achieved in 89% of the LNG 125, 89% of the LNG 250, and 78% of the LNG
500 groups, respectively, versus 56% of the men in LNG 0 (P < 0.05 for the
combination groups vs. LNG 0), but there were no significant differences b
etween the combination regimens (P = NS). All four groups gained significan
t weight compared with their baselines, although the gain tended to be grea
ter as the dosage of LNG increased (2.0 +/- 0.9, 2.9 +/- 1.1, 3.6 +/- 1.0,
and 5.4 +/- 1.0 kg gained, compared with baseline in the LNG 0, 125, 250, a
nd 500 groups respectively; P < 0.05 compared with baseline). Serum levels
of HDL cholesterol decreased in all of the groups, but the effect was large
r as the dosage of LNG increased (4 +/- 4% vs. 13 +/- 4%, 20 +/- 3%, and 22
+/- 4% decrease in HDL levels from baseline in the LNG 0, LNG 125, LNG 250
, and LNG 500 groups respectively; P = 0.06 for LNG 125 compared with LNG 0
, and P < 0.05 for LNG 250 and LNG 500 compared with LNG 0). We conclude th
at 1) the combination of physiologic exogenous T enanthate and LNG suppress
es spermatogenesis more effectively than T enanthate alone and that 2) the
combination regimen of T enanthate plus lower dosage LNG suppresses sperm p
roduction comparably to T enanthate plus higher dosage LNG, while causing l
ess weight gain and HDL cholesterol suppression. A combination regimen of p
hysiologic testosterone plus a low dosage of levonorgestrel offers great pr
omise as a safe and effective male contraceptive regimen.