Abstract:
Monthly injections of testosterone undecanoate (TU) act as a male
contraceptive by reversibly suppressing spermatogenesis to azoospermia or
severe oligoazoospermia in 95% of Chinese men. In 5% of Chinese men,
however, monthly TU administered alone fails to suppress spermatogenesis
into contraceptive ranges, or sperm "rebound," leading to occurrences of
pregnancy during treatment. Since combinations of progestins and androgens
are associated with greater degrees of sperm suppression in white men, we
hypothesized that the combination of TU and the progestin levonorgestrel
(LNG) would result in improved spermatogenic suppression in Chinese men.
Sixty-two healthy Chinese men were randomly assigned to one of the
following 3 regimens: group I (n = 21) received 4 LNG rods (75 mg each),
which were followed 4 weeks later by 500 mg of TU by intra-muscular (IM)
injection every 8 weeks for 24 weeks; group II (n = 20) received 4 LNG
implants, which were followed 4 weeks later by 1000 mg of TU by IM
injection every 8 weeks for 24 weeks; and group III (n = 21) received TU
1000 mg by IM injection every 8 weeks for 24 weeks. Sperm counts, serum
testosterone (T), luteinizing hormone, follicle-stimulating hormone, and
LNG were measured every 2 weeks before, during, and after treatment.
During treatment, group II demonstrated a trend toward a greater
attainment of azoospermia than groups I and III (90% vs 62% [group I] vs
67% [group III]; P =.09). Attainments of either azoospermia or
oligozoospermia (sperm density, <3 x 10(6)/mL) were 95%, 100%, and 86% for
groups I, II, and III, respectively (P >.05 for comparisons between
groups). Spermatogenesis in all subjects returned to the normal range
after the implants were removed. No serious adverse events and no
significant changes in serum chemistry occurred during the study. These
results demonstrate that the combination of IM injections of high-dose TU
every 2 months and LNG implants is associated with marked suppression of
spermatogenesis in Chinese men. The combination of high-dose TU every 2
months and LNG implants is a promising candidate for future large-scale
efficacy studies of hormonal male contraception in Chinese men.
