Aromatase equency of germ cell apoptosis rises under conditions of hormonal depletion, ischemia or cryptorchidism. The insufficiency in the levels of reproductive hormones following DNGTU treatment results in the severe reduction of number of germ cells per tubule, which may be subsequent to apoptotic induction and removal of germ cells from the seminiferous epithelium. Stoppage of treatment either after 2 or 3 injections reverses the adverse effect on seminiferous epithelium with qualitatively full restoration of spermatogenesis. Although the gonadotropin levels are not completely restored, the significant increase in LH concentration following withdrawal clopidogrel modulated an identical increase in serum testosterone, supporting sperm production. The present findings confirm the potential of the DNGTU combination as a potential candidate for male contraception but needs to be tested further in clinical trials. Since the metabolism of DNG will be quite different in men, the doses used in the present study may not be directly extrapolated.
However, these results will be useful for similar dose standardization studies involving human volunteers.Hormonal male contraception is best achieved by successful down regulation of gonadotropins, leading to a decrease in Leydig cell steroidogenesis and circulatory testosterone, VEGFR signaling pathway which is alternatively being maintained at physiological levels with exogenous testosterone supplementation. The combination of a progestin with a long acting testosterone ester has been shown to promote more rapid and greater spermatogenic suppression than that of testosterone alone. When testosterone was given alone, there were also differences in the rate of azoospermia achieved, which was 68%forCaucasians, 95%for Chinese and 100%for Indonesians. Although the reason for these differential sperm suppression is not very clear and sometimes ascribed to racial or ethnic differences among subjects, differences in the testicular high throughput screening activity of 5 reductase has been implicated as one of the major factors, since synthesis of the more potent androgen, 5 dihydrotestosterone, may sustain a low sperm production under adverse conditions.
Since sperm suppression is associated with a significant decline in intratesticular testosterone concentration, a reduction in substrate availability may also lead to alterations in the expression of 5 reductase gene. Although the conversion process has been extensively studied to assess the activity of the enzyme 5 reductase, the gene expression studies pertaining to the enzyme are not many. Because of their role at higher centers, progestin supplementation to testosterone based regimens increasesthe potency of gonadotropin suppression. Progestins possess the inherent antiandrogenic property, which counteracts the effects of the residual iT testosterone, leading to a better inhibition of spermatogenesis. In addition, progestins have direct inhibitory effect on Leydig cell function. Considering the fact that gonadotropin down regulation adversely affects steroidogenesis, studies on the effect of progestins in the expressions of testicular steroidogenic enzyme genes are critical and might provide vital clues to the degree of sperm suppression achieved following intervention with different hormonal contraceptives.