Relationship between Serum Gonadotropins and Spermatogenic Suppression in Men Undergoing Steroidal Contraceptive Treatment

Abstract

This study aimed to establish whether the degree of suppression of serum FSH and LH was related to sperm concentration in three testosterone (T) plus progestin contraceptive regimens. We measured serum FSH and LH using a modified, highly sensitive immunofluorometric assay in samples obtained from three published studies using T enanthate (TE; 100 and 200 mg weekly) plus daily oral doses of cyproterone acetate (CPA; 5-100 mg), levonogestrel (LNG; 150-500 micro g), or desogestrel (DSG; 150-300 micro g). Overall, men with sperm concentrations below 0.1 million/ml had significantly lower gonadotropin levels (serum FSH, approximately 0.12 IU/liter; serum LH, approximately 0.05 IU/liter) than oligospermic men (sperm concentrations, 0.1-5 million/ml; serum FSH, 0.23-0.5 IU/liter; serum LH, 0.05-0.56 IU/liter), but the relationship was weak, indicating the possible existence of other determinants. Multivariate logistic regression was used to identify the influence of candidate predictors of spermatogenic effects of the T plus progestin regimens. In the LNG and DSG studies, the marked suppression of serum LH to less than 5% of baseline values (<0.15 IU/liter) was a consistent and highly significant predictor of sperm concentration (reduced to 2-7% that seen at higher LH levels) and the likelihood of its suppression below 1 million/ml (a proposed threshold for contraceptive efficacy). Serum FSH was not a significant independent predictor. The use of DSG and CPA (but not LNG) was a significant independent predictor of sperm suppression, and regimens that contained 200 mg TE weekly caused less spermatogenic suppression than 100 mg TE weekly. These findings suggest that T-progestin contraceptive regimens suppress sperm concentration by gonadotropin-dependent and -independent mechanisms. The suppression of serum LH is a major predictor of the suppression of sperm concentration suppression in the LNG and DSG treatment studies. On the other hand, the greater spermatogenic suppression in regimens containing DSG or CPA suggests that these progestins have additional actions to suppress spermatogenesis via a gonadotropin-independent mechanism(s)

Progesterone: the forgotten hormone in men?

“…The gonadotropin suppression by progestins in the human male is mediated by genomic progesterone receptors, whereas the androgenicity of some progestins seems to contribute only minimally to gonadotropin inhibition 63 . Since excellent reviews on hormonal male contraception have been published recently; this indication for progestins in fertile men will not be treated in greater detail here [64][65][66][67][68][69] .…”

Le futur de la contraception masculine

“…Une suppression incomplète des gonadotrophines chez les nonrépondeurs serait une autre explication logique, mais aucune preuve de cela n'a jamais été obtenue [17,18]. Une dépendance différentielle de la spermatogenèse à la stimulation hormonale [17], ainsi que des différences pharmacogénétiques du taux de suppression des gonadotrophines [19] ont aussi été suggérées.…”

Update on Male Hormonal Contraception: Is the Vasectomy in Jeopardy?

“…It appears that progesterone affects gonadotropins via the hypothalamicpituitary-testis axis, however, they may function directly on the testis as well. 12,13 It is clear that in normal sperm-producing men, intratesticular testosterone levels are 100-fold higher than in serum. [14][15][16][17][18] Interestingly, LH-receptor-deficient mice can support some level of spermatogenesis, but use of an androgen receptor antagonist such as flutamide will suppress spermatogenesis completely.…”