Oral progestogen combined with testosterone as a potential male contraceptive: Additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism

The effects of a synthetic oral progestogen, desogestrel (DSG), administere d with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to target s compatible with effective male contraception. Twenty-four healthy male vo lunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to re ceive: 1) 300 mu g DSG orally daily and 100 mg T enanthate, im, weekly; 2) 300 mu g DSG and 50 mg T enanthate; or 3) 150 mu g DSG and 100 mg T enantha te for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 2 3) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% ( 23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 mu g DSG with 50 mg T enanthate combination induced a zoospermia in 8 of 8 subjects, and the suppression of sperm density was sig nificantly greater than that in the 300 mu g DSG/100 mg T enanthate group, but was not different from that in the 150 mu g DSG/100 mg T enanthate grou p. DSG (300 or 150 mu g daily) alone in the first 3 weeks suppressed LH, FS H, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Additio n of T enanthate (50 and 100 mg weekly) raised plasma T to the physiologica l range and induced a further fall in LH and FSH to the Limits of assay det ection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained det ectable in a higher proportion of samples from the group receiving 300 mu g DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein ch olesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7 %, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 mu g. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density Li poprotein cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the c ombined actions of oral DSG with low doses of T enanthate were highly effec tive in suppressing pituitary-testicular functions in adult men. The optima l regimen for inducing azoospermia was 300 mu g DSG daily with 50 mg T enan thate weekly. Oral DSG exerted discernible effects on lipid metabolism. me conclude that the combination of oral progestogens with low dose T is a pro mising approach to achieve effective reversible male contraception.