Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for 4 weeks in normal men: implications for male hormonal contraception

Abstract

Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.

Figure 1

Nadir serum testosterone (A), dihydrotestosterone (DHT) (B), and estradiol (C) concentrations (mean ± SD) prior to, during, and after oral administration of 400 mg twice daily or 800 mg once daily of testosterone enanthate (TE) in oil with dutasteride for 28 days in healthy men. The dotted lines represent the lower limits of the normal range for testosterone and DHT and the upper and lower limits of the normal range for estradiol. * indicates P < .05 compared with baseline.

Figure 2

Serum testosterone, DHT, and estradiol concentrations (mean ± SEM) over 24 hours on the 28th day of oral administration of 400 mg twice daily (A, C, E) or 800 mg once daily (B, D, F) of TE in oil with dutasteride. The dotted lines represent the lower limits of the normal range. * indicates P < .05 compared with baseline; φ P < .05 between dose groups at a given time point.

Figure 3

Serum FSH (A) and LH (B) concentrations (medians and interquartile ranges) prior to, during, and after oral administration of 400 mg twice daily or 800 mg once daily of TE in oil with dutasteride for 28 days in healthy men. The dotted lines represent the lower limits of the normal range. * indicates P < .05 compared with baseline.