Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride

Abstract

Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption.

© 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Figures

Figure 1

Study design. Treatment with oral testosterone undecanoate 200 mg twice daily for three separate 1-week periods, with 1-week wash-out periods in between dosing, co-administered with 0, 0.5 or 1.0 mg finasteride twice daily. Acyline (300 mcg/kg) was administered on days 1, 15 and 29 to induce hypogonadism. The sequence of finasteride doses was randomized to minimize carryover effect.

Figure 2

Serum testosterone (A), dihydrotestosterone (DHT) (B) and oestradiol (C) after 7 days of dosing with oral testosterone undecanoate (200 mg) by mouth twice a day alone or with 0.5 or 1.0 mg of finasteride twice a day in 11 normal men with experimentally induced hypogonadism. Each subject underwent all three treatments in random order. The short dashed lines represent the upper and lower limits of the normal range. All values are geometric means ± SE. TU, testosterone undecanoate.