Transdermal delivery of bioidentical progesterone using dutasteride (A 5α-reductase inhibitor): A pilot study

Abstract

Purpose. The bioavailability of transdermal progesterone is known to be low and variable. This can be attributed to transdermal metabolism by 5α-reductase enzymes. The objective of the current study is to evaluate the effect of dutasteride, an inhibitor of these metabolizing enzymes, on the bioavailability of transdermally delivered progesterone. Method. Twenty postmenopausal women with Follicle Stimulating Hormone levels greater than 40IU/L were recruited to take part in the study. The subjects were randomly allocated to either dutasteride (n=10) or placebo (n=10) groups. Each group applied either 500 mg of non-ionic cream or dutasteride cream (2 mg/g) to the right arm for 15 days. This was followed by applying 500 mg of progesterone (80 mg/g) or progesterone dutasteride cream (80 mg/g, 2 mg/g) for a further two weeks. On day 30, blood and saliva samples were collected over a 12-hour period and progesterone concentrations determined. Results. The baseline serum progesterone concentration on day zero was 0.1 ng/ml. On day 30, baseline serum progesterone levels increased significantly (p <0.05) to 1.40 ng/ml and 1.15 ng/ml in the progesterone and dutasteride groups, respectively. Salivary progesterone concentrations were increased by seven fold, from 0.40 ng/ml to 2.9 ng/ml. On average, salivary progesterone concentration was four times the serum levels. Conclusion. The average serum and salivary progesterone concentration, Cmax, and the AUC were slightly higher in the dutasteride group, but no significant difference could be noted. Metabolism by the 5α-reductase enzyme is unlikely to affect the bioavailability of progesterone.