Transdermal Delivery of Bioidentical Progesterone with a Steroid 5α-Reductase Inhibitor (Dutasteride): a Pilot Study
Purpose: Bioavailability of transdermal progesterone is low and variable. This may be attributed to transdermal metabolism by the 5α-reductase enzymes or the direct transport to the saliva. The objective of the current study was to evaluate the effect of enzyme inhibition on the bioavailability of transdermal progesterone. Serum and salivary progesterone levels were evaluated to gain a better insight into the mechanism progesterone transport across the skin. Method: Twenty postmenopausal women with a Follicle Stimulating Hormone > 40iu/L were recruited to take part in the study. The subjects were randomly allocated to either dutasteride (n=10) or placebo (n=10). Each group applied either 500mg of non ionic cream or dutasteride cream (2mg/g) to the right arm for 2 weeks. This was followed by applying 500mg of progesterone or progesterone dutasteride cream (equivalent to 40mg of progesterone) for a further 2 weeks. On day 30 blood and saliva were collected for over 12 hours and progesterone concentration was measured. Results: The baseline progesterone concentration on day zero was 0.1 ng/ml. On day 30 baseline progesterone levels increased significantly (p <0.05) to 1.40 ng/ml and 1.15 ng/ml in progesterone and dutasteride groups respectively. The average serum concentration of progesterone was 3.04 ng ( placebo) and 3.14 ng/ml (dutasteride). Salivary progesterone concentrations were increased by 2-9 folds. The Cmax and AUC in the placebo were 21.45 ng/ml 131.27 cm2 respectively. In the dutasteride group these values were slightly increased to 29.00 ng/ml (Cmax) and 132.60cm2(AUC). On average salivary progesterone concentration were 4 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. Direct transport of progesterone to the saliva may play an important role in transport of progesterone across the skin.