Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

OBJECTIVE: The objective of this study was to evaluate the serum levels of progesterone resulting from the application of a progesterone cream to the skin. STUDY DESIGN: Six postmenopausal women were evaluated at a university clini c over a 4-week period. RESULTS: Transdermal estradiol 0.05 mg was applied 2 days before the first application of progesterone (30 mg/d) and was continued throughout the stud y. Patches were changed twice a week, Progesterone cream was applied once a day for 2 weeks. On day 15 and for the next 2 weeks, the progesterone crea m was applied twice daily (60 mg/d). Serum 17 beta-estradiol and progestero ne were measured at 9 different times over a 24-hour period on day 1 and at weekly intervals for the 4-week duration of the study. Serum 17 beta-estra diol concentrations varied among women, with mean concentrations of 40 to 6 4 pg/mL observed. Consistency in 17 beta-estradiol concentrations was found within individual persons throughout the study. Serum progesterone concent rations also varied among women, with mean concentrations ranging from 1.6 to 3.3 ng/mL. After 2 weeks of percutaneous dosing, progesterone concentrat ions were sustained for at least 8 hours and were consistent within a given person. An appropriate increase in progesterone concentration occurred aft er 4 weeks compared with 2 weeks of application. Individually, a 0.53 corre lation. significant at P < .0001,was seen between the absorption of 17 beta -estradiol and progesterone. CONCLUSION: Significant increases in serum concentrations of progesterone w ere observed in all of the women studied. The percutaneous absorption of pr ogesterone correlates strongly with the absorption of transdermal 17 beta-e stradiol. There is variance in absorption of progesterone just as with 17 b eta-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration.