Comparative Bioavailability of Two Daily Subcutaneous Doses Versus a Single Dose of Intramuscular and Vaginal Progesterone Formulations in Healthy Postmenopausal Females

Abstract

AbstractProgesterone is a naturally occurring endocrine hormone. It is used for luteal phase support to improve success rates in assisted reproduction. This was a single‐center, comparative bioavailability, open‐label, randomized, 3‐period, 6‐sequence, crossover study to compare the rate and extent of absorption of subcutaneous (SC) progesterone 25 mg twice daily, versus vaginal (Vag) gel once daily (90 mg progesterone) and 50 mg of intramuscular (IM) progesterone injection once daily in healthy postmenopausal females. Eighteen healthy, postmenopausal, female nonsmokers aged 55–65 years were dosed. Data from 17 subjects who completed at least 2 study periods, including the test and 1 reference, were included in the pharmacokinetic analysis. The SC progesterone product administered twice daily showed a higher exposure than a single dose of the Vag formulation, with least‐squares mean (LSM) ratios (SC/Vag gel) of 219.7% for AUC0–inf and 391.8% for Cmax. The SC progesterone product administered twice daily showed comparable extent of exposure to that of the IM product, but showed higher peak concentration, with LSM ratios (SC/IM) of 92.4% for AUC0–inf and 138.0% for Cmax. Mean (SD) relative bioavailability (Frel) for SC/Vag gel was 449.6 (233.1)%, and for SC/IM was 92.3 (6.3)%. Mild injection site reactions were reported with similar frequency for SC and IM progesterone. With further research, twice‐daily SC progesterone may offer an alternative to existing available treatments for luteal phase support.