Topical preparations containing progesterone are increasingly compounded in pharmacies, and when done so, have expiration dates of 6 months post preparation or the stated expiration date of the API, whichever comes first. Using an HPLC method developed in our lab for the separation and quantitation of progesterone, we determined the room temperature (25°C) and refrigerated (4°C) stability of compounded progesterone in proprietary PLO Transdermal CreamTM and HRT CreamTM both manufactured by Medisca Inc. over a 90 day period. Area under the curve (AUC) measurements for the 30 and 60 day analysis reveal both compounded preparations retain >95% of the stated initial potency regardless of temperature storage conditions. However, a significant decrease in stability is noted during the last 30 day study period regardless of storage temperature for both preparations (71 and 73% for HRTTM at 25°C and 4°C respectively and 69 and 71% for PLO Transdermal CreamTM 25°C and 4°C respectively). Our data suggests that compounded progesterone preparations maintain chemical stability per USP standards (± 10%) for up to 60 days in each of the tested bases, regardless of storage temperature. Due to the significant loss in chemical stability, usage beyond 60 days post-preparation is not recommended.