Evidence Level
Emerging
OTC progesterone cream has a limited but growing evidence base. The Leonetti et al. (1999) RCT of 102 women showed reduced vasomotor symptoms with transdermal progesterone cream. However, the cream format raises absorption variability concerns — serum levels rise modestly while salivary levels increase dramatically, making monitoring challenging. The Endocrine Society and NAMS generally recommend prescription-grade progesterone (oral micronized or vaginal) over OTC creams for reliable dosing. Nonetheless, many integrative practitioners use OTC creams successfully for mild perimenopausal symptoms.