Objective: To provide an evidence-based safety and tolerability overview of dydrogesterone under various progesterone-deficient conditions as a commemoration of its role in managing women's reproductive health over the past 60 years.
Methods: To identify relevant publications, we used a semi-systematic approach, which included performing a structured search through the PubMed and Cochrane central databases as well as an unstructured search for publications published in English from 2010 onward with human clinical data.
Results: A total of 32 relevant clinical studies were identified. Results were reported in the context of overall adverse events (AEs) and segregated according to various progesterone-deficient conditions. AEs concerning breasts (breast cancer risk), the endometrium (endometrial cancer risk), venous thromboembolism risk, and cardiovascular risk were found to be minimal when dydrogesterone was used as part of a menopausal hormone therapy regimen lasting ≤260 weeks. Vagina-related AEs, such as bleeding, discharge, irritation, and difficult coitus, occurred less frequently with dydrogesterone when used as luteal phase support in the context of assisted reproductive techniques (ARTs). However, other common AEs, such as headache, dizziness, abdominal pain, flatulence, and nausea, occurred more frequently with dydrogesterone. No maternal complications or congenital anomalies could be linked to dydrogesterone usage during ARTs or during early pregnancy to prevent recurrent miscarriages. Studies on dydrogesterone in endometriosis and premenstrual syndrome remain scarce.
Conclusions: Post-approval, dydrogesterone has displayed a favorable safety and tolerability profile during its 60-year use, which is reassuring, considering its important role in managing women's reproductive health.
Keywords: Assisted reproductive technology; cycle regularization; dydrogesterone; endometriosis; habitual abortion; luteal phase support; menopausal hormone therapy; menstrual bleeding.