Progesterone is scientifically validated for use in treating menstrual irregularity, especially those associated with anovulatory cycles or luteal phase defects. Progesterone plays a central physiological role in regulating the menstrual cycle: it is produced after ovulation by the corpus luteum and is responsible for transforming the endometrium into a secretory state, preparing it for possible implantation. If pregnancy does not occur, the drop in progesterone triggers menstruation. In cases where ovulation does not occur (anovulation), progesterone is not produced adequately, leading to irregular periods or amenorrhea.

The clinical use of exogenous (administered) progesterone or progestins is well established in gynecology. Cyclic or sequential progesterone therapy is used to induce regular withdrawal bleeding in women with irregular cycles, particularly in those with conditions such as polycystic ovary syndrome (PCOS), perimenopause, or hypothalamic amenorrhea. Multiple clinical guidelines—including those from the American College of Obstetricians and Gynecologists—recommend progestin therapy to induce menstruation and reduce the risk of unopposed estrogen stimulation of the endometrium, which can otherwise lead to hyperplasia or cancer.

Randomized controlled trials and observational studies support the efficacy and safety of progesterone for these indications. The evidence base is stronger for synthetic progestins than for bioidentical progesterone, but both are used in practice. Overall, the scientific rationale and supporting data for progesterone in menstrual irregularity are robust, earning a high evidence rating.