Progesterone

To date, there is no compelling evidence that progesterone is an effective stand-alone treatment for PMDs. Below is a summary of the relevant evidence of which we are aware: An older meta-analysis examining luteal phase administration of progesterone as a treatment for premenstrual mood symptoms [1] found that while oral micronized progesterone (3 studies; n = 141) had small mood benefits relative to placebo, vaginal progesterone (8 studies; n = 298) performed marginally worse than placebo.

Two studies in individuals with a confirmed diagnosis of premenstrual dysphoric disorder (PMDD; n = 10 and 34) and on leuprolide [2, 3] found that administration of progesterone in the form of vaginal suppositories (200 mg twice daily) triggered symptoms over a four-week period. More specifically, it is reported in the most recent of these studies [3] that 59% of participants experienced a surge in PMDD symptoms with progesterone administration. A third study [4] (n = 22) administered leuprolide with combined estradiol and vaginal progesterone (200 mg twice daily) for three months among individuals with PMDD. Consistent with the above studies, PMDD symptoms worsened in the first month; however, symptoms subsided in months two and three.

Taken together, these findings support the view that PMDD symptoms result from an increased mood sensitivity to fluctuations in ovarian hormones rather than high, stable levels. There is therefore no theoretical basis supporting the cyclical administration of progesterone. In theory, continuous administration of progesterone at a dose that is sufficiently high to suppress ovulation could eventually improve symptoms, following initial symptom exacerbation in most individuals. Since vaginal progesterone more effectively suppresses ovulation relative to oral micronized progesterone, vaginal progesterone would theoretically be expected to minimize hormonal fluctuation more effectively. However, we know of no trials testing continuous progesterone – vaginal or oral – as a stand-alone treatment for PMDs.

In summary, while it is theoretically possible that continuous progesterone administration, through the stabilization of hormone levels, could eventually improve PMD symptoms in some, there is currently a lack of evidence supporting this possibility. What is more certain is that the administration of progesterone does trigger a short-term exacerbation of symptoms in most individuals with PMDD. Additional research is needed to identify those who are at the most significant risk of experiencing symptom exacerbation in response to a rise in progesterone.

In light of the above evidence, we urge those considering a trial of progesterone to exercise extreme caution. We also encourage anyone exploring treatment options to review IAPMD’s resources on evidence-based treatments with strong scientific support.

Note: ‘n =’ indicates the number of individuals with PMDD included in the study

📌 References

1. Wyatt, K., et al., Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review. Bmj, 2001. 323(7316): p. 776.

2. Schmidt, P.J., et al., Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. New England Journal of Medicine, 1998. 338(4): p. 209–216.

3. Wei, S.-M., et al., Differential effects of ovarian steroids in women with and without premenstrual dysphoric disorder: a replication and extension of findings. American Journal of Psychiatry, 2025. 182(10): p. 922–934.

4. Schmidt, P.J., et al., Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels. Am J Psychiatry, 2017. 174(10): p. 980–989.