Progesterone is a hormone that naturally rises during pregnancy and drops sharply after birth. This sudden change may affect mood and increase the risk of postpartum depression (PPD).

Researchers are exploring the use of progesterone to treat PPD. It isn’t currently approved by the U.S. Food and Drug Administration (FDA) for depression or an established treatment for postpartum depression. However, it’s being studied as a possible treatment approach.

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FDA-Approved Treatments for Postpartum Depression

Zuranolone (Zurzuvae) was approved by the United States Food and Drug Administration (FDA) in 2023 to treat PPD. It’s an oral medication that is taken for only two weeks.

Zuranolone mimics the effects of allopregnanolone on the brain. This is different from traditional antidepressant medication that is used to treat depression as well as PPD.

Brexanolone, a synthetic version of allopregnanolone, was sold as Zulresso in the U.S. As of Jan. 1, 2025, Zulresso is no longer commercially available in the U.S., although its FDA approval has not been withdrawn.

Zuranolone works differently from progesterone-based contraceptives or hormone replacement therapy (HRT). It stabilizes moods by affecting the brain directly rather than hormone levels.

Progesterone: A Possible Alternative?

Oral progesterone is being studied as another experimental treatment option to treat PPD. Progesterone is processed by the body into allopregnanolone. While the conversion of progesterone to allopregnanolone is biologically interesting, it hasn’t yet been shown to be effective as a treatment for postpartum depression.

Medical experts are conducting further research into whether taking progesterone may help improve mood after childbirth.

Evidence of Progesterone for PPD

Research on progesterone’s effectiveness in treating PPD is limited but shows possibility.

One theory estimated that high doses of oral progesterone could replicate the effects of drugs like brexanolone or zuranolone.

In animal studies, progesterone prevented depression-like symptoms and improved brain function in mice.

In a small human study, researchers gave participants high levels of both estrogen and progesterone and then withdrew both hormones to mimic the hormonal changes around childbirth. Some participants with a history of postpartum depression developed mood symptoms after the hormones were withdrawn. This suggests that some people with a history of PPD may be especially sensitive to changes in reproductive hormones.

One important takeaway is that progesterone appears to play a bigger role in mental health beyond just pregnancy and postpartum periods. Progesterone’s potential to affect mood highlights its potential as a target for further research on mood changes related to menstruation, reproduction, and menopause.

Although some results suggest that there may be a link between progesterone and mood changes, the research is inconclusive. Different studies on the effects of progesterone on mood have had mixed results. Large-scale clinical trials are needed to confirm if progesterone can effectively treat PPD.

Progesterone vs. Other Hormonal Treatments for PPD

Progesterone used for PPD treatment and progestin, a synthetic substitute for the hormone used for oral birth control and some HRT, aren’t the same. Progestin has a different chemical structure than progesterone. In addition, many hormonal birth control methods contain synthetic progestins rather than natural progesterone. These drugs are chemically different from progesterone and may not be processed into allopregnanolone in the same way.

One small study in healthy volunteers estimated that 400 milligrams of extended-release progesterone every six hours might produce allopregnanolone levels similar to a target used in research. However, the study did not include people with PPD or evaluate if this dose can safely or effectively treat the condition.

Safety Considerations and Breastfeeding

Progesterone-based treatments are generally safe and appear to be compatible with breastfeeding and infant health. However, the very high experimental doses proposed as treatment for PPD haven’t been adequately studied in breastfeeding postpartum patients.

In addition, as with all hormonal therapies, some people may experience side effects. Potential side effects of progesterone may include:

• Nausea
• Bloating
• Breast tissue changes

Debunking the ‘Hormone Hacking’ Myth

There’s been a recent rise in social media trends promoting “hormone hacking” to treat PPD, with social media influencers promoting dietary supplements and lifestyle changes. While healthy eating and exercise can support mental well-being, they’re not substitutes for medical treatment or FDA-approved medications. It’s important that you discuss any drug or nondrug therapies with your healthcare provider to ensure any intervention is safe and effective.