Postpartum depression (PPD) is a serious mental health condition that affects up to 1 in 8 women after childbirth, with symptoms that include sadness, fatigue, and difficulty bonding with the baby, according to March of Dimes. While the early weeks with a new baby are often portrayed as joyous, the hormonal and emotional shifts can leave many feeling overwhelmed and isolated. Researchers are exploring a treatment for PPD called progesterone, a hormone that plays an important role during and after pregnancy.

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 PPD. Scientists are now studying whether giving progesterone after birth could help treat PPD.

Postpartum Depression and Hormones

During pregnancy, hormones like progesterone and estrogen rise to very high levels. After giving birth, these levels drop quickly. This big change can affect brain chemicals that control mood. One of these chemicals, allopregnanolone, is made from progesterone and helps manage stress and anxiety. When progesterone drops, so does allopregnanolone, which might explain why some new parents develop PPD.

In addition to hormonal changes, other factors may increase the risk of PPD, including:

• Lack of sleep
• Physical recovery from childbirth
• Trouble with breastfeeding
• Stress of caring for a newborn

FDA-Approved Treatments for Postpartum Depression

Zuranolone (Zurzuvae) was approved by the U.S. Food and Drug Administration (FDA) in 2023 to treat PPD. It is an oral medication that is taken for only two weeks. Zuranolone mimics the effects of allopregnanolone on the brain. This is different from traditional antidepressants that are used to treat depression as well as PPD.

Brexanolone is a synthetic version of allopregnanolone. This medication is administered intravenously (through your veins) for over 60 hours. It was previously available to treat PPD but was taken off the market after the release of zuranolone, which works similarly and is easier to take.

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

Progesterone: A Possible Alternative?

Oral progesterone is being studied as another treatment option for PPD. Progesterone is processed by the body into allopregnanolone. This means progesterone might have similar effects to drugs like zuranolone in improving mood after pregnancy.

Evidence Regarding Progesterone

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

• One study 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 trial, participants with a history of PPD had their progesterone levels lowered on purpose — which led to increased depressive symptoms, further supporting the link between hormonal withdrawal and mood disorders.

One important takeaway is that progesterone appears to play a bigger role in mental health beyond just pregnancy and postpartum periods. Progesterone’s ability 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 progesterone may be helpful in improving depressive symptoms in PPD, the research is inconclusive. Different studies on the negative and positive effects of progesterone on mood have had mixed results. Some studies found that progesterone can even make depression worse. Large-scale clinical trials are needed to confirm if progesterone can effectively treat PPD.

Progesterone vs. Other Hormonal Treatments

Progesterone used for PPD treatment and progesterone used for oral birth control or HRT are different. Standard birth control does not provide the high doses of progesterone necessary to replicate the effects of allopregnanolone.

A 2019 study estimated that it would require 300 milligrams of oral progesterone every two hours to achieve similar results to allopregnanolone medications. The difference in the dose and the amount of drug in the body could partially explain why researchers haven’t been able to come to a conclusion about whether progesterone supplementation is helpful to prevent PPD.

Safety Considerations and Breastfeeding

Progesterone-based treatments are generally safe and appear to be compatible with breastfeeding and infant health. However, as with all hormonal therapies, some people may experience side effects. Potential side effects of progesterone include nausea, bloating, and breast tissue changes.

Debunking the ‘Hormon 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 are not substitutes for medical treatment or FDA-approved medications. It is important that you discuss any drug or nondrug therapies with your doctor to ensure the intervention is safe and effective.

Find Your Team

MyDepressionTeam is the social network for people living with all types of depression, including postpartum depression, and their loved ones. Members come together to ask questions, offer support and advice, and share their stories with others who understand life with PPD.

Did you know about the risk factors for postpartum depression before your baby was born? Do you have any advice for others managing these risks? Share your experience, or start a conversation by posting on your Activities page.