Postpartum Depression (PPD): What Dr. Lee Had to Say

From the September 2023 Issue of the Hormone Balance Hotline

Over the last several years, postpartum depression (PPD) has become a growing concern among mothers and healthcare providers. According to a recent Wall Street Journal article, some researchers estimate that one in five new mothers in the United States suffers from mood and anxiety disorders during pregnancy and up to a year after giving birth. That comes out to around 800,000 mothers every year. Tragically, many of these mothers are unable to get help for their PPD, and many are at risk of long-term depression and suicide.1

In response, pharmaceutical companies have brought two new drugs to market for the treatment of postpartum depression (PPD). The first drug, Brexanolone, is a liquid that is administered intravenously. The second drug, which the FDA approved in August 2023, is the first pill for postpartum depression in the USA. It is called Zuranolone and has the brand name “Zurzuvae”.

While the FDA has approved both of these drugs for the treatment of PPD, what would Dr. Lee have said about them? Fortunately, his research and writings give us a very clear picture of what Dr. Lee would say.

The active ingredients in brexanolone and zuranolone are synthetic, laboratory-created versions of allopregnanolone. As Dr. Lee pointed out in his writings, our own bodies create the natural version of allopregnanolone, and they create it from – you guessed it – progesterone! Here is what Dr. Lee wrote about the subject in his best-selling book, What Your Doctor May Not Tell You About Menopause in Chapter 6, “What Is Natural Progesterone?”, under “Progesterone and the Brain.”

“Progesterone has long been known to have a calming or mildly sedating effect. This effect is caused by a metabolite of progesterone called allopregnanolone that is active at GABA (gamma-aminobutyric acid) receptors. (GABA is an amino acid that acts as a neurotransmitter inhibitor and tends to have a calming effect.) Progesterone’s sedation of the central nervous system is sufficiently potent in higher doses that it has been used as an anesthetic. When used in small doses, progesterone is commonly effective in restoring normal sleep patterns and promoting a sense of calm.”

In line with Dr. Lee, the makers of brexanolone and zuranolone say that their drugs target GABA receptors to treat the symptoms of PPD. What they don’t say is that their drugs do not contain bioidentical allopregnanolone. They contain synthetic allopregnanolone that is molecularly different than the bioidentical allopregnanolone our bodies make from progesterone. In other words, brexanolone and zuranolone contain progestins:  synthetic versions of progesterone and its metabolites. As Dr. Lee points out in his writings, progestins may have some of the health effects of the progesterone that our own bodies create, but they also have side effects and health risks that bioidentical progesterone does not have.

With this in mind, what would Dr. Lee say today about the crisis of postpartum depression and the new drugs being offered to treat it? We are confident he would say the same thing that he said in What Your Doctor May Not Tell You About Menopause in Chapter 8, “Sex Hormones and the Brain”, under “Postpartum Blues”.

“Many women experience depression in the days (and weeks) following childbirth. Other symptoms include headache, irritability, and sleeplessness. The depression can be incapacitating and prolonged. Research by Brian Harris and colleagues in Wales found that among 120 women, those with the highest prenatal and lowest postnatal progesterone levels also scored highest on measures of postpartum depression scores.

“Recall that as pregnancy advances, placental production of progesterone rises to levels of 350 to 400 milligrams a day, and the ovaries’ contribution at that point is nil. With delivery, the placenta-derived progesterone is suddenly gone. The only source of progesterone at that time would be the adrenal glands. It is possible that adrenal exhaustion plays a role in a woman’s inability to provide even a modicum of progesterone in the days following childbirth. Postpartum depression is notoriously difficult to treat. It would seem appropriate to measure progesterone levels a day or two after childbirth and, if found to be low, progesterone could be promptly supplemented. It is possible that this simple and safe therapy could make postpartum depression much easier to treat.”

When Dr. Lee wrote these words, he was not saying he had absolute proof that progesterone would effectively treat PPD. What he was saying was that raising the progesterone levels of new mothers to normal, healthy levels could be a safe, natural way of dealing with depression, and that bioidentical progesterone supplements can be safely used in mothers with low progesterone levels.

Dr. Lee hoped that more research would be done on this subject to find out if bioidentical progesterone could help mothers with PPD. He knew many mothers who claimed that progesterone helped them. Sadly, the pharmaceutical industry opposes the use of bioidentical progesterone and its metabolites, as it cannot create patent-protected drugs that contain bioidentical hormones. Those patents let pharmaceutical companies make millions to billions of dollars in profits from their drugs.

Despite the power and influence of the pharmaceutical industry, Dr. Lee’s research remains relevant today. It speaks to the urgent need of millions of mothers who need relief from PPD and cannot find it. If you know one of those mothers, please share this article with them. It could make a powerful difference in their quality of life.

As always, we encourage women who are pregnant or in postpartum to consult with a qualified healthcare provider before using natural or synthetic hormones. You can find a healthcare provider who is knowledgeable about bioidentical hormones by visiting our “Find a Doctor” page on


1 Anna Mutoh, “The Tragedy of Being a New Mom in America,” Wall Street Journal, August 3, 2023.

The John R. Lee M.D. Medical Letter - Back Issues Hormone Test Kit - Saliva
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