Nobel Prize-winner Adolf Butenandt proposed that this hormone be named Leuteosterone, while other researchers preferred progestin. A compromise was reached and the corpus luteum hormone was officially named ‘progesterone’

What is Progesterone?

Progesterone is a natural hormone made by the body, primarily in the second half of the menstrual cycle. After ovulation, the corpus luteum forms and begins producing progesterone, preparing the uterus for a fertilised egg. If pregnancy does not occur, the corpus luteum breaks down and progesterone levels fall.

Although commonly associated with female reproduction, men also produce small amounts of progesterone in their adrenal glands and testes.

This article refers to bio-identical micronised progesterone, which has a molecular structure identical to the progesterone hormone that is naturally produced by the ovaries and adrenocortical glands and which can also be synthesized locally in the brain by cholesterol. This local synthesis in the brain makes progesterone a neuro-steroid, meaning it has a role in the nervous system beyond its traditional hormonal functions.

Bio-identical progesterone is synthesised from diosgenin, a plant compound found in wild yams.

Unfortunately, early hormone research (from the 1930s to the 1990s) focused mostly on progestins, leading to long-standing misconceptions that their side effects were caused by natural progesterone itself.

Progesterone vs. Progestins

Progestins are synthetic versions of progesterone with altered chemical structures. While designed to mimic progesterone, progestins often behave differently in the body. They resemble testosterone more closely and may bind to receptors other than progesterone, sometimes causing side effects such as high blood pressure, hair loss, mood disturbances (anxiety, depression), and increased risk of breast cancer.

Progestins are found in oral contraceptives, hormonal IUDs, implants, and emergency contraception. Even the “progesterone-only” pill contains progestin, not natural progesterone.


The term progestogens refers to both progesterone and progestins, which often adds to the confusion.

While both progesterone and progestins thin the uterine lining, their overall effects differ significantly.

It was only in the 1990s that bio-identical progesterone became widely available for therapeutic use. Today, research shows it can improve heart health, bone density, sleep, mood, aid in calming menstrual epilepsy and may even lower the risk of breast cancer.

Progesterone in Hormone Therapy

Traditionally, progesterone is used in combination with estradiol (a form of estrogen) in bio-identical hormone replacement therapy (BHRT) for women who still have a uterus, to reduce the risk of endometrial cancer. Unlike estrogen, however, progesterone can be safely used on its own.

Recent evidence shows that women who’ve undergone surgical menopause (bilateral oophorectomy) may still benefit from progesterone therapy—particularly for bone and sleep and mental health, even without the need to protect the uterus.

Mental Health and the Menstrual Cycle

One of the most exciting areas of research is the role of progesterone in mental health.

Progesterone can be synthesized within the brain, making it a neuro-steroid where it converts into metabolites like allopregnanolone and pregnanolone - metabolite formed by the enzyme 3α-hydroxysteroid oxidoreductase, not to be confused with pregnenolone which sounds the same but is the steroid hormone precursor to progesterone, testosterone, and cortisol. These metabolites activate GABA-A receptors—the same calming pathway in the brain that is targeted by anti-anxiety medications.

This calming effect explains why some healthcare providers are now using natural progesterone to treat anxiety, depression, postpartum depression, and even catamenial epilepsy.

Progesterone’s role in Catamenial epilepsy

This is a menstrual cycle-related seizure disorder that affects up to 70% of women with epilepsy (source: Science Direct). It is characterised by an increase in seizures during particular phases of the menstrual cycle. Three distinct patterns of catamenial epilepsy – perimenstrual, periovulatory, and inadequate luteal phase – have been described.

Progesterone reduces seizure susceptibility partly through conversion to neuro-steroids which enhances GABAA receptor function, therefore inhibiting neuronal excitability.

Natural progesterone therapy has proven effective in women with epilepsy. Moreover, neuro-steroids have been shown to be very effective inhibitors of catamenial seizures in animal models. Further research is needed, but so far, the benefits of natural progesterone are looking promising for this condition.

A Psychiatric Perspective:

Dr Rachel Jones, a UK-based psychiatrist, is one of the pioneering psychiatrists using progesterone to support mental health. In early 2025, during a podcast with world-renowned menopause specialist and GP, Dr Louise Newson, Dr Jones discussed her observations, ‘women often report feeling fine during the first half of their menstrual cycle, only to experience a sharp decline in mood in the second half—when progesterone drops’.

Standard psychiatric practice often overlooks menstrual history, but Dr Jones uses it as a diagnostic tool. She notes that many women who end up in psychiatric care present with severe symptoms like suicidal ideation and emotional instability, which often correlate with hormonal fluctuations. “When progesterone plummets before menstruation, that’s when my patients feel the most debilitated,” she explains.

By identifying this pattern, Dr Jones finds that hormone therapy can reduce the need for psychiatric medication. While antidepressants may still play a role, they often don’t address the root cause which seems to go back to hormonal imbalance.

She explains that in her clinical experience, “Progesterone is fantastic for mood, anxiety, irritability, rage, and sleep. Every single day in my clinic, women tell me it’s been life-changing.”

She believes progesterone’s psychological benefits have been overlooked for too long. While she encourages patients to remain on psychiatric medications initially, she works with them to balance their hormones—including testosterone, estrogen, and progesterone—before she considers reducing their psychiatric medication

A New View on Hormones and Mental Health

Both Dr Jones and Dr Newson agree that it’s time to integrate hormone therapy into mental healthcare, not just reserve it for menopause or contraception.

Dr. Rachel Rubin, Director-at-Large for the International Society for the Study of Women’s Sexual Health (ISSWSH), sentiment agreed with this view, in a recent interview with physician Dr. Peter Attia, she stated, “Hormones need to be addressed as part of a whole-medicine perspective—not just for BHRT.”

Progesterone is much more than a reproductive hormone.. For too long, its benefits have been confused with the risks of progestins, and its role in mental health is overlooked. Now, with growing research and the insights of leading functional and integrative medicine clinicians, bio-identical progesterone is finally being recognised as a vital hormone for both physical and emotional health.

Author

Nirali is a Peri/menopause coach, health writer and mum. She is a passionate functional medicine advocate, hoping to see a more integrative medical system allowing patients to receive the personalised treatments they deserve. Instagram: @mineralmojo4meno

Nirali Shah-Jackson