Progesterone and Your Brain: The Forgotten Hormone of Calm

Most women know estrogen and progesterone are major hormones. Estrogen typically gets top billing, with progesterone playing a supporting role. However in reality, the two hormones are equally important, and progesterone balances estrogen and does much more in a healthy body than many women realize.  

“Progesterone is the most overlooked and neglected hormone in our bodies,” says Dr. Louise Newson, a physician and menopause specialist based in the United Kingdom. While progesterone plays a role in regulating our reproductive cycle, it’s also created in our brains, where it has a profound impact on brain health, mood, anxiety and even sleep. 

For many perimenopausal and menopausal women dealing with common symptoms like insomnia or increased anxiety, the right dose of bioidentical micronized progesterone can be transformative, says Dr. Rachel S. Rubin, a board certified urologist and sexual health expert.  “When we give someone micronized progesterone, I would say a third of the patients love it and guzzle it like it’s candy, and they’re the happiest people in the world,” Rubin shared on episode 348 of Peter Attia’s The Drive podcast. “[It] helps their sleep, reduces anxiety. Oh my God, [it] changes their life. It’s absolutely life changing.”

A Quick Definition: Progestin vs. Progesterone 

Though these words are similar, one is synthetic and the other is natural. And while both of these progestogens (the umbrella term for synthetic progestin and natural progesterone) both can protect the uterine lining during menopause, decades of research shows us they can work differently in the body.

Progesterone is the natural hormone produced by our bodies, in the ovaries, adrenal glands and the brain. Today, doctors commonly prescribe oral micronized progesterone, a lab-created form that is chemically identical to what the body makes, as menopausal hormone therapy. 

Progestin is the term for synthetic forms of progesterone often used in birth control pills, shots like Depo Provera and hormonal IUDs such as Mirena. Medroxyprogesterone acetate (MPA) is the synthetic progestin that was once commonly used in menopausal hormone therapy, most famously in the Women’s Health Initiative (WHI) study. Some women report feeling mood changes while on birth control pills with synthetic hormones, and large studies have documented a link between hormonal contraception and depression diagnosis¹ that may lead to using antidepressants.

A large 2024 observational study of over 117,000 meningioma cases found that women who regularly used injectable MPA were 53% more likely to have meningioma, showing an association but not proving that MPA causes the condition. And another sizable 2022 study found that women who took estrogen along with synthetic progestin were at higher risk for breast cancer.² Micronized progesterone was not associated with an increased risk of breast cancer causing the study authors to conclude that “micronized progesterone may be the safer progestogen to be used.”

What are some signs of low progesterone?

Low progesterone can show up in several ways once women reach perimenopause and menopause. 

Mood Changes and Anxiety

An estimated 70% of women experience mood changes ³ during the menopause transition. They can range from irritation and sadness to anxiety and even rage. 

High Cortisol and Stress 

Cortisol is one of the main stress hormones, released during our fight, flight or freeze response.⁴4 It has an inverse relationship with progesterone, so when progesterone is low, cortisol rises, which can trigger racing thoughts or a sense of impending doom. Over time, this chronic stress fueled by elevated cortisol takes a toll on the brain, which has been linked to increased risk for neurodegenerative diseases⁵ like Alzheimer’s. 

Brain Fog

The fuzzy thinking and difficulty remembering names and words that many women experience in menopause is often called brain fog. In her book The Menopause Brain, acclaimed neuroscientist Dr. Lisa Mosconi says the scientific term for this is mental fatigue. Though more research is needed, a 2018 Stanford study found that progesterone levels were positively and significantly linked to verbal memory and global cognition⁶ in women who had gone through menopause within the past six years. 

Night Sweats and Insomnia

Though low estrogen gets most of the blame for these annoying vasomotor symptoms that disrupt sleep, low progesterone is guilty as well. Even in premenopausal women, research has shown that the big decline in progesterone during the late luteal phase can disrupt sleep.⁷ And layered with the wildly fluctuating estrogen levels during the zone of chaos in perimenopause, researchers are discovering that low progesterone can have a pronounced impact on sleep. 

Benefits of Micronized Progesterone

Fortunately, raising progesterone levels with oral micronized progesterone can have broad beneficial effects for mood and sleep. “I think that progesterone … is the key hormone that is forgotten about from a mental health perspective,” psychiatrist  Dr. Rachel Jones shared on Louise Newson’s podcast. “It’s just fantastic for mood, for anxiety, for irritability, for rage, for sleep, all of those symptoms. And if you prescribe the natural progesterone, it changes women’s lives.”

Better Sleep

Canadian researchers found that oral micronized progesterone helped perimenopausal women sleep more soundly.⁸ In a randomized controlled trial, nearly 200 perimenopausal women with night sweats and hot flashes took either placebo or  300 mg oral micronized progesterone for three months. At the end of the study, the women taking progesterone reported that “night sweats and sleep quality significantly improved without increased depression and it decreased perimenopause-related life interference.” A separate review of randomized controlled trials found that micronized progesterone improved sleep outcomes.⁹ That’s why many doctors recommend that patients take their micronized progesterone pill at night, about an hour before bedtime. In the United States, progesterone capsules contain peanut oil to aid absorption, and taking the medication with food, particularly fat, has been shown¹⁰ to approximately double progesterone absorption. (Women with a peanut allergy can request a formulation with sunflower oil, or get a compounded progesterone made without peanut oil.)

Improved Moods

As progesterone is metabolized in the body, it boosts production of GABA¹¹, a neurotransmitter that calms brain activity and can induce sleep. It also breaks down into other brain chemicals including allopregnanolone, which promotes sleep and lowers anxiety.¹²

However, a small number of women, particularly those with prior mood disorders or history of premenstrual dysphoric disorder (PMDD), can experience an increase in anxiety while taking certain progestogens. Though more research is needed, depression and anxiety are more often linked to synthetic progestins.  Researchers note that lower levels of progestins¹³ were linked to anxiety, while higher levels were more calming. Every woman’s body is different, so it’s important to work with a trusted clinician to find the best medication and dosage for your symptoms.

Progesterone's Role in Brain Aging

Researchers know that progesterone helps promote the growth of myelin¹⁴, a fatty coating that’s like insulation for nerve fibers. It’s being investigated for its role in supporting neuroprotection, brain plasticity and cognitive function.¹⁵ When it comes to dementia risk, menopausal hormone therapy that includes progesterone has shown some promising results for some women. In a 2023 conversation on Louise Newson’s podcast about a large review of studies, Mosconi shared that researchers found that when women started estrogen-only therapy in midlife or within 10 years of menopause, they saw a 32% reduction in Alzheimer’s and dementia risk.¹⁶ It didn’t have the same effect for women 65+, reinforcing the idea that timing of hormone therapy matters. 

Mosconi believes that the results were skewed by the Women’s Health Initiative, which used progestin. She’d like to see more studies of how micronized progesterone affects brain health. Research isn’t definitive on how hormone therapy affects dementia risk, but the findings are promising. A 2023 analysis of many studies concluded that when women begin hormone therapy early enough, it may help protect the brain from developing Alzheimer’s disease. While Mosconi says there isn't enough evidence to recommend hormone therapy as a prevention strategy for all women, she believes that a healthy level of progesterone is a key part of healthy brain aging during menopause.