How Progesterone Promotes Brain Health

Improves Cognition and Promotes Sleep

Progesterone is well known as a primary female sex hormone. It is required to regulate the menstrual cycle, vital for a woman to get pregnant (and maintain pregnancy) and needed for the early development of a human embryo. Progesterone is also considered an “endogenous steroid,” belonging to a group of steroid hormones called progestogens. 

Progesterone functions
Verywell / Brianna Gilmartin 

What Is Progesterone?

The hormonal influence on the body is very complex. Hormones are molecules made up of chemical substances. They act like messengers of sorts. They are made in one part of the body, then travel to other areas, where they each do their own job to control how cells or organs work.

Progesterone is said to be the major and most important progestogen in the body. Progestogen is a general term for hormones that act like progesterone in the uterus—this group of hormones, therefore, includes progesterone and progestins, a synthetic lookalike that closely resembles progesterone.

Progesterone plays a huge part in the female’s ability to become fertile and sustain a pregnancy—it is commonly known as the pregnancy hormone. Once peri-menopause begins, the level of progesterone begins to decline, contributing to symptoms of menopause such as hot flashes and missed periods.

But progesterone is more than just a hormone that influences the reproductive system, and many clinical research studies are beginning to discover just how much of an impact the hormone has on breast and heart health. More recently, scientists have begun to discover how progesterone also works to promote brain health.

Progesterone and Brain Health

There have been many studies involving the effects that progesterone has on women’s health. Perhaps one of the most interesting areas of clinical research is on progesterone’s effect on brain health. 

In fact, several clinical research studies have shown that progesterone may even have protective qualities in the brain—a characteristic known as "neuroprotection." 

There have been many studies involving the effects that progesterone has on women’s health.

Progesterone was also found to have zero side effects on the neurological (brain and spinal column) system. To top it off, progesterone has been linked with improvement in cognitive function, or the mental process of understanding through thought and experience, as well as in using intellectual processes such as thinking, reasoning, and remembering.

Progesterone as a Neurosteroid

Neurosteroids are steroids that are made in the brain. The function of neurosteroids includes:

  • modulation of neuroplasticity (forming nerve cell connections, particularly when learning or after traumatic brain injury)
  • regulation of behavior
  • seizure susceptibility
  • response to stress, anxiety, and depression

Progesterone has been deemed a neurosteroid because of the crucial role it plays in many vital functions of the brain, such as:

  • Neurogenesis (the growth and development of nervous system tissue)
  • Regeneration (repairing damaged brain cells)
  • Cognition
  • Mood
  • Inflammation
  • Myelination in the central nervous system (the process of forming a protective sheath around a nerve to allow nerve impulses to rapidly move from one neuron to the next)

In the brain, progesterone is produced in different areas, including the cells of the brain (neurons), the spinal cord, and the peripheral nervous system (the nerves outside of the brain and spinal column). Most of the progesterone that circulates in the bloodstream originates from the ovaries and placenta (during pregnancy) and in the adrenal glands—it also has access to the brain and the nerves.

In addition to promoting healthy brain function, progesterone is also thought to play a role in protecting the brain from damage as well as helping to repair it after an injury has occurred. Progesterone’s role in repairing the myelin sheath (and neurogenesis) is how the hormone is thought to protect and repair the brain.

Clinical Research Studies

Protective Qualities

According to a 2017 study, there has been substantial evidence in animal models that show the neuroprotective role of progesterone in central nervous system injuries, including ischemic stroke victims (a type of stroke involving the lack of blood flow and oxygen to the brain). 

The study goes on to explain that progesterone protects the brain through several different mechanisms and systems, thus reducing the rate of mortality (death rate) and morbidity (the frequency in which disease appears in a population). The study authors also note that progesterone is safe through various routes of administration such as by mouth or topically. 

Impact on Epilepsy

Another study conducted in 2013, discovered that progesterone and estrogen may have an impact on epileptogenesis in children and adults. Epileptogenesis is the process by which the normal brain develops epilepsy over time. Hormones play an important role in children and adults with epilepsy. "Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to have an impact on seizure activity in animal models and in clinical studies,” said the study authors.  

Not Effective for Traumatic Brain Injury

Although researchers were hopeful that progesterone could pose as a very promising treatment for traumatic brain injury (TBI), the most recent phase 3 clinical research trial, published in 2015, showed a 100 percent failure rate. According to the study authors, “Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials.”

Brain Development

2008 study shows that progesterone may contribute to the normal maturation of the brain in male embryos while influencing the male reproductive capacity and the neuroendocrine system. The neuroendocrine system is a chemical messenger system of sorts, made up of hormones and glands that secrete hormones into the bloodstream.

The study also found that with the dramatic increase in progesterone being used to prevent premature birth and promote lactation (milk production) in women, progesterone may influence the process of brain development in utero and in the areas of the brain involving cognitive function when taken during pregnancy.  

According to the National University of Natural Medicine, there is public evidence that progesterone during pregnancy may also result in better academic achievement results later in childhood.  

Promoting Sleep

Another well-known function of progesterone is that it has a sedative/hypnotic effect resulting from metabolites that are produced by the liver after progesterone is taken by mouth. 

Progesterone cream, which is used topically, does not produce the same sleep-inducing effects as the oral (by mouth) progesterone, which must be prescribed by the healthcare provider.

Types of Progesterone

The term “natural progesterone” is misleading because it’s made in a lab, yet it comes from natural sources such as wild yams. Progestins are another name for synthetic progesterone, which is man-made. It’s important to note that in some studies, progestin—used in synthetic hormone replacement therapy, called MPA (medroxyprogesterone acetate)—was not effective for helping with anxiety, improving cognition, or promoting other neuroprotective mechanisms in the brain. 

In fact, some research has shown that progestin “has been found to have negative effects on the nervous system and even reduces the beneficial effects of estrogen.” 

Side Effects

Most of the side effects of progesterone, such as breast tenderness, depression, and headaches, are associated with synthetic progesterone, and not the naturally induced type from wild yams. 

When using topical progesterone cream, it’s important to perform what’s called a patch test, by rubbing a small amount of cream in one area, then observing if any type of allergic reaction forms for 24 hours before continuing use. An allergic reaction from topical progesterone may include these symptoms at the local site:

  • Redness
  • Itching
  • Swelling

A Word From Verywell

Although the research on progesterone to promote brain health looks very promising, more studies are still needed to back up the growing body of research (much of which was conducted in animal studies, not human studies). As clinical trials on progesterone continue, scientists will be evaluating the safety and efficacy of the hormone for its use in humans. As with any type of hormone supplementation, it’s important to consult with a healthcare provider before taking progesterone in any form.

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