Starting a family later in life could be better for your mental health.

According to a recent study by American Geriatric Society, tests were done with 830 middle-aged women, concluding if one has their children later in life, their brainpower will be boosted while protecting one from memory loss.

Brainpower is stronger, they believe, due to the increased amount of hormones that rush the body during pregnancy.

These hormones increase brain function.


Progesterone and the Nervous System/Brain

Research Summary

In this emerging area of progesterone research, several research studies attest to the neuroprotective effects of progesterone, an absence of neurological side effects, and a benefit for cognitive function.

Progesterone and the brain

By Margaret N. Groves  Scientific Writer, ZRT Laboratory, Beaverton, Oregon

Many women are familiar with progesterone as a hormone that is essential for fertility and for sustaining a pregnancy.  In fact, the name itself means “promoting gestation.”  Once a woman’s reproductive life begins to wane and she enters perimenopause, progesterone production in the ovaries starts to decline.  By the time she reaches menopause, circulating progesterone levels are so low, they are similar to those normally seen in men.

However, progesterone is far more than a gestational agent. Research is now surfacing which shoes that the benefits of progesterone reach to breast health, cardiovascular health, and nervous system health, most importantly brain function. The rest of this article will take a closer look at just how essential progesterone is for your brain.

Progesterone as a “neurosteroid”

As a result of its critical functions in the nervous system, progesterone has been classified as a “neurosteroid”. It is so essential that it comes from two different places to reach the brain: first, cells in the brain, spinal cord, and peripheral nervous system all synthesize progesterone from cholesterol.  Secondly, progesterone that is circulating in the bloodstream also has direct access to the brain and nerves.

Normal brain function is not the only thing progesterone is required for in the nervous system. An important role of progesterone is to protect the brain from damage and promote repair after injury. It actually does this by promoting the growth and repair of the myelin sheath that protects the nerve fibers.

Progesterone protects the brain from damage after traumatic brain injury

Around 20 years ago, researchers who were studying rats after brain injury made a significant observation.  Female rats which, at the time of the brain injury, were at the stage of their reproductive cycles when progesterone levels were the highest, had significantly less brain damage than male rats or females with lower progesterone levels.  Such research led ultimately to human clinical studies, which have found that high doses of natural progesterone have significantly improved patients’ survival from traumatic brain injury.

One trial, given the name “ProTECT”, randomized intensive care patients with acute traumatic brain injury to either high dose progesterone injections for 3 days or placebo injections.  While all the patients were at a very high risk of death, only 13% of the progesterone-treated patients died of their brain injuries compared with 30% of the placebo-treated patients.

A review published this year suggests that not only should progesterone be used to treat traumatic brain injuries, but that it may also have a role in treating stroke, because of its powerful protective effects on brain tissue. This is a very exciting area of progesterone research, as researchers and clinicians acknowledge the fact that natural progesterone has an excellent safety profile without long term side effects, making it a good candidate for high dose therapy that can also be carried out in a home environment as patients recover.

Progesterone and brain development – smarter kids?

There is published evidence that the children of women who were treated with progesterone during pregnancy showed enhanced development during infancy, achieved better academic results at ages 9-10, and were significantly more likely to attend universities.  While researchers acknowledge that progesterone treatment could not be claimed to promote a new generation of “brainiacs”, the observed benefits can be explained by the fact that it is essential for optimal development of a normal brain in the fetus.  If progesterone levels are too low, normal brain development may be affected, putting an infant at a developmental disadvantage.

Progesterone eases anxiety and facilitates memory

Progesterone naturally metabolizes in brain tissues to the metabolite allopregnanolone, which is known to produce calming, anti-anxiety and possibly enhanced memory effects.  There is some speculation that it could be important in preserving cognitive function in women experiencing the decline in progesterone levels with age.  However, it’s important to note that progesterone is produced by brain tissue itself, and so the reduction in blood progesterone levels as ovarian production decreases may not be as important as other aging processes that have direct effects on the brain’s function.  It will be interesting to see further research on this as aging women increasingly use progesterone in hormone replacement.

Progesterone as a sleeping aid?

Women using an oral progesterone may notice a sedative effect, and doctors usually recommend that the oral form is taken at bedtime (actually, it is often a welcome “side effect” that helps counteract the sleeplessness of perimenopause!)  Basically, there is a large quantity of metabolites produced in the liver after oral progesterone is absorbed by the intestines.  These metabolites have known sedative and hypnotic effects.

On the other hand, women using progesterone cream do not produce metabolites in such large quantities because the progesterone is absorbed through the skin and bypasses the liver metabolism.  However, as stated before, some women may experience progesterone’s calming effect after using it in cream form.

 Progestins vs. Progesterone: Same effects?

Synthetic progestins are molecularly different from natural progesterone and therefore do not metabolize to the same compounds as natural progesterone.  They do not show benefits for cognitive or anti-anxiety function.  In fact, they have notbeen found to have any of progesterone’s neuroprotective properties.  The progestin that has been the most extensively studied and which is commonly used in synthetic hormone replacement therapy, MPA (medroxyprogesterone acetate), has been found to have negative effects on the nervous system and even reduces the beneficial effects of estrogen.

Progesterone and the Nervous System/Brain

Most of the hard facts about the physiological effects of pregnancy on the brain actually come from research on rats, where, in contrast to most human research, the evidence points to significant maternal advantages rather than deficits.

One crucial maternal brain region is the medial pre-optic area (mPOA) of the hypothalamus – a structure in the temporal lobe that is involved in memory. Damage to the mPOA has been shown to inhibit maternal behaviours such as nest-building and the grooming of pups. Pregnancy appears to prepare this brain region for the demands of motherhood. For example, research led by Lori Keyser-Marcus at Craig Kinsley’s lab at the University of Richmond showed that pregnancy or treatment with pregnancy-related hormones led to increased dendrite density in the mPOA region (dendrites are the branches of neurons that receive incoming signals from other neurons).

The same lab has also looked at dendritic spines – these are thorn-like protrusions on dendrites that improve signalling efficiency. Kinsley’s team found that dendritic spine density was increased in the hippocampus of pregnant rats and rats treated with pregnancy-related hormones, compared with virgin rats.

Yet another study in Kinsley’s lab, led by Jennifer Wartella, studied the brains of recently pregnant rats and found signs of reduced activity in the hippocampus and amygdala regions of their brains, compared with virgin rats – a sign, the researchers said, of reduced stress reactivity in the mother rats.

Crucially, all these brain changes have been linked with behavioural improvements. ‘Our rats get better at virtually everything they need to, to successfully care for their expensive genetic and metabolic investments,’says Kinsley. ‘Foraging, predation, spatial memory all improve; stress and anxiety responsiveness decreases.’

So why is there this mismatch between the pregnancy advantages shown in rats and the deficits shown in some human studies? Kinsley thinks the answer has to do with the kinds of tasks used to test pregnant women. ‘Much of the data from human mothers has been derived from asking females to demonstrate cognitive enhancements to skills, behaviours, occupations that are largely irrelevant to the care and protection of young,’ he says. ‘Once the questions and approaches become more sophisticated in the human analogs, I believe more data will support the animal work.’ Consistent with Kinsley’s prediction, a study published late last year by Rebecca Pearson and her colleagues at the University of Bristol found evidence that late human pregnancy is associated with enhanced recognition of threatening facial expressions.


During the past decade, one differentiating factor, the age of women at the time of the initiation of estrogen therapy (ET), has garnered considerable validity and led to the formulation of the critical period hypothesis, or the “window of opportunity” maxim that, to this point, provides guidelines for the necessary and sufficient conditions for the neuroprotective effects of estrogen on cognitive functioning in women.

Synthetic hormones and their effects to the brain

Though it might seem logical that the sex organs would be the primary target for progestins, in reality, their influence is largely on the brain. This is true both for their use in contraception and for the symptoms of menopause. Progestins interact with a variety of receptors, including estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. These receptors are abundant in the areas of the brain involved in reproductive function (like the hypothalamus) as well as other brain regions not directly involved in reproduction. These molecules regulate aspects of brain function from how brains cells connect to each other to the birth of new neurons to mood and cognition.

Synthetic progestins were originally developed to overcome the short half-life of progesterone and its high production cost. Progestins are derived from either progesterone or testosterone and there have been many “generations” of progestins that have evolved considerably over the years. The newer generations are generally more active and have less interaction with other types of receptors, which are both advantages.

The interaction between progestins and these receptors is a major source of the unwanted side effects seen in hormonal contraception and hormone replacement therapy, such as the increased risk of breast cancer and cardiovascular disease.

Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality.

Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men.

The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women.

This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age.

Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely.

Pituitary Gland in the Brain


The pituitary can be divided into the anterior and posterior gland. The hormones below are secreted by the anterior pituitary gland, except for ADH and oxytocin, which is secreted by the posterior pituitary gland.

  • Adrenocorticotropic hormone (ACTH)
    • Stimulates the synthesis and secretion of adrenocortical hormones (cortisol, androgens, and aldosterone).
  • Antidiuretic hormone (ADH) / Vasopressin
    • Stimulates the reabsorption of water from urine in the kidneys.
    • It also triggers vasoconstriction.
    • Both the retention of water and vasoconstriction increases blood pressure.
  • Follicle-stimulating hormone (FSH)
    • In women, it stimulates the growth of the ovarian follicle.
    • In men, it stimulates the maturation of sperm in the testes.
  • Growth hormone
    • Stimulates the synthesis of proteins and growth of cells and tissues.
  • Luteinizing hormone (LH)
    • In women, it stimulates ovulation, formation of the corpus luteum and production of estrogen and progesterone.
    • In men, it stimulates the testes to produce testosterone.
  • Oxytocin
    • Stimulates the secretion of milk from the breasts.
    • Triggers and enhances of uterine contractions.
  • Prolactin
    • Promotes the development of breasts in women and milk production and secretion.
  • Thyroid-stimulating hormone (TSH)
    • Stimulates the synthesis and secretion of thyroid hormones (thyroxine and triiodothyronine).