Studies are discovering much about the effects of progestins on the brain: Among their benefits, progestins can boost brain regeneration and metabolism, alone or in combination with estrogen. Findings from preclinical studies show that how and when progestins are used, both in contraception and in menopause, can dramatically impact neurological health and cognitive function. Still, some drawbacks have been linked to the use of progestins. The focus of this article is to discuss how progestins work on the brain, including their effects on brain regeneration and metabolism, as well as their effects on cognition.

THE TARGET OF PROGESTINS: 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. Still, long-term studies are needed to evaluate the effectiveness and safety of the newer generations of progestins, both in contraception and hormone replacement therapy, and to determine their long-term impact on women's health.

Interestingly, progesterone receptors are expressed throughout the brain and can be found in every type of brain cell, which is largely why progestin has many reproductive and non-reproductive effects in the central nervous system. The fact that these receptors are found well beyond the borders of the hypothalamus, which regulates reproductive function, sets the stage for progesterone's many effects on the brain and cognition.

BOOSTING BRAIN CELL REGENERATION

Progesterone is well known to enhance cell growth, and this effect was first noted in the breast and uterus, though it seems to pertain to the brain as well. In the adult brain, the growth of new neurons can occur in two zones. And, as in the uterus, progesterone's regulation of cell division in the nervous system is complex.