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Progestins and the Brain
Ms. Zhu is doctoral candidate, Neuroscience Program, College of Letters, Arts and Sciences, University of Southern California, and Dr. Brinton is Professor of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering and Neurology, School of Pharmacy, Viterbi USC School of Engineering and Keck USC School of Medicine, University of Southern California, Los Angeles, CA.
Progestins are a synthetic version of the naturally-occurring female reproductive hormone progesterone. The compounds were initially designed to counteract certain unwanted effects of estrogen in reproductive tissues, particularly in the uterus. Several generations of progestins have been developed both for use in contraception and in hormone replacement therapy during menopause, and they continue to evolve.
While the target of progestins used in hormone therapy is generally the uterus, progestin therapy affects every major organ system including the brain, the cardiovascular system, the immune system and the generation of blood cells.(1)(2)(3)(4)(5)(6)(7)(8) As in other systems, progestins have unique effects on the brain which ultimately could impact the long-term neurological health of users. Most of the effects of progestins on the brain are beneficial, although some research has shown that they may pose some risks.
When used as contraceptives, progestins work by preventing ovulation and pregnancy and a Table at the end of this article lists the brands currently on the market. They are often combined with estrogen to attain better control of the menstrual cycle, and to inhibit the maturation of the follicle (young egg cell) more effectively, as well as discourage ovulation. The majority of contraceptive drugs currently on the market contain estrogen and progestin in combination. Other formulations of hormones, including administration by injection, implants, vaginal rings, transdermal gels and sprays have also been used for contraception.(9) One of the most common uses of hormone therapy is, of course, to treat menopausal and perimenopausal symptoms that develop from the natural decline of the female reproductive hormones.
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.(4)(5)(6)(7) 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.(16)(17)(18)(19)(20)(21)(22)(23) 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.