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Review
. 2019 May:111:87-95.
doi: 10.1016/j.yhbeh.2018.10.010. Epub 2018 Nov 20.

Sex hormones and stroke: Beyond estrogens

Farida Sohrabji  1 , Andre Okoreeh  2 , Aditya Panta  2
Affiliations
Review

Sex hormones and stroke: Beyond estrogens

Farida Sohrabji et al. Horm Behav. 2019 May.

Abstract

Stroke risk and poor stroke outcomes in postmenopausal women have usually beeen attributed to decreased levels of estrogen. However, two lines of evidence suggest that this hormone may not be solely responsible for elevated stroke risk in this population. First, the increased risk for CVD and stroke occurs much earlier than menopause at a time when estrogen levels are not yet reduced. Second, estrogen therapy has not successfully reduced stroke risk in all studies. Other sex hormones may therefore also contribute to stroke risk. Prior to menopause, levels of the gonadotrophin Follicle Stimulating Hormone (FSH) are elevated while levels of the gonadal peptide inhibin are lowered, indicating an overall decrease in ovarian reserve. Similarly, reduced estrogen levels at menopause significantly increase the ratio of androgens to estrogens. In view of the evidence that androgens may be unfavorable for CVD and stroke, this elevated ratio of testosterone to estrogen may also contribute to the postmenopause-associated stroke risk. This review synthesizes evidence from different clinical populations including natural menopause, surgical menopause, women on chemotherapy, and preclinical stroke models to dissect the role of ovarian hormones and stroke risk and outcomes.

Keywords: FSH; Ischemic stroke; Menopause; Testosterone.

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Figures

Figure 1:
Figure 1:
Schematic representation of the pituitary-ovary axis at (A) pre-menopause and (B) menopause. (A) Pituitary gonadotrophin release acts on theca cells to stimulate androgen synthesis, while FSH increases aromatase in granulosa cells, which facilitates conversion of testosterone to estrogen. Estrogen subsequently suppresses FSH. Menopause: Age-related follicular atresia is associated with loss of granulosa cells and theca cells that accumulate as hilar cells. Pituitary secretions elevate androgens in theca cells, which is not converted to estrogens due to granulosa cell loss, thus increasing T:E ratio and FSH due to loss of negative feedback. LH: Luteinizing hormone, FSH: Follicle stimulating hormone, TC: theca cells, GC: granulosa cells, AL: anterior lobe of the pituitary, PL: posterior lobe of the pituitary.
See this image and copyright information in PMC

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