A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

Abstract

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women.

Female-Specific Considerations in Aortic Health and Disease

“… 88 , 89 Finally, follicle-stimulating hormone has also been hypothesized to promote formation of AAAs, but this has not been conclusively confirmed. 90 Together, these studies suggest a protective effect of female sex hormones and may explain why menopause and the resulting fall in estrogen and progesterone, may result in women losing this protective effect against formation of AAAs. 75 Despite these associations, the effect of hormone replacement therapy on AAA outcomes is unclear, with some observational studies showing protective effects, whereas randomized trials have shown no consistent benefit.…”

Exploring the expression and potential function of follicle stimulating hormone receptor in extragonadal cells related to abdominal aortic aneurysm

“…Although FSHR gene expression has been described as functional in other extragonadal cells [ 31 – 33 ], our findings show that we currently have no indication that FSH stimulation on the FSHR has a direct effect on the enhanced AAA development in women during the menopausal transition. We recently published a review on this topic identifying the potential direct and indirect ways that FSH could enhance AAA [ 10 ]. Our current findings lead us to consider that it may be more plausible that the indirect effects of FSH could enhance AAA progression rather than its direct effects on the vascular cell types assessed in this study.…”

“…Recently, the chronically elevated levels of follicle stimulating hormone (FSH) present during the menopausal transition have been identified as playing a role in postmenopausal osteoporosis and cardiovascular disease [ 9 ], rather than the decline in the protective effect of estrogen during and/or after the menopause. In prior work we hypothesized that FSH may play a direct and/or indirect role in AAA onset and/or progression in postmenopausal women [ 10 ]. We explore the potential direct effects of this in the current study.…”

The role of sex hormones in abdominal aortic aneurysms: a topical review

“…In a recent publication from a Dutch group the possible importance of FSH was stressed ( 59 ). The hormones FSH and LH are essential hormones that stimulate the function of ovaries in females and testis in males, contributing to a normal reproduction.…”

“…The hormones FSH and LH are essential hormones that stimulate the function of ovaries in females and testis in males, contributing to a normal reproduction. These hormones are derived from the pituitary gland, not the reproductive organs, and increase in women after menopause ( 59 ). In three prior publications on men with AAA, LH has been investigated ( 31 , 33 , 34 ).…”