Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Abstract

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17b-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

Attenuation of aortic aneurysms with stem cells from different genders

“…As androgens have been shown to play a major role in the pathogenesis of AAAs (24, 25), male MSC were treated with finasteride while in cell culture. Finasteride prevents the conversion of testosterone into the more active dihydrotestosterone (DHT) by inhibiting 5-α-reductase.…”

“…As androgens have been shown to have a detrimental effect on the inflammatory state of the aortic wall and formation of AAA (24, 25), priming MSC with finasteride, an anti-androgen drug commonly used in prostate cancer, exhibits a more significant attenuation of experimental aneurysm, as well as a decrease of the inflammatory profile of aortic tissues, when compared to unprimed male MSC. Finasteride is a potent 5-α-reductase inhibitor, but any anti-inflammatory properties this drug may possess, especially with regard to AAA formation, have not been well documented.…”

Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation

“…A number of studies have implicated testosterone and other circulating androgens play a role in the inflammation and pathogenesis of AAA 6, 25 . In previous studies, exogenous administration of dihydrotestosterone (DHT) was associated with an increased formation of AAA in apolipoprotein E (apoE) knockout mice infused with angiotensin 26 .…”

An update on the etiology of abdominal aortic aneurysms: implications for future diagnostic testing

“…Although a history of smoking is the greatest risk factor for AAA, a family history of AAA is also a significant risk factor [10][11][12], leading to an increased risk of aneurysm rupture and earlier onset of aneurysmal disease [13]. Males sex is also a risk factor but the greater prevalence in men over women is not fully understood although smoking habits and differential hormonal regulation may have a role [14]. Other risk factors include hypertension and atherosclerosis, but are not always indicative of AAA [15].…”