The importance of the (TAAAA)n alleles at the SHBG gene promoter for the severity of coronary artery disease in postmenopausal women.

OBJECTIVE: Androgen may be detrimental in the development of coronary artery disease (CAD) in women. We investigated possible associations between the (TAAAA)n polymorphism of sex hormone-binding globulin (SHBG) gene promoter, which influences transcriptional efficiency of the SHBG gene and the severity of CAD in women. DESIGN: In this prospective clinical study, 146 postmenopausal women (46-88 y) undergoing coronary angiography were studied. CAD severity, history of angina and myocardial infarction, and reproductive history were recorded and hormonal parameters measured. According to the number of SHBG gene promoter repeat polymorphisms, participants were classified into short (seven or fewer), medium length (eight), and long repeat (nine or more) allele groups. RESULTS: Significant CAD was more prevalent in the long repeat allele carrier group: 65% of the participants with three vessels with severe stenosis belonged to the long repeat allele group, whereas only 37% of participants with mild CAD belonged to this group (P=0.01). A history of angina and prevalence of hyperlipidemia was more frequent in the long repeat allele group (P<0.05). Calculated free testosterone levels were higher in the long repeat allele groups (P<0.05), whereas SHBG levels tended to be lower (P=0.06). SHBG levels correlated inversely with body mass index and waist circumference (P<0.05). CONCLUSIONS: Longer (TAAAA)n repeats in the SHBG gene promoter are associated with more severe CAD in women undergoing coronary angiography, a finding not previously reported. This association may reflect the lifelong tissue exposure to higher free androgens and supports the adverse cardiovascular effect of androgenic exposure in this highly selected group of women.

Severity of cardiovascular disease in women: relation with exposure to endogenous estrogen.

OBJECTIVES: Coronary artery disease (CAD) is more common in men than in women. Endogenous sex steroids may be the main factor responsible, as long-term estrogen action appears to be protective. The aim of the study was to investigate the predisposing factors responsible for the severity of CAD in women. METHODS: One hundred and eight women (100 menopausal) undergoing coronary angiography were studied. Reproductive function was recorded. The severity of CAD was assessed by the number of arteries with severe stenosis, the presence of angina and myocardial infarctions (MI). RESULTS: The time since menopause (TSM) was significantly longer in women with angina and with MIs compared to those without (20.3+/-8.7 years versus 15.8+/-8.7 years and 22.6+/-8.6 years versus 18.1+/-8.9 years, p<0.05), independently of chronological age. The age at menopause was significantly younger in women who had 2 MIs compared to those with 1 or 0 MI (41.5+/-3.5, 47.5+/-5.3 and 48.4+/-5.4 years, respectively; p=0.04); the total duration of menstrual cyclicity was inversely related to the number of MIs (35.6+/-5.8, 34.2+/-5.3 and 28.3+/-3.3 years, 0, 1 and 2 MIs, respectively; p=0.03). CONCLUSIONS: The severity of CAD in women referred for coronary angiography is correlated with measures of exposure to endogenous estrogen. Both the TSM and the age at menopause are aggravating factors for MI, independently of age. There is an independent protective effect of the duration of estrogen exposure on the number of MIs; this has not been reported before and supports the protective role of the length of exposure to endogenous estrogen, especially for the occurrence of MI in this selected group of women.