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Objective: To assess the association of genetic polymorphisms related to cardiovascular disease (CVD) risk with anthropometric parameters and indices of androgenicity in healthy postmenopausal women., Design: Cross-sectional study in a University Menopause Clinic., Methods: The following polymorphisms were assessed in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein E2/E3/E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G, cholesterol-7 alpha-hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-beta-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, Delta-4-androstenedione (Delta4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip ratio (WHR)., Results: MTHFR Ala222Val polymorphism was positively associated with testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had higher BMI and WHR compared with women with the wild-type variant (P=0.027 and P=0.044 respectively)., Conclusions: MTHFR Ala222Val polymorphism is associated with increased androgenicity and elevated BMI and WHR in healthy postmenopausal women. The significance of this association with respect to the CVD risk of postmenopausal women remains to be elucidated in future studies.

Objective: To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women., Design: Cross-sectional study in a university menopause clinic., Methods: Serum sex hormones and lipid-lipoprotein profile, arterial pressure, homocysteine and insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR), were assessed in 598 healthy postmenopausal women not on hormone therapy., Results: Compared with women in the lowest testosterone quartile (Q), women in the highest testosterone quartile had higher total cholesterol (Q1: 225.2 +/- 41.3 vs Q4: 246.2 +/- 38.4 mg/dl, P < 0.01), low-density lipoprotein (LDL)-cholesterol (Q1: 146.9 +/- 37.2 vs Q4: 171.8 +/- 35.3 mg/dl, P < 0.001), atherogenic index of plasma (AIP) (Q1: -0.224 +/- 0.238 vs Q4: -0.087 +/- 0.254, P < 0.01), apolipoprotein B (ApoB) (Q1: 100.7 +/- 23.1 vs Q4: 113.9 +/- 23.8 mg/dl, P < 0.001) and higher high-density lipoprotein (HDL)-cholesterol (Q1: 60.7 +/- 14.5 vs Q4: 52.9 +/- 13.0 mg/dl, P < 0.01). Accordingly, women in the highest free androgen index (FAI) quartile had higher AIP (Q1: -0.232 +/- 0.254 vs Q4: -0.078 +/- 0.243, P < 0.001) and ApoB (Q1: 102.4 +/- 25.5 vs Q4: 114.2 +/- 25.8 mg/dl, P < 0.01) and lower HDL-cholesterol (Q1: 62.0 +/- 15.7 vs Q4: 51.9 +/- 11.6 mg/dl, P < 0.001) and apolipoprotein A (Q1: 159.6 +/- 25.6 vs Q4: 147.9 +/- 24.1 mg/dl, P < 0.01) compared with women in the lowest FAI quartile. These differences remained significant after adjustment for age, body mass index (BMI), insulin resistance and social habits. The free estrogen index (FEI) exhibited similar associations to the FAI. HOMA-IR showed an independent positive association with total testosterone (Q1: 2.00 +/- 1.36 vs Q4: 2.66 +/- 1.60, P < 0.01), FAI (Q1: 1.70 +/- 1.12 vs Q4: 3.04 +/- 1.66, P < 0.001) and FEI (Q1: 1.70 +/- 0.91 vs Q4: 3.08 +/- 1.77, P < 0.001)., Conclusions: Increased androgenicity in healthy postmenopausal women is associated with an unfavorable cardiovascular risk profile. High endogenous estradiol is related to a pro-atherogenic lipid profile, an association which may, in part, be mediated by insulin resistance.