Association of Endogenous Sex Hormones and Insulin Resistance among Postmenopausal Women: Results from the Postmenopausal Estrogen/Progestin Intervention Trial

ABSTRACT Context: In postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships. Objective: Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors. Design, Setting, and Participants: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45–84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones. Main Outcome Measures: T2DM was defined based on fasting glucose and/or treatment for diabetes. Results: There were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend ≤ 0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend < 0.02). Dehydroepiandrosterone had no relationship with incident T2DM. Conclusions: Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.

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Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women

Acta Endocrinologica ◽

10.1530/eje.1.02167 ◽

2006 ◽

Vol 154 (6) ◽

pp. 907-916 ◽

Cited By ~ 51

Author(s):

Irene Lambrinoudaki ◽

George Christodoulakos ◽

Demetrios Rizos ◽

Emmanuel Economou ◽

John Argeitis ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Postmenopausal Women ◽

Sex Hormones ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Atherogenic Index ◽

Total Testosterone ◽

Model Assessment ◽

Endogenous Sex Hormones

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.

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