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Insulin Resistance, Hemostatic Factors, and Hormone Interactions in Pre- and Perimenopausal Women: SWAN

Department of Epidemiology (M.F.S., M.L.J.), University of Michigan, Ann Arbor, Michigan 48109-2029; Department of Neurology (C.D.), Albert Einstein College of Medicine, Yeshiva University, New York, New York 10461; Department of Obstetrics, Gynecology, and Women’s Health (J.I.T.), University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103; and Department of Cardiology (R.P.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: MaryFran Sowers, Ph.D., University of Michigan, Department of Epidemiology, 109 Observatory Street, Room 2624, Ann Arbor, Michigan 48109-2029. E-mail: mfsowers{at}umich.edu.

We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42–52 yr, in the Study of Women’s Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance.

After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance.

The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women’s Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women.

The National Institute on Aging, the National Institute of Nursing Research, and the Office of Research on Women’s Health of the National Institutes of Health funded the Study of Women’s Health Across the Nation (SWAN) at clinical sites, laboratories, and a coordinating center.

Abbreviations: BMI, Body mass index; CI, confidence interval(s); CVD, cardiovascular disease; FAI, free androgen index; FEI, free estradiol index; PAI-1, plasminogen activator inhibitor type 1; PCOS, polycystic ovary syndrome; SWAN, Study of Women’s Health Across the Nation; t-PA, tissue plasminogen activator; WHR, waist-to-hip ratio.

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