Insulin Resistance, Hemostatic Factors, and Hormone Interactions in Pre- and Perimenopausal Women: SWAN
MaryFran Sowers,
Carol Derby,
Mary L. Jannausch,
Javier I. Torrens and
Richard Pasternak
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 insulinresistance in relation to reproductive hormones including FSH,estradiol, testosterone, and SHBG. SHBG was used to calculatethe free estradiol index and free androgen index. We studied3,200 women, aged 42–52 yr, in the Study of Women’sHealth Across the Nation, a prospective multiethnic study ofthe menopausal transition. We measured the hemostatic factors,fibrinogen, factor VIIc, tissue plasminogen activator (t-PA),and plasminogen activator inhibitor type 1 (PAI-1), as wellas glucose and insulin to calculate insulin resistance.
After adjustment for body mass index, site, and ethnicity, SHBGwas correlated with PAI-1 (partial r = -0.30) and t-PA (partialr = -0.12). Although testosterone was associated with t-PA (partialr = 0.13) and PAI-1 (partial r = 0.07), free androgen indexwas strongly correlated with t-PA (partial r = 0.18) and PAI-1(partial r = 0.26). SHBG modified the association of hemostaticfactors with insulin resistance. Women with greater insulinresistance had lower SHBG and higher PAI-1. Estrogen measureswere not associated with insulin resistance.
The influence of sex hormones on hemostatic factors and insulinresistance is poorly understood. SHBG, which influences theamount of bioavailable hormone, significantly modified the associationof PAI-1 and t-PA with insulin resistance. The longitudinalStudy of Women’s Health Across the Nation will help usdiscern whether this interaction contributes to heart diseaseand diabetes among postmenopausal women.
The National Institute on Aging, the National Institute of NursingResearch, and the Office of Research on Women’s Healthof the National Institutes of Health funded the Study of Women’sHealth 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 inhibitortype 1; PCOS, polycystic ovary syndrome; SWAN, Study of Women’sHealth Across the Nation; t-PA, tissue plasminogen activator;WHR, waist-to-hip ratio.
This article has been cited by other articles:
T Sathyapalan and S. L Atkin Investigating hirsutism
BMJ,
April 28, 2009;
338(apr28_1):
b912 - b912.
[Full Text]
C. Maric Sex, diabetes and the kidney
Am J Physiol Renal Physiol,
April 1, 2009;
296(4):
F680 - F688.
[Abstract][Full Text][PDF]
J. Chen, M. R. Sowers, F. M. Moran, D. S. McConnell, N. A. Gee, G. A. Greendale, C. Whitehead, S. E. Kasim-Karakas, and B. L. Lasley Circulating Bioactive Androgens in Midlife Women
J. Clin. Endocrinol. Metab.,
November 1, 2006;
91(11):
4387 - 4394.
[Abstract][Full Text][PDF]
K. A. Matthews, N. Santoro, B. Lasley, Y. Chang, S. Crawford, R. C. Pasternak, K. Sutton-Tyrrell, and M. Sowers Relation of Cardiovascular Risk Factors in Women Approaching Menopause to Menstrual Cycle Characteristics and Reproductive Hormones in the Follicular and Luteal Phases
J. Clin. Endocrinol. Metab.,
May 1, 2006;
91(5):
1789 - 1795.
[Abstract][Full Text][PDF]
E. L. Ding, Y. Song, V. S. Malik, and S. Liu Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis
JAMA,
March 15, 2006;
295(11):
1288 - 1299.
[Abstract][Full Text][PDF]
M. R. Sowers, M. Jannausch, J. F. Randolph, D. McConnell, R. Little, B. Lasley, R. Pasternak, K. Sutton-Tyrrell, and K. A. Matthews Androgens Are Associated with Hemostatic and Inflammatory Factors among Women at the Mid-Life
J. Clin. Endocrinol. Metab.,
November 1, 2005;
90(11):
6064 - 6071.
[Abstract][Full Text][PDF]
M. R. Sowers, K. A. Matthews, M. Jannausch, J. F. Randolph, D. McConnell, K. Sutton-Tyrrell, R. Little, B. Lasley, and R. Pasternak Hemostatic Factors and Estrogen during the Menopausal Transition
J. Clin. Endocrinol. Metab.,
November 1, 2005;
90(11):
5942 - 5948.
[Abstract][Full Text][PDF]
N. Santoro, J. Torrens, S. Crawford, J. E. Allsworth, J. S. Finkelstein, E. B. Gold, S. Korenman, W. L. Lasley, J. L. Luborsky, D. McConnell, et al. Correlates of Circulating Androgens in Mid-Life Women: The Study of Women's Health Across the Nation
J. Clin. Endocrinol. Metab.,
August 1, 2005;
90(8):
4836 - 4845.
[Abstract][Full Text][PDF]
K. Sutton-Tyrrell, R. P. Wildman, K. A. Matthews, C. Chae, B. L. Lasley, S. Brockwell, R. C. Pasternak, D. Lloyd-Jones, M. F. Sowers, J. I. Torrens, et al. Sex Hormone-Binding Globulin and the Free Androgen Index Are Related to Cardiovascular Risk Factors in Multiethnic Premenopausal and Perimenopausal Women Enrolled in the Study of Women Across the Nation (SWAN)
Circulation,
March 15, 2005;
111(10):
1242 - 1249.
[Abstract][Full Text][PDF]
