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Endogenous androgen levels and cardiovascular risk profile in women across the adult life span

Bell, Robin J. MD, PhD1,2; Davison, Sonia L. MD, PhD1,2,3; Papalia, Mary-Anne MD1; McKenzie, Dean P. BA (Hons)4; Davis, Susan R. MD, PhD1,2

doi: 10.1097/gme.0b013e31802b6cb1

Objective: Whether endogenous androgen levels contribute to the cardiovascular disease (CVD) risk profile in women is controversial. The purpose of this study was to investigate systematically the relationships between serum levels of endogenous androgens and sex hormone-binding globulin (SHBG) and biochemical CVD risk profile, taking other known risk factors into account.

Design: This community-based cross-sectional study included 587 non-healthcare-seeking-women, aged 18 to 75 years, who were randomly recruited from the community via the electoral roll from April 2002 to August 2003. Participants were euthyroid; had no usage of exogenous steroids; had no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and did not have hyperprolactinemia or polycystic ovarian syndrome. The relationships between total testosterone, SHBG, free testosterone, dehydroepiandrosterone sulfate, and androstenedione and high-sensitivity C-reactive protein (CRP) and lipids were explored using linear regression with natural logarithm (ln) -or square root-transformed data as indicated. Issues of nonlinearity and interaction were addressed by the inclusion of extra regression terms where appropriate. We determined the change in the proportion of variation for each marker of the CVD risk profile explained by the addition of each hormone term to the models, having adjusted for age, body mass index, smoking, alcohol, and exercise.

Results: Menopausal status did not influence the statistical models for high-sensitivity CRP and high-density lipoprotein cholesterol, but for both low-density lipoprotein cholesterol and triglycerides, the proportion of variation explained by the models was substantially less in postmenopausal than in premenopausal women. Almost all of the highly statistically significant findings were related to the addition of the SHBG terms to the models. The changes in r 2 values were highly statistically significant for the addition of the SHBG terms to the models for ln CRP and ln high-density lipoprotein for both pre- and postmenopausal women (P ≤ 0.01 and < 0.001, respectively) and for ln triglycerides in postmenopausal (P < 0.001) and premenopausal women (P < 0.01).

Conclusions: Endogenous testosterone and the adrenal preandrogens per se are not significant independent determinants of circulating high-sensitivity CRP or lipoprotein lipids. Our analyses provide further support for the independent predictive value of low SHBG levels for CVD risk profile and an independent contribution of the menopausal transition to the determination of low-density lipoprotein cholesterol and triglycerides.

In a cross-sectional study of non-healthcare-seeking adult women we found that sex hormone-binding globulin (SHBG) made an independent contribution to variations in serum levels of C-reactive protein, high-density lipoprotein and triglycerides, providing support for the independent predictive value of low SHBG for cardiovascular risk profile.

From the 1Women's Health Program, Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Prahran, Victoria, Australia;2The Jean Hailes Foundation, Clayton, Victoria, Australia; 3Department of Biochemistry, Monash University, Clayton, Victoria, Australia; and 4Department of Epidemiology and Preventive Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Prahran, Victoria, Australia.

Received August 21, 2006; revised and accepted October 11, 2006.

Funding/support: This research was funded by the National Health and Medical Research Council of Australia (grants 219279 and 284484) and by a philanthropic grant from Sue Ismiel and daughters to The Jean Hailes Foundation. The funding agencies had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication.

Financial disclosure: S. R. Davis is an investigator for Procter & Gamble Pharmaceuticals and Acrux Australia, and has acted as a consultant for Procter & Gamble Pharmaceuticals, Vivus USA, and Acrux Australia. S. L. Davison, M.-A. Papalia, D. P. McKenzie, and R.J. Bell have no conflicts of interest to declare.

Address correspondence to: Associate Professor Robin J. Bell, Women's Health Program, Monash Medical School, Alfred Hospital, Commercial Road, Prahran, Victoria 3181, Australia.

©2007The North American Menopause Society