Do hormones influence cholesterol levels after menopause?

The main risk factors for heart attacks in women are elevated cholesterol, abdominal obesity and diabetes. Hormones (estrogen and testosterone) have been implicated as being protective against heart disease in women in some studies, and contributing to risk in others. Therefore we asked the question: are hormone levels in postmenopausal women related to an increase in risk of diabetes or elevated blood cholesterol and fats?

To address this we looked at the blood test results of 800 postmenopausal women recruited for an unrelated clinical study at 65 centers in the United States, Canada, Australia, UK, and Sweden between July 2004 and February 2005. Because these women were about to participate in a clinical trial we had information about their weight, height, blood pressure and a range of other clinical variables. None of the women were diabetic. The women were on average 54 years old and 6.1 years postmenopause.

First we asked the question: are estrogen or testosterone levels related to insulin resistance (elevated insulin in the setting of normal blood glucose, or ‘prediabetes'). We found that neither estrogen nor testosterone had an independent relationship with insulin resistance. Instead, the main factors we identified as being independently associated with insulin resistance were higher body mass index (ie being more overweight), systolic blood pressure, surgical menopause and a lower blood level of the protein sex hormone binding globulin (also known as SHBG)^1. SHBG has been traditionally seen as a protein that simply transports hormones such as estrogen and testosterone in the blood stream. In more recent years it has emerged that SHBG may have more important actions. Women with low SHBG levels are at greater risk for future diabetes. Our study revealed that low SHBG is associated with the step before diabetes, insulin resistance. Importantly we found that the association between SHBG and insulin resistance was independent of body weight.

The second finding, published this month², was that none of the sex steroids measured in this study were independently related to total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, or triglycerides. Independent of each other, insulin resistance and low SHBG were associated with low HDL cholesterol and higher triglycerides. Low HDL and high triglycerides are risk factors for heart disease in women.

This research refutes the myth that hormone levels are important determinants of heart disease risk in women. It provides further evidence of an independent role for the protein SHBG in diabetes risk in women. In practice this means that SHBG is a robust screening test for diabetes risk in women, and that women with very low SHBG levels need to be further evaluated for pre-diabetes and diabetes.

1. Davis SR, Robinson PJ, Moufarege A, Bell RJ. The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women. Clin Endocrinol (Oxf) 2012;77:541-7.

2. Worsley R, Robinson PJ, Bell RJ, Moufarege A, Davis SR. Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women. Menopause 2013 20(16):640-645