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Lipid profile of women with premature ovarian failure

Knauff, Erik A.H. MD1; Westerveld, Hendrika E. MD, PhD2; Goverde, Angelique J. MD, PhD1; Eijkemans, Marinus J. PhD1,4; Valkenburg, Olivier MD5; van Santbrink, Evert J.P. MD, PhD5; Fauser, Bart C.J.M. MD, PhD1; van der Schouw, Yvonne T. PhD3

doi: 10.1097/gme.0b013e31816b4509

Objective: Earlier menopause is associated with a higher incidence of cardiovascular events later in life. Concurrent with the ages of menopausal transition, a shift in lipid profile takes place. Premature ovarian failure (POF) or premature menopause allows us to study the effect of cessation of ovarian function on the lipid profile independent of effects of advanced chronological age.

Design: Fasting triglycerides (TGs), total high-density lipoprotein (HDL), and low-density lipoprotein cholesterol levels were measured in 90 women with POF not using any hormone therapy and 198 population controls of the same age range not using oral contraceptives. Correlations between lipids and ovarian function parameters were assessed.

Results: After correction for age, body mass index, and smoking, women with POF presented with significantly higher TG levels (mean difference: 0.17 log mmol/L [95% CI: 0.06-0.29]). HDL cholesterol levels were borderline significantly lower in women with POF. No age-corrected correlation between triglycerides or other lipids and estradiol levels or time of estrogen deprivation could be identified. However, the free androgen index, sex hormone-binding globulin, and testosterone concentrations showed significant correlations with TGs and/or HDL cholesterol concentrations.

Conclusions: Loss of ovarian function at a very young age (POF) coincides with subtle changes in the lipid profile (higher TG levels and marginally lower HDL). Androgens (increased free androgen index and testosterone and decreased sex hormone-binding globulin) are better markers for unfavorable lipid changes compared with estrogen levels or duration of estrogen deprivation in women with POF. Elevated TG levels in combination with increased (free) androgens may be an early manifestation of reduced insulin sensitivity.

A case-control study comparing the lipid profile of 90 women with spontaneous premature ovarian failure with 198 population controls in the same age range. Both groups did not use any hormone therapy at the time of screening. After correction for age, body mass index, and smoking, higher triglycerides and lower high-density lipoprotein cholesterol levels were found in women with premature ovarian failure, although mean values were within the limits of normal.

From the Departments of 1Reproductive Medicine and Gynecology and 2Internal Medicine, 3Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands; and Departments of 4Public Health and 5Obstetrics and Gynecology, Erasmus Medical Centre, Rotterdam, the Netherlands.

Received December 6, 2007; revised and accepted January 29, 2007.

Financial disclosure: None reported.

Address correspondence to: Erik A.H. Knauff, MD, Department of Reproductive Medicine and Gynecology, University Medical Centre, Heidelberglaan 100, PO Box 3584 CX, Utrecht, the Netherlands. E-mail:

©2008The North American Menopause Society