Bilateral oophorectomy before menopause associated with increased risk for metabolic syndrome

Issue: August 2008

Women who had bilateral oophorectomy at a young age were more likely to have metabolic syndrome.

Researchers from Oslo, Norway examined 263 women (mean age, 56.3 years) who had bilateral oophorectomy before natural menopause. All women were drawn from the Norwegian Health Study of Nord-Trondelag County (HUNT-2), a controlled, population-based study. Each woman was matched with 789 controls (mean age, 56.4 years) who had intact uterus and ovaries.

Metabolic syndrome was defined using the International Diabetes Federation and National Cholesterol Education Program Adult Treatment Panel III definitions. Using the IDF definition, 47% of women who had bilateral oophorectomy had metabolic syndrome compared with 36% of women who had natural menopause (P=.001). The numbers were also greater for women with early oophorectomy using the ATP III definition — 35% vs. 25% (P=.002).

Further, women with bilateral oophorectomy were more likely to have a Framingham risk score of 10% or greater compared with controls (22% vs. 15%; P=.005).

The high prevalence of metabolic syndrome and increased Framingham risk scores in women with surgical menopause before age 50 suggests that these women may be at increased risk for type 2 diabetes and cardiovascular disease, according to the researchers. – by Katie Kalvaitis

Gynecol Oncol. 2008;109:377-383.

The authors present interesting data concerning the prevalence of metabolic syndrome in a large sample of Norwegian women who did and did not undergo bilateral salpingo oophorectomy. After adjusting for potential confounders, they report a 1.75-fold increase in the likelihood of metabolic syndrome in the 263 women who underwent bilateral oophorectomy prior to natural menopause compared with controls who had undergone hysterectomy only. The strengths of this study include the large sample size and numerous statistical adjustments made for potentially confounding variables.

Unlike a recent report from the Women’s Health Initiative Observational Study, these authors did not find an increased cardiovascular risk profile prior to bilateral oophorectomy in the women studied. The authors are also careful to avoid causal interference. However, the obvious question raised by these results is why or how does the ovary protect against the development of metabolic syndrome? And, of course, the obvious answer would be that the endogenous estrogen produced by the ovary somehow improves waist circumference, glucose tolerance and dyslipidemia. There is evidence that exogenous estrogen does the same — yet we know that it does not appear to protect women against the long-term development of cardiovascular disease. Perhaps these data can be added to other preliminary information that suggest that younger pre-, peri- and postmenopausal women, prior to the development of more advanced atherosclerotic lesions, tend to benefit from endogenous estradiol production.

The authors have performed an excellent study but good research often raises as many questions as it answers. There was not hospital validation of the medical records, and thus it is possible that some allocations were not correct, i.e., women who had a bilateral oophorectomy might have incorrectly reported that they did not and were counted as controls and women who did not have a bilateral oophorectomy might have incorrectly reported that they did. The controls had shorter duration of time since menopause to study enrollment and thus may have had less time overall to develop metabolic syndrome. The bilateral oophorectomy group also reported much more use of hormone therapy – almost three times as much – as the controls, and one wonders if it is all about estrogen, why this large amount of use of hormone therapy did not result in a risk reduction. Finally, the bilateral oophorectomy group had a worse family history of CVD. Even though statistical adjustments were made for this finding, they are almost never perfect.

So the reader is left to wonder what factors, other than estrogen, might account for the findings of this study. The reasons for the bilateral oophorectomy are not reported. It is possible that women who underwent bilateral oophorectomy did so for reasons other than prophylactic indications. The concept of prophylactic oophorectomy to reduce the risk of ovarian cancer is not uniformly embraced by practicing gynecologists. There may be nonrandom reasons that some women underwent bilateral oophorectomy and others did not. There is also evidence the estrogen receptor biology differs between women who undergo hysterectomy compared to women who do not. Thus, it may be possible that women who underwent bilateral oophorectomy had a differing underlying biology that led to the surgery, and that this difference went undetected by the investigators. Nonetheless, the findings remain interesting and provocative and we look forward to further clarification.

– Nanette Santoro, MD

Professor and Director, Division of Reproductive Endocrinology,
Department of Ob/Gyn & Women’s Health, Albert Einstein School of Medicine