Ovary Removal Doesn't Cut CVD Risk in Women With Diabetes

Miriam E Tucker

October 23, 2015

A history of bilateral salpingo-oophorectomy does not reduce the odds of death from cardiovascular disease among postmenopausal women with type 2 diabetes, although there may be an association between oophorectomy and CVD in women  45 and younger, a new study suggests.

The findings were published online October 12 in Diabetes Care by Duke Appiah, PhD, of the University of Minnesota, Minneapolis, and colleagues.

The data, from a subset of 7977 women who participated in a larger investigation of osteoporotic fractures, suggest that hyperandrogenemia is not a primary explanation for why women with type 2 diabetes are more likely to develop heart failure and to die of a cardiovascular event than are either women without diabetes or men of the same age, with or without diabetes, the authors say.

The finding of an association between oophorectomy and cardiovascular disease in younger women doesn't undercut that interpretation, Dr Appiah told Medscape Medical News.

"Our previous work and studies by others have shown that the overall association of bilateral salpingo-oophorectomy with cardiovascular disease seems to be driven by oophorectomy performed at an earlier age."

Thus, oophorectomy "may not independently predispose to incident cardiovascular disease, and our analysis suggests that the positive associations of ovarian removal with cardiovascular disease may instead be a reflection of adverse cardiovascular health among those women who undergo oophorectomy at a young age," Dr Appiah noted.

The study findings have several clinical implications, he said.

"First, they do not provide support for the opinion that bilateral salpingo-oophorectomy negatively affects cardiovascular health directly. Second, the lack of benefit of bilateral salpingo-oophorectomy for women with diabetes suggests that treatment of their hyperandrogenism is unlikely to improve their cardiovascular health."

He added, "Our results do not challenge the current idea that hormone therapy for women undergoing bilateral salpingo-oophorectomy at an earlier age may provide benefits such as relief from hot flashes, which have been linked to cardiovascular disease risk."

Diabetes Elevates CVD Risk, Regardless of Oophorectomy

In the study 7977 women with a mean age of 71.5 years at baseline were examined — 6% (502) had diabetes and 18% (1441) had a history of bilateral salpingo-oophorectomy. Among the 502 with diabetes, 20% (101) had had an oophorectomy. The women with oophorectomy were more likely to use hormone therapy, while those with diabetes were less likely to take hormones.

A total of 4797 women died over a mean follow-up of 15 years, including 1638 attributed to cardiovascular disease.

The rate of CVD mortality was similar among those without diabetes regardless of whether or not they had oophorectomy (12.9 per 1000 for women with neither compared with 12.7 per 1000 for those with no diabetes but who underwent oophorectomy).

Overall, CVD mortality was elevated for all the women with diabetes, regardless of oophorectomy status (P < .001).

For those with diabetes and intact ovaries, the adjusted hazard ratio (HR) for CV death was 1.95 (compared with women without diabetes or oophorectomy) and for those diabetics who also underwent bilateral salpingo oophorectomy, it was 2.56, but the difference between these two groups wasn't statistically significant (P = .12).

Overall, bilateral salpingo-oophorectomy was not associated with CVD mortality (HR, 1.05), and there was no significant interaction between diabetes-oophorectomy status and hormone therapy (P = 0.34).

Link Between Oophorectomy and CVD Death Seen in Younger Women

In the analysis examining women older than 45 years vs those aged 45 or younger, CVD mortality was increased among those with diabetes regardless of age at menopause.

However, among just those with type 2 diabetes, CV death was increased in those who had bilateral salpingo-oophorectomy before or at age 45 compared with those with intact ovaries (HR, 2.75; P = 0.012), whereas there was no difference among those who had the surgery after age 45 compared with those with diabetes who had intact ovaries (HR, 0.94, P = .86).

Dr Appiah told Medscape Medical News that although other investigators have proposed that the elevated CVD risk among women who have bilateral salpingo-oophorectomy may be explained by estrogen deficiency, there is emerging evidence that women who undergo such oophorectomy at an earlier age tend to have a family history of CVD and adverse CV risk factors long before undergoing the procedure, which may be performed for a variety of reasons.

Women who have hysterectomy for dysfunctional uterine bleeding tend to be younger and have benign ovarian cysts that might influence the decision for bilateral salpingo-oophorectomy. These women may have polycystic ovary syndrome, a high-risk group for insulin resistance, diabetes, and CVD, which may be driving the elevated risk among this group of women, he said.

And, Dr Appiah pointed out, elective bilateral salpingo-oophorectomy has declined dramatically in the past 2 decades since the American College of Obstetricians and Gynecologists recommended that strong consideration be made for retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer.

"Our results are in keeping with this recommendation. The elevated risk for CVD among women with type 2 diabetes and those who have bilateral salpingo-oophorectomy at an early age requires further study."

The study from which these data were obtained was supported by the National Institutes of Health. Dr Appiah and his coauthors have no relevant financial relationships.

Diabetes Care. Published online October 12, 2015. Abstract

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