Hysterectomy: Another Diabetes Risk Factor?

An early hysterectomy may serve as an independent risk factor for developing future diabetes, according to a French cohort study.

Compared with women with an intact uterus, those who underwent a hysterectomy saw a 20% higher risk for developing incident type 2 diabetes over 16-year follow-up, after adjusting for age at menarche, menopausal status and age at menopause, use of oral contraceptive devices and hormone replacement therapy, and number of pregnancies, said Fabrice Bonnet, MD, PhD, of Centre Hospitalier Universitaire de Rennes in France.

However, when broken down by age at hysterectomy, this elevated diabetes risk only appeared to apply to women who had a hysterectomy prior to the age of 45, he explained during a presentation at the European Association for the Study of Diabetes (EASD) meeting:

• Hysterectomy before 40: HR 1.38 (95% CI 1.10-1.74, P=0.005)
• Hysterectomy before 45: HR 1.52 (95% CI 1.31-1.78, P<0.0001)

“Hysterectomy is a risk factor for future diabetes,” Bonnet noted. “We should target women with an early hysterectomy because they are at higher risk.”

In addition to age, oophorectomy was yet another factor that seemed to play into the risk for developing type 2 diabetes. Specifically, women who underwent a hysterectomy alone — preserving the ovaries — only saw a slightly higher diabetes risk versus women without a history of hysterectomy or oophorectomy (HR 1.13, 95% CI 0.99-1.30, P=0.06).

But when hysterectomy was performed with oophorectomy, women saw a significantly higher risk for incident diabetes (HR 1.26, 95% CI 1.11-1.42, P=0.0003).

In addition, women who underwent a hysterectomy also tended to experience more severe depressive symptoms than those who didn’t. Bonnet suggested that depression could be a mediating factor between the two, as it has been linked with both hysterectomy and diabetes.

Severe depression symptoms were defined as a score of 23 or higher on the Center for Epidemiologic Studies Depression Scale Revised (CES-D) questionnaire. Of women without a history of hysterectomy, 10.4% reported severe depressive symptoms versus 12.5% of those who underwent hysterectomies.

Another meditating factor could point back to reduced ovarian function, resulting in less estrogen and anti-müllerian hormone secretion after hysterectomy. “A lot of evidence suggests a protective role for ovarian secretion regarding the risk of late diabetes,” Bonnet noted.

For this analysis, the researchers analyzed data from the E3N cohort study of 98,995 French women born between 1925 and 1950 and recruited in 1993. These women completed questionnaires every 2 years, self-reporting data on lifestyle factors, hormonal factors, medications, medical events, diseases, and depression using the CES-D questionnaire. Diet was also measured using a 208-item questionnaire.

A total of 83,582 women were included in the final analysis, representing those who didn’t have diabetes at baseline. Over 16-year follow-up, 2,672 women developed diabetes: 2.9% of 64,484 women who had no history of hysterectomy and 4.2% of 16,426 women who underwent hysterectomy.

Only women who had hysterectomies for benign gynecologic conditions were ultimately included, as were those who underwent hysterectomies and/or oophorectomies prior to diabetes diagnosis. Diabetes was identified via the self-reported questionnaires for antidiabetic drug use.

At baseline, women who underwent hysterectomy tended to have a higher BMI, and were more likely to engage in more physical activity, hit menopause before age 45, and use hormone replacement therapy, and were less likely to smoke.