Hysterectomy tied to increased diabetes risk

Undergoing a hysterectomy, particularly at a young age, may be associated with an increased risk of developing diabetes, according to a study from France presented at EASD 2022.

“The findings from this large French cohort suggest that women who undergo hysterectomy before the age of 45 have a 52 percent increased risk of developing incident type 2 diabetes (T2D),” said lead author Professor Fabrice Bonnet from CHU de Rennes and The Centre for Research in Epidemiology and Population Health, Villejuif, France.

The E3N cohort comprised women aged 40–65 years when recruited in 1993. The present analysis was conducted on 83,582 women (average age 51 years) in this cohort without diabetes at baseline. Questionnaires distributed every 2 years were utilized to assess dietary intake and physical activity, while diabetes status was ascertained through questionnaires, medical records, or prescriptions for antidiabetic medications. Gynaecological cancer was an exclusion criteria.

The women were followed up for a mean 16 years, during which time, 17,141 underwent hysterectomy for benign gynaecological conditions and 2,672 were diagnosed with T2D.

Compared with women who had not undergone hysterectomy, those who had were older, had a higher BMI and physical activity levels, and were more likely to experience menopause before age 45 years and be on hormone replacement therapy, but were less likely to be current smokers.

Incident diabetes was more commonly diagnosed among women who had vs had not undergone hysterectomy (4.2 percent vs 2.9 percent; p<0.0001). [EASD 2022, abstract 151]

After adjusting for confounders*, hysterectomy was associated with a significantly increased risk of diabetes compared with no hysterectomy (adjusted hazard ratio [adjHR], 1.27, 95 percent confidence interval [CI], 1.02–1.25; p=0.02). The results were maintained following further adjustment for reproductive factors and hormonal treatments** (adjHR, 1.20, 95 percent CI, 1.09–1.33; p=0.0003).

The association was not influenced by diet quality or physical activity levels. However, age at hysterectomy appeared to have an impact. For instance, women who underwent hysterectomy at age <40 years and <45 years had a significantly elevated risk of diabetes compared with women of those respective age groups who did not undergo hysterectomy (adjHR**, 1.38, 95 percent CI, 1.10–1.74; p=0.005 and adjHR, 1.52, 95 percent CI, 1.31–1.78; p<0.0001, respectively). Conversely, undergoing hysterectomy at age ≥45 years did not affect diabetes risk (adjHR, 1.07, 95 percent CI, 0.95–1.21; p=0.23; p_interaction=0.0048).

Oophorectomy as a modifying factor?

Among women who underwent hysterectomy, the risk of diabetes was significantly elevated among women who also had an oophorectomy (adjHR**, 1.26, 95 percent CI, 1.11–1.42; p=0.0003) but was less apparent among those who did not undergo an oophorectomy (adjHR, 1.13, 95 percent CI, 0.99–1.30; p=0.06).

“This indicates that ovarian preservation might be beneficial in reducing the risk of T2D,” noted Bonnet.

Increased risk of depression

In 2005, a total of 42,340 women in the cohort were assessed for depression (based on Center for Epidemiologic Studies Depression Scale Revised [CES-D] score). Among the 4,595 women who were diagnosed with depression (CES-D ≥23), the risk was greater among women with vs without a history of hysterectomy (12.5 percent vs 10.4 percent; p<0.0001).

“[These findings suggest] depression may be a factor underlying the increased risk of developing diabetes after a hysterectomy,” said Bonnet.

Take-home message

Bonnet and co-authors noted that the results merely indicate a potential association between hysterectomy and T2D. Additionally, unmeasured confounders and self-report of lifestyle data may have influenced the outcomes. Further study is warranted to elucidate the mechanisms behind this possible link, they said.

“There are circumstances when a hysterectomy is the best choice for a woman, but we need to make sure that patients are aware of the potential health risks associated with this procedure, particularly before the age of 45, and are informed about the nonsurgical alternative therapies for fibroids, endometriosis, and prolapse, which are the leading reasons for hysterectomy,” concluded Bonnet.