Premenopausal Hysterectomy Raises Cardiovascular Disease Risk, Mainly Stroke

Premenopausal hysterectomy with or without oophorectomy increases the risk for cardiovascular disease (CVD), especially stroke, according to study findings published in JAMA Network Open.

Studies show that CVD risk increases after menopause, potentially secondary to decreased female sex hormone levels that have cardioprotective effects or hemorheological changes in blood viscosity and hematocrit levels increasing the risk for endothelial injury. This information prompted the question of whether early menopause induced by hysterectomy before age 50 increased the risk for early-onset CVD.

To answer this question, researchers in South Korea conducted a longitudinal, population-based cohort study on 135,575 women between the ages of 40 to 49 who were evaluated between January 1, 2011 to December 31, 2014 and followed until December 31, 2020 for a median of 7.9 years. Data analysis took place between December 20, 2021 and February 17, 2022.

The researchers matched the women into pairs based on specific variables. Of these 135,575 women, 55,539 (median age, 45) were included in the hysterectomy group and 55,539 in the nonhysterectomy group. They compared the risk for incidental CVD — a combination of myocardial infarction, coronary artery revascularization, and stroke.

Women in the hysterectomy group demonstrated increased risk for incidental CVD compared with the nonhysterectomy group (115 vs 96 per 100,000 person-years; hazard ratio [HR], 1.25; 95% CI, 1.09-1.44; P =.002).

When the researchers broke down the incidental CVD into each of the 3 composite subgroups, they discovered that myocardial infarction and coronary artery revascularization occurred at similar incidences in both the hysterectomy and nonhysterectomy groups. In contrast, incidence of stroke occurred at significantly higher rates in the hysterectomy group compared with the nonhysterectomy group (HR, 1.31; 95% CI, 1.12-1.53; P <.001)

The researchers analyzed the data after excluding women who also underwent simultaneous oophorectomy and discovered similar findings that women who underwent hysterectomy only still demonstrated increased risk for incidental CVD (HR, 1.24; 95% CI, 1.06-1.44; P =.004). This finding suggests that the uterus itself may exert cardiovascular protective effects independent of female sex hormones produced by the ovaries.

“In this cohort study of Korean women, we noted that hysterectomy in women younger than 50 years was independently associated with an increased risk of stroke,” the researchers noted. “Although we found that widely performed hysterectomy with a broad indication for benign diseases at premenopausal ages slightly increases the risk of CVD, the incidence is not high, so a change in clinical practice may not be needed,” they added.

The study had several limitations including its retrospective, observational design, the lack of generalizability to populations outside of South Korean women, and potential inaccuracies with medical coding. Other limitations included the inability to assess severity of underlying diseases, lack of stratification into age groups with narrower age ranges, and lack of access to relevant data, such as family history, body mass index, blood viscosity, ferritin levels, and female sex hormones.