Hysterectomy before natural menopause increases CVD risk even without concomitant oophorectomy

Hysterectomy performed for reasons other than malignancy before natural menopause remains highly prevalent, though the procedure's popularity has fallen over the last decade. Surgical removal of the uterus may be accompanied by an oophorectomy that turns off production of estrogen and progesterone, resulting in surgical menopause. It is well-known that women with premature and early menopause, both natural and surgical, are at greater risk for developing CVD later in life. However, the question remains: what is driving the CVD risk for these women? The usual explanation is estrogen deficiency. However, a large Chinese study published in Stroke on July 13, 2022 suggests that things could be more complicated.

A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after hysterectomy alone (HA) and hysterectomy with bilateral oophorectomy (HBO). Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies.

Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery (before the age of 48).

This finding of increased CVD risk after hysterectomy alone with preserved ovarian function was unexpected. The authors suggest that hysterectomy alone can result in loss of ovarian function via loss of feedback from the uterus to the ovaries, but alternative mechanisms beyond estrogen deficiency should be considered as well. It is noteworthy that study findings did not appear to support surgical menopause increasing blood levels of total and LDL cholesterol. Compared to women without surgery, these measures were unaffected by hysterectomy alone, and only slightly raised after hysterectomy with bilateral oophorectomy. More mechanistic studies are needed, but the present study may already have important clinical implications. A history of either HA or HBO should be considered when discussing preventive interventions, and additional screening for risk factors for CVD should be considered in women following HA and HBO surgery, especially if such operations are performed at younger age.


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