Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses' health study

Abstract

Objective: To report long-term mortality after oophorectomy or ovarian conservation at the time of hysterectomy in subgroups of women based on age at the time of surgery, use of estrogen therapy, presence of risk factors for coronary heart disease, and length of follow-up.

Methods: This was a prospective cohort study of 30,117 Nurses' Health Study participants undergoing hysterectomy for benign disease. Multivariable adjusted hazard ratios for death from coronary heart disease, stroke, breast cancer, epithelial ovarian cancer, lung cancer, colorectal cancer, total cancer, and all causes were determined comparing bilateral oophorectomy (n=16,914) with ovarian conservation (n=13,203).

Results: Over 28 years of follow-up, 16.8% of women with hysterectomy and bilateral oophorectomy died from all causes compared with 13.3% of women who had ovarian conservation (hazard ratio 1.13, 95% confidence interval 1.06-1.21). Oophorectomy was associated with a lower risk of death from ovarian cancer (four women with oophorectomy compared with 44 women with ovarian conservation) and, before age 47.5 years, a lower risk of death from breast cancer. However, at no age was oophorectomy associated with a lower risk of other cause-specific or all-cause mortality. For women younger than 50 years at the time of hysterectomy, bilateral oophorectomy was associated with significantly increased mortality in women who had never used estrogen therapy but not in past and current users: assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50.

Conclusions: Bilateral oophorectomy is associated with increased mortality in women aged younger than 50 years who never used estrogen therapy and at no age is oophorectomy associated with increased survival.

Level of evidence: I.

Figure 1. Multivariable-adjusteda risks of all-cause and cause-specific deaths for women with bilateral oophorectomy compared with ovarian conservation at time of hysterectomy, stratified by age at hysterectomy

HR, hazard ratio; CI, confidence interval; CHD, coronary heart disease; CVD, cardiovascular disease; NA, not analyzed due to small numbers ^a All models were adjusted for age, age at hysterectomy, body mass index in 1976, smoking status, use of estrogen therapy, past duration of oral contraceptive use, parity, physical activity, alcohol intake and aspirin use. In addition, all-cause death models were adjusted for family history of myocardial infarction before age 60, tubal ligation and family history of breast cancer; breast cancer models were adjusted for tubal ligation and family history of breast cancer; total cancer models were adjusted for tubal ligation; and CHD, stroke and CVD models were adjusted for family history of myocardial infarction before age 60. ^b p-value for interaction between oophorectomy status and age at hysterectomy The median year from study entry to all-cause death is 18.9 and 19.7 for women with ovarian conservation and both ovaries removed respectively. The median year from study entry to all-cause death for all deceased women (n=4,599) is 19.4.

Figure 2. Multivariable-adjusteda risks of all-cause and cause-specific deaths for women with bilateral oophorectomy compared with ovarian conservation at time of hysterectomy before age 50, stratified by use of estrogen therapy

HR, hazard ratio; CI, confidence interval; ET, estrogen therapy; CHD, coronary heart disease; CVD, cardiovascular disease; NA, not analyzed due to small numbers ^a see footnote "a" in Figure 1 ^b p-value for interaction between oophorectomy status and use of estrogen therapy