The removal of both ovaries before menopause was associated with a higher likelihood of chronic health conditions and worse physical function years later, especially for women who underwent the procedure early, a cross-sectional study found.
Compared with an age-matched group, women under age 46 years who underwent premenopausal bilateral oophorectomy (PBO) for a non-malignant condition -- either with or without hysterectomy -- had worse performance on the 6-minute walk test at a clinic visit two decades later and were more likely to have chronic medical conditions:
- Asthma: OR 1.74 (95% CI 1.03-2.93)
- Arthritis: OR 1.64 (95% CI 1.06-2.55)
- Obstructive sleep apnea: OR 2.00 (95% CI 1.23-3.26)
- Bone fractures: OR 2.86 (95% CI 1.17-6.98)
"These results, highlighting potential negative long-term effects of PBO, are important for women with benign or no ovarian indications at average genetic risk of ovarian cancer to weigh in their consideration of a PBO with or without hysterectomy," concluded researchers led by Michelle Mielke, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina in .
The findings, which relied on the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2), confirms that clinicians need to change practice, said Stephanie Faubion, MD, MBA, the medical director for the Menopause Society.
"This just adds to the existing literature that having your ovaries out at a younger age, particularly under the age of 46, is associated with adverse health outcomes," Faubion told 鶹ý. "At this point, I think we just need to take action."
Faubion, who is also the director of the Mayo Clinic's Center for Women's Health in Rochester, Minnesota, but was not involved in the current research, said that later PBO (in women ages 46 to 49 years) was also "not a good idea," based on the study findings. In this group, an increased odds of arthritis and sleep apnea was observed compared with their age-matched counterparts, and a higher odds of chronic obstructive pulmonary disease was seen with PBO in the full cohort.
About 90% of the PBO group underwent concurrent hysterectomy and 6% had undergone hysterectomy beforehand; in the age-matched reference group without PBO, 9% had undergone hysterectomy.
It's common practice for women to have their ovaries removed during a hysterectomy, the second most common surgery in women, in part because it can eliminate the risk for ovarian cancer, Mielke told 鶹ý.
"It has historically been thought that once your uterus is removed, you're no longer going to be reproducing anymore, and so there's no need to also have the ovaries," Mielke explained. "However, over time, more studies have been coming out that suggest that the removal of both ovaries prior to natural menopause may provide long-term consequences or long-term risk of other diseases."
If the ovaries are removed prior to natural menopause, it's "strongly suggested" that women go on estrogen therapy until about the age of 50, Mielke said.
The current study included a comprehensive in-person physical assessment of women with a documented history of PBO, whereas other studies on PBO and heath outcomes have primarily relied on the passive collection of outcomes from medical records, which cannot capture "specific domains of physical function or other aging-related measures," the researchers noted.
Study Details
Mielke and colleagues used the Rochester Epidemiology Project (REP) medical records-linkage system and data from the MOA-2 study, which identified women from Olmsted County, Minnesota who underwent PBO for a non-malignant condition from 1988 to 2007 and were not at high risk for ovarian cancer. MOA-2 participants were matched with a reference group of women without PBO.
As of 2018, when the in-person study began, a majority of the PBO and reference groups were still alive (91.6% and 93.1%, respectively).
The team enrolled 274 English-speaking women from MOA-2 who underwent PBO for an in-person follow-up visit a median 22 years later -- including 161 patients (59%) who underwent the procedure early (before age 46) and 113 patients (41%) who underwent the procedure later (46 to 49 years).
Participants needed to be 55 or older at enrollment and were excluded if a malignancy turned up on pathology for their PBO, or if they had no clinic visits in REP over the prior 5 years. They were age-matched with 240 participants without PBO from the reference group.
Overall, women had a median age of 67 years, 97-99% were white, and about 60% were never smokers.
Chronic conditions were assessed by medical records. Aside from the associations previously noted, the researchers found no link between PBO and cancer; diabetes; dementia; hypertension; hyperlipidemia; irregular heart rhythm; kidney, thyroid, or liver disease; osteoporosis, or transient ischemic attack.
The physical exam included measures of strength and mobility. Women who underwent PBO had a higher android/gynoid fat ratio compared with the age-matched reference group and performed worse on the 6-minute walk test (-14 m), which was driven by those who underwent early PBO (-18 m). In the late PBO group, women had a higher mean percent fat mass, appendicular lean mass, and spine bone mineral density compared with the reference group.
Mielke and colleagues noted that because the study was cross-sectional, causality cannot be inferred and recommend longitudinal studies. They also pointed out that the women who participated in the study may be healthier than the general population and cited the largely white population as a study limitation.
Disclosures
Mielke disclosed relationships with Biogen, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Co-authors disclosed relationships with Astellas, Mithra Pharmaceuticals, Scynexis, Womaness, SWAN-Aging Study Observational Study Monitoring, American Society of Biomechanics, Pfizer, Takeda, Biogen, and Eli Lilly.
Faubion disclosed no relationships with industry, but is related to a study author.
Primary Source
Menopause
Mielke MM, et al "Long-term effects of premenopausal bilateral oophorectomy with or without hysterectomy on physical aging and chronic medical conditions" Menopause 2023; DOI: 10.1097/GME.0000000000002254.