Ovary removal surgery before age 43 may increase the risk of Parkinson’s

Study finds 5 times higher risk in these women but estrogen therapy may help

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Women who undergo surgery to remove both of their ovaries before age 43 have a five times higher risk of developing Parkinson’s disease in the future, according to a U.S. study.

For younger women who had the procedure, called a bilateral oophorectomy, use of estrogen replacement therapy until the time of natural menopause seem to lower the risk.

The findings help to inform the potential age-related relationship between estrogen, a sex hormone highly produced in the ovaries, and Parkinson’s, which has so far been controversial. They may also help to guide the clinical practice of ovary removal for cancer prevention.

“A reduction in the practice of [preventive] bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have a substantial impact in reducing the risk of parkinsonism and PD [Parkinson’s disease],” researchers wrote.

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Estrogen therapy may help women after ovary removal surgery

Also, while estrogen therapy is not currently recommended for preventing Parkinson’s after spontaneous menopause in women ages 46-55, these data suggest that such a therapy may be “important in women whose ovaries were surgically removed younger than age 46,” Walter Rocca, MD, the study’s first author and a Mayo Clinic neurologist and epidemiologist, said in a press release.

“Particularly vulnerable are women who underwent this surgically induced menopause before age 40,” Rocca added.

The study, “Association of Premenopausal Bilateral Oophorectomy With Parkinsonism and Parkinson Disease,” was published in JAMA Network Open.

While estrogen plays a role in modulating sexual function for men and women, it’s produced at significantly higher quantities in women, with the ovaries being the main source. After menopause, estrogen production in women declines significantly.

Evidence suggests that estrogen has neuroprotective benefits that help protect against Parkinson’s. That idea could possibly underlie why men develop Parkinson’s more often than women.

A number of previous studies have evaluated whether premenopausal women who have undergone a bilateral oophorectomy are at a higher risk of developing Parkinson’s. Essentially, the procedure would be a surgically-induced early menopause by removing the main supply of estrogen.

However, data so far haven’t reached a consensus, with some studies supporting the relationship and others failing to find one.

Particularly vulnerable are women who underwent this surgically induced menopause before age 40.

To learn more, Rocca and colleagues at Mayo Clinic, in Rochester, examined long-term medical record data from women included in two independent research studies: the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2 (MOA-1 and MOA-2).

The analysis involved 5,499 women from Minnesota, 2,750 of whom had undergone a premenopausal bilateral oophorectomy in the period from January 1950 to December 2007, at a median age of 45.

Reasons for the surgery included cancer prevention or other health conditions such as cysts or endometriosis.

The remaining 2,749 women, matched by age to the oophorectomy group, had not undergone the procedure and served as a reference group.

The median follow-up time in either group was nearly 24 years.

During that time, 82 women (1.2%) were diagnosed with parkinsonism. Of these 82 women, 50 (61%) were from the oophorectomy group and 32 (39%) were in the reference group. Parkinsonism refers to a group of disorders that cause movement problems similar to Parkinson’s but may have different causes.

Moreover, 53 women (1%) were diagnosed with Parkinson’s disease. In these patients, 32 (60.4%) had undergone ovary removal surgery and 21 (39.6%) had not.

Among those in the oophorectomy group, the diagnosis came a median of 26.5 years after their surgery.

Bilateral oophorectomy was associated with a 59% increased risk of parkinsonism in all women, and a seven times higher risk among the youngest third — those who underwent the surgery before age 43.

In general, a pattern was observed in which the risk increased with younger age at surgery. The risk was lowest in women who underwent oophorectomy at or after age 50 (43% higher risk), and highest among those younger than 40 (nearly nine times higher).

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Findings have implications for women not at risk for ovarian cancer

Likewise, the risk of Parkinson’s was increased by fivefold among women who underwent bilateral oophorectomy before age 43.

“The results for PD considered alone were similar in extent and pattern to the results for parkinsonism; however, the numbers were smaller,” the team wrote.

These findings were generally consistent with an earlier analysis of data from MOA-1 alone, the team noted, but prior studies have varied widely without a “clear explanation of the conflicting results.”

The potential importance of age may have been under-recognized in earlier analyses, the researchers suggested.

Among women who had the surgery at age 45 or younger, those who received estrogen therapy after the procedure through age 50 — about the average age that menopause spontaneously occurs — had a lower risk of parkinsonism or Parkinson’s relative to those who did not receive the therapy. However, these differences failed to reach statistical significance.

The findings overall support guidelines suggesting that premenopausal women who are not at an unusually high risk of ovarian cancer should not have both their ovaries removed, Rocca said.

For women who are at high risk, the surgery may still be indicated but estrogen replacement therapy until age 50 may be a good idea.

Still, larger studies may be needed to confirm the potential relationship.