Institute for Health Transformation
(inHealth)
Joaquim Cardoso MSc
December 27, 2022
What is the message?
- In this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy.
- These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.
Key Points
Question
- Is bilateral oophorectomy performed before spontaneous menopause associated with an increased risk of parkinsonism and Parkinson disease (PD)?
Findings
- In this cohort study of 5499 women who did and did not undergo premenopausal bilateral oophorectomy, 978 women who underwent oophorectomy before age 43 years had a statistically significant higher risk of parkinsonism and PD …
- … compared with 978 women who did not undergo oophorectomy, with a number needed to harm of 27 women for parkinsonism and 48 women for PD.
- The risk increased with younger age at bilateral oophorectomy.
Meaning
- These findings suggest that reducing the performance of prophylactic bilateral oophorectomy in premenopausal women with average risk of ovarian cancer may have a substantial impact in decreasing the risk of parkinsonism and PD.
Mayo Clinic Comprehensive Cancer Center Blog
By Susan Barber Lindquist
December 7, 2022
Surgical removal of both ovaries is associated with an increased risk of Parkinson’s disease and parkinsonism in women younger than 43, Mayo Clinic researchers report in JAMA Network Open.
Using health record data from the Rochester Epidemiology Project, the study included 2,750 women who had undergone surgery to remove both ovaries, a procedure called bilateral oophorectomy, and 2,749 who had not.
The reasons for the surgery were either a benign (noncancerous) condition-such as endometriosis, cyst, or other reason-or for the prevention of cancer.
Researchers found that for every 48 women younger than 43 at the time of surgery, one additional woman developed Parkinson’s compared to women of the same age who did not have their ovaries removed.
Parkinson’s disease is a progressive disorder that affects the nervous system and parts of the body controlled by nerves.
Tremors are common, but the disorder also may cause stiffness or slowing of movement. It often is accompanied by dementia, sleep disorders, and bowel and bladder problems. Parkinsonism is a general term for slowness of movement along with stiffness, tremor or loss of balance.
Parkinson’s disease manifests almost twice as commonly in men than women in the general population, thus suggesting that sex- or gender-related factors play a role.
For women, the ovaries are the main source of the hormone estrogen.
Surgical removal of a woman’s ovaries may be recommended because of cancer, gene mutations, and other conditions.
When a woman’s ovaries are surgically removed before she goes through menopause, that source of estrogen and other hormones is lost, so removal causes an abrupt endocrine dysfunction.
The findings confirm a 2008 study …
… that suggested lack of estrogen caused by removal of both ovaries in younger women may be associated with an increased risk of Parkinson’s disease and parkinsonism.
The results support current guidelines that removal of both ovaries should not be performed to prevent ovarian cancer in women who are at average risk of cancer, says Walter Rocca, M.D., a Mayo Clinic neurologist and epidemiologist and first author of the study.
For women who carry a high-risk genetic variant for ovarian cancer, ovary removal before menopause may be indicated, but women should receive estrogen therapy after surgery up to age 50 or 51, the approximate age of spontaneous menopause, he says.
“As of today, it is not recommended to use estrogen therapy for the prevention of dementia or parkinsonism after spontaneous menopause in women who are age 46 to 55,” says Dr. Rocca.
“But this study and previous studies suggest that estrogen therapy is important in women whose ovaries were surgically removed younger than age 46. Particularly vulnerable are women who underwent this surgically induced menopause before age 40.”
This research was funded in part by the National Institute on Aging (National Institutes of Health).
A full list of authors and affiliations is in the research article.
This article was originally published in Discovery’s Edge, Mayo Clinic’s research magazine.
Originally published at https://cancerblog.mayoclinic.org on December 7, 2022.
Names mentioned
Walter Rocca, M.D., a Mayo Clinic neurologist and epidemiologist and first author of the study.
Walter Rocca, M.D., is the Ralph S. and Beverley E. Caulkins Professor in Neurodegenerative Diseases Research.
This research was funded in part by the National Institute on Aging (National Institutes of Health).
REFERENCE PUBLICATION
Association of Premenopausal Bilateral Oophorectomy With Parkinsonism and Parkinson Disease
JAMA Network
Walter A. Rocca, MD, MPH; Carin Y. Smith, BS; Liliana Gazzuola Rocca, MD; Rodolfo Savica, MD, PhD; Michelle M. Mielke, PhD
ABSTRACT
Importance
- The association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial.
Objective
- To assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy.
Design, Setting, and Participants
- This cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records–linkage system.
- A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort).
- Data were analyzed from March 1 to April 30, 2022.
- The date of oophorectomy was considered the index date for both groups.
Exposures
- Medical record documentation of bilateral oophorectomy abstracted from a medical records–linkage system (Rochester Epidemiology Project).
Main Outcomes and Measures
- Incidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review.
Results
- Among 5499 participants (median [IQR] age, 45.0 [40.0–48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0–48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0–48.0 years) at the index date were included in the reference cohort.
- Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02–2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77–33.27).
- There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50–4.15]; 46–49 years: HR, 1.55 [95% CI, 0.79–3.07]; 40–45 years: HR, 1.36 [95% CI, 0.64–2.89]; <40 years: HR, 8.82 [95% CI, 1.08–72.00]; P = .02 for trend).
- The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy.
- Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10–22.70), with a number needed to harm of 48 women.
- Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not.
- For parkinsonism, the HRs were 1.72 (95% CI, 0.54–5.53) vs 2.05 (95% CI, 0.80–5.23); for PD, the HRs were 1.53 (95% CI, 0.29–8.23) vs 2.75 (95% CI, 0.84–9.04). However, the differences were not significant.
Conclusions and Relevance
- In this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy.
- These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.
About the authors & affiliations
Walter A. Rocca, MD, MPH1,2,3; Carin Y. Smith, BS4; Liliana Gazzuola Rocca, MD1; et alRodolfo Savica, MD, PhD1,2; Michelle M. Mielke, PhD1,2,3,5
- 1Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
- 2Department of Neurology, Mayo Clinic, Rochester, Minnesota
- 3Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences, Mayo Clinic, Rochester, Minnesota
- 4Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
- 5Department of Epidemiology and Prevention,
Wake Forest University School of Medicine, Winston-Salem, North Carolina
Originally published at https://jamanetwork.com
