Association of Premenopausal Bilateral Oophorectomy With Parkinsonism and Parkinson Disease

Abstract

ImportanceThe association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial.ObjectiveTo 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 ParticipantsThis 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.ExposuresMedical record documentation of bilateral oophorectomy abstracted from a medical records–linkage system (Rochester Epidemiology Project).Main Outcomes and MeasuresIncidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review.ResultsAmong 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 RelevanceIn 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.

Associação entre a ooforectomia bilateral precoce e o desenvolvimento do parkinsonismo e Doença de Parkinson em mulheres na pré-menopausa

“…A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum, com uma incidência duas vezes maior em homens do que nas mulheres, visto que, por mecanismos fisiológicos, o estrogênio demonstra efeitos neuroprotetores, em especial na via nigroestriatal mesencefálica, na qual há um aumento da síntese da dopamina, um neurotransmissor essencial para o controle das funções motoras. Ademais, o estrogênio, além de possuir propriedades antioxidades e anti-inflamatórias, também previne a formação dos corpúsculos de Lewy e da agregação da α-sinucleína, responsáveis pela progressão da DP (ROCCA et al, 2022;CANONICO et al, 2021;CERRI et al, 2019).…”

“…Nesse sentido, essa exposição hormonal, por favorecer as mulheres e ser um fator protetor contra a DP, quando inexistente, pode aumentar o risco do desenvolvimento da patologia. Sob outra perspectiva, ainda existem dificuldades acerca desse estudo que relaciona o papel do estrogênio com a DP, principalmente pelo fato de os dados serem conflitantes, especialmente em relação ao papel da idade na menopausa e do tipo de menopausa (ROCCA et al, 2022;CANONICO et al, 2021;CERRI et al, 2019).…”

“…Assim, é primordial que, nos estudos longitudinais acerca dessa problemática, as variáveis estudadas (idade, tipo de menopausacirúrgica, não cirúrgica -, terapia hormonal pós-menopausa) gerem uma significância estatística para impor que as pesquisas em questão forneçam dados mais confiáveis (CANONICO et al, 2021;ROCCA et al, 2021;CERRI et al, 2019). Em suma, é válido salientar que a redução da prática de ooforectomia bilateral profilática em mulheres na pré-menopausa com risco médio de câncer de ovário pode ter um impacto substancial na redução do risco de parkinsonismo e DP (ROCCA et al, 2022). Por outro prisma, é crucial que a equipe médica seja hábil no rastreio e diagnóstico do câncer, no intuito de avaliar o real benefício de realização dessa intervenção cirúrgica, a qual poderia ser considerada iatrogênica.…”

“…Em vista disso, a remoção cirúrgica de ambos os ovários em mulheres na prémenopausa para a prevenção do câncer de ovário parece favorecer o surgimento da doença. Entretanto, estudos em divergência apontam resultados inconsistentes, com discrepância entre análises e limitação de poder estatístico (SECOȘAN et al, 2019;ROCCA et al, 2022).…”

Counseling in menopausal women: How to address the benefits and risks of menopause hormone therapy. A FIGO position paper

“…Surgical menopause, due to surgical removal of the ovaries, or chemotherapy‐/radiotherapy‐induced ovarian failure produce much more abrupt changes 1 . These conditions raise the risk of premature death, cardiovascular disease (CVD), dementia, parkinsonism, and Parkinson's disease significantly more than natural menopause 5–8 …”