Rocca, Liliana Gazzuola

Abstract Restless legs syndrome (RLS), a common neurologic disorder, is more prevalent in women than in men. Evidence indicates the potential role of female hormones in the pathophysiology of RLS. However, few studies have examined the relationship between premenopausal bilateral oophorectomy (BSO) and the risk of RLS. The Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2) includes all women residents of Olmsted County, Minnesota, who underwent premenopausal BSO before the age of 50 years for a non-cancer reason between 1988 and 2007 (n=1,653). In addition, 1,653 age-matched (± 1 year) referent women who did not undergo BSO prior to index-date were included. Survival analyses were used to examine the association between BSO and risk of RLS (defined by DSM-IV criteria) after adjustments using inverse probability weighting. The median (IQR) age at index-date was 40.0 (40.0-47.0) years for the BSO and 40.0 (40.0-47.0) for the non-BSO cohorts. Women who underwent BSO before menopause had a higher risk of RLS (HR,1.47; 95% CI, 1.08-2.01). In addition, women who underwent BSO before 46 years (HR:1.53, 95% CI, 1.03-2.28) or received BSO without benign ovarian indications (e.g., cysts, endometriosis, HR: 1.69, 95% CI, 1.11-2.56) were at greater risk of RLS. Estrogen use after BSO did not affect the risk of RLS. Premenopausal women who underwent BSO had an increased risk of RLS, especially those younger than 46 years and without benign medical indication. Women considering BSO for ovarian cancer prevention should be informed of the increased risk of neurological disorder including RLS.

Abstract Objective: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications. Methods: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression. Results: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001). Conclusions: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. Video Summary: http://links.lww.com/MENO/A458.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

Purpose This cohort study was established to investigate the effects of unilateral and bilateral oophorectomy on the ageing processes in women. Participants We used the records-linkage system of the Rochester Epidemiology Project (REP, http://www.rochesterproject.org ) to identify 570 women who underwent unilateral oophorectomy and 1653 women who underwent bilateral oophorectomy in Olmsted County, Minnesota from 1988 through 2007 (20 years). Each woman was matched by age (±1 year) to a population-based referent woman who had not undergone any oophorectomy (570 referent women) or bilateral oophorectomy (1653 referent women). These four cohorts are being followed to assess morbidity and mortality and to study imaging and biological markers related to ageing. Findings to date An extensive medical record abstraction using the REP has been completed for each woman to obtain demographic, reproductive and adult life characteristics and extensive clinical information about the surgical procedure and subsequent oestrogen replacement therapy (or other sex steroid therapy). The cohorts have been used to date to study the accumulation of multiple chronic conditions following bilateral oophorectomy in women with or without chronic conditions at the time of the oophorectomy (or index date). From the cohorts, we have also derived a sample of 128 pairs of women for a case–control study linking adverse childhood or adult experiences to the risk of bilateral oophorectomy. Future plans We hypothesise that the abrupt hormonal changes caused by bilateral oophorectomy in younger women have a major effect on the ageing processes across the full body. Therefore, we plan to investigate the risk of a wide range of chronic conditions following bilateral oophorectomy. Specific studies are underway for kidney diseases, psychiatric diseases and neurological diseases. In addition, we plan to invite a subsample of women from the bilateral oophorectomy cohort to participate in an in-person study involving brain imaging and the collection of biomarkers.

Objectives Bilateral oophorectomy has commonly been performed in conjunction with hysterectomy even in women without a clear ovarian indication; however, oophorectomy may have long-term deleterious consequences. To better understand this surgical practice from the woman’s perspective, we studied the possible association of adverse childhood or adult experiences with the subsequent occurrence of bilateral oophorectomy. Design Population-based case–control study. Setting Olmsted County, Minnesota (USA). Participants From an established population-based cohort study, we sampled 128 women who underwent bilateral oophorectomy before age 46 years for a non-cancerous condition in 1988–2007 (cases) and 128 age-matched controls (±1 year). Methods Information about adverse experiences was abstracted from the medical records dating back to age 15 years or earlier archived in the Rochester Epidemiology Project (REP) records-linkage system. Adverse childhood experiences were summarised using the Adverse Childhood Experience (ACE) score. Results We observed an association of bilateral oophorectomy performed before age 46 years with verbal or emotional abuse, physical abuse, any abuse, substance abuse in the household, and with an ACE score ≥1 experienced before age 19 years (OR=3.23; 95% CI 1.73 to 6.02; p<0.001). In women who underwent the oophorectomy before age 40 years, we also observed a strong association with physical abuse experienced during adulthood (OR=4.33; 95% CI 1.23 to 15.21; p=0.02). Several of the associations were higher in women who underwent oophorectomy at a younger age (<40 years) and in women without an ovarian indication for the surgery. None of the psychosocial or medical variables explored as potential confounders or intervening variables changed the results noticeably. Conclusions Women who suffered adverse childhood experiences or adult abuse are at increased risk of undergoing bilateral oophorectomy before menopause. We suggest that the association may be explained by a series of biological, emotional, and psychodynamic mechanisms.