Brandon R. Grossardt

Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause

Objective: There is increasing laboratory evidence for a neuroprotective effect of estrogen; however, the clinical and epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent cognitive impairment or dementia. Methods: We included all women who underwent unilateral or bilateral oophorectomy before the onset of menopause for a non-cancer indication while residing in Olmsted County, MN, from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 813 women with unilateral oophorectomy, 676 women with bilateral oophorectomy, and 1,472 referent women. Women were followed through death or end of study using either direct or proxy interviews. Results: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of cognitive impairment or dementia compared to referent women (hazard ratio [HR] = 1.46; 95% CI 1.13 to 1.90; adjusted for education, type of interview, and history of depression). The risk increased with younger age at oophorectomy (test for linear trend; adjusted p < 0.0001). These associations were similar regardless of the indication for the oophorectomy, and for women who underwent unilateral or bilateral oophorectomy considered separately. Conclusions: Both unilateral and bilateral oophorectomy preceding the onset of menopause are associated with an increased risk of cognitive impairment or dementia. The effect is age-dependent and suggests a critical age window for neuroprotection.

Use of a Medical Records Linkage System to Enumerate a Dynamic Population Over Time: The Rochester Epidemiology Project

The Rochester Epidemiology Project (REP) is a unique research infrastructure in which the medical records of virtually all persons residing in Olmsted County, Minnesota, for over 40 years have been linked and archived. In the present article, the authors describe how the REP links medical records from multiple health care institutions to specific individuals and how residency is confirmed over time. Additionally, the authors provide evidence for the validity of the REP Census enumeration. Between 1966 and 2008, 1,145,856 medical records were linked to 486,564 individuals in the REP. The REP Census was found to be valid when compared with a list of residents obtained from random digit dialing, a list of residents of nursing homes and senior citizen complexes, a commercial list of residents, and a manual review of records. In addition, the REP Census counts were comparable to those of 4 decennial US censuses (e.g., it included 104.1% of 1970 and 102.7% of 2000 census counts). The duration for which each person was captured in the system varied greatly by age and calendar year; however, the duration was typically substantial. Comprehensive medical records linkage systems like the REP can be used to maintain a continuously updated census and to provide an optimal sampling framework for epidemiologic studies.

Premature menopause or early menopause: Long-term health consequences

OBJECTIVE To review and summarize current evidence on the health consequences of premature menopause and early menopause. METHODS We reviewed existing literature and combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging. RESULTS Premature menopause or early menopause may be either spontaneous or induced. Women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae. The risk of adverse outcomes increases with earlier age at the time of menopause. Some of the adverse outcomes may be prevented by estrogen treatment initiated after the onset of menopause. However, estrogen alone does not prevent all long-term consequences, and other hormonal mechanisms are likely involved. CONCLUSIONS Regardless of the cause, women who experience hormonal menopause and estrogen deficiency before reaching the median age of natural menopause are at increased risk for morbidity and mortality. Estrogen treatment should be considered for these women, but may not eliminate all of the adverse outcomes.

History of the Rochester Epidemiology Project: Half a Century of Medical Records Linkage in a US Population

The Rochester Epidemiology Project (REP) has maintained a comprehensive medical records linkage system for nearly half a century for almost all persons residing in Olmsted County, Minnesota. Herein, we provide a brief history of the REP before and after 1966, the year in which the REP was officially established. The key protagonists before 1966 were Henry Plummer, Mabel Root, and Joseph Berkson, who developed a medical records linkage system at Mayo Clinic. In 1966, Leonard Kurland established collaborative agreements with other local health care providers (hospitals, physician groups, and clinics [primarily Olmsted Medical Center]) to develop a medical records linkage system that covered the entire population of Olmsted County, and he obtained funding from the National Institutes of Health to support the new system. In 1997, L. Joseph Melton III addressed emerging concerns about the confidentiality of medical record information by introducing a broad patient research authorization as per Minnesota state law. We describe how the key protagonists of the REP have responded to challenges posed by evolving medical knowledge, information technology, and public expectation and policy. In addition, we provide a general description of the system; discuss issues of data quality, reliability, and validity; describe the research team structure; provide information about funding; and compare the REP with other medical information systems. The REP can serve as a model for the development of similar research infrastructures in the United States and worldwide.

Generalizability of Epidemiological Findings and Public Health Decisions: An Illustration From the Rochester Epidemiology Project

OBJECTIVE To illustrate the problem of generalizability of epidemiological findings derived from a single population using data from the Rochester Epidemiology Project and from the US Census. METHODS We compared the characteristics of the Olmsted County, Minnesota, population with the characteristics of populations residing in the state of Minnesota, the Upper Midwest, and the entire United States. RESULTS Age, sex, and ethnic characteristics of Olmsted County were similar to those of the state of Minnesota and the Upper Midwest from 1970 to 2000. However, Olmsted County was less ethnically diverse than the entire US population (90.3% vs 75.1% white), more highly educated (91.1% vs 80.4% high school graduates), and wealthier (

Increased cardiovascular mortality after early bilateral oophorectomy.

51,316 vs

Data Resource Profile: The Rochester Epidemiology Project (REP) medical records-linkage system

41,994 median household income; 2000 US Census data). Age- and sex-specific mortality rates were similar for Olmsted County, the state of Minnesota, and the entire United States. CONCLUSION We provide an example of analyses and comparisons that may guide the generalization of epidemiological findings from a single population to other populations or to the entire United States.

Increased risk of parkinsonism in women who underwent oophorectomy before menopause

Objective: To investigate the mortality associated with cardiovascular diseases and the effect of estrogen treatment in women who underwent unilateral or bilateral oophorectomy before menopause. Design: We conducted a cohort study with long-term follow-up of women in Olmsted County, MN, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied the mortality associated with cardiovascular disease in a total of 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Women who underwent unilateral oophorectomy experienced a reduced mortality associated with cardiovascular disease compared with referent women (hazard ratio [HR], 0.82; 95% CI, 0.67-0.99; P = 0.04). In contrast, women who underwent bilateral oophorectomy before age 45 years experienced an increased mortality associated with cardiovascular disease compared with referent women (HR, 1.44; 95% CI, 1.01-2.05; P = 0.04). Within this age stratum, the HR for mortality was significantly increased in women who were not treated with estrogen through age 45 years or longer (HR, 1.84; 95% CI, 1.27-2.68; P = 0.001) but not in women treated with estrogen (HR, 0.65; 95% CI, 0.30-1.41; P = 0.28; test of interaction, P = 0.01). Mortality was further increased after deaths associated with cerebrovascular causes were excluded. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased cardiovascular mortality, especially with cardiac mortality. However, estrogen treatment may reduce this risk.

Medical records documentation of constipation preceding Parkinson disease: A case-control study

The Rochester Epidemiology Project (REP) medical records-linkage system was established in 1966 to capture health care information for the entire population of Olmsted County, MN, USA. The REP includes a dynamic cohort of 502 820 unique individuals who resided in Olmsted County at some point between 1966 and 2010, and received health care for any reason at a health care provider within the system. The data available electronically (electronic REP indexes) include demographic characteristics, medical diagnostic codes, surgical procedure codes and death information (including causes of death). In addition, for each resident, the system keeps a complete list of all paper records, electronic records and scanned documents that are available in full text for in-depth review and abstraction. The REP serves as the research infrastructure for studies of virtually all diseases that come to medical attention, and has supported over 2000 peer-reviewed publications since 1966. The system covers residents of all ages and both sexes, regardless of socio-economic status, ethnicity or insurance status. For further information regarding the use of the REP for a specific study, please visit our website at www.rochesterproject.org or contact us at info@rochesterproject.org. Our website also provides access to an introductory video in English and Spanish.

Prophylactic oophorectomy in premenopausal women and long-term health.

Objective: There is increasing laboratory evidence for a neuroprotective effect of estrogen on the nigrostriatal pathway; however, the epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent parkinsonism. Methods: We included all women who underwent either unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987 while residing in Olmsted County, MN. Each member of the oophorectomy cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed through death or end of study using a combination of direct or proxy interviews, neurologic examinations, medical records in a records-linkage system, and death certificates. Results: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with referent women (HR 1.68; 95% CI 1.06 to 2.67; p = 0.03), and the risk increased with younger age at oophorectomy (test for linear trend; p = 0.01). The findings were similar regardless of the indication for the oophorectomy, and for unilateral or bilateral oophorectomy considered separately. The findings were also consistent for Parkinson disease alone, but did not reach significance. Conclusions: Both unilateral and bilateral oophorectomy performed prior to menopause may be associated with an increased risk of parkinsonism and the effect may be age-dependent. However, our findings await independent replication.