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Cited by 481Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsHormonal and reproductive studies

Increased cardiovascular mortality after early bilateral oophorectomy

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Rivera, Cathleen M., Grossardt, Brandon R., Rhodes, Deborah J., Brown, Robert D., Roger, Véronique L., Melton, L. Joseph, Rocca, Walter A.·2009·Menopause
DOI 10.1097/gme.0b013e31818888f7PMC PMC2755630
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Abstract

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.

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Crossref · 10.1097/gme.0b013e31818888f7

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  • Surgically induced menopause before natural menopause may increase coronary heart disease risk, and this elevated risk may be most evident at younger ages.

    “The surgically-induced menopause prior to a natural menopause may increase risk of CHD among women, and this elevated risk may be most evident at a younger age (i.e., before all women reach natural menopause). (20-24)”

    From Endometriosis and Risk of Coronary Heart Disease (2016) · cites this paper as [20]

    The Results (no page supplied) associate bilateral oophorectomy before age 45 with increased cardiovascular mortality, supporting the concern about surgery before natural menopause. But the study measured deaths rather than CHD incidence, found no increase in CHD mortality considered separately, and examined mortality many years after surgery; it does not establish that the elevated risk is most evident while women are younger. (LLM, conf=0.87)

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  • Treatments for endometriosis, including hysterectomy or oophorectomy and analgesics, may increase the risk of coronary heart disease in women with endometriosis.

    “In addition, the treatments of endometriosis, such as hysterectomy or oophorectomy (20-24) and analgesics (25) may confer increased risk of CHD to women with endometriosis.”

    From Endometriosis and Risk of Coronary Heart Disease (2016) · cites this paper as [20]

    The Results (Overall cardiovascular disease mortality) associate bilateral oophorectomy before age 45 with increased cardiovascular mortality, which supports the broader concern about surgical risk. But the Results (Specific cardiovascular causes of death) report no increased coronary heart disease mortality when analyzed separately; the paper does not establish this risk specifically for women with endometriosis. The analgesics portion is attached to a different citation. (LLM, conf=0.88)

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  • Bilateral oophorectomy at ages younger than 50 has been associated with increased incidence and mortality of cardiovascular diseases, although results have been inconclusive for bilateral oophorectomy at ages older than 50.

    “bilateral oophorectomy at ages younger than 50 has been associated with an increased incidence and mortality of cardiovascular diseases, although results have been inconclusive for bilateral oophorectomy at ages older than 50.(20-22)”

    From Endometriosis and Risk of Coronary Heart Disease (2016) · cites this paper as [20]

    The Results report increased cardiovascular mortality after bilateral oophorectomy before age 45, particularly among women who did not continue estrogen treatment through age 45. The study measured mortality, not cardiovascular disease incidence; its significant finding is for under 45 rather than all women under 50, and the cited passages do not characterize results after age 50 as inconclusive. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Treatment with estrogens until age 45 years or longer may reduce the risk of cardiovascular disease and mortality.

    “Treatment with estrogens until age 45 years or longer may reduce the risk of cardiovascular disease and mortality (47,49,51).”

    From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [51]

    The Conclusions state that estrogen treatment through age 45 or longer may reduce cardiovascular mortality among women who underwent early bilateral oophorectomy; the Results report no increased cardiovascular mortality in the treated group. The cited paper does not establish a reduction in cardiovascular disease incidence or mortality generally, as the citing sentence could imply. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Treatment with estrogens through age 45 years or longer may reduce the risk of cardiovascular disease and mortality.

    “Treatment with estrogens through age 45 years or longer may reduce the risk of cardiovascular disease and mortality (47,49,51).”

    From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [51]

    The Conclusions state that estrogen treatment through age 45 years or longer may reduce the risk of death involving cardiovascular disease in women who underwent early bilateral oophorectomy. The Results report no increased cardiovascular mortality among women treated through at least age 45. The paper does not establish a separate reduction in the incidence of cardiovascular disease or in mortality from all causes. (LLM, conf=0.82)

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Research works printed but not linked: 2

  1. [26]Therneau TM Grambsch PM Modeling Survival Data: Extending the Cox Model 2000 New York Springer
  2. [33]Last JM International Epidemiological Association A Dictionary of Epidemiology 2001 4th ed. New York Oxford University Press

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Authors
Rivera, C. M., Grossardt, B. R., Rhodes, D. J., Brown, R. D., Roger, V. L., Melton, L. J., & Rocca, W. A.
Affiliations
Mayo Clinic (US)
Corresponding author
Rocca, Walter A.
ORCID
Venue
Menopause
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-01
Volume
16
Issue
1
Pages
15-23
ISSN
1072-3714 (ISSN-L)
DOI
10.1097/gme.0b013e31818888f7
PMC
PMC2755630
OpenAlex
W1970499787
Semantic Scholar
b6998a7b3b97c9d8be5d1f8987db7d807859fbc0
Cited by
481
References
49
Citations by year
2026: 25 · 2025: 20 · 2024: 23 · 2023: 42 · 2022: 31 · 2021: 32 · 2020: 32 · 2019: 29 · 2018: 37 · 2017: 31 · 2016: 34 · 2015: 21 · 2014: 14 · 2013: 32 · 2012: 19
FWCI
18.73
Type
journal article
Language
en
Open access
Locations
  • Menopause The Journal of The North American Menopause Society (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS033978, NS33978)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR030582, AR30582)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
bilateral oophorectomy, unilateral oophorectomy, cardiovascular mortality, estrogen replacement therapy, premenopausal women, cardiac mortality, cerebrovascular disease mortality, early menopause, Olmsted County cohort
MeSH terms
Adult, Age Factors, Cardiovascular Diseases, Estrogens, Female, Follow-Up Studies, Humans, Hysterectomy, Menopause, Middle Aged, Ovarian Diseases, Ovariectomy, Risk Factors, Cohort Studies, Proportional Hazards Models

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