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Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the Women's Health Initiative coronary artery calcium study

Allison, Matthew A. MD, MPH1; Manson, JoAnn E. MD, DrPH2; Langer, Robert D. MD, MPH3; Carr, J. Jeffrey MD, MSCE4; Rossouw, Jacques E. MD5; Pettinger, Mary B. MS6; Phillips, Lawrence MD7; Cochrane, Barbara B. RN, PhD8; Eaton, Charles B. MD9; Greenland, Philip MD10; Hendrix, Susan DO11; Hsia, Judith MD12; Hunt, Julie R. PhD6; Jackson, Rebecca D. MD13; Johnson, Karen C. MD, MPH14; Kuller, Lewis H. MD, DrPH15; Robinson, Jennifer MD, MPH16the Women's Health Initiative and Women's Health Initiative Coronary Artery Calcium Study Investigators

doi: 10.1097/gme.0b013e31816d5b1c

Objective: Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use.

Design: In a substudy of the Women's Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 mg/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped.

Results: Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women's Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2-3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectomy, the odds of any CAC was 1.7 (95% CI: 1.0-2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC.

Conclusions: Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectomy and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease.

In this study of over 1,000 postmenopausal women with a history of hysterectomy, those who received hormone therapy after a bilateral oophorectomy had significantly lower odds for coronary artery calcium compared to those women who did not receive hormone therapy. The results suggest that factors related to oophorectomy, and the absence of estrogen treatment in oophorectomized women, may be related to coronary heart disease.

From the 1University of California San Diego, La Jolla, CA; 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 3Geisinger Health Systems, Danville, PA; 4Wake Forest University School of Medicine, Winston-Salem, NC; 5National Heart, Lung, and Blood Institute, Bethesda, MD; 6Fred Hutchinson Cancer Research Center, Seattle, WA; 7Emory University, Atlanta, GA; 8University of Washington, Seattle, WA; 9Brown University, Providence, RI; 10Northwestern University Feinberg School of Medicine, Chicago, IL; 11Wayne State University, Detroit, MI; 12George Washington University, Washington, DC; 13Ohio State University, Columbus, OH; 14University of Tennessee Health Science Center, Memphis, TN; 15University of Pittsburgh, Pittsburgh, PA; and 16University of Iowa, Iowa City, IA.

Received December 19, 2007; revised and accepted February 11, 2008.

Funding/Support: The National Heart, Lung, and Blood Institute, US Department of Health and Human Services, funds the Women's Health Initiative (WHI), program and provided support for the WHI-Coronary Artery Calcium Study ancillary study. Wyeth provided study pills (active and placebo) for the WHI-Conjugated Equine Estrogens trial but had no other role in the study.

Financial disclosure: None reported.

*The Women's Health Initiative and Women's Health Initiative Coronary Artery Calcium Study Investigators are listed in the Acknowledgments section.

Address correspondence to: Matthew A. Allison, MD, MPH, 8950 Villa La Jolla Drive, Suite B-122, La Jolla, CA 92093-0811. E-mail:

©2008The North American Menopause Society