No Increase in Fractures After Stopping Hormone Therapy: Results From the Women's Health Initiative.
The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT.



The purpose of this study was to examine fractures after discontinuation of HT.



Two placebo-controlled randomized trials served as the study setting.



Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period.



Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy.



Total fractures and hip fractures through 5 years after discontinuation of HT were recorded.



Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03).



We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.
Mercy Health Osteoporosis and Bone Health Services, Cincinnati, Ohio 45236.
Nelson B
NB
Watts
Graduate School of Public Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Jane A
JA
Cauley
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210.
Rebecca D
RD
Jackson
Women's Health Center of Excellence, Family Medicine and Public Health, University of California, San Diego, La Jolla, California 92093.
Andrea Z
AZ
LaCroix
Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294.
Cora E
CE
Lewis
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
JoAnn E
JE
Manson
Medical College of Wisconsin Cancer Center Population Science, Division of General Internal Medicine and Center for Patient Care and Outcomes Research, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
Joan M
JM
Neuner
Atlanta VA Medical Center, Decatur, Georgia 30033.|Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.
Lawrence S
LS
Phillips
Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305.
Marcia L
ML
Stefanick
Department of Epidemiology and Environmental Health, University at Buffalo, State University of New York, Buffalo, New York 14214; and.
Jean
J
Wactawski-Wende
Division of General Internal Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
Carolyn
C
Crandall
D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000188:drug therapy*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause; D011379:Prognosis; D028761:Withholding Treatment; D016387:Women's Health