Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial.
Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.


BACKGROUND
The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented.


METHODS
Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk.


RESULTS
CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42).


CONCLUSIONS
CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.
Jackson
Rebecca D
RD
Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, OH 43210, USA. jackson.20@osu.edu
Wactawski-Wende
Jean
J
LaCroix
Andrea Z
AZ
Pettinger
Mary
M
Yood
Robert A
RA
Watts
Nelson B
NB
Robbins
John A
JA
Lewis
Cora E
CE
Beresford
Shirley Aa
SA
Ko
Marcia G
MG
Naughton
Michelle J
MJ
Satterfield
Suzanne
S
Bassford
Tamsen
T
D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D017698:Postmenopause; D012307:Risk Factors; D016896:Treatment Outcome; D016387:Women's Health
D004966:Estrogens, Conjugated (USP)