Individualizing therapy to prevent long-term consequences of estrogen deficiency in postmenopausal women.
BACKGROUND
Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions.


OBJECTIVE
To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile.


METHODS
We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects.


RESULTS
Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer.


CONCLUSIONS
Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.
Col
N F
NF
Department of Medicine, Tupper Research Institute, New England Medical Center and Tufts University School of Medicine, Boston, Mass 02111, USA.
Pauker
S G
SG
Goldberg
R J
RJ
Eckman
M H
MH
Orr
R K
RK
Ross
E M
EM
Wong
J B
JB
D019386:Alendronate / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced; D003327:Coronary Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003661:Decision Support Techniques; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000819:agonists / Q000172:deficiency*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D006620:Hip Fractures / Q000517:prevention & control; D006801:Humans; D008017:Life Expectancy; D008055:Lipids / Q000097:blood; D008390:Markov Chains; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010880:Piperidines / Q000627:therapeutic use; D017698:Postmenopause / Q000097:blood*; D020849:Raloxifene Hydrochloride; D012306:Risk; D012307:Risk Factors; D012680:Sensitivity and Specificity
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D008055:Lipids; D010880:Piperidines; D020849:Raloxifene Hydrochloride; D019386:Alendronate