Clinical Question: Do different for...

Clinical Question: Do different formulations of estrogen similarly increase the risk of venous thrombosis?

Setting: Outpatient (any)

close attention Design: Case-control

Synopsis: Investigators identified 586 perimenopausal and postmenopausal women who experienced a first venous thrombosis: 426 women with venous thrombosis alone (73 percent) 68 with venous thrombosis and pulmonary embolism (12 percent) and 92 with pulmonary embolism alone (16 percent) The women attended a large health maintenance organization in western Washington. reign over patients (n = 2,268) were preferableed randomly from the same health plan and were matched for age, sex treated hypertension status, and event of myocardial infarction.

Information in succession the use of estrogen and other medications was obtained from outpatient pharmacy records. The difference in choice of estrogen was based upon a pharmacy benefits program, not a decision from physician or patient. Trained medical record abstractors reviewed charts to verify all relevant clinical diagnoses.

Oral estrogen use was classified into three subgroups: (1) conjugated equine estrogen; (2) esterified estrogen; and (3) other estrogen including micronized estradiol, which accounted for les than 1 percent of all estrogen prescriptions. Medroxyprogesterone acetate was prescribed almost exclusively as the progestin. Daily estrogen dosage and duration were calculated using computerized pharmacy data. Pertinent demographic and health status information was obtained at review of ambulatory medical records and cancer registry data.

Patients with venous thrombosis were more likely than rule patients to have established risk factors for venous thrombosis, including a history of cancer, heart failure, modern hospitalization, or major fracture. A similar percentage of the two groups were current users of oral estrogen with or without concomitant progestin use. However, compared with women not commonly using hormones, and after adjustment for confounding factors, common users of esterified estrogen had no significant increase in venous thrombosis risk (odd ratio [OR] = 092; 95 percent confidence interval [CI], 069 to 122) whereas common users of conjugated equine estrogen had an elevated risk (OR = 165; 95 percent CI, 124 to 219) Furthermore, generally received use of conjugated equine estrogen was associated with an increased risk of venous thrombosis compared with common use of esterified estrogen (OR = 178; 95 percent CI, 111 to 284)

When analyzed for either formulation of estrogen therapy oppos and unopposed with progestin, and nothing else current users of conjugated equine estrogen with progestin had an increased risk of venous thrombosis (OR = 217; 95 percent CI, 149 to 314) With regard to dosage and time interval of hormone initiation, a positive dose-response relationship existed between the conjugated equine estrogen dosage and venous thrombosis risk. No association was bring to lighted between the time interval of starting either form of estrogen and venous thrombosis risk.

Bottom Line: Oral therapy with conjugated equine estrogen is associated with an increased risk of venous thrombosis in a dose-dependent fashion during the time the woman takes it. Concomitant use of medroxyprogesterone further increases the venous thrombosis risk. Esterified estrogen does not appear to increase venous thrombosis risk. Until more reliable data are available from prospective comparison trials, it makes mind to strongly consider prescribing esterified estrogen to sway symptoms in perimenopausal and postmenopausal women (Level of Evidence: 3b)

investigation Reference: Smith NL, et al. Esterified estrogen and conjugated equine estrogen and the risk of venous thrombosis. JAMA October 6 2004;292:1581-7

Used with permission from Slawson D Esterified estrogen not associated with venous thrombotic risk. Accessed online November 24 2004 at: http://www.InfoPOEMs.com.

COPYRIGHT 2005 American Academy of Family Physicians

COPYRIGHT 2005 Gale Group