Is hormone replacement therapy protective for venous ulcer of the lower limbs?

OBJECTIVE

Estrogen has been found to increase the risk of deep vein thrombosis (DVT), which is associated with venous ulcers. A matched case-control study was therefore performed to quantify the effect of hormone replacement therapy (HRT) on the occurrence of venous ulcers of the lower limbs.

METHODS

Women presenting to a participating vascular surgery department between January and December 1997 with a first open venous ulcer served as cases. Controls were sampled among women with sub-acute conditions such as skin problems, cold, headache/migraine, sore throat and mild ear infections, and were matched on referral site and age (+/- 5 years). Subjects were eligible for this study if they were postmenopausal, and excluded if they had non-palpable pedal pulse or any chronic active diseases. The study consisted of an interviewer-administered risk factor questionnaire. Conditional multivariate logistic regression analyses were performed adjusting for history of DVT and unbalanced distributions in important covariates.

RESULTS

Forty-four cases and 80 matched controls were recruited. The mean age of participants was 64 years. HRT users were significantly thinner (27% with body mass index (BMI = (kg/height (m2)) > or = 27 vs. 41%, p = 0.04) and less likely to have a history of DVT (12 vs. 33%, p = 0.02) and varicose veins (VV) (52 vs. 69%, p = 0.04) than non-users. A matched univariate logistic regression analysis was performed to quantify the effect of HRT on venous ulcers and generated an odds ratio (OR) of 0.14 with 95% confidence interval of (0.04, 0.49)95%: adjusting for prior DVT resulted in an OR of 0.29 (0.09, 0.93)95%. When adjusting for BMI, history of VV, exercise, education, and smoking, the OR observed was 0.03 (0.01, 0.13)95%: further adjustment for prior DVT gave an OR estimate of 0.06 (0.01, 0.50)95%CI.

CONCLUSIONS

Our study demonstrates that HRT has a protective effect on the occurrence of venous ulcers of the lower limbs. Adjusting for prior DVT moves the estimate closer to the null. DVT is a strong contraindication for HRT and therefore must be considered in order to eliminate confounding by contraindication.