Acquired protein S deficiency caused by estrogen treatment of tall stature

Objective: To evaluate the potential thrombogenic changes in the coagulatio n and fibrinolytic system related to treatment with ethinyl estradiol (200 and 300 mu g). Subjects and methods: Twenty-five healthy girls with expected final height exceeding 185 cm, as calculated by the method of Bayley and Pinneau, were t reated with 200 mu g or 300 mu g of ethinyl estradiol. Coagulation and fibr inolytic parameters were determined before and during estrogen treatment an d 2 and 4 weeks after estrogen withdrawal. Results: No difference in the effects on hemostasis was found between the 2 treatment groups. All 25 patients developed protein S deficiency during es trogen treatment, which in most girls lasted for 4 weeks after cessation of estrogen administration. During therapy, protein C activity increased, whe reas antithrombin did not change. Plasminogen and plasmin-alpha(2) antiplas min complexes significantly increased. Protein S deficiency was accompanied by significantly increased prothrombin fragment 1+2 and fibrinopeptide A. In contrast, thrombin-antithrombin complexes did not change. Conclusion: High-dose estrogen treatment to reduce the final height in tall girls is associated with a reversible acquired protein S deficiency with i ndications of a pre-thrombotic state. Risk of venous thrombo-embolism may b e enhanced, especially when additional risk factors for thrombosis are pres ent.