Obesity and Venous Thromboembolism
The annual incidence of VTE is 2 per 1000 individuals in the United States with incidence rising with increasing age. The precise number of individuals affected by VTE, however, is not well known. VTE is a multifactorial disease related to the interaction of several genetic and environmental factors. Genetic predisposition to VTE is associated with inherited thrombophilias resulting from deficiencies in intrinsic anticoagulants (such as protein C and protein S) or excesses of procoagulants (such as factor V Leiden and prothrombin). Recent surgery, smoking, prolonged immobilization, and pregnancy are also recognized as risk factors for VTE.
Individuals diagnosed with VTE are typically treated with anticoagulant therapy for a minimum of 6 months. Among reproductive-age women, anticoagulant therapy has been associated with menorrhagia and rarely with hemoperitoneum following ovarian cyst rupture. Bleeding is the most commonly noted complication of patients on chronic anticoagulation; the risk of major hemorrhage while on anticoagulation is as high as 7% per year.[53,54]
Combined OC use is a risk factor for deep vein thrombosis (DVT) through changes in the coagulation cascade. The estrogen component leads to increases in levels of fibrinogen and of coagulation factor, specifically factors VII, VIII, and X. This increase causes a procoagulant effect and thereby causes hypercoagulability.[55,56,57,58,59] Along with these changes in procoagulant factors there occurs a corresponding decrease in coagulation inhibitors (antithrombin, protein S, and activated protein C resistance). The magnitude of these changes is modest, usually not out of the range of controls, but are sufficient to lead to a prothrombotic state. Most progestins are not associated with changes in the coagulation factors or fibrinolytic variables. Third-generation progestins, however—specifically, desogestrel and gestodene—are associated with lower levels of antithrombin and higher levels of coagulation factors as compared with second-generation progestins.[58,59,60]
Obesity is an independent risk factor for the development of VTE. It has been shown to cause an increase in the procoagulant factors like factor VII, factor VIII, factor XII, and fibrinogen. These levels increase with increasing BMI. In addition, there may be an additive risk caused by venous stasis that also occurs with obesity. A survey of medical outpatients revealed that patients with a BMI >30 kg/m2 had a twofold increase in risk for DVT. Most other reviews of data examining the magnitude of increase in risk with use of OC in obese women found an additive increased risk of VTE.
Use of combined OCs is associated with increased risks of VTE in obese patients. Multiple case-control studies have revealed this increased risk. An example of one includes a population-based case-control study that was performed in The Netherlands of a group of patients with a diagnosis of VTE; controls were either male partners of these patients or controls found by random-digit dialing. Of 454 patients and controls, 261 (57.5%) were women. One hundred and seventy-five women were using OCs at time of diagnosis. Obese subjects had double the risk of thrombosis (OR, 2.3; 95% CI, 1.5 to 3.4), but obese subjects who used OC had a 10-fold increase in risk (OR, 9.8; 95% CI, 3.0 to 31.8). Normal weight women and even overweight women using OC had no appreciable increase in risk of VTE (OR, 1.0 (ref); OR, 0.9; 95% CI, 0.4 to 2.0, respectively).
Semin Reprod Med. 2010;28(2):156-163. © 2010 Thieme Medical Publishers
Cite this: Obesity and Contraception: Emerging Issues - Medscape - Mar 01, 2010.