Anorexigen-induced cardiac valvulopathy and female gender

Obesity is a chronic disorder that is associated with significant co-morbidity and early mortality. Since the 1970s, amphetamines and amphetamine analogs have been trialed for weight loss. In 1997, the anorexigen agents, fenfluramine (Pondimin; AH Robins, Richmond, VA) and dexfenfluramine (Redux; Wyeth-Ayerst, Philadelphia, PA) gained worldwide attention when reports of associated cardiac valvulopathy and pulmonary hypertension emerged. A landmark report from the Mayo Clinic describing valvular heart disease (VHD) among women exposed to the anorexigen agent combination phentermine-fenfluramine ignited widespread concern, and the products were voluntarily withdrawn from the market by the manufacturers. Currently, the causal relationship between anorexigen agent use and valvulopathy has been validated, yet the extent and complexity of this important clinical issue remains ill-defined.