2-Methoxyestradiol: A Potential Treatment for Multiple Proliferative Disorders

Evidence from several epidemiological studies suggests that endogenous human estrogens as well as estrogen replacement therapy protect women from progression of cardiovascular disease (1–3). Additional evidence for a cardioprotective action of estrogens comes from multiple animal studies and small clinical trials (1–3). In contrast, the outcomes of two large randomized clinical trials [Heart and Estrogen/progestin Replacement Study (HERS) and Women’s Health Initiative (WHI)] failed to demonstrate protection against cardiovascular disease by exogenous estrogens (4, 5). Several explanations could account for these divergent findings (3). In this regard, some argue that the HERS and WHI studies were negative because they used conjugated equine estrogens, which is a mixture of horse estrogens containing negligible amounts of estradiol, the major endogenous human estrogen. Others speculate that the HERS and WHI studies were negative because the participants were older women with established cardiovascular pathology. Still others speculate that the oral route of administration of estrogens leads to inflammation and that the transdermal route would be cardioprotective (3).