New therapies, new diagnostic tools and even new diseases threaten to overwhelm busy family physicians. Keeping up is hard work. Compounding the task is the fact that physicians have to learn some diseases twice—once for women and once for men.

Conscientious physicians appreciate that the incidence and prevalence of certain diseases vary with gender. They are also aware that some conditions have widely different presentations, respond to different therapies or have different effects and outcomes in women compared with men. Nonetheless, the situation is enough to cause physicians to throw up their hands, much like Professor Henry Higgins in My Fair Lady, and lament, “Why can't a woman be more like a man?^” Or, depending on their gender bias, “Why can't a man be more like a woman?^”

Cardiovascular disease is one area in which there are significant differences between the sexes. As Bedinghaus and associates¹ outline in this issue of American Family Physician, the presentation of cardiovascular disease is surely gender based. Compared with men, women less often have classic anginal symptoms. Instead, they frequently present with the more subtle complaints of fatigue, breathlessness, nausea and aching in the neck, one or both shoulders and/or one or both arms.² These symptoms are more likely to be misinterpreted or even discounted by women and their physicians. Atypical presentation is one reason that the diagnosis of cardiovascular disease is often delayed and the initial outcome is poorer in women.³

Clinical trials investigating primary and secondary prevention of cardiovascular disease have inadvertently or even systematically excluded women from participation. As a result, treatment of cardiovascular disease in women has been based on data derived from men.⁴ Efforts to correct this misstep have been under way for the past decade. Trials now include women, and several trials directed specifically toward women have been undertaken. These latter trials have focused on the role of estrogen in the prevention or treatment of cardiovascular disease in women.

Estrogen is thought to be the most important difference between men and women with regard to cardiovascular disease. Loss of estrogen-related protection is possibly the reason for the increased incidence of cardiovascular disease after menopause.³ The effect of estrogen replacement in primary and secondary prevention of cardiovascular disease has strong observational and epidemiologic support. Even the Heart and Estrogen/progestin Replacement Study (HERS)⁵ did not unconditionally discount a therapeutic role for estrogen replacement.

In HERS,⁵ the lack of overall protection against heart disease from estrogen replacement, which caused consternation among advocates of estrogen replacement therapy, resulted mostly from adverse effects in the first year of therapy. These early adverse effects may reflect more aprocoagulation effect of estrogen than a lack of beneficial effect on lipids. Because cardiovascular events actually decreased in the estrogen group after the initial period, a partial salutary effect of estrogen might still be construed. Other studies using estrogen and estrogen-progestin therapies are ongoing, with results expected in the next five to six years.

Until recently, clinical drug trials for primary prevention of cardiovascular disease had not included enough women for treatment conclusions to be made. The well-designed Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)⁶ used drug intervention with a statin in men and women who had “average” total and low-density lipoprotein cholesterol levels and a slightly low high-density lipoprotein cholesterol level. In the AFCAPS/TexCAPS trial, a reduction of primary cardiovascular events was demonstrated in both sexes.

Differences remain in many important issues related to cardiovascular disease. The influence of concurrent conditions and lifestyle features, especially diabetes, smoking, systolic hypertension and exercise appears to be stronger in women. Despite the emergence of evidence-based recommendations for lipid-lowering therapy in women, data continue to indicate that women may be undertreated.⁷ It appears that the prevention, diagnosis and treatment of cardiovascular disease may never be completely gender blind.