Gender Differences in Disease Max Sherman, RPh

Almost everyone knows that women live longer than men. Not everyone is as familiar, however, with the different patterns of disease between the 2 sexes. There are also sexual differences in the perception of pain and even in the response to pharmacologic agents. These facts have led to considering gender an important fundamental variable when designing and analyzing basic and clinical research. It is no longer acceptable to treat research patients as though they are all men. The study of gender differences has evolved into a mature science, and much has been learned over the past decade. Not all of the differences are related to hormones; some are the direct result of the genetic differences between the sexes.  This article will briefly explore how sex affects health, focusing on the cardiovascular, immune, pulmonary, musculoskeletal, and digestive systems. A future article will investigate gender and how it relates to drug response and pain perception. Cardiovascular Disease Normal women are more likely than men to develop early or premature heartbeats and more prolonged periods of arrhythmias. It has been known for quite sometime that certain features of an electrocardiogram (ECG) are normally different in males and females as soon as chil dren achieve puberty. The Q-T interval (the section of the ECG that indicates how long the heart takes to return to a resting state) shortens under the influence of testosterone. Thus sexually mature men’s hearts are more resistant to extra beats than women’s. Estrogen also can make the heart susceptible to abnormal rhythms, and it intensifies the sensitivity of the heart to input from the sympathetic nervous system. ECGs often are not specific enough or sensitive enough for women and are not recommended to screen female patients for coronary artery disease (CAD).1 Women, at least until menopause, have lower blood pressure (BP) while they are awake than men of the same ages, and they experience a bigger dip in BP at night. By about age 60, however, high BP is found more often in women than in men. Male and female hearts respond differently to hypertension. The left ventricle has a different pattern of enlargement in the 2 sexes as the result of hormones. Cardiovascular disease is more severe in women, and women are more likely to die from a first heart attack.  After a myocardial infarction (MI), women younger than 65 years are more than twice as likely to die as men of the same age. There is also a difference in the symptoms of an MI. Men more often present with ventricular tachycardia, and women with cardiogenic shock and cardiac arrest.2,3  Women manifest symptoms of coronary heart disease 10 to 20 years later than men and have a higher prevalence of primary risk factors.2,4,5  Physicians are just beginning to become aware that the risk factors, clinical presentation, testing modalities, therapeutic choices, and consequences of CAD are not identical in men and women.1 Immune Diseases Some autoimmune diseases are vastly predominant in women, others are not predominant in either sex, and still others are predominant in men. Included in the first category, in descending order, are Hashimoto thyroiditis, primary biliary cirrhosis, chronic active hepatitis, Graves’ hyperthyroidism, systemic lupus ery-thematosus, scleroderma, rheumatoid arthritis, and multiple sclerosis. Pemphigus and type 1 diabetes are evenly divided between women and men. Ankylosing spondylitis and Goodpas-ture’s syndrome are much more common in men.6 Some experts have thought that hormonal changes (ie, estrogen-enhanced immunologic activity) are partly responsible for these differences. Research has found, however, that rheumatoid arthritis goes into remission during pregnancy. This change is likely due to a human leukocyte antigen mismatch between the mother and the fetus rather than to pregnancy-associated hormones.7,8  Multiple sclerosis also goes into remission during pregnancy.9  Why and how hormones influence disease incidence is unclear. Hormones also may influence the frequency of autoimmune disease in men and women in ways that are independent of the immune system.7 Pulmonary Diseases Women’s lungs are smaller than those of men even when adjustment is made for the smaller size of women’s bodies.1  Women also have lower blood levels of hemoglobin and less residual lung volume. Lung cancer, chronic obstructive pulmonary disease, asthma, pulmonary hypertension, and sleep apnea have disproportionately more severe and unusual symptoms in women. Women who smoke are 3 times more susceptible to lung cancer than male smokers of the same age. Oddly enough, for the same number of cigarettes smoked, women have a 20% to 70% higher risk of developing lung cancer than men. Women have more sensitivity to the cancer-causing substances in cigarettes.10 More than 14 million Americans suffer from asthma, which ranks sixth among chronic diseases.1 Between 1982 and 1992, asthma increased by 82% in women and by only 29% in men. Hormones appear to have a striking effect on the severity and timing of asthmatic attacks. Asthmatic women near the beginning of the menstrual cycle had 4 times as many emergency room visits as other asthmatic women. The lower concentration of estrogen immediately prior to menstruation affects drug metabolism, and bronchodilators are less effective at that time as well. Primary pulmonary hypertension occurs almost exclusively in young and middle-aged women. The cause may be a defect in the cells that line the pulmonary blood vessels and may be the result of a defective gene. Musculoskeletal Disease In midlife, bone mass is relatively constant in both sexes. At menopause, however, women undergo a period of particularly rapid bone loss due to a marked increase in bone resorption that is not balanced by increased bone production. Reduced levels of estrogen are partly responsible.1  Bone loss is most rapid in the first few years after menopause but persists into the postmenopausal years. Osteoporosis (thinning or porous bone) develops when bone resorption occurs too quickly or if replacement of new bone occurs too slowly. Osteoporosis also can occur in men, but it is less common than in women. Of the 44 million Americans with osteoporosis, 68% are women.11  Men are less affected because they have larger skeletons, bone loss starts later and progresses more slowly, and there is no period of rapid hormonal change and accompanying rapid bone loss. Digestive Diseases The gastrointestinal (GI) tract has a number of gender-specific characteristics. Food, for example, takes longer to pass through a woman’s GI tract than through a man’s.1  Bile from a woman’s liver is different from a man’s bile, and there is a higher incidence of gallstones in women. Approximately 6 times as many women as men suffer from irritable bowel syndrome. Gastroesophageal reflux disease (GERD) is marginally more common in women, but the disease is more serious in men.1  Pregnant women are at an increased risk for GERD, possibly because of the impact of their high progesterone levels on esophageal contractions. Men are more likely to develop duodenal ulcers. The reason is that men secrete more stomach acid than women, possibly because testosterone stimulates the acid-producing cells of the stomach. On the other hand, estrogen is known to suppress acid secretion, and progesterone may have an added protective effect on the gastric lining. The opposite effect occurs in the pancreas. Estrogen and progesterone seem to protect women from pancreatic cancer. Men are 3 times more likely to contract this disease than women. Final Thoughts The past decade has witnessed a number of new discoveries in basic human biology, and it has been shown that many normal physiologic or pathologic functions are influenced by sex-based differences. Pharmacists will be learning more about the gender differences in the prevalence and severity of a broad range of diseases. The new knowledge also will be used to design gender-specific drug therapy. For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Campagnola, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dcampagnola@mwc.com. Note: This article is taken from http://www.pharmacytimes.com