Fact Sheet: Sex Differences in Response to Pharmaceuticals, Tobacco, Alcohol and Illicit Drugs
Pharmaceuticals (Prescription & Over-the-counter Drugs)
Differences in Reaction to Pharmaceuticals
- Basic physiological differences between men and women may influence their reactions to drugs. Women generally have lower body weight and organ sizes, and a higher percentage of body fat.4, 6
- Diazepam, a muscle relaxant that is often used to treat epilepsy, impairs the psychomotor skills (control of voluntary movements) of women more than men.7 These differences may be linked to lower body weights in women.4, 8
- Sex differences in drug reactions may also be caused by differences in the way in which men and women process drugs at the molecular level. The transport of drugs within the body and the enzymes that metabolize drugs may be particularly important in affecting drug reactions.4, 6
- Verapamil, a drug prescribed for high blood pressure, and the antibiotic erythromycin appear to be more effective in women than men. Several studies have suggested that these differences are due to an increased activity rate of the liver enzyme CYP3A4 in women. CYP3A4 is responsible for metabolizing more than 50 percent of pharmaceutical drugs.9-11 However, recent studies suggest that these sex differences may not be caused by the increased activity of CYP3A4, but by the reduced activity in women of the molecules (P-glycoproteins) that transport drugs out of the liver. This reduced transport activity makes higher concentrations of a drug available to CYP3A4 in the liver, allowing the enzyme to process more of the drug.4, 6
- Selective serotonin reuptake inhibitors (SSRI), which are used to treat depression, appear to be maintained at higher blood concentrations in women than in men. It is thought that the concentration differences are related to gender-related activity of CYP liver enzymes, such as CYP1A2 and CYP2C19. A correlation between these concentrations and their effectiveness as antidepressants has not yet been found.6
- The way antidepressant medications are absorbed, distributed, and eliminated by the body can be different in women and men. This fact may necessitate more dosage adjustments in women than in men to ensure favorable drug response, compliance, and decreased incidence of adverse events.12 Monthly hormone cycles in women may also influence the effectiveness of some antidepressants, further complicating treatment for women.13
- Sex hormones appear to influence the effects of many drugs. Thus, the menstrual cycle, pregnancy, and menopause can affect how drugs react in women’s bodies. Additionally, drugs such as oral contraceptives and hormone replacement therapy may alter drug interactions in women.17, 18
- Acetominophen is inactivated (conjugated) nearly 50 percent more in women taking an oral contraceptive compared with controls.4
- Women wake up from anesthesia (combination of propofol, alfentanil, and nitrous oxide) faster than men, and three times more women than men complain of being awake during surgery, suggesting that women are less sensitive to intended effects of the drugs.19 However, women appear to be more prone to the side effects of anesthetic drugs. Postoperatively, women are more likely than men to suffer vomiting or nausea, or to report headaches and backaches. Women also have a 25 percent slower rate of return to their preoperative health status. These differences may partially be caused by the effects of sex hormones on the cellular targets of anesthetics.20
- The anesthetics atracurium and vecuronium affect women and men differently. Women are much more sensitive to the neuromuscular blocking activity of both drugs.21, 22
- Certain types of painkillers, called kappa opiates, are more effective in providing post-operative pain relief in women than in men receiving the same treatment.23-25
- When compared with placebo, ibuprofen is less effective at providing analgesic relief for women than for men during experimentally induced pain situations.26
Sex Differences in Adverse Events
- Of the ten prescription drugs withdrawn from the United States market between January 1997 and December 2000, eight caused statistically greater health risks for women than men. For four of these eight drugs, the higher statistical risk for women may be accounted for by the fact more women than men took the drug. In four cases where drugs were more evenly prescribed to men and women, the higher risk for women may be linked to physiological differences between the sexes.1, 2
- Although men and women report about the same number of adverse events related to treatment with therapeutic drugs, those reported for women are more serious. These differences could be caused by differences in the way that men and women report adverse drug events. However, there are a number of potential factors that might explain the increased risk of serious adverse drug reactions in women, such as sex-related differences in physiology and in the way in which drugs are absorbed, metabolized, and eliminated by the body. Gender-related differences in the use of medications may also explain the higher risk for serious adverse reactions in women.3, 4
- Women consume more medications than men, including over-the-counter medications, herbal remedies, and vitamins, which may put them at higher risk for adverse drug reactions.4
- Female patients have a 1.5- to 1.7-fold greater risk of developing an adverse drug reaction compared with male patients due to differences in pharmacokinetic, immunological, and hormonal factors. Moreover the use of multiple medications is higher in women.66
- A number of anti-psychotic drugs, including chlorpromazine and fluspirilene, appear to be more effective in women than men at the same dosage. However, they may also induce more adverse events in women.4
- A much higher percentage of women than men develop the life-threatening ventricular arrhythmia torsades de pointes after taking a variety of drugs, such as antihistamines, antibiotics, anti-malaria drugs, antipsychotics, and cholesterol lowering drugs.14-16
Sex Differences in Prescription Drug Abuse
- Women are 48 percent more likely than men to use any abusable prescription drug, possibly because women are more likely to have a regular doctor than men.5
- Tobacco is responsible for 17 percent of all female deaths in the United States.27
- Most deaths attributable to tobacco are from lung cancer, coronary heart disease, and chronic airway obstruction.28
Smoking Behavior Differences
- Men and women may start smoking for different reasons. Men report starting to smoke to be more energetic and alert, whereas women start smoking for stress reduction.29
- Although fewer adult women than men smoke, the gender gap is decreasing as the number of male smokers declines at a rate faster than the number of female smokers.28, 30
- Although high school girls and boys use tobacco products at approximately equal rates,28 among those who do not smoke, girls were 54 percent more likely than boys to report that they had considered smoking and therefore could be more susceptible to advertisements for tobacco products.31
- Females appear to be more sensitive to second-hand smoke than males.35
Tobacco Use & Risk for Disease
- Women are more susceptible to tobacco-induced carcinogenesis than men.
- Smoking appears to have a more detrimental effect on cardiovascular disease in women than in men.35
- The risk of both illness and death from heart disease due to second-hand smoke in the workplace is higher in women than in men.35
- Compared to those who have never smoked, women aged 35-52 who smoke 20 cigarettes per day have a six-fold increased risk of heart attack, while male smokers have a three-fold increased risk.35, 43
- Although women are not typically prone to coronary heart disease (CHD) before menopause, smoking greatly increases the risk of CHD in younger women, likely by inhibiting the amount of estrogen available in the body.35
- Smoking appears to increase levels of LDL cholesterol (“bad” cholesterol) in women much more so than in men.35, 44
- Smoking appears to increase the risk of stroke in women two- to four-fold, in proportion to the amount smoked.35
- Women who smoke are more likely to develop chronic obstructive pulmonary disease (COPD) than their male counterparts,45 and are more likely to have symptoms of COPD at lower levels of tobacco smoke exposure.46
- Smoking appears to increase the risk of diabetes more for women than for men. Among those who smoke two or more packs per day, women have a 74 percent higher diabetes rate than women who have never smoked; the corresponding increase for men is 45 percent.35, 47
- Girls born to mothers who smoke have worse lung function than comparable boys.48
Effect of Nicotine on Women
- Nicotine appears to enhance aggressive moods in men, but to have calming effects on stress-induced mood changes in females.33
- When women smoke and drink alcohol, the nicotine appears to enhance the effects of alcohol. In men, the nicotine appears to dilute some of the sedating and intoxicating effects of alcohol.34
- Women may be more responsive than men to non-nicotine stimuli associated with smoking, such as social and behavioral cues.35-40
- Women are less successful than men in quitting smoking, although they join smoking cessation groups more often than men for social support.41
- Women experience more severe withdrawal symptoms than men when quitting smoking.29
- Women are less likely than men to benefit from nicotine replacement therapy.29
- The non-nicotinic smoking cessation medication bupropion appears to be equally effective for men and women.42
- Women who quit smoking relapse for different reasons than men. Stress, weight control, and negative emotions are reasons cited by women for relapse.41
Sex Differences in Addiction
- Socioeconomic status is a prominent predictor of alcohol dependence among men, while family history of alcohol disorders is a stronger predictor among women.49
- Female alcoholics are more likely to die from suicide, alcohol-related accidents, circulatory disorders, and cirrhosis of the liver than male alcoholics.57
- Female alcoholics report significantly greater depression, anxiety, and neuroticism compared to their male counterparts, and female problem drinkers report significantly greater depressive symptoms and health-related stressful events compared to male problem drinkers and light drinkers.68
Effects of Alcohol on Women
- Younger women naturally produce less of the gastric enzyme alcohol dehydrogenase, which breaks down ethanol in the stomach. As a result, after consuming comparable amounts of alcohol, women under 50 have higher blood alcohol content than men of the same age, even with allowance for size differences.50, 51
- Alcoholic women do not break down fatty acids as well as alcoholic men. This may lead to accumulation of fatty acids in the alcoholic woman’s liver, thereby potentially explaining why women develop alcoholic liver disease, particularly alcoholic cirrhosis and hepatitis, after a comparatively shorter period of heavy drinking and at a lower level of daily drinking than men.52, 53
- Women who consume more than two alcoholic drinks per day are more likely than non-drinkers to develop breast cancer, hypertension, and stroke. Women who drink heavily are more likely to experience infertility and miscarriage.54
- Women are susceptible to alcohol-related heart damage at lower levels of alcohol consumption than men.55
- Alcoholic women experience reduction in the size of one portion of the brain, the corpus callosum, whereas alcoholic men do not. This result suggests that women are more sensitive to alcohol-induced brain damage than men.56
- Women typically begin abusing substances later than men, are strongly influenced by peers to use, report different reasons for maintaining the use of substances, and enter treatment earlier in the course of their illnesses than their male counterparts. Substance-abusing women also typically have a higher prevalence of psychiatric disorders such as depression and anxiety than substance-abusing men.58
Effects of Drug Use
- The electric potentials within men’s brains, as measured by electroencephalograms (EEGs), are changed by cocaine use; cocaine-using women experience no such change.59
- Abnormalities in the amount of blood flow have been observed in male cocaine-user’s brains, while no such abnormalities appear in female cocaine-user’s brains.60
- Women are less likely than men to experience symptoms such as paranoia/suspiciousness and heart racing/pounding when smoking cocaine. In addition, when in the post-ovulation phase of the menstrual cycle, women get less “high” from cocaine than in the pre-ovulation phase.61
- After taking cocaine, women retain higher blood concentrations of the drug than men.62
- Women who take amphetamines perceive the effects of the drug differently depending on which phase of the menstrual cycle they are in.63, 64
- Results of one study indicated that heavy use of MDMA (ecstacy) is associated with neurotoxic effects on serotonin neurons to which women might be more susceptible to than men. MDMA-induced neurotoxic changes in several brain regions of female ex-MDMA users are reversible.69
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