Sex and Gender Differences in Alcohol Use Disorder

1. Sex and Gender Differences in Alcohol Use Disorder

2. At the end of the lecture, you will be able to: • Discuss recommended levels of drinking for males and females. • Define Alcohol Use Disorder (AUD). • Discuss sex differences in pathology seen with alcohol consumption. • Screen for AUD using validated screening tools. • Describe effective treatments for AUD. Objectives

3. What is Normal Drinking?

4. One Drink is:1

5. NIAAA (National Institute of Alcohol Abuse and Alcoholism) Recommendations Differ for Males & Females:1 *keep in mind that “low risk”, which varies between individuals, is not “NO risk”. Drinking Recommendations

6. Alcohol Metabolism

7. The form of alcohol found in the diet is ethanol, C2H6O. Ethanol is absorbed in the upper GI tract, where it enters the hepatic portal system and is taken to the liver for hepatic metabolism.1 Alcohol Metabolism

8. Metabolism:1 Ethanol to Acetaldehyde via alcohol dehydrogenase (ADH) Acetaldehyde to Acetate via aldehyde dehydrogenase (ALDH) Acetate (vinegar) is then converted to Acetyl-CoA, at which point it can participate in the citric acid cycle, lipid metabolism, or ketogenesis. Alcohol Metabolism

9. First Pass Metabolism • First pass metabolism occurs by ADH in the GI • The liver contains an ADH isoform that is active at low ethanol concentrations, and is therefore responsible for metabolizing the majority of ethanol in the body.1 • Large amounts of ethanol exceed the metabolic ability of hepatic ADH, resulting in ethanol reaching the systemic circulation. • Higher first pass metabolism in males has been reported to contribute to lower blood alcohol concentrations (BACs) compared to females, but is considered controversial.1 Alcohol Metabolism

10. Epidemiology of Alcohol Abuse

11. Average age of first drink in surveyed college students:1 16.5 years old Drinking among minors: 2,3 Early Drinking

12. Early drinking has been tied to a greater prevalence of risky consumption and development of Alcohol Use Disorder (AUD).1 • People who start drinking before 15 years of age are four times more likely to meet the criteria for alcohol use disorder later in life.2 Early Drinking

13. 1980’s • Alcohol Use Disorders were 5 X more common in males than females.1 2018 • Alcohol Use Disorders were only 1.8 X more common in males than females.2,3 Sex Differences

14. Females: • Had a later age of onset of alcohol dependence by about 3 years.1 • Are less likely to have undergone previous treatment for alcohol use.1 • Drink less per drinking day.1 • Utilize primary health care providers more often than specialty substance abuse programs for help.1 • Have greater difficulty admitting that drinking harms their health and are less likely to admit their health problems are related to drinking.2 Sex Differences

15. Females: • Heavy/problematic drinking is more common among older females who:1 • Have never married • Remarry • Are married to a spouse who drinks heavily Sex Differences

16. Females: Factors increasing the likelihood females will drink excessively:1 • Blood relatives with alcohol problems • A partner who drinks heavily • The ability to “hold her liquor” more than others • History of depression • History of childhood physical or sexual abuse Sex Differences

17. Relapse rates are similar between males and females.1 • Males • More likely to relapse when unmarried or single1,2 • Marriage protective against relapse2 • Less likely to be married to problem drinker3 Relapse

18. Females • More likely to relapse in the company of friends or romantic partners1 • More likely to be married to a problem drinker1 • Married females are more likely to relapse2,3 • Interpersonal conflict reported as a precipitating event for relapse more often4 Relapse

19. Females who drink alcohol are more likely to develop anumber of conditions, including:1 • Alcoholic hepatitis • Heart disease • Brain damage • Malestalhealth conditions • Liver disease • Traumatic injury • Several forms of cancer: mouth, esophagus, pharynx, larynx, liver, breast, colon, and rectal.2 Health Risks

20. Females • More sensitive than males to all alcohol-related cancers.1 • With as little as one drink per day, females greatly increase their risk for breast cancer.1 • 11% of breast cancers are attributed to alcohol use.1 Cancer

21. Males • Males who use risky levels of alcohol frequently present with co-morbid antisocial personality disorder and dependency on other drugs.1 Psychiatric

22. Females • Psychiatric disorders linked with risky alcohol use are more frequent in females.1 • Alcohol use disorders & co-morbid mood disorders are more prevalent in females.2 • Depressed females may experience stronger cravings to drink than depressed males.3,4 • The desire to drink alcohol when an individual is living with a depressed mood manifests more intensely in females than males.3,4 Psychiatric

23. Fetal Alcohol Spectrum Disorders • Full range of physical, learning, and behavioral problems that result from prenatal alcohol exposure.1 • Fetal Alcohol Syndrome (FAS) is the most serious of these defects. • Leading preventable birth defect in the United States.1 • According to the CDC, prevalence ranges from 0.1 to 1.5 cases per 1,000 live births.2 Birth Defects

24. Fetal Alcohol Syndrome • Characterized by facial dysmorphology, CNS abnormalities, and growth deficiency.1 • Evidence of prenatal alcohol exposure. 2 • Evidence of central nervous system (CNS) abnormalities (structural or functional). 2 • Often characterized by a pattern of three facial abnormalities: narrow eye openings, a smooth area between the lip and the nose (vs. the normal ridge), and a thin upper lip. 2 • Growth deficits can occur either prenatally, after birth, or both. 2 Birth Defects

25. Alcohol Withdrawal Syndrome (AWS) • Chronic alcohol use removes the neural “brakes” and sudden abstinence can cause the brain to be hyper-excitable. • Symptoms may appear within hours of stopping or even lowering alcohol intake. 1 • AWS can present during hospital • stays and confound the presentation • of other medical conditions. • Be aware of alcohol use to • recognize AWS, initiate prophylaxis • promptly, and maximize treatment. Alcohol Withdrawal

26. Alcohol Withdrawal Symptoms:1 • Tremor • Craving for alcohol • Insomnia • Vivid dreams • Anxiety • Hypervigilance • Agitation/irritability • Loss of appetite • Nausea/vomiting • Headache • Sweating • Delirium tremens (DTs), 5% mortality Alcohol Withdrawal

27. Alcohol Withdrawal Management:1 • Step 1: Monitor patient symptoms. • Step 2: Assess with Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scale. • Quantifies symptoms consistent with DT. • Patient’s score determines appropriate treatment. CIWA-Ar Scale: Withdrawal Management

28. Alcohol Withdrawal Pharmacotherapy:1 • Benzodiazepines are the pharmacotherapy of choice for alcohol withdrawal: • Diazepam (long-acting) • Chlordiazepoxide (long-acting) • Lorazepam (short-acting) • Requires concurrent inpatient • monitoring. • In the E.R. or inpatient setting, patients supplemented with normal saline (I.V.), thiamine, glucose, multivitamin with folate, and electrolyte replacement. Withdrawal Pharmacotherapies

29. Alcohol-Related Pathology

30. Males • Males have a higher prevalence of alcohol dependence than females; however, the prevalence of alcohol dependence is rapidly increasing in females.1, 2 General Differences General Differences

31. Females • Females are more susceptible to the toxic effects of alcohol than males.1, 2 • Develop alcohol problems later in life than males.3 • Develop alcohol use disorder faster than males (from first use of alcohol).2 • Female alcoholics have death rates 50-100% higher than those of male alcoholics.3 • Deaths include those from alcohol-related accidents, heart disease, stroke, liver cirrhosis, and suicide. General Differences

32. Alcohol use increases risk of all causes of mortality, even in people drinking lower than recommended amounts. • This is particularly true for young people.1 Cardiovascular Cardiovascular-General

33. Some positive associations between (low risk) consumption of red wine and cardiovascular health do exist.1, 2 • Studies have reported a 30% to 50% coronary risk reduction among moderate drinkers as compared to nondrinkers.1 • 50% of coronary heart disease risk reduction is attributed to alcohol-related increases in HDL cholesterol.1 • Heavy alcohol use, however, increases risk for negative complications.1 Cardiovascular-Possible Benefits

34. Females • In a Nurse’s Health Study, female subjectswho consumed one drink of alcohol per day experienced a 40% reduction in Coronary Heart Disease risk as compared with nondrinkers over a 4 year period.1 Cardiovascular-Possible Benefits

35. However, females and males who do not currently drink should not start drinking as a way to prevent cardiovascular disease.1,2 Further, avoidance of heavy alcohol consumption decreases the risk of first MI and stroke.3 Cardiovascular- Possible Benefits

36. Chronic and binge alcohol use can lead to: • Hypertension.1 • Arrhythmias including atrial fibrillation and ventricular tachycardia.1 • Stroke, even with no preexisting coronary heart disease.1 • Cardiovascular disease.1 • Alcohol use linked to decreased fibrinogen and tissue-type plasminogen activator.2 • Levels of HDL cholesterol, fibrinogen, and hemoglobin A1C accounted for 75% observed correlation between drinking frequency and myocardial infarction in females and 100% in males.2 Cardiovascular-Risks

37. Long-term drinking can lead to alcoholic cardiomyopathy.1,2 • Females are more susceptible to this condition than males. Cardiovascular-Risks

38. Heavy drinking can lead to fat deposition in the liver (steatosis), hepatitis, fibrosis, and even cirrhosis.1 Males A majority of patients who suffer from alcoholic liver disease are male.2 Liver-Risks

39. Females • Significantly higher risk of developing cirrhosis at any level of alcohol intake.1,2 • In a study where subjects consumed 28-41 drinks/week, males were found to have one-third the risk of developing cirrhosis when compared to females.1 • Females only require 20-60 g/day of alcohol to increase risk of developing cirrhosis, while males require 40-80 g/day.1 Liver-Risks

40. Heavy drinking can trigger acute pancreatitis.1 • Over 200,000 people in the United States suffer from acute pancreatitis each year and a large percentage of these cases are due to heavy alcohol consumption.1 • Repeated attacks of acute pancreatitis can lead to chronic pancreatitis.1 • Complications include reduced pancreatic function, reduced digestion, and inability to regulate the blood sugar (diabetes).1 • Death has also been reported.1 Pancreas-Risks

41. Chronic alcohol use tied to global cerebral atrophy and neurodegeneration in males and females.1 Males More susceptible to white matter losses in corpus callosum.2 Brain-Risks

42. Females • More sensitive to degenerative effects of prolonged alcohol dependence and binge alcohol intake.1 • Alcohol-dependent females show greater loss of brain matter, greater loss of brain volume, and increased sulcal and ventricular CSF than alcohol-dependent males.2 • More susceptible to white matter losses in frontal and temporal lobes.1 • White matter recovers more quickly with abstinence.1 Brain-Risks

43. Females • Have a higher risk for hippocampal injury due to binge drinking compared to males, including in:1 • Granule neuron degradation in hippocampus associated with increased loss in both spatial and navigational impairments when compared to males. • Expression of trophic support molecules decreased in females. Brain-Risks

44. Males • Alcohol consumption tied to impotence, infertility, and reduced male secondary sex characteristics.1 • Alcohol inhibits Sertoli and Leydig cell function in testes.1 • High alcohol consumption tied to reduced Testosterone levels in the blood.1 • Alcohol decreases production of LH and FSH from the pituitary gland in males.1 • May also impair hormone secretion from the hypothalamus, which regulates the male sex hormones.1 Reproductive-Risks

45. Females • Alcoholism linked to amenorrhea, irregular menorrhea, infertility, and spontaneous abortions in reproductive aged females.1 • Animal models have shown that high levels of alcohol intake alone can be associated with these gynecological changes.2 • Evidence indicates people who are heavy drinkers have decreased luteinizing hormone (LH) levels.1,2 • Pathologically, the ovaries of animals with amenorrhea resemble those of a menopausal animal suggesting that alcohol-induced amenorrhea could be misinterpreted by a physician or patient as menopause without further information.3 Reproductive-Risks

46. Alcohol Use Disorder

47. Alcohol Use Disorder (AUD) is indicated by the presence of at least 2 of the following symptoms:1 • Alcohol is often taken in larger amounts or over a longer • period than was intended. • There is a persistent desire or unsuccessful efforts to cut • down or control alcohol use. • A great deal of time is spent in activities necessary to • obtain alcohol, use alcohol, or recover from its effects. • Craving, or a strong desire or urge to use alcohol. • Recurrent alcohol use resulting in a failure to fulfill • major role obligations at work, school, or home. Alcohol Use Disorder (DSM V)

48. Alcohol Use Disorder Criteria Continued:1 • Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol. • Important social, occupational, or recreational activities are given up or reduced because of alcohol use. • Recurrent alcohol use in situations in which it is physically hazardous. • Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol. Alcohol Use Disorder (DSM V)

49. Alcohol Use Disorder Criteria Continued:1 • Tolerance, as defined by either of the following: • A need for markedly increased amounts of alcohol to achieve intoxication or desired effect. • A markedly diminished effect with continued use of the same amount of alcohol. • Withdrawal, as manifested by either of the following: • The characteristic withdrawal syndrome for alcohol as defined by DSM 5. • Alcohol (or a closely related substance, such as benzodiazepine) is taken to relieve or avoid withdrawal symptoms. Alcohol Use Disorder (DSM V)

50. The severity of the Alcohol Use Disorder is defined as:1 • Mild: the presence of 2 to 3 symptoms. • Moderate: the presence of 4 to 5 symptoms. • Severe: the presence of 6 or more symptoms. Alcohol Use Disorder (DSM V)