Jack H. Mendelson

Effects of Drugs of Abuse on Reproductive Function in Women and Pregnancy

In the United States, the prevalence of substance use and abuse in women has been increasing over the last 20 yr. According to a 1984 survey in three major metropolitan areas sponsored by the National Institute on Mental Health (NIMH), alcohol abuse and dependence ranked fourth among psychiatric disorders in women aged 18–24, and drug abuse and/or dependence was the second most common psychiatric disorder among women aged 18–241,2In a National Household Survey conducted in 1991, more than half (57.8 and 52.8%, respectively) of all women ages 18–25 and 26–34 yr reported that they had used alcohol during the previous month, and more than 1 in 10 women surveyed in these age groups (13.4 and 11.2%, respectively) had used some illicit drug during the same interval.3Prevalence estimates for alcohol, marijuana, cocaine, and heroin use are presented in Fig. 1. However, these figures may be underrepresented as this was a household survey and the prevalence of substance abuse may indeed be higher in women who have comprised socioeconomic status.

Ethnic/religious differences in the manifestation and treatment of alcoholism

A rather extensive literature now exists documenting the extent to which patterns of drinking and rates of alcoholism differ across cultural, religious, and racial boundaries (Everett er al., 1976). An important assumption underlying much of this literature is that socially learned norms, values and attitudes exert a powerful influence on drinking behavior, and that some “drinking subcultures” are more conducive than others to the development of alcoholism (Greeley et al., 1980). With a few exceptions (Westermeyer, 1974; Kane, 1981; Wanberg et al., 1978) comparative studies have focused their attention on noninstitutionalized drinkers identified through population surveys or ethnographic studies of a community. Perhaps because the word alcoholism implies the existence of a unitary disease syndrome, considerably less attention has been devoted to the study of differences in the symptoms of institutionalized alcoholics belonging to different drinking subcultures. Such an approach would seem to be important for practical as well as theoretical reasons. First, cultural factors may affect how alcohol problems are defined, what criteria are used to diagnose alcoholism, and how persons with alcohol problems gain access to treatment. Second, cultural factors may influence the etiology of different types of alcoholism. For example, culturally patterned differences in drinking styles, beverage preferences, and dietary habits have been advanced as possible explanations for differences observed in cross-national comparisons of alcoholics (Lolli et al., 1958; Babor et al., 1974). Third, to the extent that cultural factors are deemed to be important in the mainifestation of only certain kinds of alcoholic symptoms, this in itself may help to identify a common core of “biosocial universals” characterizing all alcoholics. Finally, cultural identification may influence the patient’s response to treatment. Modes of treatment may differ in their appropriateness for various population groups. Treatment personnel may respond differentially to patients by using ethnic stereotypes

Alcohol and Reproductive Hormones in Women

Alcohol use and abuse is very prevalent among women of reproductive age. According to a 1984 survey sponsored by the National Institute on Mental Health (NIMH),1 in three major metropolitan areas alcohol abuse and alcoholism were the fourth most frequent of all psychiatric disorders among young women ages 18-24. Women accounted for 24% of 10,000 first admissions to a proprietary hospital for alcoholism treatment.2 In a National Household Survey conducted in 1992,3more than half of all women ages 18-25 and 26-34 yr (53.0 and 52.8%, respectively) reported that they had used alcohol during the previous month, and 9.5 and 7.6% of these women also reported using some illicit drug during the same interval. However, these figures may be an underrepresentation, since this was a household survey and the prevalence of alcohol and substance abuse may indeed be higher in women with compromised socioeconomic status.4

Marihuana Effects on Pituitary and Gonadal Hormones in Women

A series of studies were carried out to assess the acute and chronic effects of marihuana smoking on pituitary and gonadal hormone levels in women. Plasma samples for analysis of luteinizing hormone (LH), estradiol, progesterone, and prolactin were obtained from 16 women prior to and following smoking one marihuana cigarette that contained 1.8% THC or a 1-g placebo cigarette. A small but statistically significant decrement (p < 0.02) in LH levels was observed following marihuana smoking in contrast to placebo smoking during the luteal phase of the menstrual cycle. However, the decrease in LH probably was not biologically significant since all LH levels were within the normal range for healthy adult women. Marihuana smoking was also followed by a small but statistically significant decrease in prolactin levels during the luteal phase of the menstrual cycle, but this probably was not biologically significant. The hormonal effects of daily marihuana smoking over 21 days were studied in 21 women who lived on a clinical research ward for 33 days. Women worked at a simple operant task to acquire marihuana cigarettes. Each marihuana cigarette contained 1.8% Δ9-THC. Blood samples for analysis of LH, estradiol, and progesterone were collected on alternate days before, during, and after marihuana smoking. Normal ovulatory menstrual cycles were observed, and there was no evidence of a marihuana dose-related suppression of ovulation or disruption of luteal phase function in women classified as heavy (6.1 ± 1.45 cigarettes per day), moderate (2.72 ± 0.16 cigarettes per day) or occasional (0.90 ± 0.22 cigarettes per day) marihuana smokers. These data indicate that smoking marihuana at the dose levels observed for 21 days did not disrupt the menstrual cycle in healthy adult women.

Effect of Opiates on Neuroendocrine Function Testosterone and Pituitary Gonadotropins

Among chronic opiate users, disturbances in sexual function are now commonly recognized clinical phenomena. In males, diminished libido, impotence, and delayed ejaculation have been described,(1) while amenorrhea and decreased fertility have been reported among female users of opiate drugs.(2) These observations have led to investigations of the effects of opiates on the pituitary gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and on the primary secretions of the end organs they influence (i.e., testosterone and estrogens). To date, most of these studies have utilized animal models. More recently some investigators have turned their attention to the effects of opiates in man.

Neuroendocrine Concomitants of Alcohol Reinforcement

The specific neural mechanisms underlying alcohol-induced changes in mood and feeling states are unknown. Although experimental animal studies have shown that many biologic processes in the brain are affected by ethanol, it appears unlikely that any single neurochemical or neurophysiologic system uniquely determines its reinforcing properties. At present, we postulate that multiple physiological, psychological and sociocultural factors enhance or reduce the probability for initiation and perpetuation of alcohol abuse by humans.

Effect of Opiates on Neuroendocrine Function Plasma Cortisol, Growth Hormone, and Thyrotropin

In the mammalian brain the hypothalamus serves as a central switchboard in the integration and modulation of incoming messages from higher brain areas and peripheral organs. Signals from the hypothalamus itself are mediated through the synthesis and release of small peptides, which appear to possess behavioral as well as physiological activity. These hypothalamic releasing factors modulate pituitary function and thereby also affect peripheral endocrine activities, including adrenocortical and gonadal steroidogenesis. Narcotic drugs have long been known to interfere with normal neuroendocrine function, but only recently have experimental methods permitted critical investigations with human subjects.