Review articlePuberty, hormones, and sex differences in alcohol abuse and dependence
Introduction
Males and females between the ages of 12 and 17 have similar patterns of alcohol use (frequency and quantity) as well as prevalence of DSM-IV alcohol abuse and dependence [101], [194]. By about age 17, however, the sex-specific patterns and prevalence begin to diverge and remain disparate across the ages surveyed (12–65+), with females exhibiting fewer drinking days in the past month, fewer days of drinking 5 or more drinks in the past month, and lower prevalence of alcohol abuse and dependence. In 10- and 15 year old boys and girls, pubertal stage is associated with higher rates of substance use and abuse (including alcohol) independent of age and school grade [157]. Earlier puberty in adolescent girls is associated with younger age of onset of drinking and smoking [32], [214]. The relationship between pubertal maturation and the onset of alcohol/substance use is often attributed to mediating social factors and environmental stressors. However, biological mechanisms could also contribute to the progression of sex differences in alcohol drinking patterns during puberty. These variables might include changes in reproductive hormones and stress hormone responses and their effects on adolescent brain development. The purpose of this paper is to review research on gonadal steroids, neuroactive steroids, and stress hormones and their effects on the development of sex differences in alcohol drinking and associated behaviors that emerge during puberty. Gonadal and neuroactive steroid actions on the neurotransmitter systems and neural circuits underlying alcohol seeking and reinforcement are discussed. Examples are given to illustrate potential neuropharmacological, cellular, and molecular mechanisms by which these hormone-neurotransmitter interactions may contribute to sex differences in alcohol's actions. The role of gonadal steroids in modulating the ontogeny of sex differences in the stress responsiveness to alcohol is also discussed. Finally, suggestions are proposed as to how gonadal and stress hormones might interact within structures in the brain reward circuit to promote sex-specific changes in alcohol use and misuse that occur during puberty.
Section snippets
Hormonal events associated with the onset of puberty
Puberty is a gradual physiological process that typically occurs between the ages of 6–12 years and results in the attainment of sexual maturation. This process of reproductive maturation occurs within the developmental stage of adolescence, a period when the brain is undergoing substantial structural and functional changes. For many years, the conventional belief was that puberty and adolescent brain development were two independent processes. However, the current thinking is that pubertal
Sex differences in alcohol drinking: laboratory studies
Sex differences in alcohol intake and responses to alcohol have been well characterized in human and animal laboratory studies. In humans, sex differences have been found in dose-related cognitive impairments [51], [141], behavioral, subjective, and brain metabolic responses to alcohol intoxication [51], [181], [209], and patterns of alcohol intake and lifetime prevalence for alcohol dependence [67], [213], [212].
Sex differences in alcohol self-administration have also been observed in adult
Sex differences in alcohol drinking: influence of gonadal hormones
Despite the small number of laboratory studies on sex-specific changes in alcohol drinking and other responses associated with the onset of puberty, researchers have used a number of approaches to examine the effects of gonadal hormones on these behaviors. One method, which is strictly correlational, assessed alcohol consumption throughout the menstrual cycle to determine how patterns of drinking may vary as a result of changes in levels of sex steroid hormones. Using this approach, increased
Effects of reproductive hormone changes on neural circuits associated with alcohol seeking behavior
Gonadal steroids play an organizational role during brief periods of early pre- and post-natal brain development, and during adolescence to permanently establish sex differences brain structures and functions. Although puberty is primarily linked with hormonal organization and/or activation of sexual reproductive behaviors, gonadal steroids (androgens and estrogens) are also responsible for sex differences in brain structure and function unrelated to reproduction via effects on their respective
Allopregnanolone
The term “neuroactive steroids” refers to steroids synthesized in the brain, adrenals and gonads that affect neuronal excitability by acting in a rapid nongenomic manner at the membrane surface of certain neurotransmitter receptors [7], [158], [177]. One neuroactive steroid that has received considerable attention with respect to its interaction with ethanol is the 5α-reduced, 3α-hydroxylated, progesterone metabolite allopregnanolone (3α-hydroxy-5α-pregnan-20-one) [30], [138], [139].
Interaction of stress and gonadal hormones at puberty on sex differences in alcohol drinking
Alcohol is often consumed in response to stress in humans and animals, although the conditions under which this occurs are extremely variable and depend on many factors such as genetic predisposition, a history of experiencing stress early in life, an individual's drinking patterns, the intensity and type of stressor, controllability over the stressor, one's coping ability and the availability of social support [46], [81], [114], [160], [179], [207]. In addition, even though alcohol is usually
Summary and conclusions
This review emphasized the role of gonadal hormones, neurosteroids, and stress hormones on sex differences in drinking patterns and other actions of alcohol that emerge at the stage of late puberty. Whereas there is some evidence in adult humans and animals that these hormones influence alcohol consumption and responses in a sex-specific fashion, there are very few studies that have investigated the developmental progression of these sex differences in alcohol drinking behavior and/or the
Acknowledgements
I wish to thank Linda Spear, Gary Wand, Kathy Grant, T.-K. Li, Robert Anthenelli, Lindsey Grandison, and Mark Egli for their helpful comments in preparation of this manuscript. I also wish to thank Janet Heekin for her technical assistance in completing this manuscript.
References (222)
- et al.
Drug discrimination analysis of endogenous neuroactive steroids in rats
Eur. J. Pharmacol.
(1993) - et al.
Stress and neuroactive steroids
Int. Rev. Neurobiol.
(2001) - et al.
Sex differences in the rapid and acute effects of estrogen on striatal D2 dopamine receptor binding
Brain Res.
(1994) - et al.
Diverse actions of ovarian steroids in the serotonin neural system
Front. Neuroendocrinol.
(2002) - et al.
Variations in alcohol metabolism: influence of sex and age
Pharmacol. Biochem. Behav.
(1975) Serotonin and the regulation of hypothalamic–pituitary–adrenal axis function
Life Sci.
(1996)Steroids, neuroactive steroids and neurosteroids in psychopathology
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2005)- et al.
Differences between the sexes in voluntary alcohol consumption and liver ADH-activity in inbred strains of mice
Metabolism
(1968) - et al.
Involvement of corticosterone in the modulation of ethanol consumption in the rat
Alcohol
(1994) - et al.
Voluntary ethanol consumption in male adolescent hamsters increases testosterone and aggression
Physiol. Behav.
(1998)