Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Psychiatry Reports
Published in: Current Psychiatry Reports 11/2014

01-11-2014 | Women's Mental Health (D Rubinow, Section Editor)

Ovarian Hormones and Drug Abuse

Authors: Megan M. Moran-Santa Maria, Julianne Flanagan, Kathleen Brady

Published in: Current Psychiatry Reports | Issue 11/2014

Login to get access

Abstract

There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women’s health. In this review we will discuss findings from clinical and preclinical studies of 1) reproductive cycle phase; 2) endogenous ovarian hormones; and 3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.
Literature
1.
McCance-Katz EF, Carroll KM, Rounsaville BJ. Gender differences in treatment-seeking cocaine abusers—implications for treatment and prognosis. Am J Addict. 1999;8(4):300–11.PubMedCrossRef
2.
Anglin MD, Hser YI, McGlothlin WH. Sex differences in addict careers. 2. Becoming addicted. Am J Drug Alcohol Abuse. 1987;13(1–2):59–71.PubMedCrossRef
3.
Hernandez-Avila CA, Rounsaville BJ, Kranzler HR. Opioid-, cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment. Drug Alcohol Depend. 2004;74(3):265–72.PubMedCrossRef
4.
Westermeyer J, Boedicker AE. Course, severity, and treatment of substance abuse among women versus men. Am J Drug Alcohol Abuse. 2000;26(4):523–35.PubMedCrossRef
5.
Brady KT et al. Gender differences in substance use disorders. Am J Psychiatry. 1993;150(11):1707–11.PubMed
6.
Lynch WJ, Carroll ME. Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacology (Berl). 2000;148(2):196–200.CrossRef
7.
Lynch WJ. Acquisition and maintenance of cocaine self-administration in adolescent rats: effects of sex and gonadal hormones. Psychopharmacology (Berl). 2008;197(2):237–46.CrossRef
8.
Roth ME, Carroll ME. Sex differences in the escalation of intravenous cocaine intake following long- or short-access to cocaine self-administration. Pharmacol Biochem Behav. 2004;78(2):199–207.PubMedCrossRef
9.
Kerstetter KA et al. Protracted time-dependent increases in cocaine-seeking behavior during cocaine withdrawal in female relative to male rats. Psychopharmacology (Berl). 2008;198(1):63–75.CrossRef
10.
Anker JJ, Carroll ME. Sex differences in the effects of allopregnanolone on yohimbine-induced reinstatement of cocaine seeking in rats. Drug Alcohol Depend. 2010;107(2–3):264–7.PubMedCrossRefPubMedCentral
11.
Buffalari DM et al. Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats. Physiol Behav. 2012;105(2):209–14.PubMedCrossRefPubMedCentral
12.
Freeman ME. The neuroendocrine control of the ovarian cycle of the rat. In: Knobil E, Neill JD, editors. The physiology of reproduction. New York: Raven Press; 1994. p. 613–58.
13.
Evans SM, Haney M, Foltin RW. The effects of smoked cocaine during the follicular and luteal phases of the menstrual cycle in women. Psychopharmacology (Berl). 2002;159(4):397–406.CrossRef
14.
Sofuoglu M et al. Sex and menstrual cycle differences in the subjective effects from smoked cocaine in humans. Exp Clin Psychopharmacol. 1999;7(3):274–83.PubMedCrossRef
15.
Justice AJ, de Wit H. Acute effects of d-amphetamine during the follicular and luteal phases of the menstrual cycle in women. Psychopharmacology (Berl). 1999;145(1):67–75.CrossRef
16.
White TL, Justice AJ, de Wit H. Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav. 2002;73(4):729–41.PubMedCrossRef
17.
Feltenstein MW, See RE. Plasma progesterone levels and cocaine-seeking in freely cycling female rats across the estrous cycle. Drug Alcohol Depend. 2007;89(2–3):183–9.PubMedCrossRefPubMedCentral
18.
Lynch WJ et al. Role of estrogen in the acquisition of intravenously self-administered cocaine in female rats. Pharmacol Biochem Behav. 2001;68(4):641–6.PubMedCrossRef
19.
Chen HH et al. Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice. Chin J Physiol. 2003;46(4):169–74.PubMed
20.
Kippin TE et al. Potentiation of cocaine-primed reinstatement of drug seeking in female rats during estrus. Psychopharmacology (Berl). 2005;182(2):245–52.CrossRef
21.
Lukas SE et al. Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers. Psychopharmacology (Berl). 1996;125(4):346–54.CrossRef
22.
23.
Mendelson JH et al. Cocaine pharmacokinetics in men and in women during the follicular and luteal phases of the menstrual cycle. Neuropsychopharmacology. 1999;21(2):294–303.PubMedCrossRef
24.
Sinha R et al. Sex steroid hormones, stress response, and drug craving in cocaine-dependent women: implications for relapse susceptibility. Exp Clin Psychopharmacol. 2007;15(5):445–52.PubMedCrossRef
25.
Fox HC et al. Altered levels of sex and stress steroid hormones assessed daily over a 28-day cycle in early abstinent cocaine-dependent females. Psychopharmacology (Berl). 2008;195(4):527–36.CrossRef
26.
Evans SM, Foltin RW. Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men. Neuropsychopharmacology. 2006;31(3):659–74.PubMedCrossRef
27.
Sofuoglu M, Babb DA, Hatsukami DK. Effects of progesterone treatment on smoked cocaine response in women. Pharmacol Biochem Behav. 2002;72(1–2):431–5.PubMedCrossRef
28.
Sofuoglu M, Mitchell E, Kosten TR. Effects of progesterone treatment on cocaine responses in male and female cocaine users. Pharmacol Biochem Behav. 2004;78(4):699–705.PubMedCrossRef
29.•
Fox HC et al. The effects of exogenous progesterone on drug craving and stress arousal in cocaine dependence: impact of gender and cue type. Psychoneuroendocrinology. 2013;38(9):1532–44. Relapse rates are high among cocaine-dependent individuals. To our knowldege this is the first study to examine the efficacy of exogenous progesterone on inhibiting responses to triggers of relapse in a cohort of cocaine-dependent individuals.PubMedCrossRefPubMedCentral
30.
Sofuoglu M et al. Progesterone effects on cocaine use in male cocaine users maintained on methadone: a randomized, double-blind, pilot study. Exp Clin Psychopharmacol. 2007;15(5):453–60.PubMedCrossRef
31.
Holtz NA et al. Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone. Drug Alcohol Depend. 2012;120(1–3):233–7.PubMedCrossRefPubMedCentral
32.
Ramoa CP et al. Estradiol as a mechanism for sex differences in the development of an addicted phenotype following extended access cocaine self-administration. Neuropsychopharmacology. 2013;38(9):1698–705.PubMedCrossRefPubMedCentral
33.•
Ramoa CP et al. Diminished role of dopamine D1-receptor signaling with the development of an addicted phenotype in rats. Biol Psychiatry. 2014;76(1):8–14. Data from this study suggest that estrogen plays an important role in compulisve drug seeking behavior. In addition, although the dopamine has been implicated in establishing the initial reinforcing effects of drugs of abuse, data from this study suggest that the effects of estrogen on compulsive drug seeking behavior are independent of the dopamine system.PubMedCrossRef
34.
Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005;162(8):1403–13.PubMedCrossRef
35.
Meitzen J, Mermelstein PG. Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. J Chem Neuroanat. 2011;42(4):236–41.PubMedCrossRefPubMedCentral
36.
Peterson BM, Mermelstein PG, Meisel RL. Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5. Brain Struct Funct. 2014;31.
37.
Martinez LA et al. Estradiol facilitation of cocaine-induced locomotor sensitization in female rats requires activation of mGluR5. Behav Brain Res. 2014;271:39–42.PubMedCrossRef
38.
Allen SS et al. Withdrawal and pre-menstrual symptomatology during the menstrual cycle in short-term smoking abstinence: effects of menstrual cycle on smoking abstinence. Nicotine Tob Res. 1999;1(2):129–42.PubMedCrossRef
39.
Allen SS et al. Effects of transdermal nicotine on craving, withdrawal and premenstrual symptomatology in short-term smoking abstinence during different phases of the menstrual cycle. Nicotine Tob Res. 2000;2(3):231–41.PubMedCrossRef
40.
Franklin TR et al. Retrospective study: influence of menstrual cycle on cue-induced cigarette craving. Nicotine Tob Res. 2004;6(1):171–5.PubMedCrossRef
41.
Marks JL, Pomerleau CS, Pomerleau OF. Effects of menstrual phase on reactivity to nicotine. Addict Behav. 1999;24(1):127–34.PubMedCrossRef
42.
Pomerleau CS et al. Effects of nicotine abstinence and menstrual phase on task performance. Addict Behav. 1994;19(4):357–62.PubMedCrossRef
43.•
Schiller CE et al. Association between ovarian hormones and smoking behavior in women. Exp Clin Psychopharmacol. 2012;20(4):251–7. In general findings from studies of cycle phase, endogenous estrogen and progesterone levels on drug seeking behavior are often conflicting. The results from this study suggest that absolute levels of ovarian hormones may not be sufficient. Rather studies of changes in ovarian hormones over time and/or the ratio of progesterone to estrogen may advance our understanding of the role of ovarian hormones in drug-seeking behavior.PubMedCrossRefPubMedCentral
44.
45.
46.
Sofuoglu M, Mooney M. Subjective responses to intravenous nicotine: greater sensitivity in women than in men. Exp Clin Psychopharmacol 2009;17(2):63–69. doi:10.​1037/​a0015297.
47.
Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers. Psychoneuroendocrinology. 2011;36(1):123–32.PubMedCrossRefPubMedCentral
48.
Cepeda-Benito A, Reynoso JT, Erath S. Meta-analysis of the efficacy of nicotine replacement therapy for smoking cessation: differences between men and women. J Consult Clin Psychol. 2004;72(4):712–22.PubMedCrossRef
49.
50.
Scharf D, Shiffman S. Are there gender differences in smoking cessation, with and without bupropion? Pooled- and meta-analyses of clinical trials of Bupropion SR. Addiction. 2004;99(11):1462–9.PubMedCrossRef
51.
King SL, Caldarone BJ, Picciotto MR. Beta2-subunit-containing nicotinic acetylcholine receptors are critical for dopamine-dependent locomotor activation following repeated nicotine administration. Neuropharmacology. 2004;47 Suppl 1:132–9.PubMedCrossRef
52.
Picciotto MR et al. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391(6663):173–7.PubMedCrossRef
53.
Staley JK et al. Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci. 2006;26(34):8707–14.PubMedCrossRef
54.
Cosgrove KP et al. beta2-Nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking. Arch Gen Psychiatry. 2009;66(6):666–76.PubMedCrossRefPubMedCentral
55.
Ke L, Lukas RJ. Effects of steroid exposure on ligand binding and functional activities of diverse nicotinic acetylcholine receptor subtypes. J Neurochem. 1996;67(3):1100–12.PubMedCrossRef
56.
57.•
Cosgrove KP et al. Sex differences in availability of beta2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers. Arch Gen Psychiatry. 2012;69(4):418–27. Previous studies demonstrate sex differences in treatment responses to nicotine replacementcpe Data from this study offer a potential neurobiologic basis for these differences than may be independent of ovarian hormone status.PubMedCrossRefPubMedCentral
58.
Logue PE et al. Effects of ethanol and psychomotor tests on state anxiety: interaction with menstrual cycle in women. Percept Mot Skills. 1981;52(2):643–8.PubMedCrossRef
59.
Sutker PB et al. Acute alcohol intoxication: sex comparisons on pharmacokinetic and mood measures. Alcohol Clin Exp Res. 1987;11(6):507–12.PubMedCrossRef
60.
Evans SM, Levin FR. Response to alcohol in women: role of the menstrual cycle and a family history of alcoholism. Drug Alcohol Depend. 2011;114(1):18–30.PubMedCrossRefPubMedCentral
61.
Holdstock L, de Wit H. Effects of ethanol at four phases of the menstrual cycle. Psychopharmacology (Berl). 2000;150(4):374–82.CrossRef
62.
Stewart SH et al. Relations between dietary restraint and patterns of alcohol use in young adult women. Psychol Addict Behav. 2000;14(1):77–82.PubMedCrossRef
63.
Khaylis A, Trockel M, Taylor CB. Binge drinking in women at risk for developing eating disorders. Int J Eat Disord. 2009;42(5):409–14.PubMedCrossRef
64.
Luce KH et al. Do restrained eaters restrict their caloric intake prior to drinking alcohol? Eat Behav. 2013;14(3):361–5.PubMedCrossRef
65.
DiMatteo J, Reed SC, Evans SM. Alcohol consumption as a function of dietary restraint and the menstrual cycle in moderate/heavy ("at-risk") female drinkers. Eat Behav. 2012;13(3):285–8.PubMedCrossRefPubMedCentral
66.
Torres OV et al. Female rats display enhanced rewarding effects of ethanol that are hormone dependent. Alcohol Clin Exp Res. 2014;38(1):108–15.PubMedCrossRef
67.
Roberts AJ et al. Estrous cycle effects on operant responding for ethanol in female rats. Alcohol Clin Exp Res. 1998;22(7):1564–9.PubMedCrossRef
68.
69.
Substance Abuse and Mental Health Services Administration, Non medical use of prescription pain relievers. 2004.
70.
Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. 2013: Rockville.
71.
Andersson HI et al. Chronic pain in a geographically defined general population: studies of differences in age, gender, social class, and pain localization. Clin J Pain. 1993;9(3):174–82.PubMedCrossRef
72.
Rustoen T et al. Gender differences in chronic pain–findings from a population-based study of Norwegian adults. Pain Manag Nurs. 2004;5(3):105–17.PubMedCrossRef
73.
Back SE et al. Comparative profiles of men and women with opioid dependence: results from a national multisite effectiveness trial. Am J Drug Alcohol Abuse. 2011;37(5):313–23.PubMedCrossRefPubMedCentral
74.
Sener EB et al. Effects of menstrual cycle on postoperative analgesic requirements, agitation, incidence of nausea and vomiting after gynecological laparoscopy. Gynecol Obstet Invest. 2005;59(1):49–53.PubMedCrossRef
75.
76.
Cicero TJ, Aylward SC, Meyer ER. Gender differences in the intravenous self-administration of mu opiate agonists. Pharmacol Biochem Behav. 2003;74(3):541–9.PubMedCrossRef
77.
Stewart J, Woodside B, Shaham Y. Ovarian hormones do not affect the initiation and maintenance of intravenous self-administration of heroin in the female rat. Psychobiology. 1996;24(2):154–9.
78.
Roth ME, Casimir AG, Carroll ME. Influence of estrogen in the acquisition of intravenously self-administered heroin in female rats. Pharmacol Biochem Behav. 2002;72(1–2):313–8.PubMedCrossRef
79.
Griffin ML et al. Alcohol use across the menstrual cycle among marihuana users. Alcohol. 1987;4(6):457–62.PubMedCrossRef
80.
Griffin ML et al. Marihuana use across the menstrual cycle. Drug Alcohol Depend. 1986;18(2):213–24.PubMedCrossRef
81.
Lex BW et al. Effects of acute marijuana smoking on pulse rate and mood states in women. Psychopharmacology (Berl). 1984;84(2):178–87.CrossRef
82.
Fattore L et al. Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones. Br J Pharmacol. 2010;160(3):724–35.PubMedCrossRefPubMedCentral
83.
Winsauer PJ et al. Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status. Addict Biol. 2011;16(1):64–81.PubMedCrossRefPubMedCentral
84.
85.
Schneider M, Koch M. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology. 2003;28(10):1760–9.PubMedCrossRef
86.
Pope Jr HG et al. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 2003;69(3):303–10.PubMedCrossRef
Metadata
Title
Ovarian Hormones and Drug Abuse
Authors
Megan M. Moran-Santa Maria
Julianne Flanagan
Kathleen Brady
Publication date
01-11-2014
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 11/2014
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-014-0511-7

Other articles of this Issue 11/2014

Current Psychiatry Reports 11/2014 Go to the issue

Psychiatry in the Digital Age (JS Luo, Section Editor)

Risk Factors of Internet Addiction and the Health Effect of Internet Addiction on Adolescents: A Systematic Review of Longitudinal and Prospective Studies

Genetic Disorders (W Berrettini, Section Editor)

Second Generation Antipsychotic-Induced Obsessive-Compulsive Symptoms in Schizophrenia: A Review of the Experimental Literature

Schizophrenia and Other Psychotic Disorders (SJ Siegel, Section Editor)

The Role of Cortisol in First Episode of Psychosis: A Systematic Review

Autism Spectrum Disorders (ES Brodkin, Section Editor)

Etiology of Autism Spectrum Disorder: A Genomics Perspective

Genetic Disorders (W Berrettini, Section Editor)

Genetics of Schizophrenia

Bipolar Disorders (W Coryell, Section Editor)

New Developments in the Genetics of Bipolar Disorder