The ubiquitous distribution of sex steroid receptors throughout the brain suggests that gonadal hormones are important modulators of cognitive function. Endocrine abnormalities in the hypothalamic-pituitary-gonadal axis have been documented in injection drug users (IDU) and are likely due to a combination of direct drug effects and associated co-morbidities. Our overall hypothesis is that there is cognitive dysfunction in IDU due to CNS alterations secondary to hypogonadism associated with IDU, and that poor performance on standardized cognitive tests can be improved by administering sex steroid replacement. To test our hypothesis we propose the following specific aims: (#1) To document the gonadal hormonal milieu in a population of IDU, and to understand the relationship of that milieu to cognitive performance and quality of life (QOL). (#2) To characterize patterns of cognitive performance and QOL in a defined population based on IDU and HlV status using standardized cognitive testing. (#3) To evaluate the safety and efficacy of sex hormone replacement therapy (either testosterone in men or estrogen in women) on cognitive performance and QOL in a subgroup of hypogonadal IDU. We propose two studies: a cross-sectional study of IDU to evaluate patterns of cognitive performance in relation to their gonadal hormone milieu and, a randomized, placebo-controlled, clinical trial in which hypogonadal IDU will be administered sex hormone replacement to determine the effects on cognitive performance and QOL. We have assembled a multidisciplinary team with extensive experience in studying IDU populations, endocrine abnormalities, and performance on cognitive tasks influenced by sex steroids. We will obtain a better understanding of the relationship between drug use and cognition, and also expand our understanding of the effects of sex steroids on cognitive performance, in an under-studied population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA014098-01A2
Application #
6656807
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2003-06-15
Project End
2008-05-31
Budget Start
2003-06-15
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$302,153
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Slama, Laurence; Jacobson, Lisa P; Li, Xiuhong et al. (2016) Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men. J Acquir Immune Defic Syndr 71:57-64
Zilbermint, Mihail F; Wisniewski, Amy B; Xu, Xiaoqiang et al. (2013) Relationship between sex hormones and cognitive performance in men with substance use. Drug Alcohol Depend 128:250-4
El-Maouche, Diala; Xu, Xiaoqiang; Cofrancesco Jr, Joseph et al. (2011) Prevalence of low bone mineral density in a low-income inner-city population. J Bone Miner Res 26:388-96
Paller, Channing J; Campbell, Claudia M; Edwards, Robert R et al. (2009) Sex-based differences in pain perception and treatment. Pain Med 10:289-99
Wisniewski, Amy B; Brown, Todd T; John, Majnu et al. (2007) Hypothalamic-pituitary-gonadal function in men and women using heroin and cocaine, stratified by HIV status. Gend Med 4:35-44
Brown, Todd T; Wisniewski, Amy B; Dobs, Adrian S (2006) Gonadal and Adrenal Abnormalities in Drug Users: Cause or Consequence of Drug Use Behavior and Poor Health Outcomes. Am J Infect Dis 2:130-135
Wisniewski, Amy B; Brown, Todd T; John, Majnu et al. (2006) Cortisol levels and depression in men and women using heroin and cocaine. Psychoneuroendocrinology 31:250-5