HIV-infection is increasing among women, who represent an understudied subpopulation of infected patients. Unique gender specific hormonal considerations are critical to the study of HIV-infected women. Over the past 4 years, significant progress has been made by our group in understanding the prevalence, pathophysiology and clinical consequences of androgen deficiency in women with AIDS wasting. Furthermore, we have recently completed a randomized, placebo-controlled 6-month study of physiologic testosterone in this population. Our data suggest that androgen deficiency is highly prevalent among women with AIDS wasting, occurring in over 50% of such patients. Detailed physiologic investigations of hormonal parameters in this population suggest relatively intact ovarian function, but decreased adrenal androgen production, and a relative shunting of androgen metabolism toward cortisol production and away from androgen production. Moreover, we-have shown for the first time, a significant reduction in bone density among androgen deficient women with AIDS wasting, characterized by relatively low bone formation rates. Furthermore, data from the 6 month randomized study demonstrates that testosterone at physiologic doses increases muscle function and bone formation indices in this population. Taken together, these data demonstrate a high prevalence and important clinical consequences of androgen deficiency in women with AIDS wasting. In the proposed grant renewal, we build on the data generated in the first grant hypothesizing that reversal of steroid shunting back toward androgen production and away from cortisol production will improve bone metabolism and increase markers of bone formation in HIV-infected women. Finally we will investigate the long-term effects of physiologic androgen replacement over 2 years. The novel studies outlined in this grant proposal will be the first to investigate long-term anabolic androgenic strategies on androgen sensitive endpoints, including bone, body composition and quality of life indices among the growing population of HIV-infected women. The studies outlined in this renewal constitute an important investigative initiative of a targeted, gender-specific therapy in this largely understudied population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK054167-06A1
Application #
6696390
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (05))
Program Officer
Teff, Karen L
Project Start
1998-05-15
Project End
2008-07-31
Budget Start
2003-09-02
Budget End
2004-07-31
Support Year
6
Fiscal Year
2003
Total Cost
$410,884
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Dolan Looby, Sara E; Collins, Merredith; Lee, Hang et al. (2009) Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial. AIDS 23:951-9
Dolan, Sara E; Carpenter, Sara; Grinspoon, Steven (2007) Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women. J Acquir Immune Defic Syndr 45:161-7
Koutkia, Polyxeni; Berry, Jacqueline; Eaton, Kristina et al. (2006) Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV-infected women. Am J Physiol Endocrinol Metab 290:E808-13
Dolan, Sara; Wilkie, Stephanie; Aliabadi, Negar et al. (2004) Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study. Arch Intern Med 164:897-904
Hadigan, Colleen; Meigs, James B; Wilson, Peter W F et al. (2003) Prediction of coronary heart disease risk in HIV-infected patients with fat redistribution. Clin Infect Dis 36:909-16
Dolan, Sara; Montagno, Andrea; Wilkie, Stephanie et al. (2003) Neurocognitive function in HIV-infected patients with low weight and weight loss. J Acquir Immune Defic Syndr 34:155-64
Grinspoon, Steven; Mulligan, Kathleen; Department of Health and Human Services Working Group on the Prevention and Treatment of Wasting and Weight Loss (2003) Weight loss and wasting in patients infected with human immunodeficiency virus. Clin Infect Dis 36:S69-78
Grinspoon, S; Corcoran, C; Stanley, T et al. (2001) Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome. J Clin Endocrinol Metab 86:4120-6
Huang, J S; Wilkie, S J; Sullivan, M P et al. (2001) Reduced bone density in androgen-deficient women with acquired immune deficiency syndrome wasting. J Clin Endocrinol Metab 86:3533-9
Hadigan, C; Meigs, J B; Corcoran, C et al. (2001) Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 32:130-9

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