Longitudinal Changes in Sex Hormone-Binding Globulin in Men With HIV.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
15 08 2021
15 08 2021
Historique:
received:
02
11
2020
accepted:
29
03
2021
pubmed:
16
5
2021
medline:
9
11
2021
entrez:
15
5
2021
Statut:
ppublish
Résumé
Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus. In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus. At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [β= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [β = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05]. Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.
Sections du résumé
BACKGROUND
Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus.
METHODS
In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus.
RESULTS
At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [β= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [β = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05].
CONCLUSIONS
Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.
Identifiants
pubmed: 33990494
doi: 10.1097/QAI.0000000000002723
pii: 00126334-202108150-00010
pmc: PMC8263509
mid: NIHMS1701196
doi:
Substances chimiques
Sex Hormone-Binding Globulin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1186Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL146245
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146205
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146208
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI120834
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146242
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146201
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146193
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035040
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146194
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146241
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027767
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146333
Pays : United States
Organisme : NIA NIH HHS
ID : K24 AG070078
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146192
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146204
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146202
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000004
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146240
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146203
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050410
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
T.T.B. has served as a consultant to ViiV Healthcare, Janssen, Merck, Gilead Sciences, and Theratechnologies. J.E.L. has served as a consultant to ViiV and Merck and receives research support from Gilead Sciences and CytoDyn. J.C. Price has served as a consultant to Theratechnologies and receives research support from Gilead Sciences and Merck. The remaining authors have no funding or conflicts of interest to disclose.
Références
Simo R, Saez-Lopez C, Barbosa-Desongles A, et al. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol Metab. 2015;26:376–383.
Caldwell JD, Jirikowski GF. Sex hormone binding globulin and aging. Horm Metab Res. 2009;41:173–182.
Rosner W, Hryb DJ, Khan MS, et al. Sex hormone-binding globulin: anatomy and physiology of a new regulatory system. J Steroid Biochem Mol Biol. 1991;40:813–820.
Harman SM, Metter EJ, Tobin JD, et al. Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724–731.
Davison SL, Bell R, Montalto JG, et al. Measurement of total testosterone in women: comparison of a direct radioimmunoassay versus radioimmunoassay after organic solvent extraction and celite column partition chromatography. Fertil Steril. 2005;84:1698–1704.
Fabbri E, An Y, Gonzalez-Freire M, et al. Bioavailable testosterone linearly declines over A wide age spectrum in men and women from the Baltimore longitudinal study of aging. J Gerontol A Biol Sci Med Sci. 2016;71:1202–1209.
Liu PY, Beilin J, Meier C, et al. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metab. 2007;92:3599–3603.
Monroe AK, Dobs AS, Palella FJ, et al. Morning free and total testosterone in HIV-infected men: implications for the assessment of hypogonadism. AIDS Res Ther. 2014;11:6405–6411-6.
Cousin P, Dechaud H, Grenot C, et al. Human variant sex hormone-binding globulin (SHBG) with an additional carbohydrate chain has a reduced clearance rate in rabbit. J Clin Endocrinol Metab. 1998;83:235–240.
Pathai S, Bajillan H, Landay AL, et al. Is HIV a model of accelerated or accentuated aging?. J Gerontol A Biol Sci Med Sci. 2014;69:833–842.
Effros RB, Fletcher CV, Gebo K, et al. Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions. Clin Infect Dis. 2008;47:542–553.
Goulet JL, Fultz SL, McGinnis KA, et al. Relative prevalence of comorbidities and treatment contraindications in HIV-mono-infected and HIV/HCV-co-infected veterans. AIDS 2005;19:S99–S105.
Thurn M, Gustafson DR. Faces of frailty in aging with HIV infection. Curr Hiv/aids Rep. 2017;14:31–37.
Erlandson KM, Allshouse AA, Jankowski CM, et al. Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Infect Dis. 2013;208:249–259.
Kaslow RA, Ostrow DG, Detels R, et al. The Multicenter AIDS Cohort Study: rationale, organization, and selected characteristics of the participants. Am J Epidemiol. 1987;126:310–318.
Slama L, Jacobson LP, Li X, et al. Longitudinal changes over 10 Years in free testosterone among HIV-infected and HIV-uninfected men. J Acquir Immune Defic Syndr. 2016;71:57–64.
Dybul M, Fauci AS, Bartlett JG, et al. Panel on Clinical Practices for Treatment of HIV. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Ann Intern Med. 2002;137:381–433.
Bhasin S, Jasjua GK, Pencina M, et al. Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study. Diabetes Care. 2011;34:2464–2470.
Wada NI, Bream JH, Martinez-Maza O, et al. Inflammatory biomarkers and mortality risk among HIV-suppressed men: a multisite prospective cohort study. Clin Infect Dis. 2016;63:984–990.
Wada NI, Jacobson LP, Margolick JB, et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS. 2015;29:463–471.
Castillo-Mancilla JR, Brown TT, Erlandson KM, et al. Suboptimal adherence to combination antiretroviral therapy is associated with higher levels of inflammation despite HIV suppression. Clin Infect Dis. 2016;63:1661–1667.
Castillo-Mancilla JR, Brown TT, Palella FJ Jr, et al. Partial normalization of biomarkers of inflammation and immune activation among virally suppressed men with HIV infection and high ART adherence. Open Forum Infect Dis. 2020;7:ofaa099.
Muller M, den Tonkelaar I, Thijssen JH, et al. Endogenous sex hormones in men aged 40-80 years. Eur J Endocrinol. 2003;149:583–589.
Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87:589–598.
Simo R, Barbosa-Desongles A, Hernandez C, et al. IL1beta down-regulation of sex hormone-binding globulin production by decreasing HNF-4alpha via MEK-1/2 and JNK MAPK pathways. Mol Endocrinol. 2012;26:1917–1927.
Simo R, Barbosa-Desongles A, Saez-Lopez C, et al. Molecular mechanism of TNFalpha-induced down-regulation of SHBG expression. Mol Endocrinol. 2012;26:438–446.
Carlstrom K, Hedin PJ, Jonsson L, et al. Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis. Scand J Rheumatol. 2000;29:89–94.
Sattar N, Crompton P, Cherry L, et al. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthritis Rheum. 2007;56:831–839.
Shive CL, Jiang W, Anthony DD, et al. Soluble CD14 is a nonspecific marker of monocyte activation. AIDS 2015;29:1263–1265.
Vincent FB, Saulep-Easton D, Figgett WA, et al. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013;24:203–215.
Yamazaki H, Kushiyama A, Sakoda H, et al. Protective effect of sex hormone-binding globulin against metabolic syndrome: in vitro evidence showing anti-inflammatory and lipolytic effects on adipocytes and macrophages. Mediators Inflamm. 2018;2018:3062319.
Balogh A, Karpati E, Schneider AE, et al. Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor. Sci Rep. 2019;9:4,018-36882-3.
Simo R, Saez-Lopez C, Lecube A, et al. Adiponectin upregulates SHBG production: molecular mechanisms and potential implications. Endocrinology 2014;155:2820–2830.
Nakhla AM, Leonard J, Hryb DJ, et al. Sex hormone-binding globulin receptor signal transduction proceeds via a G protein. Steroids 1999;64:213–216.
Reily C, Stewart TJ, Renfrow MB, et al. Glycosylation in health and disease. Nat Rev Nephrol. 2019;15:346–366.
Dube MP, Parker RA, Mulligan K, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: a5005s, a substudy of AIDS Clinical Trials Group Study 384. Clin Infect Dis. 2007;45:120–126.
Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715–1744.
Eichholzer M, Barbir A, Basaria S, et al. Serum sex steroid hormones and frailty in older American men of the third national health and nutrition examination survey (NHANES III). Aging Male. 2012;15:208–215.
Hidayat K, Du X, Shi BM. Sex hormone-binding globulin and risk of fracture in older adults: systematic review and meta-analysis of observational studies. Osteoporos Int. 2018;29:2171–2180.
Yeap BB, Marriott RJ, Antonio L, et al. Serum testosterone is inversely and sex hormone-binding globulin is directly associated with all-cause mortality in men. J Clin Endocrinol Metab. 2021;106:e625–37.
Leng SX, Margolick JB. Understanding frailty, aging, and inflammation in HIV infection. Curr Hiv/AIDS Rep. 2015;12:25–32.
Pramukti I, Lindayani L, Chen YC, et al. Bone fracture among people living with HIV: a systematic review and meta-regression of prevalence, incidence, and risk factors. PLoS One. 2020;15:e0233501.