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Sex Hormone-Binding Globulin Tied to Frailty,
Low BMD in Women, Not Men
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11th International Workshop on HIV & Aging Virtual Meeting, September 30 to October 2, 2020
By Mark Mascolini for NATAP and Virology Education
In a Baltimore cohort of people exposed to HCV, sex hormone-binding globulin (SHBG) was higher in those with detectable HCV and HIV load, and in women (but not men) SHBG was linked to frailty and low bone mineral density (BMD) [1]. Researchers from Johns Hopkins University noted that mechanisms explaining these associations require further study.
Synthesized in the liver, SHBG plays roles in sexual function, bone formation, muscle function, and metabolism. In the general population, the Johns Hopkins researchers pointed out, US data ties SHBG to tripled odds of frailty in men [2]. Meta-analysis of longitudinal studies in older adults links SHBG to an 18% higher relative risk of hip fracture, vertebral fracture, and nonvertebral fracture [3]. SHBG has higher circulating concentrations in people with HCV and HIV infection. To explore the role of SHBG in people with or without HCV and HIV, the Johns Hopkins team conducted this cross-sectional study.
The analysis involved HCV-exposed people (those who were HCV antibody-positive) in the Baltimore-area AIDS Linked to the IntraVenous Experience (ALIVE) cohort. ALIVE participants are current or former injection drug users. Researchers divided the cohort into four groups: HCV-negative/HIV-negative, HCV-negative/HIV-positive, HCV-positive/HIV-negative, and HCV-positive/HIV-positive.
The researchers explored associations between SHBG and several frailty and BMD outcomes: maximum grip strength, gait speed, frailty (by Fried frailty phenotype), and T-score for spine, total hip, and femoral neck determined by DXA scan. Using multivariable linear regression, logistic regression, or multinomial logistic regression, they determined whether those outcomes differed by sex after statistical adjustment for age, whole-body lean mass, total fat, HIV status, HCV status, alcohol use, smoking, active injection drug use, total testosterone, estradiol, and comorbidity index.
The 278 study participants, all African Americans, included 176 men (63%) and 102 women (37%). Men were older than women (average 57 +/- 7 vs 54 +/- 6 years, P = 0.01) and had significantly lower body mass index (25.4 +/- 5.7 vs 29.4 +/- 7.8, P < 0.001). Fat mass was higher in women than men (34.9 +/- 11.2 vs 23.5 +/- 11.2 kg, P < 0.001), lean mass was lower in women (44.0 +/- 10.5 vs 53.4 +/- 8.0 kg, P < 0.001), and women proved more likely than men to have undetectable HCV RNA (39% vs 27%, P = 0.03).
Women had significantly higher levels of SHBG (average 99 +/- 49 vs 83 +/- 40 nmol/L, P = 0.005). Among both men and women, SHBG proved significantly higher in the HCV+/HIV- and HCV+/HIV+ groups than in the HCV-/HIV- and HCV-/HIV+ groups.
Regression analysis detected no associations between SHBG level and T-scores or frailty signals in men. But in women multivariable analyses saw associations between higher SHBG and lower maximum grip strength (P < 0.05), lower lumbar spine T-score (P < 0.01), lower total hip T-score (P < 0.05), and lower femoral neck T-score (P < 0.05). In women higher SHBG independently boosted odds of frailty by the Fried criteria (odds ratio 1.42, 95% confidence interval 1.05 to 1.92, P < 0.05).
The Johns Hopkins investigators concluded that higher SHBG is associated with detectable HIV and HCV loads in women and men, and with lower grip strength, lower BMD, and higher odds of frailty in women.
References
1. Pena Dias J, Sun J, Piggott D, et al. Association of sex hormone-binding globulin with bone mineral density and physical function among adults with and without HIV and HCV. 11th International Workshop on HIV & Aging Virtual Meeting, September 30 to October 2, 2020. Abstract 9.
2. 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;15:2082-15. doi: 10.3109/13685538.2012.7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581525/
3. 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. doi: 10.1007/s00198-018-4600-z.
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