SHBG, testosterone, and type 2 diabetes risk in middle-aged African women: exploring the effect of HIV and menopause
SHBG, testosterone, and type 2 diabetes risk in middle-aged African women: exploring the effect of HIV and menopause
Context: sex hormone–binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk.
Objective: this work aimed to investigate whether the associations between SHBG, testosterone, and T2D risk differ by HIV and menopausal status in Black African women living with HIV (WH) and without HIV (WOH).
Methods: this cross-sectional observational study took place at the Health Research Unit in Soweto, Johannesburg, South Africa. A total of 81 premenopausal (57 WOH, 24 WH) and 280 postmenopausal (236 WOH, 44 WH) women from the Middle-Aged Soweto Cohort (MASC) participated. Main outcome measures included circulating SHBG and sex hormones, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (Matsuda index), secretion (insulinogenic index) and clearance, and β-cell function (disposition index, DI). Dysglycemia was defined as either impaired fasting or postprandial glucose or T2D.
Results: SHBG was higher and total and free testosterone were lower in postmenopausal WH than WOH (all P ≤ .023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance, and DI and inversely with HOMA-IR (all P < .011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (P = .043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (P = .021) and positively associated with HOMA-IR (homeostatic model assessment of insulin resistance) in premenopausal and not postmenopausal women (P = .015 for interaction).
Conclusion: we show for the first time that midlife African WH have higher SHBG and lower total and free testosterone than WOH, which corresponded to their higher β-cell function, suggesting a putative protective effect of SHBG on T2D risk in WH.
sex hormone-binding globulin, androgens, total testosterone, free testosterone, estrogen, HIV, postmenopausal, Africa
Goedecke, Julia H.
27db2aa1-04c2-44e8-9c0e-e9bbe98f2e25
Kufe, Clement N.
3b839b26-ac35-463f-9e39-ef5c4b083f05
Masemola, Maphoko
ac19dd6b-c441-4ed9-9093-2f7816deb97a
al, et
df099e87-31d7-4ccf-a9fa-b92a380537f9
Norris, Shane A.
1d346f1b-6d5f-4bca-ac87-7589851b75a4
28 April 2025
Goedecke, Julia H.
27db2aa1-04c2-44e8-9c0e-e9bbe98f2e25
Kufe, Clement N.
3b839b26-ac35-463f-9e39-ef5c4b083f05
Masemola, Maphoko
ac19dd6b-c441-4ed9-9093-2f7816deb97a
al, et
df099e87-31d7-4ccf-a9fa-b92a380537f9
Norris, Shane A.
1d346f1b-6d5f-4bca-ac87-7589851b75a4
Goedecke, Julia H., Kufe, Clement N., Masemola, Maphoko, al, et and Norris, Shane A.
(2025)
SHBG, testosterone, and type 2 diabetes risk in middle-aged African women: exploring the effect of HIV and menopause.
The Journal of Clinical Endocrinology & Metabolism, [dgaf256].
(doi:10.1210/clinem/dgaf256).
Abstract
Context: sex hormone–binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk.
Objective: this work aimed to investigate whether the associations between SHBG, testosterone, and T2D risk differ by HIV and menopausal status in Black African women living with HIV (WH) and without HIV (WOH).
Methods: this cross-sectional observational study took place at the Health Research Unit in Soweto, Johannesburg, South Africa. A total of 81 premenopausal (57 WOH, 24 WH) and 280 postmenopausal (236 WOH, 44 WH) women from the Middle-Aged Soweto Cohort (MASC) participated. Main outcome measures included circulating SHBG and sex hormones, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (Matsuda index), secretion (insulinogenic index) and clearance, and β-cell function (disposition index, DI). Dysglycemia was defined as either impaired fasting or postprandial glucose or T2D.
Results: SHBG was higher and total and free testosterone were lower in postmenopausal WH than WOH (all P ≤ .023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance, and DI and inversely with HOMA-IR (all P < .011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (P = .043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (P = .021) and positively associated with HOMA-IR (homeostatic model assessment of insulin resistance) in premenopausal and not postmenopausal women (P = .015 for interaction).
Conclusion: we show for the first time that midlife African WH have higher SHBG and lower total and free testosterone than WOH, which corresponded to their higher β-cell function, suggesting a putative protective effect of SHBG on T2D risk in WH.
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Submitted date: 28 January 2025
Accepted/In Press date: 24 April 2025
Published date: 28 April 2025
Keywords:
sex hormone-binding globulin, androgens, total testosterone, free testosterone, estrogen, HIV, postmenopausal, Africa
Identifiers
Local EPrints ID: 504670
URI: http://eprints.soton.ac.uk/id/eprint/504670
ISSN: 0021-972X
PURE UUID: d15bdba2-b6f3-448f-ab56-12a385db73c8
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Date deposited: 17 Sep 2025 16:40
Last modified: 18 Sep 2025 01:59
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Author:
Julia H. Goedecke
Author:
Clement N. Kufe
Author:
Maphoko Masemola
Author:
et al
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