Testosterone and sex hormone-binding globulin in dysglycemic women at high cardiovascular risk: A report from the Outcome Reduction with an Initial Glargine Intervention trial

Abstract

Aims: Total and free testosterone and sex hormone-binding globulin may affect cardiovascular prognosis in women. The objective was to study the association between sex hormones and prognosis in women with dysglycemia and high cardiovascular risk.

Methods: This epidemiological report included dysglycemic women from the Outcome Reduction with an Initial Glargine Intervention trial (n = 2848) with baseline total testosterone and sex hormone-binding globulin. Free testosterone was calculated with the Vermeulen formula. Cox regression analyses adjusted for variables including age, previous diseases and pharmacological treatments were used to estimate the association between these levels and the composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) and all-cause mortality per one standard deviation.

Results: Patients (73% post-menopausal) were followed for a median of 6.1 years during which 377 cardiovascular events and 389 deaths occurred. In Cox analyses, total and free testosterone were not associated with any outcomes, but sex hormone-binding globulin was related to all-cause mortality in age adjusted (HR 1.15; 95% CI 1.06-1.24; p < 0.01) and fully adjusted analyses (HR 1.14; 95% CI 1.05-1.24; p < 0.01).

Conclusions: Increasing levels of baseline sex hormone-binding globulin were associated with an increased risk of all-cause mortality in dysglycemic women at high cardiovascular risk.

Trial registration: ClinicalTrials.gov no. NCT00069784.

Keywords: Cardiovascular; diabetes; prognosis; sex hormone-binding globulin; testosterone; women.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AW has nothing to declare. HG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He has received research grant support from AstraZeneca, Eli Lilly, Merck, Boehringer Ingelheim, Abbott, Novo Nordisk and Sanofi and honoraria for speaking and/or consulting from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Abbott, Eli Lilly, Merck, Janssen and Kowa Research Institute. SL has nothing to declare. SH is an employee and shareholder of Sanofi. GP reports grants from Sanofi. LR reports grants from The European Society of Cardiology, Amgen, Bayer AG, Boehringer-Ingelheim, Merck, Family E Perssons Foundation and honoraria from Boehringer-Ingelheim, Merck, Bayer AG and Novo Nordisk. LM reports grants from Bayer AG and honoraria from Bayer AG, Sanofi, Novo Nordisk, Boehringer Ingelheim and AstraZeneca.

Figures

Figure 1.

Hazard ratio (95% CI) for the association between sex hormones and cardiovascular events and all-cause mortality by increase of one standard deviation. Model A adjusted for age. Model B adjusted for age, luteinizing hormone (log and standardized), previous cardiovascular disease, previous diabetes diagnosis, use of metformin, use of statins, systolic blood pressure, HbA1c, low-density lipoprotein cholesterol, body mass index and smoking. Model C adjusted for Model B plus menopause and no hormone therapy, menopause and hormone therapy, thyroid hormone treatment, alcohol consumption, white ethnicity, obstructive sleep apnea.