Steroid Sex Hormones, Sex Hormone–Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program

Mather, Kieren J.; Kim, C.; Christophi, Christopher; Aroda, Vanita R.; Knowler, William C.; EDELSTEIN, SHARON; Florez, José C.; Labrie, Fernand; Kahn, Steven E.; Goldberg, Ronald; Barrett‐Connor, Elizabeth

doi:10.1210/jc.2015-2328

Cited by 51 publications

(45 citation statements)

References 35 publications

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“…Among men enrolled in the Diabetes Prevention Program, positive associations were found between serum estrone concentrations and the incident development of T2DM. (Mather et al, 2015) Another study similarly found that circulating estrone levels associated with incident development of T2DM in men and, further, were a better predictor of diabetes development than serum estradiol levels. (Jasuja et al, 2013b) Changes in serum estrone levels were shown to positively correlate with BMI, and increased prevalence of both diabetes and cardiovascular disease was found among men in the highest quintile of serum estrone levels.…”

Section: Estrogens Beyond 17β-estradiol: Estrone and 17α-estradiolmentioning

confidence: 97%

Estrogens and Body Weight Regulation in Men

Rubinow

2017

Advances in Experimental Medicine and Biology

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Our understanding of the metabolic roles of sex steroids in men has evolved substantially over recent decades. Whereas testosterone once was believed to contribute to metabolic risk in men, the importance of adequate androgen exposure for the maintenance of metabolic health has been demonstrated unequivocally. A growing body of evidence now also supports a critical role for estrogens in metabolic regulation in men. Recent data from clinical intervention studies indicate that estradiol may be a stronger determinant of adiposity than testosterone in men, and even short-term estradiol deprivation contributes to fat mass accrual. The following chapter will outline findings to date regarding the mechanisms whereby estrogens contribute to the regulation of body weight and adiposity in men. It will present emergent clinical data as well as preclinical findings that reveal mechanistic insights into estrogen-mediated regulation of body composition. Findings in both males and females will be reviewed, to draw comparisons and to highlight knowledge gaps regarding estrogen action specifically in males. Finally, the clinical relevance of estrogen exposure in men will be discussed, particularly in the context of a rising global prevalence of obesity and expanding clinical use of sex steroid-based therapies in men.

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Section: Estrogens Beyond 17β-estradiol: Estrone and 17α-estradiolmentioning

confidence: 97%

Estrogens and Body Weight Regulation in Men

Rubinow

2017

Advances in Experimental Medicine and Biology

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“…As previously described,(23) sex steroids were measured using gas chromatography/mass spectrometry. The lower limits of quantification for testosterone was 0.1735 nmol/l.…”

Section: Methodsmentioning

confidence: 99%

“…The majority of men were less than 65 years of age at baseline. Approximately 55% had total testosterone concentrations greater than 10.41 nmol/l (300 ng/dl) (23), a cutpoint commonly used to define hypogonadism (24). Thus, we were able to examine whether randomization to lifestyle or metformin altered testosterone and the magnitude of the association between changes in endogenous testosterone and concurrent changes in mood.…”

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confidence: 99%

Testosterone and depressive symptoms among men in the Diabetes Prevention Program

Kim

Barrett‐Connor

Aroda

et al. 2016

Psychoneuroendocrinology

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Structured Abstract Objective We examined associations between randomization to intensive lifestyle intervention (ILS) and changes in testosterone and associations with mood among middle-aged men. Design Secondary analysis of men (n=886) participating in the Diabetes Prevention Program which randomized glucose-intolerant, overweight men to ILS, metformin, or placebo. Main Outcome Measures Changes in testosterone between baseline and 1-year follow-up and associations of these changes with mood measures (Beck Depression Inventory [BDI], Beck Anxiety Inventory [BAI]) Results Median baseline testosterone was 10.98 nmol/l and 44% (n=385) had testosterone < 10.41 nmol/l or 300 ng/dl, a common threshold for biochemical hypogonadism. Testosterone increases were greater among men randomized to ILS vs. metformin vs. placebo (1.15 nmol/l vs. −0.12 nmol/l vs. −0.27 nmol/l, p<0.001). The association between changes in testosterone and mood differed by randomization arm (p<0.001 for interaction); there were no significant associations between changes in testosterone and mood changes among men randomized to ILS or placebo. Among men randomized to metformin, increases in testosterone were significantly associated with decreases in BDI (improved depressive symptoms) (β-coefficient −0.2336, p=0.0002) indicating a 0.23 decrease in BDI for every 1 nmol/l increase in testosterone and decreases in BAI (improved anxiety symptoms) (β-coefficient −0.2147, p=0.0014). Similar patterns were observed for bioavailable testosterone. Conclusions Among overweight middle-aged men with glucose-intolerance, ILS increased endogenous testosterone slightly but without significant improvements in mood. Metformin did not increase testosterone, but among participants randomized to metformin, testosterone increases were associated with improvements in mood. Thus, interventions that increase endogenous testosterone may not also improve mood.

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“…In the PCOS population of the two centres, the median age of patients was 26 years (IQR: [21][22][23][24][25][26][27][28][29][30], and the median BMI was 28.93 kg/ m 2 (IQR: 24. 16-33.20 The women with abnormal glucose metabolism, which included prediabetes and T2DM, were older and had a higher BMI and WHR than those with normal glucose metabolism.…”

Section: Clinical and Metabolic Characteristics And Serum Steroid Hmentioning

confidence: 99%

Correlation between glucose metabolism and serum steroid hormones in patients with polycystic ovary syndrome

Zhang

et al. 2020

Clinical Endocrinology

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Objective Polycystic ovary syndrome (PCOS) is associated with an increased prevalence of dysglycaemia, which includes impaired glucose tolerance and type 2 diabetes mellitus (T2DM). Patients with PCOS demonstrate abnormal patterns of steroid hormones. Here, we analyse the correlation between glucose metabolism and serum steroid hormones in PCOS. Design Observational double‐centre study. Patients 914 patients with PCOS. Measurements We assessed the glucose metabolism status of all patients according to the 1999 WHO criteria. Serum steroid hormones were measured by liquid chromatography‐tandem mass spectrometry. Results The median age of the patients was 26 years (interquartile range: 21‐30), and 40.6% (371/914) had abnormal glucose metabolism: 29.3% (268/914) had prediabetes, and 11.3% (103/914) had T2DM. Correlation analysis not adjusting for confounding factors revealed that serum aldosterone, androstenedione, oestrone, pregnenolone and the free androgen index were positively correlated, while progesterone was negatively correlated with the risk of abnormal glucose metabolism. After adjusting for age, body mass index and fasting insulin levels in the logistic regression model, only aldosterone (P = .013), androstenedione (P = .046) and oestrone (P = .014; in quartiles) were correlated with the risk of abnormal glucose metabolism. Conclusions This study indicates a high prevalence of prediabetes and T2DM in patients with PCOS. Furthermore, there were positive correlations of serum aldosterone, androstenedione and oestrone with the risk of abnormal glucose metabolism after adjusting for confounding factors.

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Steroid Sex Hormones, Sex Hormone–Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program

Abstract: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.

Cited by 51 publications

References 35 publications

Estrogens and Body Weight Regulation in Men

Estrogens and Body Weight Regulation in Men

Testosterone and depressive symptoms among men in the Diabetes Prevention Program

Correlation between glucose metabolism and serum steroid hormones in patients with polycystic ovary syndrome

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