Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids.

OBJECTIVE: Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls. DESIGN: Cross-sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community. METHODS: We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X-ray absorptiometry. RESULTS: Current and former AAS abusers displayed lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45; -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm3 , P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers. CONCLUSIONS: Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively.

Persistently Decreased Quality of Life and its Determinants in Previous Illicit Androgen Users.

BACKGROUND AND OBJECTIVES: Quality of life (QoL) has never been assessed in previous illicit users of androgens years following androgen cessation. Therefore, the objective of this study was to assess QoL in previous illicit androgen users compared with current illicit androgen users and controls who had never used androgens. METHODS: Cross-sectional study including men involved in recreational strength training grouped according to their history of androgen use. We used the RAND Short-Form-36 questionnaire to assess physical and mental health-related QoL. RESULTS: We included 77 previous and 118 current androgen users and 39 healthy nonusers. The mean (SD) age of all participants was 33 (8) years. The elapsed duration since androgen cessation, geometric mean (95% CI), was 2.0 (1.5-2.6) years in former users. Median (25th-75th percentiles) serum total testosterone was lower in former users than controls, 14 (11-17) vs 19 (16-21) nmol/L, P < .001. Previous users displayed lower mean (SD) across both mental and physical (PCS) component summary scores, 48 (10) vs 54 (4) (P = .004) and 48 (9) vs 53 (3) (P = .002) compared with controls.Using multivariate linear regressions, evaluating physical and mental component scores as dependent variables, lower serum total testosterone, longer duration since androgen cessation, study recruitment from an endocrine outpatient clinic, and established chronic diseases were all independently associated with reduced QoL in previous users, P < .05. CONCLUSIONS: Previous illicit androgen users exhibited reduced QoL 2 years after androgen discontinuation, which may be a persistent condition.

Higher Myonuclei Density in Muscle Fibers Persists Among Former Users of Anabolic Androgenic Steroids.

CONTEXT: No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. OBJECTIVE: We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls. METHODS: A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. RESULTS: Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) -94 (-169; -18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. CONCLUSION: Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.

Serum Insulin-like Factor 3 Levels Are Reduced in Former Androgen Users, Suggesting Impaired Leydig Cell Capacity.

CONTEXT: Illicit use of anabolic androgenic steroids (AAS) is frequently observed in men and is associated with subsequent testosterone deficiency although the long-term effect on gonadal function is still unclear. Serum insulin-like factor 3 (INSL3) has been suggested to be a superior biomarker of Leydig cell secretory capacity compared to testosterone. OBJECTIVE: This study aimed to investigate serum INSL3 concentrations in AAS users. METHODS: This community-based, cross-sectional study included men aged 18 to 50 years, involved in recreational strength training and allocated to 1 of 3 groups: never-AAS users as controls (n = 44), current (n = 46), or former AAS users (n = 42) with an average duration since AAS cessation of 32 (23 ; 45) months. RESULTS: Serum INSL3 was lower in current AAS users and former AAS users than in controls, median (interquartile range), 0.04 µg/L (nondetectable [ND]-0.07 µg/L) and 0.39 µg/L (0.24-0.62 µg/L) vs 0.59 µg/L (0.45-0.72 µg/L), P less than .001. Former AAS users exhibited lower serum INSL3 levels than controls in a multivariable linear regression even after adjusting for serum total testosterone (TT) and other relevant confounders, (B) (95% CI), -0.16 µg/L (95% CI, -0.29 to -0.04 µg/L), P equal to .011. INSL3 and TT were not associated in the model, P equal to .821. Longer accumulated AAS duration (log2) was associated with lower serum INSL3 in former AAS users, (B) (95% CI), -0.08 (95% CI, -0.14 to -0.01), P equal to .022. Serum INSL3, but not inhibin B or testosterone, was associated with testicular size in a multivariate linear regression, (B) (95% CI); 4.7 (95% CI, 0.5 to 8.9), P equal to .030. CONCLUSION: Serum INSL3 is reduced years following AAS cessation in men, independently of testosterone, suggesting persistently impaired Leydig cell capacity.

Effect of Anabolic-Androgenic Steroid Abuse on the Contact Activation System.

The effect of anabolic-androgenic steroid (AAS) abuse on the contact activation system (CAS) is not known in detail. We hypothesized that current AAS abuse reduces the kallikrein-generating capacity of CAS significantly and investigated the impact of AAS on the proteins and capacity of CAS in current and former AAS abusers and healthy age-matched controls. Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers, or controls. Blood samples were collected after overnight fasting. Kallikrein generation (lag time, peak height, and endogenous kallikrein potential [EKP]), coagulation factor XII (FXII), prekallikrein, high-molecular-weight kininogen (HK), and Complement C1 esterase inhibitor (C1inh) were assessed. Groups were compared by analysis of variance or Kruskal-Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated by linear regression models. The EKP was significantly reduced in current (n = 37) AAS abusers (984 ± 328 nmol/L × min) compared with former (n = 33) abusers (1,543 ± 481 nmol/L × min) and controls (n = 30) (1,521 ± 339 nmol/L × min), p < 0.001. Current abusers had higher levels of FXII and C1inh and lower levels of prekallikrein and HK than controls, p ≤ 0.025. Stepwise regression analysis showed that EKP was associated with C1inh and prekallikrein in current AAS abusers, R 2 = 0.70, p < 0.001. We conclude that current AAS abuse reduces the kallikrein-generating capacity of CAS by increasing the concentration of C1inh and reducing the concentration of prekallikrein. These changes may contribute to the anti-inflammatory effect of testosterone.

Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study.

AIMS: Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. METHODS: This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. RESULTS: Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). CONCLUSIONS: Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.