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Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids.

ABSTRACT: The primary aim of this study was to investigate the association between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI) and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use.Two cohorts were analyzed. Cohort 1 comprised healthy volunteers given single supra-physiological doses of 500 mg testosterone (n = 25). Cohort 2 comprised 45 self-reporting AAS users. Healthy volunteers homozygous for the C-allele of the Fok1 polymorphism exhibited 30% higher LH levels than T-carriers at baseline (p = 0.04) and twice the levels 14 days after testosterone administration (p = 0.01). AAS users homozygous for the C-allele had four times higher LH levels than TT-individuals (p < 0.05). FSH levels were not associated with Fok1 polymorphism, nor were LH and FSH levels associated with the TaqI polymorphism. In conclusion, there is an association between LH levels and the Fok1 VDR polymorphism and this difference is even more pronounced in AAS users and subjects with suppressed LH levels.

SUBMITTER: Bjorkhem-Bergman L

PROVIDER: S-EPMC5775552 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids.

Björkhem-Bergman Linda L Lehtihet Mikael M Rane Anders A Ekström Lena L

BMC research notes 20180119 1

<h4>Objective</h4>The primary aim of this study was to investigate the association between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI) and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use.<h4>Results</h4>Two cohorts were analyzed. Cohort 1 comprised healthy volunteers given single supra-physiological doses of 500 mg testosterone (n = 25). Cohort 2 comprised 45 self-reporting AAS users. Healthy volunteers homozygous for the C-allele of the Fok1 ...[more]

PMID: 29351807

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Project description:BACKGROUND:A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS:A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS:In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION:This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base.

Project description:AimsAbuse 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.MethodsThis 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.ResultsFormer 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).ConclusionsFormer 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.

Project description:BACKGROUND:The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population. METHODS:Three tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis. RESULTS:We found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR)?=?1.255, 95% Confidence Interval (CI)?=?(1.118-1.409), P?<?0.001), dominant (OR?=?1.384, 95% CI?=?1.384 (1.136-1.6), P?= 0.001) and recessive models (OR?=?1.356, 95%CI?=?1.1-1.671, P?= 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR?=?1.146, 95% CI?=?1.053-1247, P?=?0.002), dominant (OR?=?1.184, 95%CI =1.018-1.376, P?= 0.028) and recessive models (OR?=?1.209, 95%CI?=?1.064-1.374, P?= 0.004) in stage II. The TT genotype was significantly higher (4.93?±?0.75 mmol/L) compared to the TC (4.67?±?0.47 mmol/L) or CC (4.66?±?0.44 mmol/L) genotype (P?=?0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43?±?5.04 ng/ mL) compared to the TC (26.24?±?4.16 ng/mL) and CC (36.76?±?8.10 ng/ mL) genotypes (P?<?0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand. CONCLUSIONS:The VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.

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Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids.

Publications

Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids.

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