Testosterone, LH levels and methylation status in hypersexual men
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Background: Hypersexual disorder integrates aspects of sexual addiction, impulsivity and compulsivity and is related to HPA axis dysregulation. Gonadal influence and the function of HPG axis in hypersexual disorder is unknown. The aim of this study was to investigate testosterone and LH levels in 67 men with hypersexual disorder compared to 39 age matched healthy controls as well as epigenetic modifications in HPA and HPG-axis coupled CpG-sites. Methods: Basal morning plasma levels of testosterone, SHGB, LH were assessed. The genome-wide methylation pattern of over 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip and adjusted for white blood cell type heterogeneity. CpG sites located within 2000 bp of the transcriptional start site of HPA and HPG axis coupled genes were included (CRH, CRHBP, CRHR1, CRHR2, FKBP5, NR3C1, GNRHR, LHCGR, ESR1, ESR2, PGR, AR, SHBG, GPER, CYP19A1, SRD5A1, OXTR, KISS1, KISS1R). We performed multiple linear regression models of methylation M-values to plasma testosterone levels and to plasma LH levels. Results: LH plasma levels were significantly higher in hypersexual patients compared to healthy volunteers. No significant differences in plasma testosterone and SHGB levels were found between the groups. 221 individual CpG sites were tested. For testosterone plasma levels, 12 were nominally significant (p < 0.05), (genes CRH, CRHBP, CRHR2, ESR1, ESR2, GPER, KISS1R, OXTR, SHBG) and twenty for LH plasma levels (genes CRHR1, CRHR2, ESR2, GPER, KISS1R, OXTR, SHBG). No individual CpG site was significant after multiple testing corrections (FDR-method). Conclusions: Our results show evidence of dysregulation of the HPG axis with increased LH plasma levels in men with hypersexual disorder.