Longer trinucleotide repeats of androgen receptor are associated with higher testosterone and low oxytocin levels in diabetic premature ejaculatory dysfunction patients

Abstract

BackgroundDespite its worldwide high occurrence, the obscurity regarding the description, epidemiology and management of premature ejaculation remains provocative. It is well established that male premature ejaculatory dysfunction is an increasing problem due to spontaneous ejaculation across a variety of general and clinical subjects. The main goal of this study was to determine the relationships between trinucleotide repeats of the androgen receptor (AR), sex steroids, and pituitary hormones with sexual function in men with type 2 diabetes mellitus (DM) and reported with acquired premature ejaculation (PE).MethodsA total of 150 normal and 250 PE + DM subjects were enrolled in this study. Each subject was invited to fill out an elaborative questionnaire to acquire precise selective information regarding BMI, duration of PE + DM, self-reported Intra-Vaginal Ejaculatory Latency Time (IELT), sexual and mental health status by using the premature ejaculation diagnostic tool (PEDT) and Beck Depression Inventory-II (BDI-II). Pearson’s correlation analysis was used to analyze the relationship between clinical, hormonal, and genetic variables. Ward’s minimum variance cluster analysis and principal component analysis were used for evaluation of dependence between genetic, clinical, and demographic parameters.ResultsThe patients who have the lowest number of (≤21) (CAG)n repeats have higher serum oxytocin levels (114.2 pg/ml; n = 54, 43.2%) than the controls (69.18 pg/ml; n = 22, 17.6%) and the patients with the highest (≥26) number of (CAG)n repeats (62.9 pg/ml; n = 108, 43.2%).On the other hand, patients who have the highest numbers of (CAG)n repeats (≥26) have higher serum testosterone (6.1 ng/ml; n = 108, 43.2% of cohort) lower prolactin (3.01 ng/ml; n = 108, 43.2% of cohort) levels than the controls and patients with the lowest numbers (≤21) of (CAG)n repeats and their TSH (1.53 mIU/L, P < 0.05) levels are lower than those of controls. In the Pearson correlation model, self-estimated IELT demonstrated significantly negative correlation with both (CAG)n and (GCC)n repeats (r = − 0.16, p = 0.0001; r = − 0.19, p = 0.0001) respectively. These repeats have positive correlation with PEDT (r = 0.28, p = 0.0001: r = 0.24, p = 0.0001, whole model) and inversely correlated with BDI-II (r = − 0.25, p = 0.0001).ConclusionThis study indicates that androgen receptor polymorphism modulates the endocrine effect on ejaculatory reflex and depends strongly on its “cofactors”. Moreover, our results also confirmed an association between long tri-nucleotide repeats of androgen receptor, sex steroids, pituitary, and thyroid hormones in relation to acquired premature ejaculatory dysfunction in diabetic patients. However, endocrine regulation of PE reflex is a complex phenomenon that requires further investigation.

Premature Ejaculation and Endocrine Disorders: A Literature Review

“…5-HT2C receptor agonists have been reported to improve glucose tolerance and insulin sensitivity in obese and diabetic mice [ 53 ]. It has been reported that DM patients with PE have lower levels of thyroid stimulating hormone (TSH) and PRL, which are also responsible for PE etiology, than healthy controls [ 54 ].…”

Understanding and treating ejaculatory dysfunction in men with diabetes mellitus

“…It has been shown that DM patients with PE have a strong association with a polymorphism constituting a long trinucleotide (CAG triplet) repeat sequence in the gene coding for the AR, compared to diabetics without PE 93 . The DM‐related PE in this study was diagnosed/measured using the IELT and score on the premature ejaculation diagnostic tool, both of which had significant correlation with the length of the CAG trinucleotide repeats in the AR gene 118 . The authors postulated this polymorphism may reflect hormonal modulation in the patient that mediates the PE; more specifically a raised T level and low oxytocin levels.…”

“…93 The DM-related PE in this study was diagnosed/measured using the IELT and score on the premature ejaculation diagnostic tool, both of which had significant correlation with the length of the CAG trinucleotide repeats in the AR gene. 118 The authors postulated this polymorphism may reflect hormonal modulation in the patient that mediates the PE; more specifically a raised T level and low oxytocin levels. The former would seem to support studies proposing raised T levels increase the risk of PE.…”

“…Whilst sexual dysfunction has been shown to be strongly linked with psychological disorders, 122,123 the presence of depression/anxiety in patients specifically with DM has been found to increase the proba-bility of concurrent EjD, namely PE. 118,124,125 Furthermore, a recent observational study investigating aetiological factors of acquired PE found just over 30% of patients with DM-related PE have either depression or anxiety. 125 Supporting this strong relationship between sexual dysfunction and depression, a recent meta-analysis revealed a bidirectional association between the two, such that those with depression are more likely to exhibit sexual dysfunction (adjusted odds ratio of 1.7) and those with sexual dysfunction are more likely to have depression (adjusted odds ratio of 3.2).…”

Serotonin transporter (5‐HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation

“…Previous studies have reported that longer ( CAG )n repeats are considerably compromised the androgen receptor transcriptional activity, whereas short stretches are the cause of prostate cancer. However, the role of ( GGC )n repeats is still undefined (Khan et al ., a).…”