Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study

Background. No study has assessed the possible involvement of GGC androgen receptor (AR) polymorphism in sexual function. Our aim is to evaluate the association between CAG and GGC AR polymorphisms in this function. Methods. We retrospectively examined eighty-five outpatients. Clinical, biochemical, and genetic parameters were considered. Sexual assessment was performed using the International Index of Erectile Function (IIEF) which evaluates erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). Results. In the whole sample, CAG repeats were inversely correlated with EF, OF, and total IIEF-15 score, whereas GGC tracts did not show any significant correlation with sexual function. CAG relationship with IIEF items retained significance only in the eugonadal but not in the hypogonadal cohort. On the other hand, GGC tracts were not found to be significantly correlated with IIEF variables in either eugonadal or hypogonadal subjects. In eugonadal subjects, logistic regression pointed out that a higher number of CAG triplets were associated with lower values of EF, OF, SD, OS, and total IIEF independently from other confounders. Conclusions. GGC polymorphism seems not to exert any influence on sexual function, whereas CAG polymorphism appears to affect sexual parameters only in eugonadal subjects

Gut: A key player in the pathogenesis of type 2 diabetes?

The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible of the secretion of molecules that may impair insulin secretion/action. At the same time, intestinal milieu regulates the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin, CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism in general and in particular glucose metabolism. Thus, the aim of this paper is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases

Effetti del polimorfismo CAG del recettore degli androgeni sui principali outcomes della terapia sostitutiva con testosterone in soggetti affetti da ipogonadismo ipogonadotropo post-chirurgico.

Lo scopo di questo lavoro è stato quello di valutare il ruolo indipendente del polimorfismo CAG del gene del recettore degli androgeni (AR), sugli effetti metabolici, ossei, di composizione corporea e sessuali della terapia sostitutiva con testosterone nell’ipogonadismo ipogonadotropo post-chirurgico maschile, una condizione spesso associata ad ipopituitarismo e in cui gli effetti testosterone-correlati su quegli outcomes sono combinati con quelli derivanti dalla somministrazione concomitante di terapie sostitutive della funzione ipofisaria. Sedici uomini affetti da ipogonadismo ipogonadotropo post-chirurgico sono stati valutati prima e dopo terapia con testosterone. Sono stati studiati i fattori di rischio cardiovascolare (CVRFs), i parametri di funzione sessuale e del metabolismo osseo, i parametri di composizione corporea, gli effettori periferici degli ormoni ipofisari e il polimorfismo CAG del gene AR. Il testosterone, l’insulin-like growth factor-1 (IGF-1) e l’estradiolo erano i soli ormoni che significativamente cambiavano prima e dopo la somministrazione di testosterone. Tutti i CVRFs miglioravano significativamente dopo TRT. Un’uguale tendenza si osservava per i parametri di funzione sessuale (questionario IIEF) e del metabolismo osseo (densità minerale ossea). Il grasso centrale diminuiva significativamente dopo terapia ormonale, mentre le altre misure della composizione corporea non cambiavano in modo significativo. Alla regressione lineare multipla, dopo correzione per Δ-testosterone, associazioni positive sono state riscontrate tra il numero di triplette CAG e Δ-CVRFs. Inoltre, associazioni negative sono state trovate tra la lunghezza del tratto CAG e il miglioramento dei parametri di funzione sessuale. Per quanto riguarda il metabolismo osseo, associazioni negative sono state trovate tra la lunghezza del tratto CAG e il miglioramento della densità minerale ossea a livello del femore e della colonna lombare. Infine, per quanto riguarda la composizione corporea, un’associazione positiva è stata trovata tra la lunghezza del tratto CAG e la diminuzione del grasso viscerale. In conclusione, nell’ipogonadismo ipogonadotropo post-chirurgico, la minor lunghezza del tratto CAG del gene AR sembra esercitare effetti positivi sul metabolismo, sulla funzione sessuale, ossea e sulla composizione corporea dopo terapia con testosterone, indipendentemente dagli effetti delle terapie sostitutive della funzione ipofisaria.The aim of this work was to evaluate the independent role of Androgen Receptor (AR) gene CAG repeat polymorphism on the sexual, metabolic, bone and body composition effects of testosterone replacement therapy in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the testosterone-related effects on those outcomes are combined with the ones deriving from the concomitant administration of pituitary-function replacement therapies. Sixteen men affected by post-surgical hypogonadotropic hypogonadism were evaluated before and after testosterone therapy. Cardiovascular risk factors (CVRFs), sexual function parameters, bone metabolism, body composition parameters, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. Testosterone, insulin-like growth factor-1 (IGF-1) and estradiol were the only hormones, which significantly changed before and after testosterone administration. All CVRFs significantly improved after TRT. A similar trend was observed for sexual function parameters (IIEF questionnaire) and bone metabolism (bone mineral density). Central fat diminished significantly after hormonal therapy, whereas other body composition measures did not change significantly. At multiple linear regression, after correction for ∆-testosterone, positive associations were found between the number of CAG triplets and Δ-CVRFs. Also, negative associations were found between CAG repeat length and the improvement of sexual function parameters. As far as bone metabolism is concerned, negative associations were found between CAG repeat length and the improvement of bone mineral density at femoral and lumbar spine. Finally, regarding body composition, positive association was found between CAG length and the decrease of visceral fat. In male post-surgical hypogonadotropic hypogonadism, shorter AR gene CAG tract length seems to exert positive effects on metabolic, sexual, bone and body composition profile after testosterone therapy, independently of the effects of the concomitant pituitary-function replacement therapies

Dysregulation of the hypothalamic-pituitary-adrenal axis increases central body fat accumulation in males affected by diabetes mellitus and late-onset hypogonadism

OBJECTIVE: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH). METHODS: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered. RESULTS: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 [interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 [interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 [P<.001]; β = 1.156 [P<.001]; β = -7.675 [P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH. CONCLUSION: Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation

Synergistic effect of androgen receptor (CAG repeat length) and endothelial nitric oxide synthase (Glu298Asp variant) gene polymorphisms on seminal parameters in men with idiopathic oligoasthenozoospermia

[No abstract available