Liver steatosis is a key pathology in non-alcoholic or metabolic associated fatty liver disease. Though largely ignored for decades it is currently becoming the focus of research in hepatology. It is important to consider its origin and current opportunities in terms of pharmacotherapy. Essential phospholipids (EPLs) rich in phosphatidylcholine (PCH) is a widely used treatment option for fatty liver disease, and there is a solid amount of consistent clinical evidence for the regression of steatosis after treatment with EPLs. As knowledge of PCH (a key component of EPLs) pharmacodynamics and mode of action driving this widely observed clinical effect is currently insufficient, we aimed to explore the potential molecular and metabolic pathways involved in the positive effects of PCH on steatosis regression.

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BACKGROUND: Gonadotropin therapy in boys with congenital isolated hypogonadotropic hypogonadism helps to increase testes volume and induce spermatogenesis in comparison with testosterone therapy. However, difficulties with dose titration, partial therapy success, absence of generally accepted regimen protocols don’t allow to use this therapy in order to induce puberty in adolescents with Kallmann syndrome or normosmic hypogonadotropic hypogonadism.AIM: To assess the effectiveness of combination hormonal replacement therapy via human chorionic gonadotropin and recombinant follicle stimulation hormone in adolescents with congenital isolated normosmic hypogonadotropic hypogonadism and with Kallmann syndromeMATERIALS AND METHODS: This is an open single-center prospective non-controlled study. Boys with hypogonadotropic hypogonadism were receiving hormonal replacement therapy for 12 months. Initial dose of human chorionic gonadotropin was 500 IU per week. Initial dose of recombinant follicle stimulation hormone was 37.5 IU per week. Doses were doubled in 6 months. Antropometric data, Tanner stage, testes volumes, inhibin B and anti-Mullerian hormone (AMH) levels were evaluated in all the patients before the treatment, after 6 and 12 months of the therapy.RESULTS: 8 boys with hypogonadotropic hypogonadism were included into the study. Median age before therapy initiation was 15.7 years [15.33; 16.41]. In 12 months after the therapy initiation puberty development, testosterone increase from 0.44 [0.34;0.62] to 4.39 [0.88;10.51] nmol/l (p=0.012), AMH decrease from 35.70 [18.00;59.00] to 14.41 [11.60;16.65] ng/ml were noted in all the patients (p=0.017). Testes volumes increase and inhibin B level increase were not statistically significant.CONCLUSION: Gonadotropin therapy is effective in order to puberty initiation in adolescents with congenital hypogonadotropic hypogonadism. In helps to achieve not only androgenization, but also to Sertoli cells maturation.

Congenital isolated hypogonadotropic hypogonadism includes a group of diseases related to the defects of secretion and action of gonadotropin-releasing hormone (GNRH) and gonadotropins. In a half of cases congenital hypogonadism is associated with an impaired sense of smell. It’s named Kallmann syndrome. Now 40 genes are known to be associated with function of hypothalamus pituitary gland and gonads. Phenotypic features of hypogonadism and therapy effectiveness are related to different molecular defects. However clinical signs may vary even within the same family with the same molecular genetic defect. Genotype phenotype correlation in patients with congenital malformations prioritizes the search for mutations in candidate genes. There are data of significant contribution of oligogenicity into the phenotype of the disease are presented in the review. Moreover, an issue of current isolated hypogonadotropic hypogonadism definition and classification revision is raised in the review due to hypogonadotropic hypogonadism development while there are mutations in genes not associated with GNRH neurons secretion and function.