Effectiveness of gonadotropin administration for spermatogenesis induction in hypogonadotropic hypogonadism: a possible role of androgen receptor CAG repeat polymorphism and therapeutic measures.
Endocr Metab Immune Disord Drug Targets
; 12(3): 236-42, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22385118
ABSTRACT
Prepuberal-onset (PRHH) and postpuberal-onset (PSHH) Hypogonadotropic Hypogondism (HH) refer to a heterogeneous group of patients, showing a broad spectrum of clinical signs and symptoms of androgen deficiency in consideration of the different possible aetiologies and the age at onset. These patients, though, required Gonadotropin treatment (GnTh) by means of administration of both the ß Human Chorionic Gonodadotropin (ß HCG) and the Follicle Stimulating Hormone (FSH) to obtain mature sperms in the ejaculate aiming to reach fertility levels. However, the response to GnTh is always unpredictable concerning either the effectiveness or the duration of the therapy. Consequently, different studies have been carried out to identify clinical (i.e. cryptorchidism, gynecomastia, testis size, etc) and biochemical markers [serum Testosterone (T) and Inhibin B (IB)] that can be useful to predict the effectiveness of GnTh. Given that the actions of T, even those directed at inducing and maintaining spermatogenesis, are mediated by its interaction with the Androgen Receptor (AR), we measured the AR CAG repeat polymorphism in men with HH, in order to examine whether the CAG polymorphism extensions could co-regulate the GnTh effectiveness. Twenty-three HH subjects were subdivided according to the age at onset (pre- and postpubertal) and treated with the same scheme and doses of GnTh, extending the period of treatment up to 30 months. Thirty-five healthy and fertile men served as a control group (CG). Twelve HH subjects (3 PRHH and 9 PSHH), who reached complete spermatogenesis within 12 months, showed the length of AR CAG repeat number [20 (19-23) = median (interquartile range 25th - 75th percentile)] not statistically different from our CG [20 (19-22)], while CAG repeat number [23 (20-25)] of 11 HH patients (9 PRHH and 2 PSHH) who obtained mature sperms in their ejaculate beyond a year to within 30 months, was significantly higher. Our results suggest that the length of AR CAG repeat polymorphism might affect the response to GnTh in men suffering from HH, in particular in those patients with prepubertal-onset hypogonadism.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Espermatogénesis
/
Receptores Androgénicos
/
Repeticiones de Trinucleótidos
/
Terapia de Reemplazo de Hormonas
/
Gonadotropinas
/
Hipogonadismo
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Endocr Metab Immune Disord Drug Targets
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
ENDOCRINOLOGIA
/
METABOLISMO
/
TERAPIA POR MEDICAMENTOS
Año:
2012
Tipo del documento:
Article
País de afiliación:
Italia