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 β Human Chorionic Gonodadotropin (β 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.
Keywords: Androgen deficiency syndrome, CAG repeat length polymorphism, gonadrophin therapy, hypogonodatropic
hypogondism, inhibin B, testosterone, Corticotropin, Androgen receptor, Free Thyroxine, Free Triiodothyronine, Gonadropins, Gonadotropin-releasing hormone, Prolactin.
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