Hypothalamic and Gonadal Components of Hypogonadism in Boys with Prader-Labhart-Willi Syndrome

Urs Eiholzer, Dagmar L’Allemand, Valentin Rousson, Michael Schlumpf, Theo Gasser, Jurg Girard, Annette, Gruters, and Manuela Simoni

Journal of Clinical Endocrinology & Metabolism 2006; 91:892

Summary by Jamie H. Bassel, D.C., P.C.

A study performed at the Institute of Growth Puberty and Adolescence in Zurich, Switzerland focused on uncovering the mystery behind the type of hypogonadism typically seen in PWS males.   The objective was to determine the specific cause of Gonadal deficiency.  The cause of hypogonadism may be "primary" or "central." In primary hypogonadism, the testes themselves do not function properly. In central hypogonadism, the centers in the brain that control the gonads (hypothalamus and pituitary) do not function properly.  The design of the study placed 2 sets of PWS boys ( 8 infants and 6 around the age of puberty) .  Each group was given injections of hCG (human chorionic gonadotropin) of varying concentrations (2x500-1500 U on a weekly basis) and was followed from the onset of puberty (13.5 years through the time of publication). 

The following levels were monitored closely serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH).  Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are called gonadotropins because stimulate the gonads - in males, the testes, and in females, the ovaries.  LH stimulates secretion of sex steroids from the gonads. In the testes, LH binds to receptors on Leydig cells, stimulating synthesis and secretion of testosterone. FSH is important for sperm production. It supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation.

Inhibin B and Testosterone were also monitored in this study.  The inhibin concentration is higher in men with apparently normal fertility than in those with infertility and abnormal sperm production. Serum Inhibin B is the direct serum marker of sperm production in men with testicular disorders.

The researchers also closely followed the patient’s overall skeletal development.   The results demonstrated that infants with PWS had normal LH and Testosterone Levels when compared to infants without PWS.  It was noted that 67% of the PWS infants in this study had undescended testes.  Inhibin B levels were considered significantly low in infants with PWS and showed a steady decline between infancy and puberty.  FSH levels were showed the reverse pattern.  Bone maturation ceased at approximately 13.9 years of age.  When hCG was administered, testosterone levels increase and reduced FSH levels, however, testicular volume and inhibin B also remained low. 

In conclusion, children with PWS demonstrate a mixed form of central (hypothalamic (low LH levels)) and primary (low inhibin B and high FSH levels) hypogonadism.  This study suggests a flaw in the Sertoli cell function or an early loss of sperm cell maturation.  It has been accepted that hCG promotes testosterone production and development of male sex characteristics.

  Abstract - click here

 Edited: 03/23/2010