Hypogonadotropinism in Prader-Willi syndrome: Induction of puberty and spermatogenesis by clomiphene citrate

Abstract

Prader-Willi syndrome is characterized by infantile hypotonia, mental retardation, hyperphagia with obesity, and hypogonadism. Three affected male patients, ages nineteen, twenty and twenty-three, were found to have hypogonadotropic hypogonadism. Pituitary function was otherwise normal. Testicular biopsy revealed prepubertal tubules with abnormalities of interstitial tissue in one patient and arrest of tubular development in another. One patient was treated with clomiphene citrate for forty days and plasma luteinizing hormone (LH), testosterone and urinary gonadotropin levels rose to the normal range for males. These hormonal levels remained normal for at least eighty days after treatment was stopped. Normal Spermatogenesis was present on repeat testicular biopsy, and physical signs of puberty were evident. Hypogonadism in Prader-Willi syndrome appears to be the result of hypothalamic dysfunction. Clomiphene citrate may be effective treatment for male hypogonadism in this syndrome.