Raivio T et al. (2007) Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med 357: 863–873

A congenital defect in the release or action of gonadotropin-releasing hormone (GnRH) can cause idiopathic hypogonadotropic hypogonadism, a condition that results in male infertility. Patients with this condition have incomplete or absent sexual maturation by the age of 18 years and were previously thought to require life-long treatment. Raivio and colleagues carried out a study to investigate whether discontinuation of hormonal therapy could cause neuroendocrine and gonadal reversal of idiopathic hypergonadotropic hypogonadism.

Patients with a diagnosis of idiopathic hypogonadotropic hypogonadism were eligible for inclusion. Following discontinuation of treatment, reversal was defined as a normal adult endogenous serum testosterone level of ≥270 ng/dl.

Out of 50 men with idiopathic hypogonadotropic hypogonadism, 5 patients met the criteria for reversal of hypogonadism prospectively a mean (± SD) of 6 ± 3 weeks after treatment discontinuation, and 10 patients were identified retrospectively. Of the 15 men, 6 had absent puberty and 9 had partial puberty at first presentation. All had abnormal secretion of GnRH-induced luteinizing hormone and had received hormonal treatment to encourage fertility. Mean levels of endogenous testosterone, luteinizing hormone, follicle-stimulating hormone and testicular volume increased in patients who experienced reversal of hypogonadism.

This study reports a reasonably high incidence of sustained reversal. Patients with idiopathic hypogonadotropic hypogonadism should be informed of the possibility of spontaneous reversal of hypogonadism and fertility after discontinuation of reproductive hormonal therapy.