Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy in patients with congenital hypogonadotropic hypogonadism: a multicentre clinical study

Background: Pulsatile gonadotropin-releasing hormone (GnRH) therapy may restore function of the hypothalamus-pituitary-gonad axis and induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH). The study sought to test the reliability of a newly developed Innopump (R) hormone pump, and to confirm the efficacy and safety of pulsatile GnRH therapy (by Innopump (R) hormone pump) in CHH patients. Methods: From November 2017 to November 2018, 28 male patients with CHH were treated with pulsatile GnRH at Peking Union Medical College Hospital, Beijing Chaoyang Hospital, and Shandong Provincial Hospital. A prospective, self-controlled, 7-day clinical trial was conducted. The primary outcome measures were the efficacy and safety of pulsatile GnRH therapy (which was administered via the Innopump (R) hormone pump). The secondary outcome measures included total serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. Results: All of the patients participated the clinical study. For 7 days, a dosage prescribed by doctors was accurately administered by the Innopump (R) hormone pump, and recorded by the pump. During the treatment, LH and FSH levels gradually increased to 2.66 +/- 1.74 and 5.05 +/- 3.03 IU/L, respectively. Upper respiratory tract infection in 1 patient and slight nausea in another patient were reported, which were confirmed to be unrelated to the pulsatile GnRH therapy. Conclusions: The Innopump (R) hormone pump was found to be reliable in drug administration, and to have an accurate alarming system. It effectively and safely treated patients with CHH. Pulsatile GnRH therapy may produce a physiological pattern of GnRH secretion, and re-establish pituitary-gonad axis function by increasing gonadotropin levels.