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Hypogonadotropic Hypogonadism
Hypogonadotropic hypogonadism is the cause of infertility in a small percentage of patients and can be either congenital or acquired. Congenital hypogonadotropic hypogonadism (Kallmannís syndrome) results from the abnormal production or secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and may be associated with other congenital anomalies such as anosmia, deafness, cleft palate, and renal anomalies.79 Causes of acquired hypogonadotropic hypogonadism include pituitary tumors, isolated gonadotropin deficiency, panhypopituitarism, pituitary trauma, and anabolic steroid use.
The initial evaluation of a patient with hypogonadotropic hypogonadism should include a head CT or MRI to rule out the possibility of a pituitary tumor that may require surgical extirpation. In addition, a serum prolactin level should be obtained and hyperprolactinemia, if present and not requiring surgical treatment of a tumor, medically treated prior to initiation of gonadotropin replacement therapy.
In patients with gonadotropin deficiency, normal spermatogenesis can frequently be restored by treatment with exogenous gonadotropins or GnRH. Human chorionic gonadotropin (hCG), which possesses LH-like activity, and human menopausal gonadotropin (hMG), which contains both FSH and LH, have been the replacement agents used most frequently in the treatment of these patients. Treatment usually is begun with hCG (1,500-3,000 I.U.) administered subcutaneously three times per week. After 8-12 weeks of hCG therapy, hMG therapy is added at a dose of 37.5-150 I.U. administered subcutaneously 2-4 times per week. Serum testosterone levels and semen analyses are followed serially during the course of treatment.
Treatment of hypogonadotropic hypogonadism with pulsatile GnRH analogs has been reported with similar success. Whitcomb and Crowley reported restoration of fertility in 8 of 9 patients with idiopathic hypogonadotropic hypogonadism using pulsatile GnRH therapy.80 The GnRH is given either intravenously or subcutaneously in a pulsatile fashion with a portable infusion pump or intranasally. Patients who fail to respond to hCG/hMG therapy may respond to GnRH therapy. In addition, patients with hypogonadotropic hypogonadism who fail to respond to conventional gonadotropin therapy or GnRH agonists may respond to a combination of growth hormone and gonadotropins.
Hypogonadotropic hypogonadism is the cause of infertility in a small percentage of patients and can be either congenital or acquired. Congenital hypogonadotropic hypogonadism (Kallmannís syndrome) results from the abnormal production or secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and may be associated with other congenital anomalies such as anosmia, deafness, cleft palate, and renal anomalies.79 Causes of acquired hypogonadotropic hypogonadism include pituitary tumors, isolated gonadotropin deficiency, panhypopituitarism, pituitary trauma, and anabolic steroid use.
The initial evaluation of a patient with hypogonadotropic hypogonadism should include a head CT or MRI to rule out the possibility of a pituitary tumor that may require surgical extirpation. In addition, a serum prolactin level should be obtained and hyperprolactinemia, if present and not requiring surgical treatment of a tumor, medically treated prior to initiation of gonadotropin replacement therapy.
In patients with gonadotropin deficiency, normal spermatogenesis can frequently be restored by treatment with exogenous gonadotropins or GnRH. Human chorionic gonadotropin (hCG), which possesses LH-like activity, and human menopausal gonadotropin (hMG), which contains both FSH and LH, have been the replacement agents used most frequently in the treatment of these patients. Treatment usually is begun with hCG (1,500-3,000 I.U.) administered subcutaneously three times per week. After 8-12 weeks of hCG therapy, hMG therapy is added at a dose of 37.5-150 I.U. administered subcutaneously 2-4 times per week. Serum testosterone levels and semen analyses are followed serially during the course of treatment.
Treatment of hypogonadotropic hypogonadism with pulsatile GnRH analogs has been reported with similar success. Whitcomb and Crowley reported restoration of fertility in 8 of 9 patients with idiopathic hypogonadotropic hypogonadism using pulsatile GnRH therapy.80 The GnRH is given either intravenously or subcutaneously in a pulsatile fashion with a portable infusion pump or intranasally. Patients who fail to respond to hCG/hMG therapy may respond to GnRH therapy. In addition, patients with hypogonadotropic hypogonadism who fail to respond to conventional gonadotropin therapy or GnRH agonists may respond to a combination of growth hormone and gonadotropins.
