Potential diagnostic utility of intermittent administration of short-acting gonadotropin-releasing hormone agonist in gonadotropin deficiency

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To determine if intermittent, low-dose, short-acting gonadotropin-releasing hormone agonist (GnRH-agonist) administration sufficiently up-regulates pituitary-gonadal function in gonadotropin deficiency to be of diagnostic or therapeutic value. Case-control study. General clinical research center. Normal adult volunteers and gonadotropin-deficiency patients. Low-dose leuprolide acetate administered subcutaneously at 4- to 5-day intervals up to 1 year. Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid responses. In normal men and women, low-dose GnRH-agonist repetitively transiently stimulated gonadotropins in a gender-dimorphic manner. In congenitally gonadotropin-deficient men (n = 6) and women (n = 1), none of whom had a normal LH response to an initial GnRH-agonist test dose, this regimen consistently stimulated LH to the normal baseline range within 2 weeks. Long-term GnRH-agonist administration to a partially gonadotropin-deficient man did not alleviate hypogonadism, however. Women with hypothalamic amenorrhea (n = 2) responded normally to a single GnRH-agonist injection; however, repeated dosing did not seem to induce the normal priming effect. The subnormal LH response to GnRH-agonist in patients with congenital gonadotropin deficiency normalized in response to repetitive intermittent GnRH-agonist administration but not sufficiently to improve hypogonadism. Hypothalamic amenorrhea patients lacked the priming response to repeated GnRH-agonist but otherwise had normal hormonal responses to GnRH-agonist. We conclude that intermittent administration of a short-acting GnRH-agonist is of potential diagnostic value in distinguishing hypothalamic from pituitary causes of gonadotropin deficiency.