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


METHODS
Case-control study.


METHODS
General clinical research center.


METHODS
Normal adult volunteers and gonadotropin-deficiency patients.


METHODS
Low-dose leuprolide acetate administered subcutaneously at 4- to 5-day intervals up to 1 year.


METHODS
Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid responses.


RESULTS
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.


CONCLUSIONS
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.
Zimmer
Carrie A
CA
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Ehrmann
David A
DA
Rosenfield
Robert L
RL
D000293:Adolescent; D000328:Adult; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000209:etiology; D016729:Leuprolide / Q000008:administration & dosage*; D008297:Male; D010507:Periodicity; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
D004304:Dosage Forms; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide