Puberty is heralded by the appearance of episodic gonadotropin secretion. Men with idiopathic hypogonadotropic hypogonadism have an abnormality in gonadotropin release and do not undergo normal puberty. Since idiopathic hypogonadotropic hypogonadism is thought to represent a disorder of gonadotropin-releasing-hormone (GnRH) secretion, we used long-term low-dose subcutaneous GnRH, administered in an episodic fashion by a portable infusion pump, in an effort to establish a normal adult pattern of gonadotropin secretion in six men. All subjects noted spontaneous erections, nocturnal emissions, and breast tenderness, which were associated with elevations of serum testosterone levels (77 +/- 13 ng per deciliter [mean +/- S.E.] before therapy vs. 520 +/- 182 ng after one month of treatment; P less than 0.001). Gonadotropin levels rose to normal adult ranges within one week of therapy and to supraphysiologic levels by 14 days. Testis size increased in four patients, and spermatogenesis was achieved in three patients by 43 weeks of therapy. These results suggest that long-term episodic GnRH administration can reverse idiopathic hypogonadotropic hypogonadism.
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Nitsch, M. J., Banakar, U. V.
(1994). Implantable Drug Delivery. J Biomater Appl
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Bennett, M. A., Allen, R. D.
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3: 40-47
[Abstract]
FINKELSTEIN, J. S., KLIBANSKI, A., NEER, R. M., GREENSPAN, S. L., ROSENTHAL, D. I., CROWLEY, W. F. Jr
(1987). Osteoporosis in Men with Idiopathic Hypogonadotropic Hypogonadism. ANN INTERN MED
106: 354-361
[Abstract]
SPRATT, D. I., FINKELSTEIN, J. S., O'DEA, L. ST.L., BADGER, T. M., RAO, P. N., CAMPBELL, J. D., CROWLEY, W. F. Jr.
(1986). Long-Term Administration of Gonadotropin-Releasing Hormone in Men with Idiopathic Hypogonadotropic Hypogonadism: A Model for Studies of the Hormone's Physiologic Effects. ANN INTERN MED
105: 848-855
[Abstract]
Witorsch, R. J.
(1986). Use of Gonadotropic Hormones and Sex Steroids in Assessing Male Reproduction. International Journal of Toxicology
5: 235-247
[Abstract]
SWERDLOFF, R. S., OVERSTREET, J. W., SOKOL, R. Z., RAJFER, J.
(1985). Infertility in the Male. ANN INTERN MED
103: 906-919
[Abstract]
Hammond, C. B., Ory, S. J.
(1985). Diagnostic and Therapeutic Uses of Gonadotropin-Releasing Hormone. Arch Intern Med
145: 1690-1697
[Abstract]
CUTLER, G. B. Jr., HOFFMAN, A. R., SWERDLOFF, R. S., SANTEN, R. J., MELDRUM, D. R., COMITE, F.
(1985). Therapeutic Applications of Luteinizing-Hormone-Releasing Hormone and Its Analogs. ANN INTERN MED
102: 643-657
[Abstract]