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Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate

Lookup NU author(s): Dr R Neely, Dr Richard Quinton


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Objective: Inhibition of pituitary gonadotropin secretion in men by T is principally mediated by aromatization to estrogen (E), which inhibits hypothalamic secretion of GnRH. We hypothesized that adult-onset isolated hypogonadotropic hypogonadism (IHH) might result from an altered central set-point for E-mediated negative feedback. Design and Setting: Longitudinal clinical investigation unit-based evaluation of the clinical and biochemical response to E-receptor blockade. Patient(s): A 31-year-old man presenting with an 18-month history of sexual dysfunction resulting from severe adult-onset IHH (LH 1.7 U/L, FSH 2.0 U/L, T 3.5 nmol/L). Intervention(s): Initial therapy with 50 mg of clomiphene citrate (CC) three times a day for 7 days, with overnight LH pulse profiling and 9 am T levels evaluated at baseline and on completion. A 2-month washout period, followed by low-dose maintenance therapy (25-50 mg/d) for 4 months. Main Outcome Measure(s): Baseline and stimulated T levels and LH pulsatility; effect on sexual function. Result(s): Clomiphene therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. Conclusion(s): Isolated hypogonadotropic hypogonadism may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. On theoretical grounds, reversal of gonadotropin deficiency with CC might be expected to have a similar biological effect. © 2006 American Society for Reproductive Medicine.

Publication metadata

Author(s): Ioannidou-Kadis S, Wright PJ, Neely RD, Quinton R

Publication type: Article

Publication status: Published

Journal: Fertility and Sterility

Year: 2006

Volume: 86

Issue: 5

Pages: 1513 e5-e9

ISSN (print): 0015-0282

ISSN (electronic): 1556-5653

Publisher: Elsevier Inc.


DOI: 10.1016/j.fertnstert.2006.03.065

Notes: Presented at the 12th International Congress of Endocrinology, Lisbon, Portugal, August 31 to September 2, 2004.


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