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


METHODS
Longitudinal clinical investigation unit-based evaluation of the clinical and biochemical response to E-receptor blockade.


METHODS
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).


METHODS
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.


METHODS
Baseline and stimulated T levels and LH pulsatility; effect on sexual function.


RESULTS
Clomiphene therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function.


CONCLUSIONS
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.
Ioannidou-Kadis
Stella
S
Department of Endocrinology, Royal Victoria Infirmary and University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom.
Wright
Pat J
PJ
Neely
R Dermot
RD
Quinton
Richard
R
D000328:Adult; D002996:Clomiphene / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D020127:Recovery of Function / Q000187:drug effects; D012735:Sexual Dysfunction, Physiological / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
D004965:Estrogen Antagonists; D002996:Clomiphene