CLOMIPHENE CITRATE IN MEN: INCREASE OF CORTISOL, LUTEINIZING HORMONE, TESTOSTERONE AND STEROID-BINDING GLOBULINS

in Journal of Endocrinology
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SUMMARY

The effects of clomiphene citrate were studied in nine normal men, in three patients with partial panhypopituitarism, and in four patients with isolated gonadotrophin deficiency. The administration of this drug to the normal subjects in a dosage of 3 mg/kg/day for 10 days resulted in a mean rise in serum luteinizing hormone (LH) of 107%, in plasma 17β-hydroxyandrogens (17-OHA) of 114%, and in plasma total cortisol of 86%. The rise of testosterone concentration in normal subjects was associated with a doubling of the non-protein bound fraction, and also with increased binding of testosterone to sex hormone-binding globulin (SHBG). In contrast, plasma non-protein bound and urinary unconjugated cortisol remained unchanged. The percentage of plasma cortisol not bound to protein fell, indicating that the rise in total plasma cortisol was secondary to increased protein binding. This was confirmed by finding increased binding of both cortisol and testosterone to their specific binding globulins at 1 °C, due apparently to increased concentrations of SHBG and corticosteroid-binding globulin after clomiphene administration. All the responses to clomiphene were prevented by simultaneous administration of fluoxymesterone in two normal subjects.

All the hypopituitary patients showed no rise of LH, 17-OHA or cortisol. The hypogonadotrophic patients, however, showed a normal total cortisol rise.

It is suggested that clomiphene has two actions. First, it interferes with the hypothalamic feed-back mechanisms for testosterone, resulting in increased LH secretion, and secondly it has an oestrogen-like effect in stimulating production of steroid-binding globulins.

 

      Society for Endocrinology

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