Effect of Cyproterone Acetate Therapy on Gonadotropin Response to Synthetic Luteinizing Hormone-Releasing Hormone (LRH) in Girls with Idiopathic Precocious Puberty

Abstract

50 mg daily of cyproterone acetate (CA) were orally administered for 8 to 35 months to 7 girls with idiopathic precocious puberty. Plasma levels of FSH, LH, cortisol, testosterone, estradiol, and progesterone were measured in 6 patients before treatment. Compared with control subjects of the same chronological age, significantly higher values were found for gonadotropins, testosterone, and estradiol. After treatment, no significant variation was observed in FSH and LH levels; testosterone was reduced in the majority of the cases without significant decline in mean values; estradiol fell significantly and returned in the prepubertal range. The plasma gonadotropin pattern following exogenously administered luteinizing hormone-releasing hormone (LRH, 100 μg iv) was characterized before treatment by an exaggerated LH response both in terms of maximum level (32.02 ± 4.35 se mlU/ml; prepubertal controls: 16.20 ± 1.45 se mlU/rnl) and maximum increment above baseline values (25.36 ± 2.84 se mlU/ml; prepubertal controls: 13.78 ± 1.71 mlU/ml); plasma FSH response was similar to prepubertal subjects. Treatment with CA caused a significant reduction of mean LH response (P > .025 in comparison with pre-treatment values for maximum level and maximum increment), whereas effect on FSH response was minimal. In all patients examined, a gonadotropin release from the pituitary after the injection of synthetic LRH was evident also after several months of therapy. This suggests that the action of CA upon the hypothalamic-hypophyseal complex in precocious puberty cannot be solely antigonadotropic. The diminished responsiveness of LH to synthetic LRH may be attributed to the progestagenic effect of CA and/or to the CA-induced decrease in circulating estradiol. The possibility of a depressed steroid biosynthesis at the ovarian level has to be considered.