Acceleration of puberty in boys with delayed puberty by clomiphene citrate. A clinical and laboratory study.

Abstract

Abstract. Clomiphene citrate was administered at a dose of 50 mg/day for 3 months to 29 boys with delayed puberty, 15 in a stage of early puberty (group 1) and 14 in stages of mid puberty (group 2). In both groups a significant acceleration in the advancement of pubertal signs was noted in the 6-month period following initiation of therapy as compared to a non-treated control group. A significant rise in the mean (± sd) basal plasma LH levels, from 1.0 ± 0.4 to 2.7 ± 2.2 mU/ml in group 1 (P < 0.05) and from 1.0 ± 0.6 to 2.2 ± 1.7 mU/ml in group 2 (P < 0.05) was observed following the treatment period with clomiphene. Concomitantly there was a rise of the mean basal plasma FSH level from 1.1 ± 0.4 to 2.0 ± 1.5 mU/ml in group 1 (P ± 0.05) and from 1.9 ± 1.6 to 3.4 ± 3.0 mU/ml in group 2 (P < 0.02). The mean LH peak response to an iv bolus of LRH (50 μg/m2 iv) rose from 8.3 ± 4.2 to 13.0 ± 5.3 mU/ml in group 1 (P < 0.05) and from 9.2 ± 5.8 to 12.6 ± 6.8 mU/ml in group 2 (NS). The mean peak plasma FSH response to LRH rose from 2.0 ± 0.6 to 5.9 ± 4.2 mU/ml in group 1 (P < 0.05) and from 4.3 ± 4.0 to 7.0 ± 6.8 mU/ml in group 2 (NS). Clomiphene therapy caused a rise of the basal plasma testosterone level from 68 ± 53 to 313 ± 270 ng/100 ml in group 1 (P < 0.01) and from 103 ± 67 to 392 ± 248 ng/100 ml in group 2 (P < 0.01). The plasma testosterone response to one hCG stimulation (5000 U im), tested in 4 boys immediately before and after the 3-month period of clomiphene administration revealed an increase in both the basal and the peak testosterone levels (P < 0.05 and P < 0.001, respectively). A standard clomiphene test consisting of the administration of 100–200 mg/day clomiphene citrate for 8 days was performed in 8 boys before initiation of clomiphene treatment for the 3-month period. In 4, including 2 boys in an early stage of puberty, there was a suppression of the basal level of gonadotrophins and their response to synthetic LRH. The other 4 boys, all of them in stages of mid-puberty, showed an increase in the basal and peak plasma gonadotrophin levels following LRH stimulation. In all 8 boys there was a significant rise of the basal plasma testosterone level. Despite the varying response to the short clomiphene test in these 8 boys, all gave a good response to the prolonged administration of clomiphene citrate. It was concluded that treatment with small doses of clomiphene citrate for a period of 3 months induces an acceleration of puberty in boys with delayed or slowlyprogressing puberty, once the stage of initiation of puberty has been passed.