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Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Clinical Center (K.D.H., J.J., S.C.H.), National Institutes of Health Bethesda, Maryland 20892
The Department of Pediatrics, University of Minnesota (O.H.P.) Minneapolis, Minnesota 55455
Address requests for reprints to: Dr. Penelope K. Manasco, Building 10, Room 10-N-262, National Institutes of Health, Bethesda, Maryland 20892.
To determine whether puberty resumes normally after long term LHRH agonist (LHRHa) treatment, we studied 16 children with central precocious puberty treated with LHRHa (D-Trp6,Pro9,NEt-LHRH) for 1–4 yr (mean, 3.3 yr). Treatment was discontinued at a mean age of 11.6 ± 1.3 (±SD) yr. Plasma hormone levels, growth velocity, rate of bone maturation, and pubertal stage were assessed at the end of treatment and 3 and 12 months later.
Basal plasma sex steroid and basal and LHRH-stimulated gonadotropin levels returned to near-pretreatment levels 3 months after discontinuation of therapy and were fully restored to pretreatment levels at 12 months. Growth velocity, which had been 7.8 cm/yr before treatment, was stable after discontinuation of treatment at approximately 2.6 cm/yr. The predicted height, which had increased during treatment (P < 0.01), remained stable at approximately 5 cm above the pretreatment predicted height. The rate of bone age advancement (
bone age/chronological age) increased gradually from 0.4 at the end of treatment to the normal value of 0.9 12 months posttreatment. Breast and pubic hair pubertal stages, which were stable throughout treatment and were 4.0 ± 0.8 (±SD) and 3.6 ± 1.0 at the end of treatment, increased to 4.9 ± 0.2 and 4.5 ± 1.0. This approximated the normal rate of 1 stage/yr. Menses occurred in 8 of 12 girls within 1 yr after treatment and in an additional 3 by 20 months after treatment. Six of the girls had menstruated before treatment, and all of these menstruated within 14 months after discontinuing therapy.
We conclude that gonadotropin and sex steroid secretion and the clinical progression through puberty appear to resume normally after discontinuation of long term LHRHa treatment of central precocious puberty. Long term follow-up will be required, however, to determine whether the improvement in predicted height of these patients will be achieved, and whether adult reproductive function will be normal
Received January 12, 1988.
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