A dose finding study of a super long-acting luteinizing hormone-releasing hormone analog (leuprolide acetate depot, TAP-144-SR) in the treatment of central precocious puberty. The TAP-144-SR CPP Study Group.
The effect of leuprolide acetate (D-Leu6-[des-Gly10-NH2]-LH-RH ethylamide acetate) for depot suspension (TAP-144-SR), a synthetic analog of luteinizing hormone-releasing hormone, was examined in three doses in 36 patients (34 girls, 2 boys) with central precocious puberty. TAP-144-SR was injected subcutaneously every four weeks for twelve weeks, and clinical symptoms and plasma and urinary levels of various hormones were followed every four weeks. Eleven girls given 10 micrograms/kg showed a significant decrease in peak plasma LH and FSH responses to LH-RH test, but basal plasma LH and FSH did not change significantly. In 13 patients (11 girls and 2 boys) given 30 micrograms/kg and 12 girls given 90 micrograms/kg, both basal and peak LH and FSH were significantly suppressed. Urinary excretion of LH decreased significantly in all groups except in the 10 micrograms/kg group. Urinary excretion of FSH did not change significantly in the 10 and 30 micrograms/kg groups, but it decreased significantly in the 90 micrograms/kg group. In girls, plasma and urinary estradiol also fell greatly, but the difference was insignificant except in the 90 micrograms/kg group. Regression of sexual characteristics was observed in almost half of the patients at the 12th week of the treatment. Side effects were minimal. A dose of more than 30 micrograms/kg of TAP-144-SR is effective in suppressing gonadotropins and causing improvement of clinical symptoms, and appears to be useful in treating children with central precocious puberty.
Tanaka
T
T
Division of Endocrinology & Metabolism, National Children's Hospital, Tokyo, Japan.
Hibi
I
I
Kato
K
K
Saito
S
S
Shimizu
N
N
Suwa
S
S
Nakajima
H
H
D015065:17-Hydroxycorticosteroids / Q000652:urine; D015068:17-Ketosteroids / Q000652:urine; D000311:Adrenal Glands / Q000187:drug effects; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D003687:Dehydroepiandrosterone / Q000097:blood; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000652:urine; D006801:Humans; D015592:Immunoradiometric Assay; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016729:Leuprolide / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000652:urine; D008297:Male; D011629:Puberty, Precocious / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood
D015065:17-Hydroxycorticosteroids; D015068:17-Ketosteroids; D003692:Delayed-Action Preparations; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide