Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose?

Abstract

Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose. Methods: Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate. Results: Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001). Conclusion: Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.

Can Body Mass Index Affect Height Growth at Menarche among Girls Receiving Treatment for Early Puberty? A Retrospective Study in Korean Girls

“…ICPP and EP were diagnosed based on the presence of secondary sexual characteristics [ 30 ], including BA greater than the chronological age (CA) [ 30 ] and peak luteinizing hormone (LH) levels > 5 IU/L according to a standard intravenous GnRH stimulation test [ 4 ], and the absence of central nervous system lesions on brain magnetic resonance imaging [ 4 ]. GnRHa was administered intramuscularly every 28 days, as a depot formulation of the GnRH analog leuprorelin, at a dose of 0.2–0.3 mg/kg/dose every 4 weeks [ 4 ]. GnRHa treatment was initiated before the age of 8 years (ICPP, range: 6.17–7.92) and between 8 and 9 years (EP, range: 8.00–8.92).…”

“…This condition limits the final adult height owing to rapid growth velocity and early epiphyseal closure [ 3 ]. GnRH agonist (GnRHa) therapy is considered the standard treatment for this condition [ 4 ]. CPP treatment aims to delay the early progression of puberty, inhibit epiphyseal growth to prevent shorter adult height, and to allow normal sexual maturation to reduce psychosocial problems [ 4 , 5 ].…”

Final adult height in children with central precocious puberty – a retrospective study

“…Doses of GnRHa for optimal HPG suppression are not well defined and they vary in different countries. Lower doses (3.75 mg/28 days, 80-120 µ/kg/28 days) are preferred in Europe and Asia, whereas in the US doses are higher (7.5-15 mg/ 28 days, 200-300 µ/kg/28 days) (43). A Japanese study concluded that the minimum effective suppressive dose is already 30 µg/kg (44).…”

“…A Japanese study concluded that the minimum effective suppressive dose is already 30 µg/kg (44). A Turkish study suggests that higher doses may be required for cases at advanced stages and increased body weight (>36.2kg) or BMI (>1.64 SDS) (43). Of note, the concerns of over suppression are suppression of growth, a possible transient…”

Effects of High-Glucose and High-Fat Condition on Estrogen Receptor- and Sexual Precocity-Related Genes in GT1-7 Cells

“…The incidence of sexual development disorders in children, especially precocious puberty, has increased significantly in recent years and has become one of the most common pediatric endocrine diseases [9,10], and idiopathic central precocious (idiopathic central precocious puberty, ICPP) is especially important. The direct cause of ICPP is early initiation of the GnRH secretion pulse in the hypothalamus and the increase of the overall level, which activates the pituitary and downstream gonadal organs such as the ovaries and uterus, and makes the HPG axis reach the puberty state prematurely [11,12]. However, the mechanism underlying the abnormal increase in GnRH secretion requires elucidation and is the subject of current research.…”