Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty

Abstract

The use of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of central precocious puberty (CPP), especially in girls, has increased rapidly in recent years. In the context of a secular trend towards earlier puberty onset, many girls now treated for CPP are healthy children experiencing puberty onset within the early end of the normal range. Justifications for GnRHa treatment include the preservation of adult height (AH) potential and the alleviation of presumed distress of early maturation and menarche. With a case of a family requesting treatment for an 8-year-old girl in early puberty as a background, studies of the effect of untreated CPP and of GnRHa treatment of CPP on AH are reviewed. In addition, the limited evidence relating CPP to significant psychological distress – in part due to early menses, and for the amelioration of such distress by GnRHa treatment – is discussed. Taken together, current information suggests that for girls with mildly early onset of puberty (ages 7–9 years), an informed assent discussion with the family should include the consideration of reassurance and observation for many girls who might otherwise receive 2–4 years of GnRHa treatment for a poorly defined benefit and at a cost of at least $20–30,000 per year.

Etiology of Increased Referrals for Evaluation of Early Puberty in a Tertiary Care Center in Turkey: True Precocious Puberty, Obesity, or Parental Anxiety and Lack of Knowledge?

“…Pediatric endocrine society (PES) has revisited the normal timing of pubertal maturation in girls in 1995, based on a study by Herman-Giddens et al 11 PES suggested that the youngest age for the first sign of puberty in girls that is considered normal should be changed from 8 to 7 years in Caucasian and to 6 years in African-American girls and treatment with GnRH analogs should be reserved for girls with the onset of puberty before the age of 7 years. 12 - 14 Despite this recommendation statement by PES, most pediatric endocrinologists still prefer to use the age cut off of 8 years for the diagnosis of precocious puberty in girls to avoid missing the rare cases of early puberty with an underlying pathology between the ages 6 and 8 years. However, most girls with the onset of puberty between the ages of 6 and 8 years are normal variants and do not need any intervention.…”

Comparative Efficacy and Safety of Three Current Clinical Treatments for Girls with Central Precocious Puberty: A Network Meta-Analysis

“…Each centimeter cost approximately €2,700 ($3,064 [USD]) per patient. Another study showed that approximately 2 to 4 years of GnRHa treatment of girls with CPP costs at least $20,000 to $30,000 per year (53). A retrospective cohort study including 172 patients who used the GnRHa treatment found that the annual health care costs increased by $10,103 after their diagnosis (54).…”

Girls with Premature Thelarche Younger than 3 Years of Age May Have Stimulated Luteinizing Hormone Greater than 10 IU/L

“…In our opinion the peak LH/FSH ratio is more valuable for distinguishing between a pubertal and a prepubertal response. As highlighted in recent years, there is still uncertainty regarding the diagnosis and treatment of early puberty, and the evaluation of the biochemical results with the clinical findings and the age of the patient is one of the most important points to avoid unnecessary treatment ( 21 , 22 ).…”