Elevated Pre-injection Basal Luteinizing Hormone Concentrations are Common in Girls Treated for Central Precocious Puberty

Abstract

Objective: A consensus on how to monitor girls with central precocious puberty (CPP) during gonadotropin-releasing hormone agonist (GnRHa) treatment is lacking. Increased, unstimulated basal luteinizing hormone (LH) concentrations have been suggested to indicate lack of suppression. The aim was to evaluate pre-injection basal LH concentrations during GnRHa (leuprorelin 3.75 mg) treatment every four weeks in girls with CPP. Methods: Medical records were reviewed for girls with CPP treated at a single center from 2014-2019. Clinical characteristics and laboratory findings during treatment were systematically recorded. Results: A total of 587 GnRHa pre-injection basal LH concentrations were analyzed in 74 girls. Basal LH was pubertal (≥0.3 IU/L) in 53.5% of blood samples and 87.8% of all girls had a pubertal basal LH concentration at least once. A GnRH test (n=29) was repeated in 23 girls due to suspicion of clinical progression, elevated basal LH or recordable estradiol concentrations. None had a stimulated LH >3.1 IU/L. The predictability of treatment suppression (specificity) of basal LH concentrations was 12.0% when compared to repeated GnRH stimulation tests. Despite shortening the GnRHa injection interval to three weeks, basal LH concentrations remained pubertal in 85.7% girls. A significant reduction in height standard deviation score (p<0.001) and bone age advance (p<0.001) was observed during treatment. Conclusion: Pre-injection basal LH remains at pubertal concentrations during treatment with leuprorelin 3.75 mg in girls with CPP. Clinical monitoring of pubertal progression is preferable to routine basal LH concentrations. Repeat GnRH stimulation testing should be regarded as the gold standard.

Benefits from the first year of GnRHa therapy in boys with idiopathic central precocious puberty when initiating treatment after age 9 years: findings from a real-world retrospective study

“…And the persistent elevation or the temporal decline in basal unstimulated LH during subsequent treatments have also been observed. This confirms previous conclusions that elevated concentrations of basal unstimulated LH values fail to demonstrate insufficient pituitary suppression, as other hormonal parameters and non-hormonal parameters suggest apparent pubertal suppression, and are thus unsuitable for routine therapeutic monitoring [24][25][26]. Suppression of sex steroids caused a progressive decrease in bone maturation, as demonstrated here, the BA/CA ration tapered off over time.…”

The Use of Morning Urinary Gonadotropins and Sex Hormones in the Management of Early Puberty in Chinese Girls

“…Peak plasma LH levels of less than 2 IU/L are considered indicative of biochemical suppression ( 24 ). Efforts were made to simplify this test by using preinfection serum basal LH, but they failed ( 25 ); so researchers tried to replace GnRHST by evaluating FMV urinary hormone levels before the administration of GnRHa. Zung et al ( 26 ) found that 8% of uLH levels in 36 CPP patients with adequate gonadotropin suppression were above the prepubertal threshold.…”

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty

“…The primary outcome measure, the basal LH has been shown by many to be suitable for monitoring the effects of GnRH agonist treatment, and basal LH <0.6 IU/L was suggested as a cutoff for adequate suppression in CPP (22,40). Throughout treatment, the basal LH level was well suppressed to below this cutoff value, suggesting that gonadotropic axis suppression was effectively achieved (Figure 4A) (20-22, 41), the basal FSH level was maintained at a prepubertal level (<2.5 IU/L; Figure 4B) (23), and the LH/FSH ratio was maintained below the 0.66 cutoff for nonprogressive precocious puberty (Figure 4C) (24,25,42).…”