Reproducibility and Refinement of Urinary LH in the Screening of Progressive Puberty in Girls.

CONTEXT: First-voided urinary LH (FVU-LH) has been suggested as an alternative to GnRH stimulation test for detection of precocious puberty. OBJECTIVE: To evaluate the reproducibility of FVU-LH, its correlation with basal and GnRH-stimulated gonadotropins, and its diagnostic value for differentiating progressive from nonprogressive puberty. DESIGN AND PARTICIPANTS: Clinical and endocrine data were obtained from the medical records of 95 girls with suspected progressive puberty who underwent 2 consecutive FVU-LH tests. In 55 of these participants, GnRH stimulation test was performed close to the FVU-LH test. The reported cutoff levels of 5 IU/L and 1.16 IU/L for GnRH-stimulated LH and FVU-LH, respectively, were used as markers of progressive puberty, clinically defined as bone age advancement of ≥1 year and/or growth velocity SD score ≥2, in addition to thelarche. RESULTS: The 2 consecutive measurements of FVU-LH were highly correlated (r = 0.830; P < 0.001). The higher of the 2 results was better correlated with basal gonadotropins and GnRH-stimulated LH. Furthermore, it aligned better with the clinical outcome of girls with early thelarche, which supports the approach of double tests of FVU-LH to distinguish progressive from nonprogressive puberty. By comparison to GnRH-stimulated LH, the higher FVU-LH value had better sensitivity (68%), whereas peak LH had better specificity (91%) for the diagnosis of progressive puberty. Both tests had high positive predictive value and poor negative predictive value. CONCLUSIONS: The higher value of paired FVU-LH tests can be used to screen girls with suspected progressive puberty and can reduce the need for GnRH stimulation test.

Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods.

AIM: The objective of this study was to validate basal, post-gonadotropin-releasing hormone analogue (post-GnRHa) and first-voided urinary LH (ULH) as alternatives to an LHRH stimulation test in monitoring treatment efficacy in central precocious puberty (CPP). METHODS: Seventeen girls with CPP were followed over 22.5±9.1 months during GnRHa (triptorelin) treatment. ULH and post-GnRHa LH levels were obtained every 4 months before and 24 h after GnRHa administration, respectively, along with clinical and bone age (BA) evaluation. LHRH stimulation tests were performed annually. RESULTS: A total of 36 LHRH stimulation tests demonstrated adequate suppression with a peak LH of 0.57±0.33 IU/L. The corresponding basal LH was 0.27±0.16 IU/L. Ninety post-GnRHa LH measurements were similar to LHRH-stimulated LH levels (0.56±0.31 IU/L), whereas 8% of ULH levels were above prepubertal threshold. Fourteen episodes of growth acceleration and ten episodes of BA advancement resolved without treatment modification. CONCLUSION: Suppressed basal and post-GnRHa LH levels indicate adequate suppression of puberty. Clinical breakthroughs during treatment are transient and resolved spontaneously.

The diagnostic value of first-voided urinary LH compared with GNRH-stimulated gonadotropins in differentiating slowly progressive from rapidly progressive precocious puberty in girls.

OBJECTIVE: Characterization of pubertal progression is required to prevent unnecessary intervention in unsustained or slowly progressive (SP) precocious puberty (PP), while delivering hormonal suppression in rapidly progressive (RP) PP. We aimed to assess the diagnostic value of first-voided urinary LH (ULH) compared with GNRH-stimulated gonadotropins in differentiating these forms of PP. METHODS: A total of 62 girls with PP underwent both GNRH stimulation and ULH assay. Fifteen girls with peak LH ≥ 10 IU/L started treatment immediately, whereas the other 47 girls were evaluated after 6 months for pubertal advancement, height acceleration, and bone-age maturation. Based on these criteria, the participants were assigned to five subgroups: pubertal regression, no progression or progression by one, two or three criteria. The first three subgroups were defined as SP-PP (n=29), while the other two subgroups were defined as RP-PP (n=18). An additional 23 prepubertal girls were evaluated for ULH. RESULTS: ULH but not serum gonadotropins could distinguish girls with two and three criteria from less progressive subgroups. By comparison with SP-PP (i.e. regression group and groups 0 and 1), those with RP-PP (group 2+3) had lower peak FSH (9.28±2.51 vs 12.57±4.30; P=0.007) and higher peak LH:FSH ratio (0.42±0.30 vs 0.22±0.12; P=0.022) and ULH (1.63±0.65 vs 1.05±0.26 IU/l; P<0.001). Based on receiver operating characteristics analysis, a ULH cutoff of 1.16 IU/l had a better sensitivity (83%) and positive and negative predictive values (65 and 88% respectively) than the other two parameters, with a specificity of 72%. CONCLUSIONS: ULH assay is a noninvasive, reliable method that can assist in the distinction between SP- and RP-PP.

Breast development in the first 2 years of life: an association with soy-based infant formulas.

OBJECTIVE: To evaluate the estrogenic effect of soy-based formulas in female infants. These formulas contain significant amounts of phytoestrogens, compounds with structural similarity to estradiol. PATIENTS AND METHODS: A cross-sectional study consisting of 694 female infants ages 3 to 24 months that consecutively attended 10 general pediatric clinics, none of them having been referred for breast development. The presence of breast buds served as a marker for the endocrine effect of soy-derived phytoestrogens. RESULTS: Of the participants, 92 had consumed soy formulas for more than 3 months. Breast tissue was more prevalent in the second year of life in infants fed soy-based formula vs those that were breast-fed and those fed dairy-based formula (22.0% vs 10.3%; P = 0.02) with an odds ratio of 2.45 (95% confidence interval 1.11-5.39). No differences in breast bud prevalence were observed during the first year of life. Unlike infants on dairy-based formulas and breast-feeding, infants fed a soy-based formula did not demonstrate a decline in the prevalence of breast during the second year of life. CONCLUSIONS: We suggest that phytoestrogens impose a preserving effect on breast tissue that is evolved in early infancy, leading eventually to a slower waning of infantile breast tissue.