Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls.

To study potential environmental influences on puberty in girls, we investigated urinary biomarkers in relation to age at menarche. Phenols and phthalates were measured at baseline (6-8 years of age). Menarche was ascertained over 11 years for 1051 girls with menarche and biomarkers. Hazards ratios were estimated from Cox models adjusted for race/ethnicity and caregiver education (aHR, 95% confidence intervals [CI] for 5th vs 1st quintile urinary biomarker concentrations). 2,5-Dichlorophenol was associated with earlier menarche (aHR 1.34 [1.06-1.71]); enterolactone was associated with later menarche (aHR 0.82 [0.66-1.03]), as was mono-3-carboxypropyl phthalate (MCPP) (aHR 0.73 [0.59-0.91]); the three p-trends were <0.05. Menarche differed by 4-7 months across this range. Enterolactone and MCPP associations were stronger in girls with below-median body mass index. These analytes were also associated with age at breast development in this cohort. Findings from this prospective study suggest that some childhood exposures are associated with pubertal timing.

Prepubertal glucocorticoid status and pubertal timing.

CONTEXT: Whether prepubertal glucocorticoid status impacts on the timing of puberty is not clear. OBJECTIVE: The objective of the study was to examine the relationship between prepubertal glucocorticoid status and early or late pubertal markers, independent of adrenarchal and nutritional status. DESIGN AND PARTICIPANTS: Prospective cohort study of healthy Caucasian children (n = 111, 56 boys) who provided both 24-h urine samples and weighed dietary records 1 and 2 yr before the start of pubertal growth spurt [age at take-off (ATO)]. MEASUREMENTS: Major urinary glucocorticoid and androgen metabolites determined by gas chromatography-mass spectrometry analysis were summed to assess daily overall cortisol (ΣC21) and adrenal androgen secretion; urinary free cortisol and cortisone measured by RIA were summed (UFF+UFE) as an indicator of potentially bioactive free glucocorticoids. MAIN OUTCOMES: The main outcomes included ATO, age at peak height velocity, age at menarche/voice break, ages at Tanner stage 2 for breast (girls) and genital (boys) development, and pubic hair. RESULTS: In girls ΣC21, but not UFF+UFE, was associated with pubertal markers after adjusting for overall adrenal androgen, urinary nitrogen, and body fat. Girls with higher ΣC21 (fourth quartile) reached ATO 0.7 yr (P = 0.01) and menarche 0.9 yr later (P = 0.006) than girls with lower ΣC21 (first quartile). The ΣC21 tended to be also positively associated with age at Tanner stage 2 for breast (P = 0.1), Tanner stage 2 for pubic hair (P = 0.1), and age at peak height velocity (P = 0.06). In boys, neither the ΣC21 nor UFF+UFE was related to pubertal timing. CONCLUSION: An individually higher prepubertal glucocorticoid secretion level, even in physiological range, appears to delay early and late pubertal timing of healthy girls, particularly their onset of pubertal growth spurt and menarche.

Urinary free cortisol increases in adolescent caucasian females during perimenarche.

Urinary free cortisol (UFC) excretion has been thought to be constant during female reproductive maturation when normalized for body surface area. We sought to determine whether there are longitudinal changes in urinary free cortisol excretion during perimenarche in adolescent females. We performed a longitudinal study of 24-h UFC excretion obtained at 6-month intervals over a 4-yr period in a cohort of 112 adolescent non-Hispanic white perimenarchal females from south central Pennsylvania. The overall mean values (mean +/- SD) for UFC/24 h for all measurements between ages 12 and 17 yr was 67.4 +/- 43.8 micro g/24 h (to convert to nanomoles per day, multiply by 2.759). In our model, we found a significant positive association between UFC excretion with both gynecological age (P = 0.002) and chronological age (P = 0.0001). For every incremental increase in Tanner stage, the UFC/BSA increased by 3.0 microg/24 h per square meter. Correcting the UFC values by both creatinine and BSA creates a fairly constant number (6.3 +/- 3.1 microg/mg per square meter per 24 h) over the age range 12-17 yr represented in this study. An increase in cortisol excretion may be part of normal reproductive maturation.

Monthly urinary LH and FSH secretory patterns in normal children and patients with sexual disorders.

Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Using consecutive 30-d first morning voided urine specimens from normal children and from patients with sexual disorders, we have studied the monthly patterns of nighttime gonadotropin secretion. In normal prepubertal girls, the levels of urinary LH were low with few variations and those of urinary FSH were higher with episodic fluctuations. In early pubertal girls, the levels of urinary LH increased with striking, rhythmic fluctuations. The same changes were seen in urinary FSH. A single big surge of urinary gonadotropins was observed in postmenarcheal girls. In normal boys, the secretory patterns of urinary gonadotropins were similar to those of normal girls, but varied less. In patients with idiopathic precocious puberty, the patterns of urinary gonadotropins were similar to those of normal subjects matched for sexual stage. The measurement of 30-d first morning voided urinary gonadotropins can provide a simple and physiologic test of gonadotropin function in children.