TY - JOUR

T1 - High urinary phthalate concentration associated with delayed pubarche in girls

AU - Frederiksen, H

AU - Sørensen, K

AU - Mouritsen, A

AU - Aksglaede, L

AU - Hagen, Casper

AU - Petersen, Jørgen Holm

AU - Skakkebaek, N E

AU - Andersson, Anna-Maria

AU - Juul, A

N1 - © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

PY - 2012/6

Y1 - 2012/6

N2 - Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes in pubertal timing among girls, although controversies exist. We determined the concentration of 12 phthalate metabolites in first morning urine samples from 725 healthy Danish girls (aged 5.6-19.1 years) in relation to age, pubertal development (breast and pubic hair stage) and reproductive hormone levels (luteinizing hormone, oestradiol and testosterone). Furthermore, urinary phthalates were determined in 25 girls with precocious puberty (PP). In general, the youngest girls with less advanced pubertal development had the highest first morning urinary concentration of the monobutyl phthalate isoforms (¿MBP((i+n)) ), monobenzyl phthalate (MBzP), metabolites of di-(2-ethylhexyl) phthalate (¿DEHPm) and of di-iso-nonyl phthalate (¿DINPm). After stratification of the urinary phthalate excretion into quartiles, we found that the age at pubarche was increasing with increasing phthalate metabolite quartiles (except for MEP). This trend was statistically significant when all phthalate metabolites (except MEP) were summarized and expressed as quartiles. No association between phthalates and breast development was observed. In addition, there were no differences in urinary phthalate metabolite levels between girls with PP and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls.

AB - Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes in pubertal timing among girls, although controversies exist. We determined the concentration of 12 phthalate metabolites in first morning urine samples from 725 healthy Danish girls (aged 5.6-19.1 years) in relation to age, pubertal development (breast and pubic hair stage) and reproductive hormone levels (luteinizing hormone, oestradiol and testosterone). Furthermore, urinary phthalates were determined in 25 girls with precocious puberty (PP). In general, the youngest girls with less advanced pubertal development had the highest first morning urinary concentration of the monobutyl phthalate isoforms (¿MBP((i+n)) ), monobenzyl phthalate (MBzP), metabolites of di-(2-ethylhexyl) phthalate (¿DEHPm) and of di-iso-nonyl phthalate (¿DINPm). After stratification of the urinary phthalate excretion into quartiles, we found that the age at pubarche was increasing with increasing phthalate metabolite quartiles (except for MEP). This trend was statistically significant when all phthalate metabolites (except MEP) were summarized and expressed as quartiles. No association between phthalates and breast development was observed. In addition, there were no differences in urinary phthalate metabolite levels between girls with PP and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls.

U2 - 10.1111/j.1365-2605.2012.01260.x

DO - 10.1111/j.1365-2605.2012.01260.x

M3 - Journal article

C2 - 22428786

VL - 35

SP - 216

EP - 226

JO - International Journal of Andrology

JF - International Journal of Andrology

SN - 0105-6263

IS - 3

ER -