The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study

Abstract

We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989-1991, 1377 had antenatal serum stored without thawing at K80 8C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Mü llerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography-tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 samples available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche (PZ0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (PZ0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Sall phth.m) were protective against PCOS in adolescence (PZ0.001 and PZ0.005 respectively). There were negative associations of MEP with PCO (PZ0.022) and of MEP with serum AMH (PZ0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients

“…Several measures were taken, especially as serum data for PMs should be interpreted carefully due to probable contamination issues Hart et al, 2014). All samples were analyzed taking all measures to avoid even possible enzymatic transformation of DEHP to its metabolites after storage (Hart et al, 2014).…”

“…All samples were analyzed taking all measures to avoid even possible enzymatic transformation of DEHP to its metabolites after storage (Hart et al, 2014). We included a large number of procedural blanks (3 blanks for each batch of 20 samples) and all were found negative for PMs and BPA.…”

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…In many countries its use in the manufacture of plastic bottles has been phased out. However, BPA along with phthalates are frequently measurable within urine (182), serum (141), follicular fluid (187), umbilical cord blood (162), and the amniotic fluid (162). Of particular concern was the finding that the amniotic fluid concentrations of BPA were five times greater than serum, presumably due to fetal renal clearance (162).…”

“…Limited human data exist, although by measuring the metabolites of phthalates in stored maternal blood, our group demonstrated a trend toward an earlier menarche in Western Australian girls, a degree of hypogonadism with a reduction in early follicular phase serum FSH associated with the phthalate metabolite MEHP (141). Of particular concern was the finding that maternal exposure to MEP, widely found in cosmetics, was associated with a reduction in their daughters' serum AMH in adolescence, a marker of antral follicles (ovarian reserve) and granulosa cell function (141). In addition, higher MEP exposure was associated with a reduced prevalence of PCOS in adolescence and reduced antral follicle count (141).…”

“…Of particular concern was the finding that maternal exposure to MEP, widely found in cosmetics, was associated with a reduction in their daughters' serum AMH in adolescence, a marker of antral follicles (ovarian reserve) and granulosa cell function (141). In addition, higher MEP exposure was associated with a reduced prevalence of PCOS in adolescence and reduced antral follicle count (141). A similar finding was observed in a small study of patients with PCOS where lower urine concentrations of mBP and mBzP were detected in women with PCOS (352).…”