OBJECTIVE: Several untoward health effects of phthalates, which are a group of industrial chemicals with many commercial uses including personal-care products and plastic materials, have been defined. The most commonly used, di-(2-ethylhexyl)-phthalate (DEHP), is known to have antiandrogenic or estrogenic effects or both. Mono-(2-ethylhexyl)-phthalate (MEHP) is the main metabolite of DEHP. In this study, we aimed to determine the plasma DEHP and MEHP levels in pubertal gynecomastia cases.
PATIENTS AND METHODS: The study group comprised 40 newly diagnosed pubertal gynecomastia cases who were admitted to Hacettepe University Ihsan Doğramacı Children's Hospital. The control group comprised 21 age-matched children without gynecomastia or other endocrinologic disorder. Plasma DEHP and MEHP levels were measured by using high-performance liquid chromatography. Serum hormone levels were determined in some pubertal gynecomastia cases according to the physician's evaluation.
RESULTS: Plasma DEHP and MEHP levels were found to be statistically significantly higher in the pubertal gynecomastia group compared with the control group (P < .001) (DEHP, 4.66 ± 1.58 and 3.09 ± 0.90 μg/mL, respectively [odds ratio: 2.77 (95% confidence interval: 1.48–5.21)]; MEHP, 3.19 ± 1.41 and 1.37 ± 0.36 μg/mL [odds ratio: 24.76 (95% confidence interval: 3.5–172.6)]). There was a statistically significant correlation between plasma DEHP and MEHP levels (r: 0.58; P < .001). In the pubertal gynecomastia group, no correlation could be determined between plasma DEHP and MEHP levels and any of the hormone levels.
CONCLUSIONS: DEHP, which has antiandrogenic or estrogenic effects, may be an etiologic factor in pubertal gynecomastia. These results may pioneer larger-scale studies on the etiologic role of DEHP in pubertal gynecomastia.
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Two recent studies in leading pediatric journals have reported implausibly high concentrations of two phthalate biomarkers in blood: di-2 -ethylhexyl phthalate DEHP and its hydrolytic monoester mono-2-ethylhexyl phthalate MEHP. Serum MEHP was reported to be above 3000 ug/L,1,2 with similarly improbable concentrations of DEHP; a few other reports are also questionable.3-6 It is very likely that the high phthalate serum concentrations in these studies reflect problems in specimen collection, storage, handling and analysis techniques.7 Blood phthalate measurements almost inevitably represent contamination by phthalates of equipment and materials, and thus cannot be used to examine associations of phthalates with health effects.
Indeed, for this reason, the phthalate diesters cannot be used as biomarkers of exposure at all, and monoesters, other than those in urine, are also suspect.7 In the preponderance of the literature, DEHP has not been detected, even among persons with known high exposures,8-11 and the MEHP concentrations in these studies1,2 are far above those previously reported in persons with well-defined high exposures.8-11 For example, four of the six papers in question report both DEHP and MEHP in blood averaging >1,000 ug/L.1,2,4,5 These levels are inconsistent with highest levels reported in urine, which always exceed concentrations in blood.9-11
We know of no known exposure scenario that could account for these DEHP and MEHP blood levels. The likely explanation is contamination.
(1) Durmaz E, Ozmert EN, Erkekoglu P, Giray B, Derman O, Hincal F, et al. Plasma phthalate levels in pubertal gynecomastia. Pediatrics 2010 Jan;125(1):e122-e129. (2) Zhang Y, Lin L, Cao Y, Chen B, Zheng L, Ge RS. Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr 2009 Oct;155(4):500-4. (3) Cobellis L, Latini G, De FC, Razzi S, Paris I, Ruggieri F, et al. High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis. Hum Reprod 2003 Jul;18(7):1512-5. (4) Colon I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect 2000 Sep;108(9):895-900. (5) Latini G, De FC, Presta G, Del VA, Paris I, Ruggieri F, et al. In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect 2003 Nov;111(14):1783-5. (6) Luisi S, Latini G, De FC, Sanseverino F, di PD, Mazzeo P, et al. Low serum concentrations of di-(2-ethylhexyl)phthalate in women with uterine fibromatosis. Gynecol Endocrinol 2006 Feb;22(2):92-5. (7) Koch HM, Calafat AM. Human body burdens of chemicals used in plastic manufacture. Philos Trans R Soc Lond B Biol Sci 2009 Jul 27;364(1526):2063 -78. (8) Koch HM, Bolt HM, Angerer J. Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium -labelled DEHP. Arch Toxicol 2004 Mar;78(3):123-30. (9) Inoue K, Kawaguchi M, Yamanaka R, Higuchi T, Ito R, Saito K, et al. Evaluation and analysis of exposure levels of di(2-ethylhexyl) phthalate from blood bags. Clin Chim Acta 2005 Aug;358(1-2):159-66. (10) Mettang T, Thomas S, Kiefer T, Fischer FP, Kuhlmann U, Wodarz R, et al. The fate of leached di(2- ethylhexyl)phthalate in patients undergoing CAPD treatment. Perit Dial Int 1996 Jan;16(1):58-62. (11) Koch HM, Angerer J, Drexler H, Eckstein R, Weisbach V. Di(2- ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors. Int J Hyg Environ Health 2005;208(6):489-98.
Conflict of Interest:
None.