Authors:
Colón, I., Caro, D., Bourdony, CJ., Rosario, O.

Title:
Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development.

Journal:
Environmental Health Perspectives, 108(9), 2000

Summary:
The onset of puberty in females typically starts after the age of 8 and is characterized by the enlargement of the breasts, ovaries, uterus as well as the initiation of pubic and axiliary hair growth. Frequently female babies show some hyperplasia of the breasts after birth and until 6 months of age due to the placental passage of estrogen. However, if this development persists or occurs before the age of 8 it is known as precocious thelarche. Females with thelarche often have one or both breasts enlarged without any other physical signs of the onset of puberty. One of the highest incidences of thelarche in the world is in Puerto Rico. The incidence has been reported at 8 cases per 1000 female births and is over 18.5 times higher than that found in a US study. The reason for the unusually high incidence of precocious thelarche in Puerto Rico remains unknown. Previously, the presence of anabolic steroids in poultry, consumption of soy-based formula with high phytoestrogen content have been associated with premature puberty in Puerto Rican infants. However, none of these other explanations can account for the dramatic differences in the age of pubertal onset observed in Puerto Rico. Therefore, environmental agents are thought to play a role.

Phthalates are chemicals that are used extensively as plasticizers. They are ubiquitous in the environment and several different phthalates have been tested for their oestrogenic properties. Colón et al suggest that the environmental load of plasticizers is very high in Puerto Rico due to the fact that it is an island and many dietary products are imported in plastic containers. Therefore, the authors designed a case-control study that measured phthalate ester levels in Puerto Rican girls with premature thelarche. Cases were girls between the ages of 6 months and 8 years of age with a diagnosis of premature thelarche between 1994 and 1998 (n=41). Control subjects were female girls from 6 months to 10 years of age with no evidence of premature sexual development (n=35). Serum samples of the cases were provided by the Pediatric Endocrinology Section and the control samples were provided by the general clinic of the San Juan City Hospitial. Serum samples were collected via venipuncture and analyzed and measured for phthalates. Phthalate esters have been detected as impurities in solvents, water, glassware, and many items used in clinical and laboratory settings. Therefore, the authors examined several analytical blanks for their interference and contamination with the real samples throughout the sampling, storage, extraction and/or analysis phases.

Colón et al found that phthalate esters were significantly higher in girls with thelarche than in the control group with high levels of phthalate esters being found in 68% of the cases. Only one sample of the control group contained DOP (dioctyl phthalate) and 5 (14%) contained DEHP (di-[2-ethylhexyl] phthalate).

This study was highly publicized in the media for its results but there are several limitations that should be noted. First, the sample size was very small, limiting the precision of the study. In addition, phthalates are ubiquitous in the environment and are one of many substances that are presumed to be estrogenic. Also, the detection of phthalate is troublesome since these metabolites are rapidly metabolized and would not be expected to be found in serum. Lastly, the biological mechanism by which phthalates would be contributing to precocious thelarche is not known. Studies designed to look into the unique environmental, cultural, dietary, and genetic differences that may be playing a role in the high levels of precocious puberty in Puerto Rico compared with other countries would be of value.