Fairfax, VA, USA. Because testosterone is essential to the production of a masculine brain, researchers are concerned that fetal exposure to antiandrogens, such as phthalates, has the potential to alter typical masculine brain development. Two recent reports fuel these concerns with new data.

A study of preschool children shows that prenatal exposure to elevated concentrations of common phthalates can result in sons less likely to play with male-typical toys and games (e.g., trucks and play fighting). [C1] Other investigators have documented the first known association between phthalate exposure and ADHD symptoms in school-aged children. [C2]

An antiandrogen (or, androgen antagonist) is any of a group of hormone receptor antagonist compounds that have the native capability to disrupt the biologic effects of male sex hormones (androgens) on body tissues. Generally, antiandrogens obstruct androgen pathways in the endocrine system by blocking receptors and competing for binding sites on cell surfaces. Thus, endocrine disruptors act in the endocrine system like hormones, but disrupt the physiologic function of native (endogenous) hormones. They are sometimes also referred to as endocrine disrupting chemicals (EDC) or hormonally active agents.

Phthalates (phthalate esters) are chemicals used to soften plastics and have become important components of many consumer products, including toys, cleaning materials, plastics, and personal care items.

They are also found in vinyl and plastic tubing, household products, and many personal care products such as soaps and lotions.

Because testosterone is essential to the production of a masculine brain, researchers are concerned that fetal exposure to antiandrogens, such as phthalates, has the potential to alter typical masculine brain development.

An antiandrogen (or, androgen antagonist) is any of a group of hormone receptor antagonist compounds that have the native capability to disrupt the biologic effects of male sex hormones (androgens) on body tissues.

Generally, antiandrogens obstruct androgen pathways in the endocrine system by blocking receptors and competing for binding sites on cell surfaces.

Thus, endocrine disruptors act in the endocrine system like hormones, but disrupt the physiologic function of native (endogenous) hormones. They are sometimes also referred to as endocrine disrupting chemicals (EDC) or hormonally active agents.

Studies to date on phthalates have been inconsistent, with some linking exposure to these chemicals to hormone disruptions, birth defects, asthma, and reproductive problems, while others have found no significant association between exposure and adverse effects.

Scientific research increasingly associates them with metabolic abnormalities, reduced testosterone in babies and adults, and genital defects.

There have been sporadic reports of phthalates in the urine of pregnant women with associations to genital changes in their male infants.

The effects included a shortened (more female-like) anal-genital distance, incomplete testes descent, and scrotum and penis measurements below the median lengths. The extent of radical anogenital distances in humans has yet to be definitively determined.

More recent studies have shown that the major source of human exposure to the two phthalates of most concern (DEHP and DBP) is through food.

These phthalates are used primarily in polyvinyl chloride (PVC), so any steps in the processing, packaging, storage, or heating of food that use PVC-containing products can introduce them into the food chain.

The U.S. Centers for Disease Control and Prevention, in the Summary of their 2005 Third National Report on Human Exposure to Environmental Chemicals, state that "very limited scientific information is available on potential human health effects of phthalates at levels" found in the U.S. population.

A federal law passed in 2008 banned six phthalates from use in toys such as teethers, play bath items, soft books, dolls and plastic figures.

Phthalates and Masculine Development

A study of preschool children at the University of Rochester Medical Center reports that when the concentrations of two common phthalates in mothers' prenatal urine are elevated their sons are less likely to play with male-typical toys and games, such as trucks and play fighting. The findings appear in the International Journal of Andrology, [C1] which covers the male health specialty that deals with problems in the male reproductive system and unique male urological issues.

The lead author of this study is Shanna H. Swan, Ph.D., professor of Obstetrics and Gynecology, director of the URMC Center for Reproductive Epidemiology, and an expert in phthalates.

Swan's interest in phthalates stems from her early investigations into the environmental causes of reproductive health problems.

Since 1998 Swan has led the federally funded, multi-center Study for Future Families (SFF), which established a large database from which to explore various scientific questions about toxins.

In Swan's current study, higher concentrations of metabolites of two phthalates, di(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP), were associated with less male-typical behavior in boys on a standard play questionnaire. No other phthalate metabolites measured in-utero was linked to the less-masculine behavior. Girls' play behavior was not associated with phthalate levels in their mothers, the study concluded.

The current study focused on a small sample of SFF mothers who delivered children between 2000 and 2003. The mothers provided urine samples around the 28th week of pregnancy. The urine was analyzed for phthalate metabolites by the Centers for Disease Control and Prevention (CDC).

Swan hypothesized that phthalates may lower fetal testosterone production during a critical window of development — somewhere within eight to 24 weeks gestation, when the testes begin to function — thereby altering brain sexual differentiation.

To explore the question, researchers reconnected with mothers from the SFF sample and asked them to complete a standard research questionnaire, called the Preschool Activities Inventory (PSAI), for 145 of their their preschool children, ages 3.5 to 6.5 years.

The PSAI is designed to discriminate play behavior within and between the sexes, and in the past has been shown to reflect the endocrine-disrupting properties of other toxins, such as PCBs and dioxins. The PSAI addressed three aspects of play: types of toys children choose (trucks versus dolls), activities (rough-and-tumble play, for example), and child characteristics.

However, researchers were concerned about how the choice of toys available in any given household might skew results, so in addition they asked about parental views toward atypical play. For example, the survey asked, "What would you do if you had a boy who preferred toys that girls usually play with?" The possible answers included "strongly encourage" (him to play this way) to "strongly discourage."

The final survey scores are designed to reflect sex-typical play. Higher scores meant more male-typical play and lower scores meant more female-typical play.

Researchers then examined boys play-behavior scores in relation to the concentration of phthalate metabolites in their mothers' prenatal urine samples, finding that higher concentrations of DEHP and DBP metabolites were associated with less masculine play behavior scores.

Earlier studies by Swan and others have shown that phthalate exposure during pregnancy might affect the development of genitals of both male rodents and baby boys. Scientists refer to this cluster of genital alterations as the "phthalate syndrome," and research suggests that in rodent pups, the syndrome can have adverse consequences for later sexual development.

If endocrine disrupters such as phthalates can impair genital development and hormone levels in the body, the play-behavior study noted, then a deeper examination of how these chemicals impact the brain is warranted.

"Our results need to be confirmed, but are intriguing on several fronts," Swan said. "Not only are they consistent with our prior findings that link phthalates to altered male genital development, but they also are compatible with current knowledge about how hormones mold sex differences in the brain, and thus behavior. We have more work to do, but the implications are potentially profound."

Phthalates and Attention-deficit / Hyperactivity Disorder (ADHD)

Another report adds to the potentially alarming findings about phthalates. [C2] Researchers in Koprea measured urine phthalate concentrations in school-aged children and evaluated symptoms of attention-deficit / hyperactivity disorder (ADHD) using teacher-reported symptoms and computerized tests that measured attention and impulsivity.

The investigators found a significant positive association between phthalate exposure and ADHD, meaning that the higher the concentration of phthalate metabolites in the urine, the worse the ADHD symptoms and/or test scores.

Although this study was performed in a Korean population, their levels of exposure are likely comparable to a U.S. population.

These findings appear in the journal Biological Psychiatry. Senior author Yun-Chul Hong, MD, PhD, explained that "these data represent the first documented association between phthalate exposure and ADHD symptoms in school-aged children."

The current findings do not prove that phthalate exposure caused ADHD symptoms. However, John Krystal, MD, the Editor of Biological Psychiatry, also commented: "This emerging link between phthalates and symptoms of ADHD raises the concern that accidental environmental exposure to phthalates may be contributing to behavioral and cognitive problems in children. This concern calls for more definitive research."

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Effects of Phthalate Exposure on Male Development
Thursday, 19 November 2009

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There are known known's and known unknown's - - - , I sh

20 November 2009     

I shouldn't be too flippant about this. Its been over ten years since phthalates were implicated in atypical sex role behaviors. http://www.guardian.co.uk/uk/2...lth.gender I posted a blog article on endocrine disruptors earlier in the year. http://joanneproctor-hbs.blogs...s-sex.html Since that time I have learned that a full 40% of males who's mothers were prescribed DES during pregnancy experience transsexualism. DES was,, of course, the first of the endocrine disruptors and was hailed as a 'wonder drug' at the time. Phthalates are ubiquitous. One of the worst things anyone can do is microwave food covered by 'cling-wrap'. The rate of phthalate transferal increases almost exponentially upon heating!

Joanne

Joanne, I don't get the "flippant" reference. Anyway, re

20 November 2009     

I don't get the "flippant" reference. Anyway, regarding the effects of DES during pregnancy, you said: Since that time I have learned that a full 40% of males who's mothers were prescribed DES during pregnancy experience transsexualism. Can you share the references for that statement? Thank you.
Sharon S. Gaughan

DES Research, Hi Sharon You asked for some source mate

20 November 2009     

Hi Sharon You asked for some source material on the implications of DES. I hope you find this information helpful. DES Research. These papers are available from OII. http://www.intersexualite.org/Kerlin.html See In particular: Scott P. Kerlin, Ph.D. The Presence of Gender Dysphoria, Transsexualism, and Disorders of Sexual Differentiation in Males Prenatally Exposed to Diethylstilbestrol: Initial Evidence from a 5-Year Study. Paper Presented at 6th Annual E-Hormone Conference New Orleans, October 27-30, 2004 "More than 150 network members with "confirmed" or "strongly suspected" prenatal DES exposure status indicated they are either transsexual (pre- or post-operative, 90 members), transgender (48 members), "gender dysphoric" (17 members), or intersex (3 members)." http://www.intersexualite.org/P-DES-10-04.html See also: Milton Diamond, Clinical Implications of the Organizational and Activational Effects of Hormones. Hormones and Behavior 55 (2009) 621–632. http://www.hawaii.edu/PCSS/bib...html#ref41 Hope you all find this information interesting and helpful.

Joanne

Correction to my earlier comment., I originally wrote: S

20 November 2009     

I originally wrote: Since that time I have learned that a full 40% of males who's mothers were prescribed DES during pregnancy experience transsexualism. I was working off my poor memory. In re-reading I note that the actual number was 36%. That is still an extraordinary statistic. Especially when read in conjunction with other DES males who experienced various degrees of gender role confusion.
Joanne

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