[Pharmwaste] Preschool Puberty, and a Search for the Causes

[Tenace, Laurie]

http://www.nytimes.com/2006/10/17/science/17puberty.html?_r=1&oref=slogin

Preschool Puberty, and a Search for the Causes 
 Lou Beach

By DARSHAK M. SANGHAVI
Published: October 17, 2006
Parents often think their children grow up too quickly, but few are prepared
for the problem that Dr. Michael Dedekian and his colleagues at the
University of Massachusetts Medical School reported recently.

At the annual Pediatric Academic Society meeting in May in San Francisco,
they presented a report that described how a preschool-age girl, and then her
kindergarten-age brother, mysteriously began growing pubic hair. These cases
were not isolated; in 2004, pediatric endocrinologists from San Diego
reported a similar cluster of five children. 

It turns out that there have been clusters of cases in which children have
prematurely developed signs of puberty, outbreaks similar to epidemics of
influenza or environmental poisonings. In 1979, the medical journal The
Lancet described an outbreak of breast enlargement among hundreds of Italian
schoolchildren, probably caused by estrogen contamination of beef and
poultry. Similar epidemics in Puerto Rico and Haiti were tracked by the
Centers for Disease Control and Prevention in the 1980's. 

Increasingly - though the science is still far from definitive and the
precise number of such cases is highly speculative - some physicians worry
that children are at higher risk of early puberty as a result of the
increasing prevalence of certain drugs, cosmetics and environmental
contaminants, called "endocrine disruptors," that can cause breast growth,
pubic hair development and other symptoms of puberty. 

Most commonly, outbreaks of puberty in children are traced to accidental drug
exposures from products that are used incorrectly. 

Dr. Dedekian's first patient was evaluated for possible genetic endocrine
problems and a rare brain tumor before the cause of her puberty was
discovered. It turned out that her testosterone level was almost 100 times
normal, in the range of an adult man. The same problem affected her brother. 

The doctors realized that the girl's father was using a concentrated
testosterone skin cream bought from an Internet compounding pharmacy for
cosmetic and sexual performance purposes. From normal skin contact with their
father, the children absorbed the testosterone, which caused pubic hair
growth and genital enlargement. The boy, in particular, also developed some
aggressive behavior problems.

Sex hormones are potent because they are easily absorbed through the skin and
resist degradation better than many other hormones. Unlike protein-based
hormones like insulin, sex hormones like testosterone and estrogen are
technically steroids, meaning they are derived from cholesterol. 

Primarily made by the liver, cholesterol begins with tiny pieces of sugar
that are joined, twisted and oxidized in a dizzying series to make an end
product that resembles the interlinked rings of the Olympic emblem. Dr.
Joseph L. Goldstein, Nobel Laureate and a biochemist in Texas, once called it
"the most highly decorated small molecule in biology," because 13 Nobel
Prizes have been awarded for its study.

Through further processing, primarily in the gonads and adrenal glands,
cholesterol is converted into sex hormones like estrogen and testosterone.
Kenneth Lee Jones, the former chief of pediatrics at the University of
California, San Diego, noted pediatric cases similar to those described by
Dr. Dedekian in a 2004 report in the journal Pediatrics. 

At that time, unregulated "prohormones" like Andro, famously used by Mark
McGwire, the former St. Louis Cardinals power hitter, and banned by federal
law in 2005, were available as topical sprays used to enhance libido. Dr.
Jones said the sprays used by adults in some households permeated the
children's bedsheets, and the early puberty stopped only when the adults
stopped using the sprays and also discarded old sheets.

Testosterone-containing products are not the only trigger of disordered
puberty in children.

In a 1998 paper in the journal Clinical Pediatrics, Dr. Chandra Tiwary, the
former chief of pediatric endocrinology at Brook Army Medical Center in
Texas, reported an outbreak of early breast development in four young
African-American girls who used shampoos that contained estrogen and
placental extract. The early puberty reversed once the shampoo was stopped. 

In the tradition of previous physicians who deliberately exposed themselves
to possible pathogens, Dr. Tiwary tried the shampoos on himself. He carefully
measured his own levels of various male and female sex hormones to establish
his baseline, used the shampoos for a few days, then repeated the tests. 

While Dr. Tiwary is quick to admit that his unpublished findings must be
interpreted with great caution, some of his sex hormone levels changed by
almost 40 percent after he used the shampoos. In some cases, substances other
than sex steroids may also disrupt normal sexual development. In Boston at
the annual Endocrine Society meeting in June, Clifford Bloch of the
University of Colorado School of Medicine presented several cases of young
men who had developed marked breast enlargement from using shampoos
containing lavender and tea tree oils, which are widely used essential oil
additives that present no problem for adults. (Unlike Dr. Dedekian's cases,
these cases were not a result of passive transfer from parents. The boys
themselves used the shampoos.) 

Dr. Bloch collaborated with scientists at the National Institute of
Environmental Health Sciences in North Carolina to test the oils on human
breast cells grown in test tubes. Lavender and tea tree oil had the same
effect on the cells as estrogen. 

Dr. Bloch speculates that the findings, which he is submitting for
publication in a peer-reviewed journal, may explain the boys' breast growth.
He noted, however, that cells in a test tube are a far cry from humans, so
the relationship of the essential oil to breast growth remains hypothetical. 

While pediatric endocrinologists have implicated pharmaceutical or personal
care products for causing pubertal problems in children, some environmental
scientists also claim that some widespread industrial and pharmaceutical
pollutants harm the normal sexual development of fish and animals. By
extension, they may also contribute to earlier or disrupted puberty in
children, these scientists contend. Robert Havelock, a senior reproductive
toxicologist at the Environmental Protection Agency, said these concerns
"caused a shift in worry from cancer to noncancer" effects of environmental
pollution over the past decade. 

In 1994, scientists found that estrogen-like chemicals from plastics
manufacturing plants that had contaminated sewers in England caused
genetically male fish to develop into females. In the early 1980's, major
spills of the DDT-like pesticide dicofol in Florida led to the "feminization"
of the reproductive tracts of male alligators

Robert Cooper, the chief of endocrinology at the reproductive toxicology
division of the Environmental Protection Agency, says various sources of
endocrine disruptors, like manufacturing chemicals, may be leaching into the
environment. While their relation to pubertal problems in children remains
highly speculative, he believes further study is needed.

Past epidemiological evidence, however, does worry Dr. Cooper, because some
chemical exposures have been associated with early puberty. In 1973,
thousands of Michigan residents ate food contaminated by a flame retardant,
PBB, which was later correlated with earlier menstruation in girls. In Puerto
Rico, which has some of the world's highest rates of early puberty, the
condition was linked to higher levels of a plasticizer called phthalate in
affected children.

Governmental efforts to create a systematic method to assess possible
endocrine disruptors from environmental sources have stalled.

In 1996, Congress directed the E.P.A. to develop a comprehensive screening
program for possible endocrine disruptors within three years. Dr. Cooper says
no such program has begun operation, a failure he attributed largely to
stonewalling by chemical industry representatives who serve on an advisory
committee for the program. Now the proposed rollout is December 2007, but Dr.
Cooper said, "They may be dreaming." Critics cite the program's high
potential costs and lack of reliable laboratory tests.

Protecting children from endocrine disrupters in cosmetics and prescription
drugs may also be difficult in the near future. 

In 1989, the Food and Drug Administration proposed allowing up to 10,000
units of estrogen per ounce of cosmetic, the approximate oral daily dose of
hormone replacement therapy for postmenopausal women. Dr. Tiwary said that in
the early 1990's he filed an adverse drug report with the agency about
hormone-containing shampoos but that to his knowledge, it never came to
anything.

Reached by e-mail, a spokeswoman for the F.D.A. said that the agency was
"aware of some reports describing premature sexual devolepment" with shampoos
but that it had concluded that "there is no reason for consumers to be
concerned." 

At this time, "placental materials are neither prohibited by cosmetic
regulations nor restricted" by the F.D.A., she wrote.

Dr. Dedekian said that while prohormones like Andro are no longer
commercially available, lax regulation of so-called compounding pharmacies
allows the manufacture and sale of concentrated testosterone creams, like the
one affecting his patient, without government oversight.

Topical lotions and creams containing testosterone may become more common. In
2000, Solvay Pharmaceuticals secured F.D.A. approval for Androgel, a lotion
to treat a syndrome the company calls low T, referring to low testosterone.
According to the company's Web site, the condition affects 13 million men
over 45. From 2000 to 2004, the number of testosterone prescriptions doubled
to over 2.4 million a year. 

Solvay Pharmaceuticals referred questions on Androgel's possible risks to
Natan Bar-Chama, an associate professor of urology at Mount Sinai School of
Medicine. 

Dr. Bar-Chama acknowledged the theoretical risks of transfer of the hormone
through skin contact with children, but he said he had never seen a case
among the hundreds of men he has treated. He added, however, that it was
prudent to take precautions when using the product, including hand-washing
after handling the gel and wearing clothing to avoid skin-to-skin contact
with others.

In 2003, an Institute of Medicine report stated, "There has been increasing
concern about the increase in the number of men using testosterone and the
lack of scientific data on the benefits and risks of this therapy." 

Dr. Dan Blazer, a psychiatrist at Duke who was chairman of the committee,
said, "In no way did we find a condition that we defined as low T."

The major clinical trial of Androgel's effectiveness for low T, published in
The Journal of Clinical Endocrinology and Metabolism in 2000, included
neither a placebo group (patients who received an inactive dummy lotion) nor
a control group (patients who did not have low T) for comparison.

Dr. Ronald Swerdloff, the chief of endocrinology at Harbor-U.C.L.A. Medical
Center in Torrance, Calif., and a consultant for Solvay, who ran the study,
said the trial was limited in scope since it examined "a new route of
administration for an already established drug."

Laurie J. Tenace
Environmental Specialist
Florida Department of Environmental Protection
2600 Blair Stone Road, MS 4555
Tallahassee, Florida 32399-2400
PH: (850) 245-8759
FAX: (850) 245-8811
Laurie.Tenace at dep.state.fl.us  
 
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