New York Times  [Printer-friendly version]
October 17, 2006


[Rachel's introduction: Something is causing early sexual development
in pre-school children.]

By Darshak M. Sanghavi**

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

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
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

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

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. Dr. Dedekian is a pediatric cardiologist at the University
of Massachusetts Medical School.

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
Kavlock, 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

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.

Ralph L. 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

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."

** Darshak M. Sanghavi is a pediatric cardiologist at the University
of Massachusetts Medical School.

Copyright 2006 The New York Times Company