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 1980s.
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. Dedekians 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 girls 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 childrens 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. Dedekians 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 1980s, 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 worlds 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 programs 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 1990s 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 companys 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 Androgels 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 Androgels 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.
