Obesity

The trend of rising childhood obesity seems to be the most commonly mentioned potential factor contributing to early puberty in girls.  What might be the connection?

Here is a link to a WebMD article on the topic:

Our fat cells make [the hormone,] leptin. The more fat we have, the more leptin in our systems. Leptin seems to play a key role in regulating appetite, body type, and reproduction.  Leptin doesn't trigger puberty on its own. But there's evidence that for puberty to start, a child has to have enough leptin in her system, Kaplowitz [Paul Kaplowitz, MD, PhD, Chief of the Division of Endocrinology at Children's National Medical Center] says. Girls who have high leptin levels -- because they are overweight -- could be more prone to early puberty.

For those of you who are interested in more scientific details, there are several other pathways for how the increased prevalence of overweight and obesity could trigger early pubertal development.  In their article the authors, CM Solorzano and CR McCartney, discuss some of those.

The primary article referenced to support the obesity and early puberty link seems to be one published in 1997 by ME Herman-Giddens et al.  In a large cross-sectional study [side note: see my earlier post about study designs; cross-sectional is not the best, but a large sample is good[, they found that obesity as measured by Body Mass Index, BMI, was significantly associated with early puberty, although the association was less strong in African-American girls than in white girls.  What this means is that girls who are obese appear to be more likely than girls who are not obese to experience early puberty.  However, please keep in mind that showing an association does not equal proving a causal link between the two.

Part of my discomfort with what sometimes seems like a default focus on the obesity-early puberty connection in the literature and general media is that I know girls who have never been overweight or obese who have been diagnosed with central precocious puberty.  If obesity is a contributing factor, it must not be the only one.

All Studies Are Not Created Equal

Before discussing specific studies related to precocious puberty, it is important to understand that not all studies are created equal.

Often people see results from a study reported in the media and they conclude, "Research has shown ..." without any assessment of the design, strengths and weaknesses of that particular analysis.

Conclusions drawn from a well-designed study have more credibility than a poorly designed one --, but yet often the media don't give any indication of the quality of the studies on which they report. This can be a serious disservice to the public who often take what they read at face value and make health-related decisions based on that.

One aspect of the public health field of epidemiology is the study of risk factors, things that increase the chances of something happening, such as disease. For example, smoking is a risk factor for lung cancer. There are numerous study designs to test the relationship between risk factors and disease. The following observational study types are listed according to the hierarchy from least dependable strength of evidence to most dependable. 

Least Dependable: Case Report
A case report describes the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient with PP (for example). There may be many reasons for that patient's experience. Thus, one case study does not give analytic evidence regarding what is a risk factor for a PP within the broader population.

Case Series
A case series is a descriptive report of a group of patients. Similar to the case report, this is descriptive rather than analytical by nature and is not rigorous, e.g., does not report on enough patients, to be able to scientifically identify risk factors for a disease.

Ecologic Studies
Ecologic studies base their results on data at the population-level (e.g. average childhood obesity rates within the U.S.) rather than individual-level data (presence of obesity in individual girls). The problem with this is that conclusions that are true for averages may not help us understand what is true for the individual. For example, it seems that many girls who develop PP are not in fact obese, so what led to PP for them?

Cross-Sectional Study

Cross-sectional studies look at potential risk factors and outcomes, using data collected just at one point in time. With this approach, there is the question of which comes first, the risk factor or the PP. All you can see is that both are found at a particular point in time.

Case-Control Study

Case-control studies identify cases, people who have the outcome of interest (e.g., girls who have precocious puberty) and controls (girls who have not developed precocious puberty) and looks backwards in time using medical records and other collected data using tools like patient surveys to test which factors or characteristics have a higher association with PP.

This is an improvement from cross-sectional studies, because at least you can look for risk factors that happened before PP was diagnosed.

Most Dependable: Cohort Study

Cohort studies - also called panel studies, use data collected on a group of people over time to determine the effect of different type of risk factors on developing the outcome of interest. To test the associations between risk factors and PP, this would be the ideal study design, i.e. a large sample of girls chosen to participate from the time they are born going forward, looking to see who develops PP and who does not.

Ultimately, to prove causality, an experimental study, rather than an observational ones, gives the best evidence. The gold standard of experimental studies is the randomized controlled trial (RCT), during which one group is exposed in a highly controlled way to a particular exposure and the other group is not. However ethical considerations often make conducting such studies on humans (particularly children) a non-option. Researchers are therefore left to make conclusions based on observational studies or based on experimental studies on animals -- a practice that has its own ethical and methodological limitations.

As I look at specific studies about precocious puberty, I will address some of these study design points, such as:

1. The type of study -- and how much we should rely on its conclusions, based on its design

2. How many people were studied, i.e., the sample size

3. Did the study include only those with precocious puberty (cases), or were those who did not have precocious puberty (controls) also included for scientific comparison?
4. Do the conclusions made in the study match the evidence, taking into account these factors as well as other potential biases in the study?

I would love to see a long-term cohort study that collects data about children beginning with their mother's pregnancies with them and including information related to all of the potential risk factors for precocious puberty (genetics, environmental exposures, nutrition, family environment, etc).  As far as I know this study does not yet exist.   

Media coverage of rise of precocious puberty in 2nd graders

Growing up too soon? Puberty strikes 7-year-old girls
Study in 3 major cities finds precocious puberty rising among 2nd graders

By Linda Carroll

msnbc.com contributor

updated 8/9/2010 7:41:13 PM

The changes in Kiera’s body scared her parents. Though the 8-year-old seemed her usual chipper self, she’d started to develop headaches and acne. More alarming to her mom, Sharon, were the budding breasts on Kiera’s thin little chest.  

For Kiera, whose last name is being withheld to protect her privacy, it was all so embarrassing. None of her friends seemed to be experiencing what she was. When they asked about the acne and her expanding chest, Kiera was evasive. “I didn’t want to tell them what was going on,” says the Pittsburgh girl, now age 9. “So I had to kind of lie to them.”“I thought, she’s too young,” remembers the Pittsburgh mom. “She’s still fearful about sleeping by herself. An 8-year-old just isn’t mature enough to handle this.”

When Kiera’s parents took their daughter to the doctor, he assured them that nothing was wrong with the girl. Kiera was simply starting puberty early.

As it turns out, puberty at age 7 or 8 isn’t so unusual these days. A new study, published Monday in the journal Pediatrics, shows that more American girls are maturing earlier and earlier. Typically, U.S. girls hit puberty around age 10 or 11.

Exactly what this shift means for girls isn’t clear yet — either on a group or individual level.  But there are budding concerns. For instance, studies have linked an early start to menstruation with an elevated risk of breast cancer. And other research has shown that girls who go through puberty early tend to have lower self-esteem and a poor body image. They are also more likely to engage in risky behaviors which can result in unplanned pregnancies, experts say.

The possible link to breast cancer was what sparked the new study. To take a long-term look at the impact of puberty and other factors on breast cancer, researchers enrolled 1,239 girls between the ages of 6 and 8 from three sites in the U.S.: New York’s East Harlem, the greater Cincinnati metropolitan area and the San Francisco Bay area.

The study revealed a surprisingly large bump in the number of girls going through puberty between the ages of 7 and 8. For example, the researches found that 10 percent of 7-year-old white girls had some breast development as compared to 5 percent in a study published in 1997. Similarly, 23 percent of the 7-year-old black girls had started puberty as compared to 15 percent in the 1997 study.

Nobody’s sure what is driving the declining age of puberty. But the rise in obesity could be at least partly to blame, says the study’s lead author, Dr. Frank Biro, director of adolescent medicine at Cincinnati Children’s Hospital.

That makes a lot of sense to Dr. Luigi Garibaldi, a professor of pediatrics and clinical director of pediatric endocrinology at Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center.

Back in the 1700s, girls didn’t start to menstruate till they were 17 or 18, Garibaldi says. That had a lot to do with malnutrition. The assumption is that the steady decline in age since then has to do with more abundant food.

There may be other environmental factors at work, too, says Dr. Stanley Korenman, an endocrinologist at the University of California, Los Angeles.

For example, Korenman says, environmental exposure to estrogens in plastics, chemicals and foods has been going up. “And estrogens do stimulate breast development,” he adds.

Until we know what the cause is, the best way to slow puberty may be to “start living green,” says Biro. “It may help for families eat together and to consume well-balanced diets. Regular physical activity may help, too.”

Another finding from the study may back that concept up. The rate of early puberty was much lower in the San Francisco group: 7 percent among white 7-year-olds from northern California versus 14 percent among Ohioans of the same age. Among black 7-year olds, 27 percent of Californians hit puberty early as compared to 31 percent of the New Yorkers. Northern California’s temperate climate fosters more outdoor activities and the emphasis on healthy foods results in a better diet.

Why all the fuss about early puberty?

Beyond the possible breast cancer connection, there’s also the issue of emotional maturity, Biro says. “Just because a girl has matured physically, doesn’t mean she’s socially or psychologically mature,” he explains.

There’s also the issue of stature. There are some studies, Biro says, that show that kids who mature early don’t grow as tall.

As part of her work-up, Kiera had a bone exam. Doctors concluded that at age 8 she had the bone development of a 10 year old, which meant her growth might be stunted.

For Kiera and her family, the answer was simple: slow puberty down. She now has an implant placed under the skin of her upper arm that doles out regular doses of a drug that blocks the spiking hormones that were taking her into early sexual maturity.

Kiera was happy to see her breasts stop budding and to once again feel like she fits in with all her friends. These days she says she’d be perfectly happy if those breasts didn’t start to swell again till she was 16.

Potential Causes

Most cases of central precocious puberty (CPP) are without a known cause, which is called "idiopathic" CPP.  It has been estimated that 69 to 98% of CPP in girls is idiopathic.

Amidst this uncertainty, many theories about what might be causing early puberty have been explored and discussed.  I will list all possible causes or factors related to early puberty that I have heard or read about, in the medical literature or elsewhere. (If you know of more please send them to me and I will see what I can find out.)

It's one thing to write all these down, but quite another thing to comprehend their implications.  Many of the items on the "environmental exposures" list are used in a wide variety of household products, especially in plastics.   It is equally troublesome to wonder if the food you buy at the store for your children could actually be harmful, rather than healthy.  Panic and sensationalism don't help us, though.  As hard as it is to look at the evidence calmly, that's what has the best chance of helping us find real answers.

In future blog posts I will go through everything on the list, one by one, to examine and discuss the strength of the evidence.

My list includes:

1.  The rise of childhood obesity

2.  Environment exposures including:

      - DDT metabolites
      - PBBs
      - Phthalates
      - Bisphenol A
      - DEHA
     -  Parabens

3.  Nutritional hypotheses

     - the consumption of soy products
    -  the consumption of milk, particularly non-organic milk produced using synthetic growth hormones
    -  the consumption of meat, particularly when animals were raised using synthetic growth hormones
    -  the consumption of food preservatives, such as BHT and BHA
    -  tap water (fluoride, etc)

4.  Factors within the family and early childhood experiences

5.  The impact of migration from a developing country to a developed country

6.  Genetic factors

7.  Vitamin D connection

8.  Lavender and tea tree oil

9.  All others

CPP: Not Happening Within a Vacuum

Central Precocious Puberty is not happening within a vacuum.

What I mean by this is that over time the average age of pubertal changes has dropped. (Here is a related article, although it's dense and covers many other aspects of this issue, as well.)

Younger starting ages have become normalized in the sense that as the age has dropped, we seem to continue to say, "Well, maybe that's just happening these days..."

As an example, the PubMed Health (U.S. National Library of Medicine) link included in my first blog post says, "Some evidence suggests that it may be normal for these changes to occur as early as age 7 in Caucasian girls and age 6 in African-American girls."

If precocious puberty is considered to be under eight for girls now, next year will we say that age seven is normal? And why make a statement that brings the normal age even lower for African-American girls?  

One article I found says, "All puberty that appears to begin with breast development when a girl is age 6 or 7 is not precocious puberty.  Puberty among those with early onset may be progressing at a slower pace, or the initial appearance of breast growth may not herald the real onset of puberty."

The author's argument suggests that early breast development that is not then followed by more advanced breast development or the earlier start of menstruation should not count as precocious puberty.

I would argue that even slight breast development can seriously affect a six or seven year old girl's interactions with friends, her comfort changing in the girls locker room, the way boys and other people see her, and the way she thinks about herself.  If so, how unhelpful to ask the parent to wait to see how fast the puberty progresses, particularly given that once it does, it is usually impossible to reverse its effects.

Rather than taking a "this is the new normal" attitude, we should try to protect childhood more and ask harder questions about what is going on here.

Some Background: Normal Steps to Puberty and the 2 Types of Precocious Puberty

I appreciate the clear background given by the Mayo Clinic site, and so am essentially re-posting it here:

A Review of How Puberty Normally Starts

First: Part of the brain makes a hormone called gonadotropin-releasing hormone (Gn-RH).

Second: Gn-RH causes the pituitary gland — a small bean-shaped gland at the base of your brain — to release two more hormones. The hormones are called luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Third: LH and FSH cause the ovaries to produce hormones involved in the growth and development of female sexual characteristics (estrogen) and the testicles to produce hormones responsible for the growth and development of male sexual characteristics (testosterone). The body will also begin to make estrogen and testosterone.

Fourth: The production of estrogen and testosterone causes the physical changes of puberty.

The Two Types of Precocious Puberty

The reason puberty begins early in some children depends on the type of precocious puberty they have: central precocious puberty or peripheral precocious puberty.

In central precocious puberty (CPP), the brain starts the process of puberty too soon. Although they begin earlier than they should, the pattern and timing of the steps in the process are otherwise normal. For the majority of children with this condition, there's no underlying medical problem and no identifiable reason for the early puberty.

Peripheral precocious puberty (PPP) is less common than central precocious puberty and happens without the involvement of your brain triggering the start of puberty. Instead, the cause is release of estrogen or testosterone into the body because of problems with the ovaries, testicles, adrenal glands or pituitary gland or some other cause.

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Because most cases of precocious puberty are CPP, that's what this blog will address. Based on what's written above, CPP starts when the brain for some reason sends the "start puberty now" message early -- but what might explain why this is happening?

Precocious Puberty: The Basics

I wish that there was no reason to write this blog, but there is and it's a big one.

A disturbing phenomenon has been underway.  Maybe you've heard about it through the media. Maybe you know someone who is dealing with it within their own family.

The condition is called "precocious puberty" and it has been on the rise for reasons largely unknown.

There are plenty of Web-sites offering medical information about precocious puberty.  The basic symptom of this condition is when any sign of puberty is detected in girls younger than eight or in boys younger than 9.

So what we are talking about is very young children, mostly girls, who, along with their families, are confronting this reality much sooner than anyone had expected -- and in the majority of cases the cause is unknown.

This is where things get really interesting.

Yes, in the majority of cases the cause is unknown, but there is plenty of research and speculation about what could be behind the rise of precocious puberty.  The purpose of this blog is to go through these hypotheses and studies one by one to evaluate the rigor of their methods and to discuss their findings.