Mar. 21 2017

What the Hygiene Hypothesis Is Telling Us About Early Puberty

Through a Provost’s Diversity Grant, Jasmine McDonald is exploring the connection between childhood infections and pubertal timing in girls

According to the hygiene hypothesis, growing up in a home cleaned to contemporary standards can increase a child’s risk for developing allergies. Using Lysol and other disinfectants kills microorganisms that play a role in the development of an immune system that won’t overreact when confronted with say pollen or peanut butter.

Taking the hypothesis a step further, Jasmine McDonald, assistant professor of Epidemiology, is studying whether a similar phenomenon is responsible for the increasing number of girls who are experiencing an earlier age of puberty.

Over the last 50 years, the median age of puberty for girls in the United States and other wealthy countries has dropped where breast development is up to a year earlier, and some girls show signs of breast development as early as age 5. Not only is experiencing these changes at a young age socially awkward, it’s also linked to risk for breast cancer, cardiovascular disease, and type 2 diabetes.

Explanations for earlier puberty in girls are varied: some suggest obesity and endocrine-disrupting chemicals could be causal factors. There is also growing evidence that the immune system may play a role. In a 2016 review article in the Journal of Developmental Origins of Health and Disease, McDonald reported an association between childhood infections and later age of breast development.

An evolutionary lens is helpful to understand the link. Over millennia our immune systems have developed to fight life-threatening infections so we can survive to reproductive age. This process helps set the clock for puberty.

During most of human history—and in some developing countries today—infectious diseases like malaria are still common. When a young girl got an infection, she expended energy to fight off pathogens, from inflammatory respiratory viruses to anti-inflammatory illnesses like schistosomiasis, an infection from a parasitic worm.

According to this theory, these infections activate a child’s immune system. Once a girl’s immune system becomes adapted to the pathogenic challenges in her environment, resources can now be directed to the energy-intensive process of puberty. On the other hand, in more sterile environments, energy that would otherwise be fighting infections may be directed to puberty sooner rather than later.

In her new study, funded through a Columbia University Junior Faculty Diversity Grant, McDonald is looking behind the curtain at the biological underpinnings of this process using the New York site of the LEGACY Girls Cohort. The study is the first to look at multiple pubertal outcomes—breast development, pubic hair, and menarche—as well as prospective measures of molecular markers for immune and hormone signaling in a cohort of 37 girls ages 8 to 14 years. The Provost award allows McDonald to scale up her study to over 150 girls with assessments at several time points, where half of these girls are at increased risk of breast cancer due to a family history of the disease.

“We know the immune system communicates with the endocrine system,” she says. “When your immune system is kicking in, you don’t have the same kind of hormonal response.”

While the immune systems of the girls in the study cohort haven’t been challenged to the extent they would in a developing nation, they still likely would have encountered pathogens like herpes simplex virus 1, the bug behind cold sores. Some may have been hospitalized with severe respiratory virus or even gotten a worm infection. McDonald expects to find that girls who were exposed to more infections during childhood experienced puberty later than their counterparts with fewer infections.

“I’ve been looking at the girls who have not gone through breast development, looking at immune markers in blood taken at various time points, asking the question of whether levels of immune factors are associated with pubertal timing,” she says. The study will also look for evidence of how and when the immune system signals to the endocrine system to open the hormonal floodgates for puberty.

The first physical sign of puberty in girls, breast development, normally precedes menarche. With age at menarche remaining relatively stable and breasts developing at an earlier age, this gap has widened. Because puberty involves changes on the cellular level, girls’ bodies may be more vulnerable during this time to genetic mutations—a likely reason why earlier age at puberty increases a girl’s risk for later developing breast cancer.

Snips and Snails and Puppy Dogs Tails

Unlike girls, there is scant evidence that boys are going through puberty any younger than they ever have. One possible explanation, says McDonald, is that our society hold girls to a higher standard for cleanliness than boys, giving the former fewer opportunities for microbial exposures. Even as gender norms change, the nursery rhyme equating boys to snips, snails, and puppy dog tails still applies: little Billy is more likely to play in dirt and eat food that’s fallen on the ground than his sister (girls, the rhyme goes, are made of “sugar and spice and everything nice”). As a result, the effects of hygienic environment may be exacerbated for girls.

As part of her ongoing study, McDonald is looking at evidence for another hygiene-related factor in early puberty: antibiotics. Many parents push their pediatricians to prescribe antibiotics even when they’re not needed—such as for a cold or flu. “A slight fever is a sign that your child is actually fighting an infection adequately,” she says.

Of course, the hygiene hypothesis shouldn’t be seen as an argument to skip antibiotics altogether. Our hygienic environment, created by public health advances like antibiotics, sanitation, and vaccines, has saved countless millions of lives. Even so, McDonald says she hopes parents will be less fearful of letting their daughters get dirty or weather a cold.

“An infection isn’t all bad,” she says. “I want them to know it can prime their child’s immune system to fight infections more effectively and may help keep puberty on schedule.”