Tag: precocious puberty

Categories : Environmental Effects PaediatricsTags :

Girls may Start Puberty Early Due to Chemical Exposure

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Girls exposed to certain endocrine-disrupting chemicals (EDCs) may be more likely to start puberty early, according to new research published in Endocrinology, the flagship basic science journal of the Endocrine Society. EDCs mimic, block or interfere with hormones in the body’s endocrine system.

There has been an alarming trend toward early puberty in girls, suggesting the influence of chemicals in our environment. Early puberty is associated with an increased risk of psychosocial problems, obesity, diabetes, cardiovascular disease, and breast cancer.

“We conducted a comprehensive screen of 10 000 environmental compounds with extensive follow-up studies using human brain cells that control the reproductive axis, and our team identified several substances that may contribute to early puberty in girls,” said study author Natalie Shaw, MD, MMSc, of the National Institute of Environmental Health Sciences (NIEHS).

Those substances include musk ambrette, which is a fragrance used in some detergents, perfumes, and personal care products, and a group of medications called cholinergic agonists.

“More research is needed to confirm our findings,” noted Shaw. “But the ability of these compounds to stimulate key receptors in the hypothalamus – the gonadotropin-releasing hormone receptor [GnRHR] and the kisspeptin receptor [KISS1R] – raises the possibility that exposure may prematurely activate the reproductive axis in children.”

According to the research team, musk ambrette is potentially concerning because it can be found in personal care products, and some rat studies have suggested it can cross the blood-brain barrier. Children are less likely to encounter cholinergic agonists in their daily lives.

Canadian and European regulations restrict musk ambrette use because of its potential toxicity, and the U.S. Food and Drug Administration removed the fragrance from its “generally recognized as safe” list. Yet it is still available on the market in some personal care products.

“This study suggests that, out of an abundance of caution, it is important for parents to only use personal care products for their children that are federally regulated,” Shaw said.

As part of the study, the research team screened a Tox21 10 000-compound library of licensed pharmaceuticals, environmental chemicals and dietary supplements against a human cell line overexpressing GnRHR or KISS1R. They conducted follow-up analysis using human hypothalamic neurons and zebrafish, finding that musk ambrette increased the number of GnRH neurons and GnRH expression.

“Using human hypothalamic neurons and zebrafish provides an effective model for identifying environmental substances that stimulate the KISS1R and GnRHR,” said co-author Menghang Xia, PhD, from the National Center for Advancing Translational Sciences (NCATS) “This study was a multidisciplinary team effort, and it showed that we can efficiently reduce the time and cost of assessing environmental chemicals for their potential effects on human health.”

Source: Endocrine Society

Categories : Cardiovascular Disease PaediatricsTags :

Earlier Puberty Onset in Girls may Affect Adult Cardiometabolic Health

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Experiencing puberty earlier, compared to same-age peers, may be one of the mechanisms through which childhood risk factors influence adult cardiometabolic health issues, according to a study published March 27, 2024 in the open-access journal PLOS ONE by Maria Bleil from the University of Washington, USA and colleagues.

Adverse experiences in childhood are frequently linked to poor health in adulthood. Most of the conceptual models describing adversity-related changes that may be adaptive to stress in the short-term but are risky to long-term health don’t specifically include puberty, which links childhood and adulthood and is itself also sensitive to the child’s environment. Earlier onset of puberty is often linked to factors like race (with Black and Latina girls developing earlier than White girls), mother’s age at her first period, infant weight gain and childhood obesity, and adverse experiences like childhood socioeconomic disadvantage, stressful parent-child relationships, and other stressful life events.

Here, Bleil and colleagues modeled pubertal timing and health risks in a cohort of women who had participated in the 30-year NICHD Study of Early Child Care and Youth Development prospective study of children and their families. Participants were followed from birth to adolescence (1991–2009) to examine trajectories of child health and development, with an additional in-person study follow-up (2018–2022) among participants ages 26 to 31 to capture social, behavioural, and health status information in adulthood. The authors fit models to data from the full sample of 655 women.

The authors found that later pubertal onset (later breast development, pubic hair onset, and first period) predicted lower adulthood cardiometabolic risk. These puberty indicators were also found to mediate the effects of factors like mother’s age at her first period, race, BMI percentile, and childhood socioeconomic status on adult cardiometabolic risk. 

It’s important to note that this study maps predictive relationships between childhood risk factors, timing of puberty, and adulthood cardiometabolic risks, but cannot prove causation. That said, the pattern of results provides strong longitudinal evidence for the role of puberty onset as a pathway linking early life exposures and adulthood cardiometabolic health – and suggests targeting puberty onset may improve health more broadly in at-risk girls. The authors hope future studies will both replicate their findings and better characterise the nature of the links identified here.

The authors add: “This study suggests the timing of pubertal development in girls is an important pathway through which early life risk factors, such as prepubertal body mass index and socioeconomic position, influence cardiometabolic health in adulthood. The implications of this work are that pubertal development and its timing should be considered, and potentially targeted, in efforts to improve cardiometabolic health.”

Categories : Metabolic Disorders PaediatricsTags :

Cholesterol may Explain The Link Between Childhood Obesity and Early Puberty

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As childhood obesity increases the world, children are entering puberty earlier and earlier – particularly girls. According to a survey, the onset of puberty occurs on average three months earlier for girls in every decade since 1977. Early, or precocious, puberty can leave children with psychological and social problems, as well leading to shorter adult heights. Studies also suggest that early puberty can increase the risk of developing cancer, diabetes, depression and cardiovascular disease later on in life.

While a scientific explanation has been lacking, the link between childhood obesity and early puberty has long been apparent. The more body fat a child has, the greater their likelihood of beginning puberty at an earlier age. Now, researchers have found what may be part of the answer in Drosphila fruit flies, publishing their results in Current Biology.

“Cholesterol is a fat. So, if you’re overweight, your body fat harbours more cholesterol. And it turns out that higher cholesterol is a key to earlier maturation in the fruit fly, our model organism. Our results demonstrate that the amount of cholesterol in adipose tissue and in certain support cells in the brain affects the growth of fruit flies and controls when they reach maturity,” explains Professor Kim Rewitz, a lead author of the study.

He adds, “And because the systems in fruit flies and humans are remarkably similar, we believe that the same may apply to humans – ie, that cholesterol in adipose tissue may help explain the connection between childhood obesity and early puberty.”

Puberty at ‘critical weight’

Professor Rewitz and the University of Copenhagen’s Department of Biology research team tested their hypothesis by putting fruit fly larvae on a “fatty diet” of cholesterol-packed foods. The development of these larvae was compared with larvae on a normal diet.

“We observed that larvae on the cholesterol diet consistently grew faster and entered ‘puberty’ sooner. It turned out that the increase of cholesterol stored in the fruit flies’ body fat and support cells in the brain increases the release of growth hormones that cause the animals to grow faster. Growth and size is a signal to the body for when to trigger puberty,” says Kim Rewitz. 

The professor explains that in fruit flies, the signal to undergo maturation is when their weight and amount of body fat reach a certain point during development:

“In one way or another, animals need to know when they’re large enough to reach sexual maturity and be able to reproduce. Organisms have a checkpoint in their development that they must pass to enter puberty known as ‘Critical Weight’. This checkpoint is found in fruit flies and most likely in humans too. This means that both fruit fly larvae and children probably need to reach a certain body size and have a certain amount of fat stored to enter puberty. What we’ve found is that the amount of cholesterol stored in body fat plays an important role in this process.

“We see that fruit flies have a mechanism that senses how much cholesterol is stored in their body fat and support cells in the brain. At a certain point, the system then sends a signal to the brain centres that triggers maturation by producing steroid hormones. In humans, these correspond to testosterone and oestrogen.”

However, it also means that if the amount of stored cholesterol increases, the organism can actually fail to estimate its overall size accurately, so that it hits the critical weight checkpoint earlier than it normally would:

“Because overweight children have more body fat, they will probably also have stored more cholesterol at an earlier point in their development. So, if our assumption that the same mechanism exists in humans holds true, it could help to explain early puberty in obese children,” says the researcher.

Cholesterol may influence cancer as well

Professor Rewitz concludes that with part of the puzzle in hand, scientists can search for more clues and treatment. In the meantime, lifestyle changes remain the best solution for childhood obesity.

Professor Rewitz and his research colleagues have now started to look deeper into the significance of the cholesterol mechanism for cancer development. Their research also shows that, via the same mechanism, cholesterol can activate cell growth that leads to cancer.

Source: University of Copenhagen