In the Journals

Obesity's effect on reproductive hormones begins in early puberty

Boys and girls with obesity already display hallmarks of reproductive dysfunction during the early stages of puberty, including differences in hormone levels that are partially influenced by high insulin secretion, according to findings from a cross-sectional analysis.

“This study suggests that adverse effects of obesity on reproductive hormones seen in adults are already present in early puberty,” Megan Moriarty Kelsey, MD, MS, associate professor of pediatric endocrinology at the University of Colorado School of Medicine and medical director of metabolic and bariatric surgery at Children’s Hospital Colorado, told Endocrine Today. “Specifically, obese boys show signs of low total testosterone and high estradiol, whereas obese girls seem to have higher bioavailable testosterone. Of note, bioavailable testosterone was not impacted in the obese boys. We did not find any relationship between reproductive hormones and estimates of insulin sensitivity or secretion.”

Kelsey and colleagues analyzed data from 50 boys (median age, 12 years) and 54 girls (median age, 10 years) with and without obesity in early puberty (Tanner stages 2 and 3), recruited between 2009 and 2015 for the Health Influences of Puberty study, a longitudinal study evaluating the effects of obesity on glucose metabolism during puberty. Children with obesity underwent a 75 g oral glucose tolerance test; those with impaired glucose tolerance or type 2 diabetes were excluded. After a screening visit and a 3-day macronutrient diet (55% carbohydrates, 30% fat, 15% protein), children were admitted to Children’s Hospital Colorado Clinical and Translational Research Center to provide fasting blood samples to assess levels of glucose, insulin, dehydroepiandrosterone sulfate (DHEAS), estradiol, total testosterone and sex hormone-binding globulin (SHBG). Children also underwent a frequently sampled IV glucose tolerance test after an infusion of 0.3 g/kg of 25% dextrose given over 90 seconds.

Compared with normal weight boys (n = 27), researchers found that boys with obesity (n = 23) had lower concentrations of SHBG (median, 18 vs. 57 nmol/L; P < .0001) and lower total testosterone (median, 43 vs. 81 ng/dL; P < .0001); however, there was no between-group difference in free androgen index (median, 213.6 vs. 164.8; P = .9).

Compared with normal weight girls (n = 24), girls with obesity (n = 30) had lower SHBG levels (median, 18.5 vs. 59.5 nmol/L; P < .0001) but had a higher free androgen index (median, 91.7 vs. 26.7; P = .03).

Researchers found that boys and girls with obesity had a higher acute insulin response to glucose and lower insulin sensitivity compared with normal weight children. Higher insulin response to glucose was associated with higher BMI z score in boys (P < .0001) and girls (P < .0001). In boys, higher acute insulin response to glucose was also associated with higher levels of DHEAS (P = .003) and lower levels of SHBG (P < .0001) and testosterone (P = .001), whereas higher insulin sensitivity was associated with higher SHBG and total testosterone and lower DHEAS and luteinizing hormone levels.

In girls, a higher acute insulin response to glucose was associated with higher free androgen index and lower SHBG, whereas higher insulin sensitivity was associated with higher SHBG and lower free androgen index.

“It is important to get a measure of bioavailable testosterone when evaluating for pubertal disorders in obese boys,” Kelsey said. “In addition, the very high insulin secretion seen in obese youth in early puberty is associated with extremely low SHBG in youth, which has a differential impact on testosterone in girls and boys.”

Kelsey said it is important to better understand the impact of exposure to obesity early in puberty on long-term reproductive health and sex differences.

“The study did not help us understand why girls are more likely to get diabetes during puberty than boys, a sex difference that is not seen in adults,” Kelsey said. “Future studies are needed to understand this sex difference in youth-onset diabetes.” – by Regina Schaffer

For more information:

Megan Moriarty Kelsey, MD, MS, can be reached at Children’s Hospital Colorado, 13123 East 16th Ave., Box B265, Aurora, CO 80045; email: megan.kelsey@childrenscolorado.org.

Disclosures: The authors report no relevant financial disclosures.

Boys and girls with obesity already display hallmarks of reproductive dysfunction during the early stages of puberty, including differences in hormone levels that are partially influenced by high insulin secretion, according to findings from a cross-sectional analysis.

“This study suggests that adverse effects of obesity on reproductive hormones seen in adults are already present in early puberty,” Megan Moriarty Kelsey, MD, MS, associate professor of pediatric endocrinology at the University of Colorado School of Medicine and medical director of metabolic and bariatric surgery at Children’s Hospital Colorado, told Endocrine Today. “Specifically, obese boys show signs of low total testosterone and high estradiol, whereas obese girls seem to have higher bioavailable testosterone. Of note, bioavailable testosterone was not impacted in the obese boys. We did not find any relationship between reproductive hormones and estimates of insulin sensitivity or secretion.”

Kelsey and colleagues analyzed data from 50 boys (median age, 12 years) and 54 girls (median age, 10 years) with and without obesity in early puberty (Tanner stages 2 and 3), recruited between 2009 and 2015 for the Health Influences of Puberty study, a longitudinal study evaluating the effects of obesity on glucose metabolism during puberty. Children with obesity underwent a 75 g oral glucose tolerance test; those with impaired glucose tolerance or type 2 diabetes were excluded. After a screening visit and a 3-day macronutrient diet (55% carbohydrates, 30% fat, 15% protein), children were admitted to Children’s Hospital Colorado Clinical and Translational Research Center to provide fasting blood samples to assess levels of glucose, insulin, dehydroepiandrosterone sulfate (DHEAS), estradiol, total testosterone and sex hormone-binding globulin (SHBG). Children also underwent a frequently sampled IV glucose tolerance test after an infusion of 0.3 g/kg of 25% dextrose given over 90 seconds.

Compared with normal weight boys (n = 27), researchers found that boys with obesity (n = 23) had lower concentrations of SHBG (median, 18 vs. 57 nmol/L; P < .0001) and lower total testosterone (median, 43 vs. 81 ng/dL; P < .0001); however, there was no between-group difference in free androgen index (median, 213.6 vs. 164.8; P = .9).

Compared with normal weight girls (n = 24), girls with obesity (n = 30) had lower SHBG levels (median, 18.5 vs. 59.5 nmol/L; P < .0001) but had a higher free androgen index (median, 91.7 vs. 26.7; P = .03).

Researchers found that boys and girls with obesity had a higher acute insulin response to glucose and lower insulin sensitivity compared with normal weight children. Higher insulin response to glucose was associated with higher BMI z score in boys (P < .0001) and girls (P < .0001). In boys, higher acute insulin response to glucose was also associated with higher levels of DHEAS (P = .003) and lower levels of SHBG (P < .0001) and testosterone (P = .001), whereas higher insulin sensitivity was associated with higher SHBG and total testosterone and lower DHEAS and luteinizing hormone levels.

PAGE BREAK

In girls, a higher acute insulin response to glucose was associated with higher free androgen index and lower SHBG, whereas higher insulin sensitivity was associated with higher SHBG and lower free androgen index.

“It is important to get a measure of bioavailable testosterone when evaluating for pubertal disorders in obese boys,” Kelsey said. “In addition, the very high insulin secretion seen in obese youth in early puberty is associated with extremely low SHBG in youth, which has a differential impact on testosterone in girls and boys.”

Kelsey said it is important to better understand the impact of exposure to obesity early in puberty on long-term reproductive health and sex differences.

“The study did not help us understand why girls are more likely to get diabetes during puberty than boys, a sex difference that is not seen in adults,” Kelsey said. “Future studies are needed to understand this sex difference in youth-onset diabetes.” – by Regina Schaffer

For more information:

Megan Moriarty Kelsey, MD, MS, can be reached at Children’s Hospital Colorado, 13123 East 16th Ave., Box B265, Aurora, CO 80045; email: megan.kelsey@childrenscolorado.org.

Disclosures: The authors report no relevant financial disclosures.