Hyper-androgenemia and obesity in early-pubertal girls

Abstract

Purpose The aim of this study was to examine the hormonal profile in early-pubertal girls with obesity. We hypothesized that these patients might already present hormonal alterations with POCS-like features. Methods Cross-sectional study in a sample of 283 peri-pubertal girls (prepubertal and early-puberty subgroups), aged 6.1–12.0 years, diagnosed with obesity (BMI-SDS > 2.0, 97th percentile), so-called obesity group. They all underwent clinical examination and blood testing for hormonal measurements (leptin, TSH, FT4, IGF-1, IGFBP3, prolactin, insulin, FSH, LH, estradiol, ACTH, cortisol, 17-OH-P, DHE-S, androstenedione, testosterone and free testosterone). A control group was recruited: 243 healthy girls, aged 6.3–12.1 years, with normal BMI status. Results Prepubertal girls with obesity had significantly higher values (p < 0.05) for BMI-SDS, leptin, insulin and HOMA-IR levels than control group. Early-pubertal girls with obesity also had significantly higher values (p < 0.05) for BMI-SDS, leptin, IGF-1, IGFBP3, insulin and HOMA-IR, LH, ratio LH/FSH, ACTH, DHE-S, androstenedione, testosterone and free testosterone levels than control group. In early-pubertal girls with obesity (not prepubertal girls), there was a positive correlation (p < 0.01) between leptin levels with LH, androstenedione and testosterone, and HOMA-IR with LH and testosterone levels. There was also a positive correlation (p < 0.01) between IGF-1 levels with LH, androstenedione, DHE-S and testosterone; and LH levels with testosterone. Conclusion The results obtained support our hypothesis that an abnormal hormonal profile with POCS-like features can already be detected (insulin resistance and hyperinsulinemia, increased secretion of LH and ACTH, and overproduction of ovarian and adrenal androgens) in early-pubertal girls with obesity.

Serum cortisol and insulin-like growth factor 1 levels in major depressive disorder and schizophrenia

“…In the present study, there was no correlation between cortisol and IGF-1 levels in any of the groups. Consistent with the present results, a cross-sectional study found no significant correlation between IGF-I and cortisol in patients with MDD or schizophrenia or control subjects 35 , 39 , 63 . However, a longitudinal study examining antipsychotic treatment-induced changes in antipsychotic naïve patients reported a significant positive correlation between changes in cortisol and IGF-I levels in patients with schizophrenia 35 .…”

Not Only Metabolic Complications of Childhood Obesity

“…Furthermore, in the increased amount of adipose tissue in the course of obesity occurs an intense aromatization of adrenal and ovarian androgens to estrogen, which is reflected in earlier adrenarche and thelarche in girls [ 81 ]. In addition, it was shown that obese prepubertal girls had significantly higher BMI-SDS, leptin, insulin, and HOMA-IR values than the control group, and that girls with obesity in early puberty presented higher BMI-SDS, leptin, IGF-1, IGFBP3, insulin, HOMA-IR, LH, LH/FSH ratio, ACTH, DHEA-S, androstenedione, testosterone, and free testosterone values than the control group [ 82 ]. Consequently, the hyperinsulinemia that occurs in girls experiencing obesity is considered to play a facilitating role in early puberty by leading to stimulation of adrenal and ovarian androgen production, decreased hepatic synthesis of sex hormone-binding globulin (SHBG), and increased aromatase activity in adipocytes [ 80 , 83 , 84 ].…”

Peak serum luteinising hormone cut‐off during gonadotropin‐releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight

“…14,15 Lastly, increased adrenocorticotrophic hormone secretion secondary to increased peripheral metabolism of cortisol in obese individuals causes increased production of adrenal androgens which can be converted to oestrogens. 16,17 Most of the previous studies of GnRH and GnRHa tests in diagnosing CPP did not specifically analyse serum LH cut-offs for diagnosing CPP in girls with overweight and obesity (OW/OB). [18][19][20] A few studies which analysed peak serum LH concentrations during GnRH test in CPP girls with OW/OB in comparison with CPP girls with normal weight (NW) found lower peak serum LH concentrations in girls with OW/OB.…”

“…However, emerging evidence showed that monosaccharides (glucose and fructose)‐induced lipogenesis reduced human SHBG production in transgenic mice and HepG2 hepatoblastoma cells 14,15 . Lastly, increased adrenocorticotrophic hormone secretion secondary to increased peripheral metabolism of cortisol in obese individuals causes increased production of adrenal androgens which can be converted to oestrogens 16,17 …”