Early menarche linked to insulin resistance and NAFLD in obese adolescents: Study

Although early menarche cannot be considered as a pathological and then treatable event, it is associated with increased morbidity (i.e., obesity, diabetes, insulin resistance [IR], metabolic syndrome, cardiovascular disease [CVD], and stroke), and mortality later in life. Researchers from Italy in a recent study demonstrated in girls with obesity that early menarche is associated with glucose derangement and NAFLD(non-alcoholic fatty liver disease).

To date, evidence regarding the potential mechanism linking early puberty and obesity is poor, but the interaction between leptin and the kisspeptin system seems to be the most promising hypothesis. Also the peripheral actions of adipose tissue could act as mediators linking the onset of puberty to obesity . On the other hand, puberty plays a role in worsening obesity-related comorbidities.

A total of 318 menstruating girls with a mean age of 12.31 ± 2.95 years and Body Mass Index (BMI)>95th percentile attending the obesity clinic were enrolled with age at menarche between 8-12 years. Patients with precocious puberty, delayed puberty and taking any medication or alcohol potentially affecting liver function tests or potentially determining fatty liver were excluded. All patients underwent OGTT, fasting lipid profile, liver function tests. Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR) and insulin sensitivity was assessed by Matsuda index. Hepatic steatosis was screened by radiologist.

Key findings of the study are:

1. Researchers found that the mean age at menarche of all the enrolled (with and without early menarche) was 11.21 ± 1.40 years and 61.1% of the enrolled patients presented early menarche.

2. Upon analysis it was found that patients with early menarche showed higher HOMA-IR levels, lower Insulinogenic index(IGI) and Matsuda Index levels (p=0.04 and p=0.01, respectively).

3. Patients with early menarche showed higher ALT levels and higher prevalence of NAFLD(41.1%) even in early adolescence, confirming also an effect of early menarche on NAFLD already in adolescence.

4. It has been observed that girls with early menarche are significantly more often overweight or obese.

However, it is unclear whether childhood adiposity is a trigger of age at menarche, or if menarche age itself leads to differences in adiposity during the pubertal period that persists into adult life. The pathogenic link between menarcheal age and overweight/ obesity has not been fully elucidated, but it might be considered the result of the interaction of complex physiological and biological factors such as genetics and environment . The underlying potential mechanism may be related to metabolic impairments – such as insulin resistance and hyperinsulinemia – and hormonal factors – such as hyperandrogenism, estrogen, sex-hormone-binding globulin, and leptin.

Authors conclude-"It is mandatory for the pediatricians to follow primary prevention strategies counteracting modifiable factors such as obesity and promoting a healthy lifestyle to prevent future cardiometabolic related morbidity and early mortality."

Source: Di Sessa A, Grandone A, Marzuillo P, Umano GR, Cirillo G, Miraglia Del Giudice E. Early menarche is associated with insulin-resistance and non-alcoholic fatty liver disease in adolescents with obesity. J Pediatr Endocrinol Metab. 2021 Apr 7;34(5):607-612. doi: 10.1515/jpem-2020-0684.