Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone
sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism
in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children,
warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional,
and environmental factors or differences in the characteristics of participants. In an attempt to understand,
in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified
according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated
during their second decade of life. Furthermore, different entities associated with PA, such as polycystic
ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and
the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn.
However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that
may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing
a patient-oriented approach are recommended.
Natural History of NAFLD