Adrenal hypoandrogenism in adolescents with premature ovarian insufficiency

Premature ovarian insufficiency (POI) affects 1 in 10,000 children, with its molecular causes largely unknown. Adult studies suggest that low androgen levels induce ovarian insufficiency, but data on about this in children is limited. This study aims to assess the prevalence of low androgen levels in childhood POI and its relationship with adrenal insufficiency.

Idiopathic POI adolescents were categorized into two groups based on DHEAS and total testosterone (TT) measured by chemiluminescence. Low androgen group (LAG) was defined using cut-offs according to Tanner pubarche staging. Demographic, clinical, and laboratory data were compared. Morning cortisol <7 μg/dL and/or ACTH >96 or <5 pg/mL were planned to undergo ACTH stimulation testing, with a peak cortisol response <18 μg/dL considered insufficient.

Forty-three adolescents, mean age 15.5 ± 1.3 years with a 46, XX karyotype, normal FMR1 mutation, FSH levels >40 mIU/mL, and low AMH levels were included. In 14 cases (37.8 %), DHEAS and TT were low. In the LAG, pubarche was absent in seven patients, and initial height SDS was significantly lower. Morning cortisol ranged from 7.9 to 23.5 μg/dL, with an ACTH of 29.4 ± 9.7 pg/mL. No differences in adrenal steroids or correlations between DHEAS and ACTH were observed.

Diminished androgen levels are prevalent in children with idiopathic POI. The potential for this condition to increase the risk of adrenal insufficiency and its impact on secondary ovarian insufficiency remains unclear. This study, the first of its kind in children, underscores the potential role of genetic factors in zona reticularis and ovarian development.