Clinical Science| Volume 113, 154392, December 2020

Circulating profile of Activin-Follistatin-Inhibin Axis in women with hypothalamic amenorrhea in response to leptin treatment

Published:October 09, 2020DOI:


      • Women with HA that responded to leptin treatment, i.e. ovulated and restored menstruation, show a distinct hormonal profile compared to non-responders.
      • This hormonal profile is characterized by higher LH/FSH ratio and higher circulating levels/peak values of Inhibin A and E2 compared to non-responders.
      • AMH may serve as a marker of ovarian recovery under HA treatment.



      Chronic energy deficiency observed in women that exercise strenuously affects reproductive function, often leading to hypothalamic amenorrhea (HA). In such conditions, hypoleptinemia and robust changes in the Activin-Follistatin-Inhibin Axis (AFI) are observed. Treatment with leptin restores menstruation in many (60% responders) but not all (40% non-responders) women, suggesting that leptin is not the only regulator of reproductive function related to energy balance. In this work, we aimed to identify differences in hormonal profiles between leptin responders and non-responders among women with HA, with particular focus on the AFI axis.


      AFI axis and reproductive hormones (LH, FSH, Estradiol, ΑΜΗ) were measured in blood in: a) An open-label interventional study, b) a randomized placebo-controlled trial, both investigating responders versus non-responders/women with HA treated with leptin.


      Women with HA that responded to leptin treatment have higher circulating levels/peak values of Inhibin A, Estradiol (E2), higher LH/FSH ratio and a trend to lower AMH compared with non-responders.


      Components of the AFI axis are associated with improvement of reproductive function in women with HA treated with leptin. ΑΜΗ may serve as a marker of ovarian recovery under HA treatment.


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