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Background <p>Anti-Müllerian hormone (AMH) is widely used as a marker of ovarian reserve. However, its reliability in functional hypothalamic amenorrhea (FHA) remains debated. FHA is characterized by reduced gonadotropin secretion and impaired folliculogenesis, which may influence AMH expression and lead to an underestimation of reproductive potential.</p> Methods <p>We conducted a case–control study including women diagnosed with FHA and age-matched healthy controls. FHA patients were stratified according to the presence or absence of polycystic ovarian morphology (PCOM). Serum gonadotropins, estradiol, androgens, and AMH were measured and compared between groups. Correlation analyses were performed to explore associations among hormonal parameters.</p> Results <p>Overall, AMH concentrations in FHA patients were comparable to those of controls. However, stratification revealed that FHA without PCOM was associated with significantly reduced AMH, whereas FHA with PCOM displayed increased values. FHA patients also showed reduced gonadotropins, estradiol, and androgens compared with controls. In the non-PCOM FHA subgroup, AMH correlated positively with androgens and negatively with estradiol. These findings suggest that suppression of gonadotropins and consequent androgen deficiency may contribute to reduced AMH levels in FHA.</p> Conclusions <p>This pilot study indicates that low AMH in FHA may reflect hypothalamic suppression of gonadotropins rather than true ovarian reserve potentially leading to misinterpretation in fertility counseling. These observations should be interpreted with caution given the small sample size, but they support the hypothesis that AMH levels might recover with restoration of hypothalamic–pituitary activity and menstrual cycles. Larger, longitudinal studies are warranted to confirm the reversibility of AMH and clarify its prognostic value in FHA.</p> Graphical abstract <p>Proposed mechanism linking hypothalamic suppression to reduced AMH levels in functional hypothalamic amenorrhea (FHA). Reduced GnRH pulsatility leads to decreased LH secretion and consequent reduction in ovarian androgen production. The resulting hypoandrogenic environment impairs granulosa cell function and attenuates AMH production, reflecting a functional and potentially reversible suppression rather than an irreversible depletion of ovarian reserve.</p> <p></p>

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Functional hypothalamic amenorrhea and anti-Müllerian hormone: insights for fertility assessment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月6日

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  • Giovanna Notaristefano,
  • Anna Tropea,
  • Anastasiya Samasiuk,
  • Monia Ranalli,
  • Martina Asia Policriti,
  • Alice Diterlizzi,
  • Tullio Ghi,
  • Antonio Lanzone,
  • Rosanna Apa

摘要

Background

Anti-Müllerian hormone (AMH) is widely used as a marker of ovarian reserve. However, its reliability in functional hypothalamic amenorrhea (FHA) remains debated. FHA is characterized by reduced gonadotropin secretion and impaired folliculogenesis, which may influence AMH expression and lead to an underestimation of reproductive potential.

Methods

We conducted a case–control study including women diagnosed with FHA and age-matched healthy controls. FHA patients were stratified according to the presence or absence of polycystic ovarian morphology (PCOM). Serum gonadotropins, estradiol, androgens, and AMH were measured and compared between groups. Correlation analyses were performed to explore associations among hormonal parameters.

Results

Overall, AMH concentrations in FHA patients were comparable to those of controls. However, stratification revealed that FHA without PCOM was associated with significantly reduced AMH, whereas FHA with PCOM displayed increased values. FHA patients also showed reduced gonadotropins, estradiol, and androgens compared with controls. In the non-PCOM FHA subgroup, AMH correlated positively with androgens and negatively with estradiol. These findings suggest that suppression of gonadotropins and consequent androgen deficiency may contribute to reduced AMH levels in FHA.

Conclusions

This pilot study indicates that low AMH in FHA may reflect hypothalamic suppression of gonadotropins rather than true ovarian reserve potentially leading to misinterpretation in fertility counseling. These observations should be interpreted with caution given the small sample size, but they support the hypothesis that AMH levels might recover with restoration of hypothalamic–pituitary activity and menstrual cycles. Larger, longitudinal studies are warranted to confirm the reversibility of AMH and clarify its prognostic value in FHA.

Graphical abstract

Proposed mechanism linking hypothalamic suppression to reduced AMH levels in functional hypothalamic amenorrhea (FHA). Reduced GnRH pulsatility leads to decreased LH secretion and consequent reduction in ovarian androgen production. The resulting hypoandrogenic environment impairs granulosa cell function and attenuates AMH production, reflecting a functional and potentially reversible suppression rather than an irreversible depletion of ovarian reserve.