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

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.