Restoring ovulation in functional hypothalamic amenorrhea: impact of polycystic ovarian morphology on hormonal response to pulsatile GnRH.

OBJECTIVE

Up to 50% of women with functional hypothalamic amenorrhea (FHA) exhibit polycystic ovarian morphology (PCOM) on ultrasound. We aimed to compare the hormonal response to ovulation induction with pulsatile GnRH therapy in FHA patients with and without PCOM.

METHODS

In this single-center observational study, 41 patients with FHA underwent 3 months of pulsatile GnRH therapy to induce ovulation. Patients were categorized into a PCOM group (n = 24) and a non-PCOM group (n = 17). Serum levels of Anti-Muellerian-hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, sex hormone-binding globulin (SHBG), testosterone, and thyroid-stimulating hormone (TSH) were assessed at baseline and after 3 months of treatment.

RESULTS

At baseline, median AMH levels were significantly higher in the PCOM group (6.21 ng/ml [IQR 4.03-8.87]) compared to the non-PCOM group (1.7 ng/ml [IQR 1.14-2.20]; p < 0.001). After 3 months of pulsatile GnRH therapy, AMH levels significantly increased in the non-PCOM group (1.94 [IQR 1.39-2.49], p < 0.001), whereas no significant change was observed in the PCOM group (p = 0.218). LH, FSH, and estradiol levels increased in both groups. Pulsatile GnRH therapy effectively induced ovulation (1 dominant follicle in each patient), irrespective of ovarian morphology.

CONCLUSION

The significant AMH rise in women with FHA without PCOM likely reflects restored folliculogenesis. In contrast, the absence of an AMH rise in the PCOM group was expected, given their already elevated baseline levels. Importantly, these findings suggest that pulsatile GnRH therapy does not exacerbate AMH levels in most patients.