Restoring ovulation in functional hypothalamic amenorrhea: impact of polycystic ovarian morphology on hormonal response to pulsatile GnRH.
Pulsatile GnRH therapy induced ovulation in women with functional hypothalamic amenorrhea, with significant hormonal changes observed primarily in those without polycystic ovarian morphology.
Where it sits
this study against the rest of the buserelin corpusSummary and findings
This study measured the hormonal response to pulsatile GnRH therapy in 41 women with functional hypothalamic amenorrhea (FHA), categorized into polycystic ovarian morphology (PCOM, n=24) and non-PCOM (n=17) groups. After 3 months of treatment, median AMH levels increased significantly in the non-PCOM group, while no significant change was observed in the PCOM group. The therapy induced ovulation in all patients.
Abstract
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.
Background
This paper addresses the hormonal response to pulsatile GnRH therapy in women with functional hypothalamic amenorrhea (FHA), particularly focusing on the impact of polycystic ovarian morphology (PCOM). Prior studies have indicated that a significant proportion of women with FHA exhibit PCOM, which may influence hormonal dynamics. Understanding these differences is crucial for optimizing treatment strategies in this population.
Methods
This was a single-center observational study involving 41 patients diagnosed with FHA. Participants were divided into two groups: those with PCOM (n=24) and those without (n=17). They underwent 3 months of pulsatile GnRH therapy, with hormonal assessments including AMH, FSH, LH, estradiol, prolactin, SHBG, testosterone, and TSH at baseline and after 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 treatment, AMH levels in the non-PCOM group increased to 1.94 ng/ml [IQR 1.39-2.49], p<0.001, while no significant change was observed in the PCOM group (p=0.218). Additionally, LH, FSH, and estradiol levels increased in both groups.
Interpretation
The findings indicate that pulsatile GnRH therapy can effectively restore folliculogenesis in women with FHA without PCOM, as evidenced by the significant rise in AMH levels. However, the lack of change in the PCOM group raises questions about the clinical relevance of the findings, particularly given the already elevated baseline AMH levels. The small sample size and single-center design limit the ability to generalize these results to a broader population.
Key findings
- Median AMH levels at baseline were 6.21 ng/ml in the PCOM group vs 1.7 ng/ml in the non-PCOM group, p<0.001.
- After 3 months, AMH levels increased to 1.94 ng/ml in the non-PCOM group, p<0.001.
- No significant change in AMH levels in the PCOM group after treatment, p=0.218.
- LH, FSH, and estradiol levels increased in both groups.
- Pulsatile GnRH therapy induced ovulation in all patients, with 1 dominant follicle in each.
Limitations
- Observational study design.
- Small sample size (n=41).
- Single-center study limits generalizability.
- Short duration of follow-up (3 months).
- No control group.