Tao Yuehong, Si Caiyun, Li Haiyan, Han Jing, Hou Huidan, Yang Mei
Department of Pediatrics, Yangzhou University Clinical Medical College & Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Dalian Medical University, Dalian 116000, China.
Ann Palliat Med. 2020 Jan;9(1):53-62. doi: 10.21037/apm.2020.01.04.
Gonadotropin-releasing hormone analog (GnRHa) is the mainstream treatment for central precocious puberty (CPP). However, its effect on the ovarian reserve in CPP girls remains unclear. This study was designed to analyze the changes of ovarian reserve in CPP girls during and after GnRHa therapy, with an attempt to achieve the early prediction of the effect of GnRHa treatment on the reproductive function of CPP girls, eliminate the concerns of girls and their parents on the potential toxicities of GnRHa treatment, and improve the patients' adherence to treatment.
The clinical data of 383 CPP girls who had been treated with GnRHa for more than half a year in our hospital within the past 10 years were retrospectively analyzed. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), FSH/LH, estradiol (E2), and anti-Müllerian hormone (AMH) levels, as well as uterine and ovarian volumes, were measured before treatment, at various time points during treatment, and after menarche or resumption of menses (ROM) after treatment discontinuation.
GnRHa treatment had similar effects on uterine/ovarian volumes, LH, FSH, and E2: these indicators were significantly inhibited during the treatment (compared with the pre-treatment levels), gradually returned normal after drug withdrawal, and became significantly higher than the pre-treatment levels after menarche or ROM (both P<0.05 for LH and FSH levels and P>0.05 for E2 and uterine/ovarian volumes). AMH level transiently decreased 6 months after GnRHa treatment (2.70±1.76 vs. 3.56±2.21, t=3.227, P=0.001); however, the AMH levels after 12, 18, and 24 months of treatment were similar to the pre-treatment level (P>0.05). The FSH/LH ratio significantly increased after 12 months of treatment compared with the pre-treatment (P<0.05), and the FSH/LH ratio after menarche or ROM was significantly lower than the pre-treatment value (1.34±0.66 vs. 5.69± 6.85, t=3.068, P=0.006). When FSH/LH and FSH level were used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was higher than at pre-treatment (FSH/LH ratio: 100% vs. 46%, χ2=27.586, P<0.05; FSH level: 100% vs. 99%, P>0.05). When AMH level was used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was slightly lower than at pre-treatment (87% vs. 93%, P>0.05).
The ovarian reserve of CPP girls is somehow inhibited during GnRHa treatment but is gradually restored after drug discontinuation. Thus, GnRHa treatment does not affect ovarian reserve in CPP children after the treatment stops.
促性腺激素释放激素类似物（GnRHa）是中枢性性早熟（CPP）的主流治疗方法。然而，其对CPP女童卵巢储备功能的影响尚不清楚。本研究旨在分析CPP女童在GnRHa治疗期间及治疗后的卵巢储备功能变化，以期早期预测GnRHa治疗对CPP女童生殖功能的影响，消除女童及其家长对GnRHa治疗潜在毒性的担忧，并提高患者的治疗依从性。
回顾性分析我院近10年内接受GnRHa治疗半年以上的383例CPP女童的临床资料。于治疗前、治疗期间各时间点、停药后月经初潮或月经恢复（ROM）后，检测血清促黄体生成素（LH）、促卵泡生成素（FSH）、FSH/LH、雌二醇（E2）及抗苗勒管激素（AMH）水平，以及子宫和卵巢体积。
GnRHa治疗对子宫/卵巢体积、LH、FSH及E2的影响相似：这些指标在治疗期间显著受抑制（与治疗前水平相比），停药后逐渐恢复正常，月经初潮或ROM后显著高于治疗前水平（LH和FSH水平均P<0.05，E2及子宫/卵巢体积P>0.05）。GnRHa治疗6个月后AMH水平短暂下降（2.70±1.76 vs. 3.56±2.21，t=3.227，P=0.001）；然而，治疗12、18及24个月后的AMH水平与治疗前水平相似（P>0.05）。治疗12个月后FSH/LH比值较治疗前显著升高（P<0.05），月经初潮或ROM后的FSH/LH比值显著低于治疗前值（1.34±0.66 vs. 5.69±6.85，t=3.068，P=0.006）。以FSH/LH及FSH水平反映卵巢储备功能时，月经初潮或ROM后卵巢储备功能正常的CPP女童比例高于治疗前（FSH/LH比值：100% vs. 46%，χ2=27.586，P<0.05；FSH水平：100% vs. 99%，P>0.05）。以AMH水平反映卵巢储备功能时，月经初潮或ROM后卵巢储备功能正常的CPP女童比例略低于治疗前（87% vs. 93%，P>0.05）。
CPP女童的卵巢储备功能在GnRHa治疗期间受到一定抑制，但停药后逐渐恢复。因此，GnRHa治疗停止后不影响CPP儿童的卵巢储备功能。
