Blumenfeld Z, Ritter M, Shen-Orr Z, Shariki K, Ben-Shahar M, Haim N
Rambam Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Am J Reprod Immunol. 1998 Jan;39(1):33-40. doi: 10.1111/j.1600-0897.1998.tb00331.x.
Inhibin A concentrations in serum may reflect the ovarian granulosa cell compartment. To characterize the correlation between ovarian function after gonadotoxic chemotherapy for Hodgkin's or non-Hodgkin's lymphoma in young women, the immunoreactive inhibin A concentrations in the sera of these patients was measured before, during, and after the gonadotoxic chemotherapy.
A prospective clinical protocol was undertaken in 20 cycling women with lymphoma, aged 15-40 years. A monthly injection of depot D-TRP6-GnRH-a (Decapeptyl CR, Ferring) was administered from before starting the chemotherapy until its conclusion, up to a maximum of six monthly injections. Most of the patients were treated with the mustargen-oncovin-procarbazine-prednisone (MOPP)/actinomycin D-bleomycin-vincristine (ABV) chemotherapy combination; 13 with and 7 without radiotherapy. A hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), testosterone (T), progesterone (P4), insulin-like growth factor (IGF)-1, IGF-BP3, and prolactin (PRL)] was taken before starting the gonadotropin-releasing hormone agonist (GnRH-a)/chemotherapy co-treatment and monthly thereafter until resuming spontaneous ovulation and menstrual cyclicity. This group of prospectively treated lymphoma patients was compared with a control group of 22 regularly cycling women who had been treated with chemotherapy (mostly MOPP/ABV) with or without radiotherapy for Hodgkin's or non-Hodgkin's lymphoma. Inhibin A immunoactivity developed by Nigel Groome was measured by an enzyme-linked immunoadsorbent assay (ELISA) commercial kit (Serotec).
Whereas all but one (40 years of age) of the surviving patients in the GnRH-a/chemotherapy co-treatment group resumed spontaneous ovulation and menses within 6 months, only one half of the patients in the "control" group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P < 0.05). The remaining 50% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by approximately one third of the patients resuming cyclic ovarian function, suggesting a reversible ovarian damage in a larger proportion of women than those experiencing POF. The inhibin A immunoactive concentrations decreased during the GnRH-a/chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared to low levels in menopausal women and those who had developed POF.
If these preliminary data are consistent in a larger group of patients, inhibin A concentration may serve as a prognostic factor for predicting the resumption of ovarian function, in addition to the levels of FSH, LH, and E2.
血清中抑制素A的浓度可能反映卵巢颗粒细胞情况。为了明确年轻女性在接受针对霍奇金淋巴瘤或非霍奇金淋巴瘤的性腺毒性化疗后卵巢功能之间的相关性，对这些患者在性腺毒性化疗前、化疗期间及化疗后的血清中免疫反应性抑制素A的浓度进行了测定。
对20名年龄在15至40岁之间处于月经周期的淋巴瘤女性患者实施了一项前瞻性临床方案。从化疗开始前直至化疗结束，每月注射一次长效D-色氨酸6-促性腺激素释放激素类似物（曲普瑞林缓释剂，辉凌制药），最多注射6次。大多数患者接受了氮芥-长春新碱-丙卡巴肼-泼尼松（MOPP）/放线菌素D-博来霉素-长春新碱（ABV）联合化疗；13例接受了放疗，7例未接受放疗。在开始促性腺激素释放激素激动剂（GnRH-a）/化疗联合治疗前以及此后每月采集一次激素谱[促卵泡生成素（FSH）、促黄体生成素（LH）、17-β-雌二醇（E2）、睾酮（T）、孕酮（P4）、胰岛素样生长因子（IGF）-1、IGF结合蛋白3（IGF-BP3）和催乳素（PRL）]，直至恢复自发排卵和月经周期。将这组接受前瞻性治疗的淋巴瘤患者与22名接受过化疗（大多为MOPP/ABV）、患霍奇金淋巴瘤或非霍奇金淋巴瘤且接受或未接受放疗的月经周期规律的女性组成的对照组进行比较。通过酶联免疫吸附测定（ELISA）商业试剂盒（赛默飞世尔科技公司）检测由奈杰尔·格鲁姆研发的抑制素A免疫活性。
GnRH-a/化疗联合治疗组中除一名患者（40岁）外，所有存活患者均在6个月内恢复了自发排卵和月经，而“对照组”（未接受GnRH-a联合化疗的化疗组）中只有一半患者恢复了卵巢功能和规律的周期性活动（P<0.05）。其余50%经历了卵巢早衰（POF）。恢复周期性卵巢功能的患者中约三分之一暂时出现FSH浓度升高，这表明与经历POF的女性相比，有更大比例的女性存在可逆性卵巢损伤。在GnRH-a/化疗联合治疗期间，抑制素A免疫活性浓度下降，但与绝经女性及发生POF的女性的低水平相比，恢复规律卵巢周期和/或自然受孕的患者其抑制素A免疫活性浓度升高至正常水平。
如果这些初步数据在更大规模的患者群体中得到证实，那么除了FSH、LH和E2水平外，抑制素A浓度可能作为预测卵巢功能恢复的一个预后因素。
