育龄期系统性红斑狼疮患者卵巢功能的评价及其影响因素

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doi:10.19723/j.issn.1671-167X.2024.06.012

摘要：

目的: 探讨育龄期系统性红斑狼疮(systemic lupus erythematosus，SLE)女性患者的卵巢功能及其影响因素。方法: 选取2017年1月至2024年5月于北京大学人民医院就诊明确诊断的SLE女性患者107例，年龄20~40岁，同时选取40例年龄在20~40岁之间的健康女性作为对照。采用化学发光法检测健康对照及SLE患者血清中抗缪勒氏管激素(anti-Müllerian hormone，AMH)水平，通过病例检索形式收集SLE患者的一般临床特征、用药情况(包括激素、免疫抑制剂及生物制剂)，分析SLE患者接受生物制剂治疗前后血清中AMH水平的变化。结果: (1) SLE患者的AMH水平显著低于健康对照组[1.475(0.344, 3.030) μg/L vs. 2.934(1.893, 4.761) μg/L，P < 0.001]。(2)SLE患者月经正常组AMH水平显著高于月经不规律组[1.931(0.638，3.414) μg/L vs. 0.335(0.159，1.527) μg/L，P=0.004]，AMH降低组与AMH正常组在临床特征及实验室指标方面差异无统计学意义。(3)多因素Logistic回归分析结果显示，年龄(OR=1.124，95%CI1.033~1.224，P=0.007)和病程(OR=1.100，95%CI1.017~1.190，P=0.018)是AMH下降的危险因素。(4)接受泰它西普治疗6个月后，患者AMH水平显著高于治疗前[治疗后2.050(0.763，4.259) μg/L vs.治疗前1.988(0.473，2.822) μg/L，P=0.043]；接受利妥昔单抗治疗6个月后，患者AMH水平与治疗前差异无统计学意义[治疗后2.026(0.376，2.267) μg/L vs.治疗前1.545(0.503，3.414) μg/L，P=0.127]。结论: 育龄期SLE患者存在卵巢功能下降，年龄和病程是其危险因素；生物制剂的使用对于育龄期SLE患者的卵巢功能有较好的安全性。

关键词: 系统性红斑狼疮, 卵巢功能, 抗缪勒氏管激素

Abstract:

Objective: To explore the ovarian function and its influencing factors in women of childbearing age with systemic lupus erythematosus (SLE). Methods: A total of 107 female patients diagnosed with SLE at Peking University People' s Hospital from January 2017 to May 2024, aged between 20 and 40 years, were included in the study. At the same time, 40 matched healthy women aged between 20 and 40 years were selected as controls. Serum levels of anti-Müllerian hormone (AMH) were measured using the chemiluminescence method in both the control group and the SLE patients. The general clinical characteristics and medication history (including hormones, immunosuppressants, and biological agents) of the SLE patients were obtained through case retrieval. Changes in serum AMH levels before and after treatment with biological agents in the SLE patients were analyzed. Results: (1) The AMH levels in the SLE patients were significantly lower than those in the healthy control group [1.475 (0.344, 3.030) μg/L vs. 2.934 (1.893, 4.761) μg/L, P < 0.001]. (2) The level of AMH in the SLE patients with normal menstruation was significantly higher than that in the patients with irregular menstruation [1.931 (0.638, 3.414) μg/L vs. 0.335 (0.159, 1.527) μg/L, P=0.004]. No statistical differences were found in clinical characteristics and laboratory indicators between the groups with decreased AMH group and normal AMH group. (3) The multivariate logistic regression analysis revealed that age (OR=1.124, 95%CI: 1.033-1.224, P=0.007) and disease duration (OR=1.100, 95%CI: 1.017-1.190, P=0.018) were identified as significant risk factors for the decline in AMH levels. (4) After 6 months of treatment with telitacicept, the AMH level was significantly higher than that before treatment [2.050 (0.763, 4.259) μg/L vs. 1.988 (0.473, 2.822) μg/L, P=0.043]. There was no significant difference in AMH level between patients receiving rituximab treatment for 6 months [2.026 (0.376, 2.267) μg/L vs. 1.545 (0.503, 3.414) μg/L, P=0.127]. Conclusion: Ovarian function is decreased in SLE patients of childbearing age, and age and disease duration are the risk factors. The utilization of biological agents demonstrates favorable safety profiles regarding ovarian function in childbearing-age patients with SLE.

Key words: Systemic lupus erythematosus, Ovarian function, Anti-Müllerian hormone

中图分类号:

R593.2

陈丹丹, 李云, 卢情怡, 相晓红, 孙峰, 李英妮, 赵静, 王红彦, 李春. 育龄期系统性红斑狼疮患者卵巢功能的评价及其影响因素[J]. 北京大学学报（医学版）, 2024, 56(6): 1023-1028.

Dandan CHEN, Yun LI, Qingyi LU, Xiaohong XIANG, Feng SUN, Yingni LI, Jing ZHAO, Hongyan WANG, Chun LI. Ovarian function in patients of childbearing age with systemic lupus erythematosus[J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1023-1028.

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Parameters	SLE (n=107)
Age/years, M (P₂₅, P₇₅)	31 (25, 34)
Disease duration/years, M (P₂₅, P₇₅)	4 (1, 10)
Rash, n (%)	64 (59.8)
Photosensitivity, n (%)	18 (16.8)
Oral ulcers, n (%)	17 (15.9)
Arthritis, n (%)	62 (57.9)
Serositis, n (%)	31 (29.0)
Renal disorder, n (%)	54 (50.5)
Neurologic disorder, n (%)	30 (28.0)
Hematologic disorder, n (%)	54 (50.5)
Antinuclear antibody positive, n (%)	101 (94.4)
Anti-dsDNA antibody positive, n (%)	66 (60.7)
Anti-Sm antibody positive, n (%)	19 (17.8)
GC, n (%)	74 (69.1)
HCQ, n (%)	69 (64.5)
MMF, n (%)	45 (42.1)
CTX, n (%)	5 (4.7)
RTX, n (%)	20 (18.7)
Telitacicept, n (%)	19 (17.8)

Parameters	AMH normal (n=59)	AMH decreased (n=48)	U/ χ² value	P value
Age/years, M(P₂₅, P₇₅)	29.00 (24.00, 32.00)	33.00 (28.00, 36.00)	855.0	0.001
Disease duration/years, M (P₂₅, P₇₅)	2.00 (0.50, 7.00)	6.50 (3.00, 12.00)	860.5	< 0.001
Clinical symptoms
Rash, n (%)	33 (55.9)	31 (64.6)	0.824	0.364
Photosensitivity, n (%)	9 (15.3)	9 (18.8)	0.231	0.631
Oral ulcers, n (%)	8 (13.6)	9 (18.8)	0.534	0.465
Arthritis, n (%)	32 (54.2)	30 (62.5)	0.742	0.389
Serositis, n (%)	19 (32.2)	12 (25.0)	0.667	0.414
Renal disorder, n (%)	30 (50.8)	24 (50.0)	0.008	0.931
Neurologic disorder, n (%)	14 (23.7)	16 (33.3)	1.210	0.271
Hematologic disorder, n (%)	29 (49.2)	25 (52.1)	0.091	0.763
Laboratory parameters
Antinuclear antibody positive, n (%)	57 (96.6)	44 (91.7)	1.559	0.459
Anti-dsDNA antibody positive, n (%)	37 (62.7)	28 (58.3)	0.213	0.645
Anti-Sm antibody positive, n (%)	8 (13.6)	11 (22.9)	1.587	0.208
IgA, M (P₂₅, P₇₅)	2.285 (1.758, 3.245)	2.800 (1.600, 3.570)	1 236.0	0.414
IgG, M (P₂₅, P₇₅)	13.70 (10.90, 17.54)	13.68 (9.07, 17.00)	1 322.0	0.794
IgM, M (P₂₅, P₇₅)	1.085 (0.690, 1.450)	0.826 (0.470, 1.340)	1 078.0	0.066
C3, M (P₂₅, P₇₅)	0.716 (0.528, 0.437)	0.610 (0.437, 0.943)	1 236.0	0.323
C4, M (P₂₅, P₇₅)	0.121 (0.080, 0.237)	0.140 (0.080, 0.214)	1 345.0	0.768
Immunosuppressant
MMF, n (%)	25 (42.4)	20 (41.7)	0.490	0.783
CTX, n (%)	2 (3.4)	3 (6.3)	0.003	0.953
Biologics
RTX, n (%)	12/53 (20.3)	8/42 (16.7)	0.452	0.502
Telitacicept, n (%)	12/53 (20.3)	7/42 (14.6)	0.817	0.366
SLEDAI-2000, M(P₂₅, P₇₅)	9.0 (5.0, 14.0)	9.0 (5.3, 14.0)	1 333.0	0.605

Variables	Univariate					Multivariate
Variables	B	Wald	P	OR	95%CI	B	Wald	P	OR	95%CI
Age	0.141	11.485	0.001	1.152	1.061-1.250	0.117	7.281	0.007	1.124	1.033-1.224
Disease duration	0.123	10.018	0.002	1.131	1.048-1.221	0.095	5.619	0.018	1.100	1.017-1.190
IgA	0.135	0.901	0.343	1.144	0.866-1.512
IgG	0.001	0.001	0.979	1.001	0.947-1.057
IgM	-0.306	0.981	0.322	0.736	0.401-1.350
C3	-0.874	1.909	0.167	0.417	0.121-1.442
C4	0.253	0.017	0.895	1.288	0.030-55.334
MMF	-0.223	0.553	0.457	0.800	0.444-1.440
CTX	0.642	0.472	0.492	1.900	0.304-11.861
RTX	-0.405	0.789	0.374	0.667	0.273-1.631
Telitacicept	-0.539	1.284	0.257	0.583	0.230-1.482
SLEDAI-2000	0.008	0.069	0.792	1.008	0.949-1.071