性激素与口腔扁平苔藓间的因果关系

doi:10.13591/j.cnki.kqyx.2026.08.002

Abstract

Abstract:

Objective To investigate the causal relationship between serum sex hormone levels and oral lichen planus (OLP) using Mendelian randomization (MR), with supplementary serological validation. Methods A bidirectional two-sample MR analysis was conducted using publicly available genome-wide association study(GWAS) summary statistics for total testosterone (TT), bioavailable testosterone (BT), estradiol (E2), sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAs), alongside OLP data from the FinnGen database. The inverse variance weighted (IVW) method served as the primary analytical approach, supported by sensitivity analyses, while serum SHBG analysis was conducted for verification. Results Genetically predicted higher serum SHBG levels were associated with an increased risk of OLP in males (OR=1.26, P=0.04), but not in females. No causal effects were observed between TT, BT, E2, or DHEAs and OLP in either gender (P>0.05). Reverse MR analyses showed no causal effect of OLP on serum sex hormone levels. Sensitivity analyses supported the stability of these findings. Serological analyses in males showed trends consistent with the MR results, although the differences were attenuated after age adjustment. Conclusion Elevated serum SHBG levels are causally linked to an increased risk of OLP in males, while no significant causal associations are found for TT, BT, E2, or DHEAs.

Key words: Mendelian randomization, oral lichen planus, sex hormone, sex hormone-binding globulin

CLC Number:

R778.1

SUN Xinyi, XIONG Meizhen, TANG Yiming, WANG Feng, CHEN Wei, LI Zhi. Causal relationship between sex hormones and oral lichen planus[J]. Stomatology, 2026, 46(8): 567-573.

Figures/Tables 8

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References 34

[1]	Carrozzo M, Porter S, Mercadante V, et al. Oral lichen planus: A disease or a spectrum of tissue reactions? Types, causes, diagnostic algorhythms, prognosis, management strategies[J]. Periodontol 2000, 2019, 80(1): 105-125. doi: 10.1111/prd.12260 pmid: 31090143
[2]	Li CC, Tang XQ, Zheng XY, et al. Global prevalence and incidence estimates of oral lichen planus: A systematic review and meta-analysis[J]. JAMA Dermatol, 2020, 156(2): 172-181. doi: 10.1001/jamadermatol.2019.3797 pmid: 31895418
[3]	Hoffmann JP, Liu JA, Seddu K, et al. Sex hormone signaling and regulation of immune function[J]. Immunity, 2023, 56(11): 2472-2491. doi: 10.1016/j.immuni.2023.10.008 pmid: 37967530
[4]	Hammond GL. Diverse roles for sex hormone-binding globulin in reproduction[J]. Biol Reprod, 2011, 85(3): 431-441. doi: 10.1095/biolreprod.111.092593 pmid: 21613632
[5]	Gholizadeh N, Sadeghi A, Mirzaii-Dizgah I, et al. Serum level of estrogen in Iranian patients with oral lichen planus[J]. Asian Biomed, 2021, 15(3): 145-150. doi: 10.2478/abm-2021-0018
[6]	Hughes GC, Choubey D. Modulation of autoimmune rheumatic diseases by oestrogen and progesterone[J]. Nat Rev Rheumatol, 2014, 10(12): 740-751. doi: 10.1038/nrrheum.2014.144 pmid: 25155581
[7]	Kim JW, Kim HA, Suh CH, et al. Sex hormones affect the pathogenesis and clinical characteristics of systemic lupus erythematosus[J]. Front Med, 2022, 9: 906475. doi: 10.3389/fmed.2022.906475
[8]	Xuan YH, Zhang X, Wu HX. Impact of sex differences on the clinical presentation, pathogenesis, treatment and prognosis of Sjögren’s syndrome[J]. Immunology, 2024, 171(4): 513-524. doi: 10.1111/imm.v171.4
[9]	Zheng J, Baird D, Borges MC, et al. Recent developments in Mendelian randomization studies[J]. Curr Epidemiol Rep, 2017, 4(4): 330-345. doi: 10.1007/s40471-017-0128-6 pmid: 29226067
[10]	Tang RZ, You XQ, Yuan BT, et al. Sex hormones and 14 autoimmune diseases: The causal relationship from a bidirectional 2-sample Mendelian randomization study[J]. Medicine, 2025, 104(36): e44160. doi: 10.1097/MD.0000000000044160
[11]	Richmond RC, Davey Smith G. Mendelian randomization: Concepts and scope[J]. Cold Spring Harb Perspect Med, 2022, 12(1): a040501. doi: 10.1101/cshperspect.a040501
[12]	Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The STROBE-MR statement[J]. JAMA, 2021, 326(16): 1614-1621. doi: 10.1001/jama.2021.18236 pmid: 34698778
[13]	Zhou T, Sun D, Li X, et al. Educational attainment and drinking behaviors: Mendelian randomization study in UK Biobank[J]. Mol Psychiatry, 2021, 26(8): 4355-4366. doi: 10.1038/s41380-019-0596-9
[14]	Schmitz D, Ek WE, Berggren E, et al. Genome-wide association study of estradiol levels and the causal effect of estradiol on bone mineral density[J]. J Clin Endocrinol Metab, 2021, 106(11): e4471-e4486. doi: 10.1210/clinem/dgab507 pmid: 34255042
[15]	Prins BP, Kuchenbaecker KB, Bao YC, et al. Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations[J]. Sci Rep, 2017, 7(1): 11008. doi: 10.1038/s41598-017-10812-1 pmid: 28887542
[16]	Li YJ, Zhang YY, Liu WP, et al. Epstein-Barr virus infection increases the risk of depression: A cross-sectional study and Mendelian randomization analysis[J]. J Affect Disord, 2025, 387:119488. doi: 10.1016/j.jad.2025.119488
[17]	Zhong S, Yang WZ, Zhang ZY, et al. Association between viral infections and glioma risk: A two-sample bidirectional Mendelian randomization analysis[J]. BMC Med, 2023, 21(1): 487. doi: 10.1186/s12916-023-03142-9 pmid: 38053181
[18]	Zhang K, Shi W, Zhang XL, et al. Causal relationships between COVID-19 and osteoporosis: A two-sample Mendelian randomization study in European population[J]. Front Public Health, 2023, 11: 1122095. doi: 10.3389/fpubh.2023.1122095
[19]	Cao SY, Wei YH, Yue YH, et al. Omeprazole and risk of osteoarthritis: Insights from a Mendelian randomization study in the UK Biobank[J]. J Transl Med, 2024, 22(1): 504. doi: 10.1186/s12967-024-05255-y pmid: 38802944
[20]	Fang P, Liu XZ, Qiu Y, et al. Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: A bidirectional Mendelian-randomization study[J]. Front Immunol, 2023, 14: 1285106. doi: 10.3389/fimmu.2023.1285106
[21]	Qu XQ, Donnelly R. Sex hormone-binding globulin(SHBG)as an early biomarker and therapeutic target in polycystic ovary syndrome[J]. Int J Mol Sci, 2020, 21(21): 8191. doi: 10.3390/ijms21218191
[22]	Narinx N, David K, Walravens J, et al. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology[J]. Cell Mol Life Sci, 2022, 79(11): 543. doi: 10.1007/s00018-022-04562-1 pmid: 36205798
[23]	Roy S, Banerjee D, Banerjee A, et al. Sex hormones and gender differences in immune responses and anticancer immunity: A comprehensive review[J]. Biol Futur, 2026, 77(1): 1-27.
[24]	Balogh A, Karpati E, Schneider AE, et al. Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes membrane receptor[J]. Sci Rep, 2019, 9(1): 4. doi: 10.1038/s41598-018-36882-3
[25]	Dai MH, Mei B, Zheng F, et al. Sex hormones and epigenetic dysregulation in autoimmune disease[J]. Curr Opin Immunol, 2025, 95: 102595. doi: 10.1016/j.coi.2025.102595
[26]	Nukaly HY, Halawani IR, Alghamdi SMS, et al. Oral lichen planus: A narrative review navigating etiologies, clinical manifestations, diagnostics, and therapeutic approaches[J]. J Clin Med, 2024, 13(17): 5280. doi: 10.3390/jcm13175280
[27]	Agrawal H, Patil RK, Singh V, et al. Salivary and serum estrogen level assessment in oral lichen planus patients and its correlative analysis with OLP and stress[J]. J Family Med Prim Care, 2024, 13(5): 1998-2005. doi: 10.4103/jfmpc.jfmpc_1332_23 pmid: 38948558
[28]	Mohan RPS, Gupta A, Kamarthi N, et al. Incidence of oral lichen planus in perimenopausal women: A cross-sectional study in western Uttar pradesh population[J]. J Midlife Health, 2017, 8(2): 70-74. doi: 10.4103/jmh.JMH_34_17 pmid: 28706407
[29]	Merz WM, Fischer-Betz R, Hellwig K, et al. Pregnancy and autoimmune disease: Diseases of the nervous system, connective tissue, and the bowel[J]. Deutsches Ärzteblatt Int, 2022, 119(9):145-152.
[30]	Yamazaki H, Kushiyama A, Sakoda H, et al. Protective effect of sex hormone-binding globulin against metabolic syndrome:Evidence showing anti-inflammatory and lipolytic effects on adipocytes and macrophages[J]. Mediators Inflamm, 2018, 2018: 3062319.
[31]	Rezazadeh F, Lavaee F, Dezhkameh S, et al. The serum evaluation of sex hormones including DHEAs, DHT, testosterone in oral lichen planus patients[J]. Sci Rep, 2025, 15: 16679. doi: 10.1038/s41598-025-01750-4
[32]	Girardi C, Luz C, Cherubini K, et al. Salivary Cortisol and dehydroepiandrosterone(DHEA)levels, psychological factors in patients with oral lichen planus[J]. Arch Oral Biol, 2011, 56(9): 864-868. doi: 10.1016/j.archoralbio.2011.02.003 pmid: 21377142
[33]	Baurecht H, Freuer D, Welker C, et al. Relationship between periodontitis and psoriasis: A two-sample Mendelian randomization study[J]. J Clin Periodontol, 2022, 49(6): 573-579. doi: 10.1111/jcpe.13620 pmid: 35362630
[34]	Kastelan D, Korsic M. High prevalence rate of pituitary incidentaloma: Is it associated with the age-related decline of the sex hormones levels?[J]. Med Hypotheses, 2007, 69(2): 307-309. pmid: 17280790

暴露因素	年份	人群	样本量	SNP	网络来源
TT-M	2020	欧洲人群	199 569	12 321 875	https://opengwas.io/datasets/ieu-b-4865
TT-F	2020	欧洲人群	199 569	12 321 875	https://opengwas.io/datasets/ieu-b-4864
BT-M	2020	欧洲人群	184 205	12 321 875	https://opengwas.io/datasets/ieu-b-4868
BT-F	2020	欧洲人群	180 386	12 321 875	https://opengwas.io/datasets/ieu-b-4869
E2-M	2021	欧洲人群	147 690	7 489 424	https://opengwas.io/datasets/ebi-a-GCST90020091
E2-F	2021	欧洲人群	163 985	7 488 193	https://opengwas.io/datasets/ebi-a-GCST90020092
SHBG-M	2020	欧洲人群	185 221	12 321 875	https://opengwas.io/datasets/ieu-b-4871
SHBG-F	2020	欧洲人群	214 989	12 321 875	https://opengwas.io/datasets/ieu-b-4870
DHEAs	2017	欧洲人群	9 722	21 770 677	https://opengwas.io/datasets/ebi-a-GCST004941

暴露	结局	nSNP	逆方差加权法		MR-Egger回归法		加权中位数法		简单众数法		加权众数法
暴露	结局	nSNP	P	OR	P	OR	P	OR	P	OR	P	OR
TT-M	OLP	146	0.44	1.11	0.84	0.95	0.90	1.03	0.69	1.20	0.99	1.00
TT-F	OLP	98	0.80	0.95	0.83	1.08	0.58	1.20	0.52	0.66	0.94	1.03
BT-M	OLP	69	0.78	0.94	0.34	0.64	0.99	1.00	0.37	1.81	0.63	0.82
BT-F	OLP	116	0.41	0.86	0.74	0.89	0.42	1.26	0.39	0.60	0.52	1.21
E2-M	OLP	11	0.59	1.08	0.49	0.74	0.69	1.07	0.50	1.19	0.65	1.10
E2-F	OLP	19	0.76	1.08	0.66	1.26	0.24	1.38	0.64	0.79	0.37	1.39
SHBG-M	OLP	186	0.04	1.26	0.99	1.00	0.34	1.19	0.28	1.49	0.25	1.26
SHBG-F	OLP	178	0.07	1.26	0.69	1.09	0.94	0.98	0.84	0.91	0.73	1.09
DHEAs	OLP	6	0.30	1.29	0.55	1.27	0.34	1.30	0.17	2.27	0.57	1.19

暴露	结局	nSNP	逆方差加权法		MR-Egger回归法		加权中位数法		简单众数法		加权众数法
暴露	结局	nSNP	P	OR	P	OR	P	OR	P	OR	P	OR
OLP	TT-M	4	0.71	1.00	0.79	1.03	0.84	1.00	0.64	1.01	0.43	1.01
OLP	TT-F	4	0.60	1.00	0.57	0.98	0.76	1.00	0.98	1.00	0.74	1.00
OLP	BT-M	4	0.98	1.00	0.23	0.94	0.79	1.00	0.67	1.01	0.59	1.01
OLP	BT-F	4	0.70	1.00	0.63	0.96	0.63	1.00	0.32	1.02	0.40	1.02
OLP	E2-M	3	0.35	0.97	0.40	0.83	0.41	0.97	0.59	0.97	0.44	0.95
OLP	E2-F	3	0.32	1.03	0.54	0.89	0.27	1.04	0.34	1.06	0.34	1.06
OLP	SHBG-M	4	0.81	0.99	0.47	1.13	0.23	0.99	0.34	0.98	0.24	0.98
OLP	SHBG-F	4	0.64	0.99	0.68	1.05	0.35	0.99	0.34	0.97	0.60	1.01
OLP	DHEAs	5	0.18	0.97	0.62	1.05	0.21	0.97	0.17	0.94	0.30	0.97

暴露	结局	异质性检验				MR-Egger截距检验
暴露	结局	方法	Q	自由度	P	截距	标准误	P
TT-M	OLP	IVW	143.627	145	0.517	0.007	0.009	0.443
TT-F	OLP	IVW	116.854	97	0.083	-0.005	0.012	0.676
BT-M	OLP	IVW	74.058	68	0.287	0.015	0.016	0.350
BT-F	OLP	IVW	130.689	115	0.150	-0.001	0.013	0.936
E2-M	OLP	IVW	7.601	10	0.668	0.061	0.064	0.368
E2-F	OLP	IVW	28.569	18	0.054	-0.017	0.049	0.729
SHBG-M	OLP	IVW	183.172	185	0.524	0.011	0.008	0.170
SHBG-F	OLP	IVW	165.081	177	0.730	0.006	0.008	0.447
DHEAs	OLP	IVW	3.388	5	0.640	0.003	0.038	0.945
OLP	TT-M	IVW	11.553	3	0.009	-0.009	0.025	0.748
OLP	TT-F	IVW	2.249	3	0.522	0.006	0.011	0.615
OLP	BT-M	IVW	3.559	3	0.313	0.020	0.011	0.222
OLP	BT-F	IVW	10.832	3	0.013	0.015	0.024	0.591
OLP	E2-M	IVW	1.936	2	0.380	0.046	0.039	0.448
OLP	E2-F	IVW	1.291	2	0.525	0.041	0.036	0.460
OLP	SHBG-M	IVW	39.171	3	<0.001	-0.038	0.041	0.446
OLP	SHBG-F	IVW	20.960	3	<0.001	-0.017	0.031	0.631
OLP	DHEAs	IVW	6.990	4	0.136	-0.025	0.029	0.449

变量	回归系数	95%CI	P
组别(OLP/对照)	9.30	[-9.15,27.76]	0.302
年龄	0.66	[-0.01,1.32]	0.053

Causal relationship between sex hormones and oral lichen planus

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[3]	LI Kaiyi, HE Wenxiu, REN Xiaomeng, LUO Haiyan, LI Chunlei, HUA Hong. Clinical and histopathological characteristics of oral lichen planus patients with type 2 diabetes mellitus [J]. Stomatology, 2022, 42(9): 802-806.
[4]	ZHANG Xuelian, GUAN Cuiqiang, JIN Enlong. Correlation between 4-1BB and CD8 expression in oral lichen planus [J]. Stomatology, 2022, 42(4): 296-299.
[5]	HUANG Xinzhao, ZHONG Liangjun. Research advances in the relationship between human β defensin-2 and oral lichen planus [J]. Stomatology, 2022, 42(3): 276-279.
[6]	SUN Yutong, JIANG Lu. Role of biologics in the treatment of oral lichen planus [J]. Stomatology, 2022, 42(3): 261-265.
[7]	. Meta-analysis and systematic evaluation of the efficacy of combined total glucosides of paeony capsules in the treatment of oral lichen planus [J]. , 2019, 39(6): 523-529.
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