Document Type : Original Research


1 Immunoregulation Research Center, Shahed University, Tehran, I.R. Iran

2 Dept. of Ophthalmology, Shahed University, Tehran, I.R. Iran

3 Dept. of biology, Faculty of Basic Sciences, Shahid Bahonar University of Kerman, Kerman, I.R Iran

4 Dept. of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, I.R. Iran

5 Institute of Biochemistry and Biophysics, Tehran University, Tehran, I.R. Iran


Background and objective Aside from direct toxic effects, Sulfur Mustard (SM) induced serum hormone abnormalities may aggravate ocular complaints, including Ocular Surface Discomfort (OSD) (burning, itching, and redness), dry eye sensation, photophobia, blurred vision, foreign body sensation, and pain. The aim of the current study was to investigate the possible association of ocular complaints with serum hormone concentrations in chronic phase of Sulfur Mustard (SM) exposure.
Methods:As a part of Sardasht Iran Cohort Study (SICS), 372 SM-exposed patients and 128 non-exposed participants were enrolled. Ocular complaints and ocular surface biomicroscopic conditions and serum hormones were compared.
Results:The exposed with tearing group had significantly higher mean serum levels of testosterone and prolactin (ng/mL) than controls (5.75 vs. 4.75, P=0.031; 11.71 vs. 8.42, P=0.009). The exposed with OSD group had significantly higher mean serum levels of prolactin than controls (12.48 vs. 6.90, P=0.002). The exposed with photophobia group had significantly higher mean serum levels of testosterone than the matched exposed (6.25 vs. 5.65, P=0.013). The exposed with blurred vision group had significantly higher mean serum levels of Thyroglobulin (Tg) (ng/mL) than the matched exposed (65.73 vs. 32.6, P=0.003).
Conclusion: Higher mean serum levels of testosterone (in exposed with tearing and photophobia) and prolactin (in exposed with tearing and OSD) may play protective roles against SM effects. Higher mean serum levels of Tg may deteriorate the tear film integrity and optical surface, which causes blurred vision. In the chronic phase of SM toxicity, some ocular surface problems are associated with alterations in the serum concentrations of testosterone, prolactin, and Tg.


Main Subjects

  1. Aasted A, Darre E, Wulf HC. Mustard gas: clinical, toxicological, and mutagenic aspects based on modern experience. Annals of plastic surgery. 1987;19(4):330-3.
  2. Iovieno A, Anand S, Dart JK. Late-onset Peripheral Ulcerative Sclerokeratitis Associated With Alkali Chemical Burn. American Journal of Ophthalmology. 2014;158(6):1305-9.e4.
  3. Tewari-Singh N, Jain AK, Inturi S, Ammar DA, Agarwal C, Tyagi P, et al. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries. Toxicology and Applied Pharmacology. 2012;264(1):23-31.
  4. Panahi Y, Sahebkar A, Davoudi SM, Amiri M, Beiraghdar F. Efficacy and Safety of Immunotherapy with Interferon-Gamma in the Management of Chronic Sulfur Mustard-Induced Cutaneous Complications: Comparison with Topical Betamethasone 1%. The Scientific World Journal. 2012;2012:285274.
  5. Panahi Y, Davoudi SM, Beiraghdar F, Amiri M. Doxepin cream vs betamethasone cream for treatment of chronic skin lesions due to sulfur mustard. Skinmed. 2011;9(3):152-8.
  6. Panahi Y, Davoudi SM, Sahebkar A, Beiraghdar F, Dadjo Y, Feizi I, et al. Efficacy of Aloe vera/olive oil cream versus betamethasone cream for chronic skin lesions following sulfur mustard exposure: a randomized double-blind clinical trial. Cutan Ocul Toxicol. 2012;31(2):95-103.
  7. Boskabady MH, Amery S, Vahedi N, Khakzad MR. The effect of vitamin E on tracheal responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. Inhal Toxicol. 2011;23(3):157-65.
  8. Azizi F, Jalali N, Nafarabadi M. The effect of chemical weapons on serum concentrations of various hormones. Iran J Med Sci. 1989;14:46-50.
  9. Sullivan DA. Tearful relationships? Sex, hormones, the lacrimal gland, and aqueous-deficient dry eye. The ocular surface. 2004;2(2):92-123.
  10. Versura P, Fresina M, Campos EC. Ocular surface changes over the menstrual cycle in women with and without dry eye. Gynecological endocrinology. 2007;23(7):385-90.
  11. Foulks GN. Pharmacological management of dry eye in the elderly patient. Drugs & aging. 2008;25(2):105-18.
  12. O’Brien PD, Collum LM. Dry eye: diagnosis and current treatment strategies. Current allergy and asthma reports. 2004;4(4):314-9.
  13. Scuderi G, Contestabile MT, Gagliano C, Iacovello D, Scuderi L, Avitabile T. Effects of phytoestrogen supplementation in postmenopausal women with dry eye syndrome: a randomized clinical trial. Canadian Journal of Ophthalmology/Journal Canadien d'Ophtalmologie. 2012;47(6):489-92.
  14. Scott G, Yiu SC, Wasilewski D, Song J, Smith RE. Combined esterified estrogen and methyltestosterone treatment for dry eye syndrome in postmenopausal women. American journal of ophthalmology. 2005;139(6):1109-10.
  15. Dujić M. [Neuroendocrine response in patients with uveitis]. Srpski arhiv za celokupno lekarstvo. 1997;126(1-2):13-7.
  16. Pieragostino D, Bucci S, Agnifili L, Fasanella V, D'Aguanno S, Mastropasqua A, et al. Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma. Molecular bioSystems. 2012;8(4):1017-28.
  17. Costagliola S, Many M-C, Denef J-F, Pohlenz J, Refetoff S, Vassart G. Genetic immunization of outbred mice with thyrotropin receptor cDNA provides a model of Graves’ disease. Journal of Clinical Investigation. 2000;105(6):803.
  18. Ghasemi H, Ghazanfari T, Babaei M, Soroush MR, Yaraee R, Ghassemi-Broumand M, et al. Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran. Cutan Ocul Toxicol. 2008;27(4):317-26.
  19. Ghazanfari T, Faghihzadeh S, Aragizadeh H, Soroush MR, Yaraee R, Mohammad Hassan Z, et al. Sardasht-Iran cohort study of chemical warfare victims: design and methods. Arch Iran Med. 2009;12(1):5-14.
  20. Schirra F, Gatzioufas Z, Scheidt J, Seitz B. [Testosterone reduces the expression of keratinization-promoting genes in murine Meibomian glands]. Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2013;110(3):230-8.
  21. Beauregard C, Brandt P. Down regulation of interleukin-1β-induced nitric oxide production in lacrimal gland acinar cells by sex steroids. Current eye research. 2004;29(1):59-66.
  22. Luo F, Zhang H, Sun X. [The change of tear secretion and tear film stability in castrated male rabbits]. [Zhonghua yan ke za zhi] Chinese journal of ophthalmology. 2001;37(6):458-61.
  23. Amirzargar MA, Yavangi M, Rahnavardi M, Jafari M, Mohseni M. Chronic mustard toxicity on the testis: a historical cohort study two decades after exposure. International journal of andrology. 2009;32(4):411-6.
  24. Safarinejad M. Testicular effect of mustard gas. Urology. 2001;58(1):90-4.
  25. Azizi F, Keshavarz A, Roshanzamir F, Nafarabadi M. Reproductive function in men following exposure to chemical warfare with sulphur mustard. Medicine, Conflict and Survival. 1995;11(1):34-44.
  26. Sasser LB, Cushing JA, Dacre JC. Two-generation reproduction study of sulfur mustard in rats. Reproductive toxicology. 1996;10(4):311-9.
  27. Balali‐Mood M, Hefazi M. The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning. Fundamental & clinical pharmacology. 2005;19(3):297-315.
  28. Zhou L, Wei R, Zhao P, Koh SK, Beuerman RW, Ding C. Proteomic analysis revealed the altered tear protein profile in a rabbit model of Sjögren's syndrome‐associated dry eye. Proteomics. 2013;13(16):2469-81.
  29. Ubels JL, Gipson IK, Spurr-Michaud SJ, Tisdale AS, Van Dyken RE, Hatton MP. Gene expression in human accessory lacrimal glands of Wolfring. Investigative ophthalmology & visual science. 2011;53(11):6738-47.
  30. Pohanka M, Sobotka J, Jilkova M, Stetina R. Oxidative stress after sulfur mustard intoxication and its reduction by melatonin: efficacy of antioxidant therapy during serious intoxication. Drug Chem Toxicol. 2011;34(1):85-91.
  31. Askari N, Vaez-Mahdavi MR, Moaiedmohseni S, Khamesipour A, Soroush MR, Moin A, et al. Association of chemokines and prolactin with cherry angioma in a sulfur mustard exposed population--Sardasht-Iran cohort study. Int Immunopharmacol. 2013;17(3):991-5.
  32. Nakamura H, Motomura M, Ichikawa T, Nakao K, Kawasaki E, Tanaka M, et al. Prevalence of interrelated autoantibodies in thyroid diseases and autoimmune disorders. Journal of endocrinological investigation. 2008;31(10):861-5.
  33. Zeher M, Horvath IF, Szanto A, Szodoray P. Autoimmune thyroid diseases in a large group of Hungarian patients with primary Sjögren's syndrome. Thyroid. 2009;19(1):39-45.
  34. Azizi F, Amini M, Arbab P. Time course of changes in free thyroid indices, rT3, TSH, cortisol and ACTH following exposure to sulfur mustard. Experimental and clinical endocrinology. 1992;101(5):303-6.
  35. Lisi S, Marinò M, Pinchera A, Mazzi B, Di Cosmo C, Sellari-Franceschini S, et al. Thyroglobulin in orbital tissues from patients with thyroid-associated ophthalmopathy: predominant localization in fibroadipose tissue. Thyroid. 2002;12(5):351-60.