Features of anemia syndrome in women with endometrial hyperplasia working under the influence of organic solvents and depending on obesity

Introduction. Organic solvents have a hematotoxic effect, which leads to the development of anemia. Endometrial hyperplasia may also be the cause of a decrease in blood hemoglobin levels. The phenotype of anemia in combination of these diseases is still insufficiently studied. Exposure to organic solvents is associated with a carcinogenic risk, while their role in the development of precancerous conditions is little known.

The study aims to research the features of anemia in patients with endometrial hyperplasia under the influence of organic solvents and depending on the obesity factor.

Materials and methods. The design of the study is a single–center, single-stage observational. The researchers formed 2 groups of women with endometrial hyperplasia confirmed by histological examination, who worked under conditions of exposure to organic solvents (n=140, the main group, 70 of them obese according to WHO criteria) or who had no health risks (n=140, the comparison group, 68 of them obese). The patients of the main group are painters at a machine-building enterprise. Organic solvents concentrations at the workplace air were 1.2–5.0 times above occupational exposure limits, length of service was 21.5 (18; 28) years.

Results. Scientists have registered anemia in 72.9% of obese workers, 54.2% of non-obese workers, 33.8% and 25.0% of patients in the comparison group with obesity and normal body weight, respectively, χ²=8.2, p=0.008. In contact with organic solvents, 60.7% of patients had anemia normal- or macrocytic, normal- or hyperchromic, hyporegenerative. In the subgroup of obesity and atypical endometrial hyperplasia, we have watched the minimum values of hemoglobin — 95 (90; 105) g/l and reticulocytes — 1 (0.5; 2), the maximum values of the average erythrocyte volume — 98 (92; 107) fl and the average hemoglobin content in the erythrocyte — 35(34; 38) pg. The researchers have determined the association of this variant of anemia with atypical endometrial hyperplasia by logistic regression, OR 2.51, 95% CI 1.08–5.85, p=0.033. In comparison group, all patients had iron-deficiency anemia.

Limitations. The limitations of the study are related to the recruitment of patients in one center.

Conclusion. Anemia in women with endometrial hyperplasia in conditions of organic solvents exposure is normo- or hyperchormic, normo- or macrocytic, hyporegenerative, most prominent in patients with obesity, and associated with atypical histological type of the disease.

Ethics. The authors have carried out the study in compliance with the Ethical principles of conducting scientific medical research with human participation, set out in the Helsinki Declaration of the World Medical Association and in accordance with the Ethical norms and rules provided for by the Bulletin of the Higher Attestation Commission of the Ministry of Education of Russia No. 3 of 2002 "On the procedure for conducting biomedical research in humans". The study was approved by the Ethics Committee of the Federal State Budgetary Educational Institution of the Russian Ministry of Health.

Contribution:
Lisova E.S. — research concept and design, data collection, data analysis and interpretation, writing the text
Marinkin I.O. — research concept and design, data analysis and interpretation, writing the text
Shpagina L.A. — research concept and design, data analysis and interpretation, writing the text
Kotova O.S. — data collection, writing the text
Karmanovskaya S.A. — data collection
Loktina K.E. — data collection

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 27.02.23 / Accepted: 17.03.2023 / Published: 10.04.2023

1. On the state of sanitary and epidemiological welfare of the population in the Russian Federation in the year 2021: State Report. Moscow, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing; 2022 (in Russian).

2. Zyubina L.Yu., Panacheva L.A., Shpagina L.A., Kareva N.P., Kotova O.S., Zueva M.A., Gorobey A.M. Evolutionary peculiarities of hematological syndromes and blood diseases from exposure to occupational hazards. Med. truda i prom. ekol. 2019; 1: 45–50. https://doi.org/10.31089/1026-9428-2019-1-45-50 (in Russian).

3. Fesenko M.A., Sivochalova O.V., Fedorova E.V. Occupational reproductive system diseases in female workers employed at workplaces with harmful working conditions. Analiz riska zdorov’yu. 2017; 3: 92–100 https://doi.org/10.21668/health.risk/2017.3.11 (in Russian).

4. Galkin S.S. (editor), Bobylev S.N., Burlakova E.A., Vagan I.S., Vasil'ev I.V., Volkov I.N. et al. Russian Statistical Yearbook 2022. Stat.book/Rosstat, M; 2022.

5. Ladeira C., Gajski G., Meneses M., Gerić M., Viegas S. The genotoxicity of an organic solvent mixture: A human biomonitoring study and translation of a real-scenario exposure to in vitro. Regul Toxicol Pharmacol. 2020; 116: 104726. https://doi.org/10.1016/j.yrtph.2020.104726

6. Cavallo D., Tranfo G., Ursini C.L., Fresegna A.M., Ciervo A., Maiello R., et al. Biomarkers of early genotoxicity and oxidative stress for occupational risk assessment of exposure to styrene in the fibreglass reinforced plastic industry. Toxicol Lett. 2018; 298: 53–9. https://doi.org/10.1016/j.toxlet.2018.06.006

7. Lai C., Wu F., Wang Y., Wang W, Li Y., Zhang G., et al. Specific epigenetic microenvironment and the regulation of tumor-related gene expression by trichloroethylene in human hepatocytes. Ecotoxicol Environ Saf. 2021; 208: 111453. https://doi.org/10.1016/j.ecoenv.2020.111453

8. Toyooka T., Yanagiba Y., Ibuki Y., Wang R.S. Trichloroethylene exposure results in the phosphorylation of histone H2AX in a human hepatic cell line through cytochrome P450 2E1-mediated oxidative stress. J. Appl. Toxicol. 2018; 38: 1224–32. https://doi.org/10.1002/jat.3632

9. Salman M.C., Usubutun A., Boynukalin K., Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol. 2010; 21(2): 97–101. https://doi.org/10.3802/jgo.2010.21.2.97

10. Vilos G.A., Oraif A., Vilos A.G., Ettler H., Edris F., Abu-Rafea B. Long-term clinical outcomes following resectoscopic endometrial ablation of non-atypical endometrial hyperplasia in women with abnormal uterine bleeding. J Minim Invasive Gynecol. 2015; 22(1): 66–77. https://doi.org/10.1016/j.jmig.2014.07.009

11. Doherty M.T., Sanni O.B., Coleman H.G., Cardwell C.R., McCluggage W.G., Quinn D., et al. Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis. PLoS One. 2020; 15(4): e0232231. https://doi.org/10.1371/journal.pone.0232231

12. Izmerov I.F. (editor). Occupational diseases. Moscow, GEOTAR-Media; 2011 (in Russian).

13. Adamyan L.V., Andreeva E.N., Artymuk N.V., Bashmakova N.V., Bezhenar V.F., Belokrinickaya T.E. et al. Endometrial hyperplasia. Federal clinical guidelines. https://cr.minzdrav.gov.ru/schema/646_1 (in Russian).

14. Raffone A., Travaglino A., Saccone G., Insabato L., Mollo A., De Placido G., et al. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet. 2019; 299(5): 1233–42. https://doi.org/10.1007/s00404-019-05103-1

15. Alberti K.G.M.M., Zimmet P., Shaw J. Metabolic syndrome — a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006; 23: 469–80. https://doi.org/10.1111/j.1464-5491.2006.01858.x

16. Bojanic D., Ljubojevic M., Krivokapic D., Gontarev S. Waist circumference, waist-to-hip ratio, and waist-to-height ratio reference percentiles for abdominal obesity among Macedonian adolescents. Nutr Hosp. 2020; 37(4): 786–93. https://doi.org/10.20960/nh.03006

17. Zhang Z., Liu X., Guo C., Zhang X., Zhang Y., Deng N., et al. Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes in a Follow-Up Study on Petrochemical Workers. Toxics. 2022; 10(9): 502. https://doi.org/10.3390/toxics10090502

18. Loseva M.I., Shpagina L.A., Shaparov V.I., Grek O.R. The composition of fatty acids in erythrocyte membranes and the state of lipid peroxidation in painters. Gigiena truda i professional'nye zabolevaniya. 1991; 2: 19 (in Russian).

19. Shpagina L.A., Loseva M.I., Suharevskaya T.M., Sharapov V.I., Sazonova O.V., Tret'yakov S.V. Optimization of the diagnosis and treatment of anemia under the aromatic organic solvents exposure. Terapevticheskij arhiv. 1996; 12: 15.

20. Spinder N., Prins J.R., Bergman J.E.H., Smidt N., Kromhout H., Boezen H.M., et al. Congenital anomalies in the offspring of occupationally exposed mothers: a systematic review and meta-analysis of studies using expert assessment for occupational exposures. Hum Reprod. 2019; 34(5): 903–19. https://doi.org/10.1093/humrep/dez033

21. Alrezaki A., Aldawood N., Mansour L., Ahmed M., Sirotkin A.V., Alwasel S., et al. Toluene Can Disrupt Rat Ovarian Follicullogenesis and Steroidogenesis and Induce Both Autophagy and Apoptosis. Biology (Basel). 2021; 10(11): 1153. https://doi.org/10.3390/biology10111153