Clinicopathological Patterns and Biochemical Markers in Serum of Uterine Leiomyoma Patients

• Sundas Akram

  Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

  Author

• Amaila Akmal

  Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

  Author

• Shaaf Ahmad

  Mayo Hospital, King Edward Medical University, Hospital Road, Lahore, 54000, Pakistan

  Author

  https://orcid.org/0000-0003-0749-187X

• Husna Ahmad

  Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

  Author

• Nabila Roohi

  Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0000-0002-2396-5433

Background: Uterine fibroids (leiomyomas) are exceedingly common reproductive neoplasms with foremost public health impact. A cross-sectional study was performed to systematically investigate the marker enzymes, clinicopathological correlations, and electrolyte profile in myoma.

Method: This study enrolled 44 control and 46 leiomyoma subjects, aged 21- 50 years. Anthropometric parameters, detailed history of disease and clinicopathological outcomes were documented via a standardized questionnaire followed by uterine ultrasound investigation. Venous blood samples were taken for the measurement of marker enzymes and serum electrolyte concentration with commercially accessible kits.

Results: In the age group between 30-40 years high incidence of myoma (43.5%) was found. Majority of fibroids were observed single (52%) and Intramural uterine fibroids were found more common type (61%) of leiomyomas. Menorrhagia was frequent clinical demonstration with 63% leiomyoma cases. In 26% myoma women positive family history of leiomyomas was also observed. A significant increase in diastolic blood pressure (DBP) and body mass index (BMI) while in parity a significant decrease was recorded in leiomyoma patients in comparison with controls. Serum electrolytes investigation revealed a substantial increase in the calcium (Ca²⁺) as well as chloride (Cl^–) concentration and significant drop in potassium (K⁺) concentration in myoma subjects when compared to the controls. While for serum sodium (Na⁺) concentration, a non-significant difference was documented between comparable groups. Analysis of marker enzymes manifested a significant increase in the serum concentration of aspartate transaminase (AST), alanine transaminase (ALT) and acid phosphatase (ACP) in fibroid patients in comparison to controls whereas non-significant variations were recorded for serum alkaline phosphatase (ALP) concentration.

Conclusion: A reduced serum K⁺ concentrations and raised Ca²⁺, Cl^–and Na⁺ levels in the leiomyoma patients illustrate increased estrogen concentration, that may be responsible for fibroid growth and serum concentration of AST, ACP and ALP are sustainable diagnostic markers of uterine fibroids.

1. Sundas Akram, Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

   Ph.D. Scholar at Institute of Zoology, University of the Punjab, Lahore. 

2. Amaila Akmal, Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

   Institute of Zoology, University of the Punjab

3. Shaaf Ahmad, Mayo Hospital, King Edward Medical University, Hospital Road, Lahore, 54000, Pakistan

   Mayo Hospital, King Edward Medical University.

4. Husna Ahmad, Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

   Institute of Zoology, M.S. Student

5. Nabila Roohi, Institute of Zoology, University of the Punjab, Quaid-i-Azam, Campus, Lahore, 54590, Pakistan

   Professor of Zoology

Abdullah, L., & Gomaa, W. (2013). The Clinicopathological Characteristics of Uterine Leiomyomas: A Tertiary Care Centre Experience in Saudi Arabia. Life Science Journal, 10(4), 3167-3171.

Akinlua, I., & Ojo, O. C. (2013). Biochemical changes in fibroid patients. Advances in Life Science & Technology, 13, 6-8.

Armanini, D., Sabbadin, C., Donà, G., Bordin, L., Marin, L., Andrisani, A., & Ambrosini, G. (2018). Uterine fibroids and risk of hypertension: implication of inflammation and a possible role of the renin‐angiotensin‐aldosterone system. The Journal of Clinical Hypertension, 20(4), 727. https://doi.org/10.1111/jch.13262

Atkinson D. (2018). Hormonal Therapy Before Surgery for Uterine Fibroids. The American Journal of Nursing, 118(11), 19. https://doi.org/10.1097/01.NAJ.0000547657.69144.62

Baird, D. D., Dunson, D. B., Hill, M. C., Cousins, D., & Schectman, J. M. (2007). Association of physical activity with development of uterine leiomyoma. American Journal of Epidemiology, 165(2), 157-163.

https://doi.org/10.1093/aje/kwj363

Baird, D. D., Travlos, G., Wilson, R., Dunson, D. B., Hill, M. C., D'Aloisio, A. A., London, S. J., & Schectman, J. M. (2009). Uterine leiomyomata in relation to insulin-like growth factor-I, insulin, and diabetes. Epidemiology, 20(4), 604–610. https://doi.org/10.1097/EDE.0b013e31819d8d3f

Bariani, M. V., Rangaswamy, R., Siblini, H., Yang, Q., Al-Hendy, A., & Zota, A. R. (2020). The role of endocrine-disrupting chemicals in uterine fibroid pathogenesis. Current Opinion in Endocrinology, Diabetes, and Obesity, 27(6), 380. https://doi.org/10.1097%2FMED.0000000000000578

Boschitsch, E., Mayerhofer, S., & Magometschnigg, D. (2010). Hypertension in women: the role of progesterone and aldosterone. Climacteric, 13(4), 307-313.

https://doi.org/10.3109/13697131003624649

Boyles, A. L., Beverly, B. E., Fenton, S. E., Jackson, C. L., Jukic, A., Sutherland, V. L., Baird, D. D., Collman, G. W., Dixon, D., Ferguson, K. K., Hall, J. E., Martin, E. M., Schug, T. T., White, A. J., & Chandler, K. J. (2021). Environmental factors involved in maternal morbidity and mortality. Journal of Women's Health, 30(2), 245–252. https://doi.org/10.1089/jwh.2020.8855

Chougule, A., Hussain, S., & Agarwal, D. P. (2008). Prognostic and diagnostic value of serum pseudocholinesterase, serum aspartate transaminase, and serum alanine transaminase in malignancies treated by radiotherapy. Journal of Cancer Research and Therapeutics, 4(1), 21.

https://www.cancerjournal.net/text.asp?2008/4/1/21/39601

Ciarmela, P., Islam, M. S., Reis, F. M., Gray, P. C., Bloise, E., Petraglia, F., Vale, W., & Castellucci, M. (2011). Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Human Reproduction Update, 17(6), 772–790. https://doi.org/10.1093/humupd/dmr031

Collins, S. C., Martin, J. R., & Pal, L. (2021). Amenorrhea and Abnormal Uterine Bleeding. In Contemporary Obstetrics and Gynecology for Developing Countries (pp. 525-541). Springer, Cham. https://doi.org/10.1007/978-3-030-75385-6_49

Dolmans, M. M., Cacciottola, L., & Donnez, J. (2021). Conservative Management of Uterine Fibroid-Related Heavy Menstrual Bleeding and Infertility: Time for a Deeper Mechanistic Understanding and an Individualized Approach. Journal of Clinical Medicine, 10(19), 4389.

https://doi.org/10.3390/jcm10194389

Flake, G. P., Andersen, J., & Dixon, D. (2003). Etiology and pathogenesis of uterine leiomyomas: a review. Environmental Health Perspectives, 111(8), 1037-1054.

https://doi.org/10.1289/ehp.5787

Giuliani, E., As‐Sanie, S., & Marsh, E. E. (2020). Epidemiology and management of uterine fibroids. International Journal of Gynecology & Obstetrics, 149(1), 3-9.

https://doi.org/10.1002/ijgo.13102

Halder, S. K., Goodwin, J. S., & Al-Hendy, A. (2011). 1, 25-Dihydroxyvitamin D3 reduces TGF-β3-induced fibrosis-related gene expression in human uterine leiomyoma cells. The Journal of Clinical Endocrinology & Metabolism, 96(4), E754-E762. https://doi.org/10.1210/jc.2010-2131

Hapangama, D. K., & Bulmer, J. N. (2016). Pathophysiology of heavy menstrual bleeding. Women’s Health, 12(1), 3-13.

https://doi.org/10.2217/whe.15.81

He, Y., Zeng, Q., Dong, S., Qin, L., Li, G., & Wang, P. (2013). Associations between uterine fibroids and lifestyles including diet, physical activity, and stress: a case-control study in China. Asia Pacific Journal of Clinical Nutrition, 22(1), 109–117. https://doi.org/10.6133/apjcn.2013.22.1.07

Hoffman, D. J., Powell, T. L., Barrett, E. S., & Hardy, D. B. (2021). Developmental origins of metabolic diseases. Physiological Reviews, 101(3), 739-795.

https://doi.org/10.1152/physrev.00002.2020

Karumanchi, S. A., & Bdolah, Y. (2004). Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology, 145(11), 4835-4837. https://doi.org/10.1210/en.2004-1028

Katzer, K., Hill, J. L., McIver, K. B., & Foster, M. T. (2021). Lipedema and the potential role of estrogen in excessive adipose tissue accumulation. International Journal of Molecular Sciences, 22(21), 11720.

https://doi.org/10.3390/ijms222111720

Ke, X., Cheng, Z., Qu, X., Dai, H., Zhang, W., & Chen, Z. J. (2014). High expression of calcium channel subtypes in uterine fibroid of patients. International Journal of Clinical and Experimental Medicine, 7(5), 1324.

Kirschen, G. W., AlAshqar, A., Miyashita-Ishiwata, M., Reschke, L., El Sabeh, M., & Borahay, M. A. (2021). Vascular biology of uterine fibroids: connecting fibroids and vascular disorders. Reproduction, 162(2), R1-R18.

https://doi.org/10.1530/REP-21-0087

Lim, D., & Oliva, E. (2019). Gynecological neoplasms associated with paraneoplastic hypercalcemia. Seminars in Diagnostic Pathology, 36(4), 246–259. https://doi.org/10.1053/j.semdp.2019.01.003

Maggio, M., Lauretani, F., Basaria, S., Ceda, G. P., Bandinelli, S., Metter, E. J., Bos, A. J., Ruggiero, C., Ceresini, G., Paolisso, G., Artoni, A., Valenti, G., Guralnik, J. M., & Ferrucci, L. (2008). Sex hormone binding globulin levels across the adult lifespan in women--the role of body mass index and fasting insulin. Journal of Endocrinological Investigation, 31(7), 597–601. https://doi.org/10.1007/BF03345608

Marshall, L. M., Spiegelman, D., Manson, J. E., Goldman, M. B., Barbieri, R. L., Stampfer, M. J., Willett, W. C., & Hunter, D. J. (1998). Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking. Epidemiology, 9(5), 511–517.

http://www.jstor.org/stable/3702527.

Newman, D. K., & Banfield, J. F. (2002). Geomicrobiology: how molecular-scale interactions underpin biogeochemical systems. Science, 296(5570), 1071-1077.

https://doi.org/10.1126/science.1010716

Noel, N. L., Gadson, A. K., & Hendessi, P. (2019). Uterine Fibroids, Race, Ethnicity, and Cardiovascular Outcomes. Current Cardiovascular Risk Reports, 13(9), 1-7. https://doi.org/10.1007/S12170-019-0622-0

Ojo, O. C., & Oyeyemi, A. O. (2013). Evaluation of marker enzymes in fibroid patients. IOSR Journal of Environmental Science, Toxicology and Food Technology,5, 29-31.

Okolo, S. (2008). Incidence, aetiology, and epidemiology of uterine fibroids. Best practice & research Clinical Obstetrics & Gynaecology, 22(4), 571-588.

https://doi.org/10.1016/j.bpobgyn.2008.04.002

Parker, W. H. (2007). Etiology, symptomatology, and diagnosis of uterine myomas. Fertility & Sterility, 87(4), 725-736. https://doi.org/10.1016/j.fertnstert.2007.01.093

Sarkodie, D., Dzefi-Tettey, K., Obeng, H., KwadwoAdjei, P., & Coleman, J. (2012). Prevalence and sonographic patterns of uterine fibroid among Ghanaian women (Uterine Fibroid-The Ghanaian situation).

Shen, Y., Wu, Y., Lu, Q., & Ren, M. (2016). Vegetarian diet and reduced uterine fibroids risk: A case–control study in Nanjing, China. Journal of Obstetrics and Gynaecology Research, 42(1), 87-94. https://doi.org/10.1111/jog.12834

Sheng, B., Song, Y., Liu, Y., Jiang, C., & Zhu, X. (2020). Association between vitamin D and uterine fibroids: A study protocol of an open label, randomised controlled trial. BMJ Open, 10(11), e038709. http://dx.doi.org/10.1136/bmjopen-2020-038709

Skinner, H. C. W. (2005). Biominerals. Mineralogical Magazine, 69(5), 621-641. https://doi.org/10.1180/0026461056950275

Szydłowska, I., Nawrocka-Rutkowska, J., Brodowska, A., Marciniak, A., Starczewski, A., & Szczuko, M. (2022). Dietary natural compounds and vitamins as potential cofactors in uterine fibroids growth and development. Nutrients, 14(4), 734. https://doi.org/10.3390/nu14040734

Truong, N. U., Edwardes, M. D. D., Papavasiliou, V., Goltzman, D., & Kremer, R. (2003). Parathyroid hormone–related peptide and survival of patients with cancer and hypercalcemia. The American Journal of Medicine, 115(2), 115-121. https://doi.org/10.1016/S0002-9343(03)00310-3

Turocy, J., & Williams, Z. (2022). 16 - Early and recurrent pregnancy loss: Etiology, Diagnosis, Treatment (D. M. Gershenson, G. M. Lentz, F. A. Valea, & R. A. B. T.-C. G. (Eighth E. Lobo (eds.); pp. 323-341.e3). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-323-65399-2.00025-5

Williams, G. H. (2005). Aldosterone biosynthesis, regulation, and classical mechanism of action. Heart Failure Reviews, 10(1), 7-13. https://link.springer.com/article/10.1007/s10741-005-2343-3

Yafang, T., & Nadarajah, R. (2022). Challenges in the diagnosis and treatment of extrauterine leiomyomas: case series. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 11(1), 232-237.

http://www.ijrcog.org/index.php

Yang, Q., Ciebiera, M., Bariani, M. V., Ali, M., Elkafas, H., Boyer, T. G., & Al-Hendy, A. (2022). Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment. Endocrine Reviews, 43(4), 678-719. https://doi.org/10.1210/endrev/bnab039

Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020). Glutamine reliance in cell metabolism. Experimental & Molecular Medicine, 52(9), 1496–1516. https://doi.org/10.1038/s12276-020-00504-8

Zakeri, Z., Quaglino, D., & Ahuja, H. S. (1994). Apoptotic cell death in the mouse limb and its suppression in the hammertoe mutant. Developmental Biology, 165(1), 294-297.

https://doi.org/10.1006/dbio.1994.1255

• PDF

Copyright (c) 2022 Sundas Akram, Amaila Akmal, Shaaf Ahmad, Husna Ahmad, Nabila Roohi (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.