Updated: June 27, 2023
Uterine fibroids or uterine leiomyomas are among the most understudied gynecological phenomena studied in the world. Fibroids are considered benign neoplasms or new, abnormal tissue growth. In rare incidences, leiomyomas can become malignant growths called leiomyosarcoma (Bharambe et al., 2014). Fibroids affect over 11 million patients in the United States. Of these patients: 21% are Asian, 35% are Black, 12% are Hispanic, and 10% are White (Krewson, 2023). The patients diagnosed with uterine fibroids face additional symptoms such as heavy menstrual bleeding, pelvic pain, infertility, and more. Two major challenges facing stakeholders are the timing of intervention and identification of the appropriate treatment.
Risk factors for Developing Uterine Fibroids:
- Family History
- Cardiovascular Disease
- Vitamin D deficiency
- No history of pregnancy, and;
- Exposure to environmental endocrine disruptors
What treatments exist for uterine fibroids?
Intervention for uterine fibroids targets the symptoms. Patients are provided with pain relievers (NSAIDs) and other therapeutics that suppress smooth muscle contractions:
- Botulinum Toxin
Treatments for Heavy Menstrual Bleeding (Menorrhagia)
Treatments for heavy menstrual bleeding associated with uterine fibroids include non-peptide small molecule drugs that are synthetic combinations of reproductive hormones (estradiol, progesterone, or gonadotropin releasing hormone):
- ORIAHNN™ (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules)
- MYFEMBREE® (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg)
- Yselty® (Linzagolix; gonadotrophin releasing hormone (GnRH) receptor antagonist)
Surgical Treatments for Uterine Fibroids
Surgical treatments include myomectomy (surgical removal of fibroids) or hysterectomy, complete removal of the uterus. While companies such as Nesa Medtech and Gynesonics Inc that developed minimally invasive or “incisionless” technologies that reduce fibroids by radiofrequency ablation sparing patients from surgical intervention.
Hormonal treatments that suppress the reproductive axis have been effective for temporarily managing the growth of fibroids. However, because fibroids are most common in women of reproductive age, oral contraceptives that prevent ovulation are not ideal for patients who desire pregnancy. Therefore, alternatives are necessary to treat the fibroids while maintaining reproductive function.
Potential Biomarker Targets to Treat Uterine Fibroids
A 2011 study revealed somatic mutations within the gene MED12 were detected in over 70% of uterine leiomyomas (Mäkinen et al., 2011) and associated with mutations in collagen, type IV alpha 5 and alpha 6 (COL4A5-COL4A6), fumarate hydratase (FH), and high mobility group AT-hook 2 (HMGA2) (Äyräväinen et al., 2020; Yang et al., 2022).
What animal models exist to study uterine fibroids?
The first in vivo models for uterine fibroids were established in 1995 with the Eker rat model. This model uses Long-Evans rats with a mutation in the tuberous sclerosis 2 gene (Tsc-2) that is involved in renal cell carcinoma, hemangiosarcoma, and spontaneous formation of uterine fibroids. This model for almost 30 years, this model remains a valuable model to study uterine fibroids. Recently, new models in nude mice and rats with xenograft transplants into the uterus have been developed to assess therapeutics that reduce the size of fibroids while maintaining reproductive function (Suzuki et al, 2018). These models allow for simplified and controlled fibroid formation.
Are animal models for uterine fibroids translational to humans?
A challenge with translational animal models for uterine fibroids is that most symptoms do not naturally occur in the most commonly used species. Symptoms of heavy menstrual bleeding (menorrhagia), menstruation associated pain (dysmenorrhea), and infertility must be induced and typically each symptoms is studied individually but not in parallel replicating the patient experience. As a result, therapeutics are limited. Studying dysmenorrhea and menorrhagia in mouse models poses another challenge because rodents do not naturally menstruate. However, studies originating in Australia and China have identified translational models that may address these challenges and provide useful tools for Sponsors developing treatments for gynecological disorders.
At AniLocus, we identified the most appropriate models for uterine fibroid therapies and can readily assist you in developing a translational model ideal for your therapeutic or medical device. We are excited to support Sponsors in the journey to develop therapeutics for unmet needs. There are over 11 million patients in the United States alone in need of treatment. We strive to conduct research that will enable patient access to life-saving treatments. Let’s discuss options for your preclinical animal studies. Contact us for a free consultation.
- Äyräväinen, A., Pasanen, A., Ahvenainen, T., Heikkinen, T., Pakarinen, P., Härkki, P., & Vahteristo, P. (2020). Systematic molecular and clinical analysis of uterine leiomyomas from fertile-aged women undergoing myomectomy. Human reproduction (Oxford, England), 35(10), 2237–2244. https://doi.org/10.1093/humrep/deaa187
- Beaver, J. A., Coleman, R. L., Arend, R. C., Armstrong, D. K., Bala, S., Mills, G. B., Sood, A. K., & Herzog, T. J. (2019). Advancing Drug Development in Gynecologic Malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research, 25(16), 4874–4880. https://doi.org/10.1158/1078-0432.CCR-19-0619.
- Bellofiore, N., McKenna, J., Ellery, S., & Temple-Smith, P. (2021). The Spiny Mouse-A Menstruating Rodent to Build a Bridge From Bench to Bedside. Frontiers in reproductive health, 3, 784578. https://doi.org/10.3389/frph.2021.784578.
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- Mäkinen, N., Mehine, M., Tolvanen, J., Kaasinen, E., Li, Y., Lehtonen, H. J., Gentile, M., Yan, J., Enge, M., Taipale, M., Aavikko, M., Katainen, R., Virolainen, E., Böhling, T., Koski, T. A., Launonen, V., Sjöberg, J., Taipale, J., Vahteristo, P., & Aaltonen, L. A. (2011). MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science (New York, N.Y.), 334(6053), 252–255. https://doi.org/10.1126/science.1208930
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- Press Release from AbbVie (NYSE: ABBV), in cooperation with Neurocrine Biosciences, Inc. (Nasdaq: NBIX). FDA Approves the First Oral Medication for the Management of Heavy Menstrual Bleeding Due to Uterine Fibroids in Pre-menopausal Women. < https://news.abbvie.com/news/press-releases/fda-approves-first-oral-medication-for-management-heavy-menstrual-bleeding-due-to-uterine-fibroids-in-pre-menopausal-women.htm >.
- Stewart, E. A., Cookson, C. L., Gandolfo, R. A., & Schulze-Rath, R. (2017). Epidemiology of uterine fibroids: a systematic review. BJOG : an international journal of obstetrics and gynaecology, 124(10), 1501–1512. https://doi.org/10.1111/1471-0528.14640.
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- 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.
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- Wang, G., Ishikawa, H., Sone, K., Kobayashi, T., Kim, J. J., Kurita, T., & Shozu, M. (2014). Nonobese diabetic/severe combined immunodeficient murine xenograft model for human uterine leiomyoma. Fertility and sterility, 101(5), 1485–1492. https://doi.org/10.1016/j.fertnstert.2014.01.054.