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*Corresponding Author: Joanna Pietras, Department of Perinatology, Gynecological Obstetric Clinical Hospital of Poznan University of Medical Sciences, Polna 33, 60-535, Poznan, Poland.
Citation: Joanna Pietras, Anna Markowska, Stefan Sajdak, (2024), Overview of Uterine Fibroid Treatment Procedures; Review Article, International Journal of Clinical Case Reports and Reviews, 19(3); DOI:10.31579/2690-4861/549
Copyright: © 2024, Joanna Pietras. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 20 September 2024 | Accepted: 04 October 2024 | Published: 22 October 2024
Keywords: uterine fibroids; pharmacological treatment; interventional radiological techniques; surgical treatment
Myomas are benign uterine tumours found in 40-70% of women of reproductive age. About 30% of them cause various ailments (bleeding, pain, infertility) that reduce the quality of women’s life.
Uterine fibromas are the cause of 40-60% of hysterectomies.
Different treatment methods are used depending on the size, number, location of myomas and the patient's preferences. Conservative treatment includes nonsteroidal anti-inflammatory drugs, hormonal therapies as contraceptives, GnRH agonists or antagonists, selective progesterone receptor modulators and levonorgestrel.
Radiologic intervention types include are UAE (uterine artery embolization), high-intensity focused ultrasound (HIFU), magnetic resonance (MRgFUS), and radiofrequency ablation (RFA).
There are also more radical methods, namely surgical treatments, such as myomectomy (hysteroscopic, laparoscopic, robotic or abdominal) and hysterectomy. The oldest of methods is abdominal hysterectomy, while in some women, vaginal hysterectomy can be applied. Recently, laparoscopic or robotic hysterectomy (using the da Vinci robot) has been used. The latter procedures are associated with a better quality of life following treatment.
Uterine fibroids are benign tumors composed of involuntary muscle and fibroblasts, occurring in 40-70% of women of reproductive age. Their wide incidence range depends on the studied population and diagnostic methods used. Most women do not report any symptoms; in about 30%, uterine fibroids affect the quality of life, causing: abnormal uterine bleeding, heavy menstruation, pelvic pain and pressure, and infertility [1,2,3,4,5]. Lockwood showed that aberrant angiogenesis underlines abnormal bleeding associated with myomas and endometrial polyps. As it turns out, vascular flow disorders the influence of the etiopathogenesis of uterine fibroids and many other uterine pathologies. [6,7] The term "fibroids" was first introduced in the 1860s. Hippocrates, a Greek physician (460-375 BC), termed them "uterine stones" (womb stones), and Galen (2nd century) described them as "scleromas" [5,8]. Numerous factors have been identified as playing a role in the pathogenesis and epidemiology of fibroids. Stewart et al. [9], based on 60 publications, showed that 12 factors are involved in the development of fibroids, the dominant one being African American women. The critical role of ovarian steroid hormones - estrogens and progesterone has been established in epidemiological, clinical and experimental studies. Progesterone is essential for developing and proliferating fibroid cells, while estrogens are required for sensitising fibroid cells to progesterone [10,11,12]. It has been shown that chromosomal aberrations are found in 40-50% of patients with uterine fibroids [13,14]. In their review, Yang et al. [5] described four types of molecular mutations: in MED12, overexpression in HMGA2, deficiency in fumarate hydratase (FH), and deletions in COL4A5/COL4A6. Mutations in MED12 are the dominant type and occur more frequently in African women. They are associated with smaller fibroid sizes and subserosal locations. Studies have also shown that stem cells participate in developing fibroids using the Wnt/ßcatenin signaling pathway. Increased expression of VEGF-A has been found in the uterine fibroids of young women, which may be a sign of increased angiogenesis and intensive tumor growth. According to literature data, a close relationship has also been demonstrated between impaired VEGF gene expression and the development of ovarian tumors. [15,16] The involvement of cytokines and chemokines with pro-inflammatory and profibrinolytic features has also been suggested in developing fibroids. Vitamin D deficiency has been studied to play a role in the growth of myomas [5,17]. It turns out that vaginal dysbiosis plays a crucial role in the development of uterine fibroids and many other diseases of the uterus, including endometrial cancer [18,19] Fibroid treatment includes numerous methods, from conservative pharmacological treatment to various types of surgical procedures. The choice depends on various factors, such as the size, number, location of fibroids, symptoms, the patient's age, health condition, and individual expectations, e.g., maintaining fertility [5,20,21,22]. Conservative treatment involves regular monitoring of small asymptomatic fibroids.
The purpose of this article is to provide a comprehensive summary of the various pharmacological and surgical options available for uterine fibroid treatment, highlighting their benefits, risks, and potential outcomes.
Pharmacological treatment
It is a group of analgesic and anti-inflammatory drugs that inhibit cyclooxygenase, thereby reducing the synthesis of prostaglandins at the endometrial level. This mechanism leads to a reduction in heavy menstrual bleeding and painful menstruation [20,23,24]. Tranexamic acid reduces menstrual blood loss by inhibiting fibrinolysis via reversible plasminogen blockade. It is often used in laparoscopic or abdominal myomectomy to reduce blood loss [20,22].
Recent studies indicate the beneficial role of vitamin D and epigallocatechin gallate (Epicatechin-3-gallate-EGCG) - catechin belonging to polyphenols contained in green tea (Camellia sinensis) [24,25,26]. Vitamin D regulates cell proliferation and differentiation, inhibits angiogenesis and stimulates apoptosis [27]. EGCG inhibits the proliferation of myoma cells and induces apoptosis by inhibiting the COMT enzyme (catechol-O-methyl transferase) associated with the pathogenesis of myomas [28]. Both of these compounds can be used together or separately. Currently, a prospective randomized FRIEND study (from 2022-2025) is ongoing, involving 200 patients with uterine fibroids and a history of infertility, assessing the efficacy of EGCG in reducing the volume of fibroids and their impact on infertility [29].
Contraceptives are commonly used to treat abnormal uterine bleeding and heavy periods. Studies have shown a reduction in menstrual blood loss after six months of use by up to 72% [20]. In some cases, combined pills containing estrogen and progesterone can help with menstrual pain [12]. The role of hormonal contraception in the development of fibroids is minimal [30]. However, some studies show it is a protective factor against developing fibroids [31].
LNG-IUS is a contraceptive method that is also effective in treating heavy menstrual bleeding. It affects the endometrium locally, reducing the duration and intensity of menstruation. It has also been noted that it does not impact the size of pre-existing fibroids. However, it is not recommended for women with submucous fibroids due to the possibility of expulsion of the device [20,30].
SPRMs reduce fibroid cell proliferation by inducing apoptosis and reducing collagen synthesis and extracellular matrix. This results in a 20–57% reduction in fibroid volume [20,26,30]. In 2012, the European Medicines Agency (EMA) approved ulipristal acetate (Esmya) for the treatment of moderate to severe symptoms associated with fibroids in women of reproductive age [26]. Studies have shown that UPA (ulipristal acetate) causes significant changes in the expression of four genes in uterine fibroids. UPA treatment significantly reduced the expression of the integrin subunit beta 4, tenascin C and surviving gene. In those who did not respond to UPA treatment, the expression of delta-two catenin increased [32]. Although UPA significantly reduced bleeding, the size of fibroids and the size of the uterus and was used by over 765,000 women, this drug caused severe liver damage in 5 women, of which four required transplantation [33]. As of 2020, the EMA Risk Assessment Committee indicates that UPA may only be used for intermittent treatment in premenopausal women, especially in cases where surgical interventions, including embolization, are unsuitable or ineffective [20,26,33].
The use of GnRH analogs (Leuproid, Goserelin) is a well-known method of treating uterine fibroids. By inhibiting the pulsatile secretion of GnRH, they reduce the production of LH and FSH, which leads to hypoestrogenism. It has also been found that GnRH analogs disrupt the production of matrix metalloproteinases and induce apoptosis. This mechanism leads to a reduction in the size of fibroids during the first months of medication use, but in some cases, a regrowth of fibroids is observed after discontinuation of the therapy. The use of GnRH analogs leading to the inhibition of ovarian hormone secretion causes undesirable menopausal symptoms. GnRH analogues should only be used for large fibroids in the short term - especially before procedures - e.g., myomectomy, which beneficially reduces blood loss during surgery [20,26,30,34]. GnRH antagonists are considered drugs for long-term use. Blocking the GnRH receptor leads to hypoestrogenism with the risk of menopause. Add-back therapy (ABT) has been used together with the use of antagonists. It involves adding estrogen-progestogen or progestogen-only therapy to GnRH antagonist treatment to alleviate menopausal symptoms without reducing the effectiveness of the treatment. So far, three drugs for symptoms associated with fibroids have been registered: Relugolix, Elagolix and Linzagolix. The first of the medications, apart from relugolix (40 mg), also contains estradiol (1 mg) and norethisterone acetate (0.5 mg). The trade name of the medication is Ryeqo. Elagolix - 300 mg contains the same amounts of estradiol and norethisterone acetate. Its trade name is Oriahnn. Linzagolix contains only linzagolix in doses of 100mg or 200mg. Its brand name is Yselty. In May 2020, the FDA approved using Elagolix in clinical practice and then, in 2021, the use of Relugolix. The European Medicines Agency (EMA) approved Relugolix (Ryeqo) for use in 2021. Linzagolix received approval from the EMA in 2022 [35].
Interventional radiological techniques
This is a non-invasive procedure used for the treatment of fibroids. UAE was first introduced in France in the 1990s as an alternative method of treating fibroids for women who wish to avoid traditional surgical methods or are not suitable for them [36]. UAE involves blocking the blood flow to the myomas by using various embolization agents (e.g., hydrophilic microspheres or polyvinyl alcohol (PVA)). Contraindications to UAE include pedunculated submucosal or subserosal fibroids [12,20,37].
Quality of life studies in 6 randomized clinical trials did not show any differences with other minimally invasive procedures used to treat fibroids (e.g. myomectomy) [38,39]. Conflicting data exists regarding the frequency of re-intervention after UAE. According to the aforementioned randomized studies, UAE is associated with increased re-intervention rates, while in another study of 152 women who underwent this procedure, the recurrence rate was even lower than in patients after myomectomy (14.3% vs 31.6%, respectively) [40].
It is a non-invasive method of treating fibroids that has been used for 20 years. This method uses a precisely directed high-energy ultrasound beam within the fibroid. The procedure can be performed under MRI or ultrasound guidance [20, 30, 41, 42]. It causes an increase in temperature in the myoma and its necrosis. Patel et al. [41], based on the analysis of 14 studies, concluded that HIFU is an equivalent therapy to surgery, allowing for the preservation of fertility. The reduction of the myoma size was 68-75
In recent years, methods for treating uterine fibroids have developed. This applies to pharmacological treatment, interventional radiological techniques, and minimally invasive surgical procedures. This progress is associated with improving the quality of life of treated women and possibly preserving fertility. Nevertheless, there is still a lack of an ideal method that minimizes risk, has no side effects, and is highly effective.
Author 1: Joanna Pietras led the conceptualization of the review, conducted the literature search, and drafted the initial manuscript.
Author 2: Anna Markowska contributed to the selection and analysis of key articles, organized the structure of the review, and critically revised the manuscript.
Author 3: Stefan Sajdak provided expertise in the subject matter, reviewed the content for accuracy, and oversaw the final editing and approval of the manuscript.
The authors declare no conflict of interests.
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