Tratamentul fibroamelor uterine: review al literaturii

Introduction

Uterine fibroids (UFs) are a common benign pathology in women, with a worldwide prevalence of more than 220 million. According to recent literature, the global age-standardized incidence rate of UFs increased from 1990 to present. Regionally, Eastern Europe, Latin America, India and Brazil experience the highest uterine fibroids social and economic burden. Globally, women aged 35-39 and older are at the highest risk for this pathology⁽¹⁾. Although mostly asymptomatic, uterine fibroids cause abnormal uterine bleeding, heavy menstrual flow, anemia, chronic pelvic pressure and pain, urinary problems, constipation and infertility. For pregnant women, uterine fibroids are an independent risk factor for adverse perinatal outcomes. Moreover, hysterectomies due to uterine fibroids account for more than half of total hysterectomies and for 18-44% of hysterectomies in younger women. In recent years, there has been a shift towards medical treatment and minimally invasive procedures, leaving surgery as a last resort⁽²⁾.

The aim of this review is to highlight the main treatment options for uterine fibroids.

Materials and method

A PubMed and Google Scholar search for peer-reviewed and original articles related to the management of uterine fibroids written in English published until May 2026 was performed, and the main updates were evaluated. We also added examples of images from cases admitted in the gynecology department of the University Emergency Hospital Bucharest, Romania.

Results and discussion

The pathophysiology of uterine fibroids is very complex, involving epigenetic, molecular and hormonal mechanisms. Uterine fibroids start with stem cell precursors of uterine smooth muscle cells that are influenced by risk factors such as age, ethnicity and obesity. By hormonal and genetic pathways, these cells transform into abnormal fibroid cells. Leiomyomas respond to estrogen and progesterone stimuli, and tend to shrink as those hormones decline at menopause. Nowadays, the focus has shifted from estrogen to progesterone-linked pathways, due to evidence that estrogen is involved in the induction of progesterone receptors. Studies found that a high density of progesterone receptors may stimulate UF growth^(3,4).

The first-line technique for the diagnosis of uterine fibroids is transvaginal ultrasound (Figure 1).

The FIGO classification is used to map the location of the leiomyoma, and the sonographic morphological criteria offer a more detailed description of the fibroma, including vascularization. Magnetic resonance imaging (MRI) is superior when investigating large uteruses with numerous fibroids, coexisting endometriosis or for a differential diagnosis with uterine sarcomas. Sonohysterography and hysteroscopy are minimally invasive techniques that are increasingly being used nowadays to diagnose UFs. Hysteroscopy is widely used to diagnose and to remove submucosal uterine fibroids. Some recent studies mention elastography and other complementary techniques used to differentiate leiomyomas from adenomyosis^(5,6).

The main symptoms of leiomyomas are heavy or abnormal menstrual bleeding, pelvic pain and impaired fertil­ity. In asymptomatic patients or with very mild symptoms, experts recommend avoiding overtreatment and, after an informed-decision making with the patient, the expectative management is usually preferred⁽⁷⁾. Therefore, treatment options are focused on the severity of these symptoms and on the patient’s situation regarding her age, fertility preservation and concomitant pathologies.

Treatment of abnormal uterine bleeding and bulk symptoms

Studies found that 79% of women who experience abnormal uterine bleeding prefer to avoid surgery or to postpone it for several years. There are several medical and minimally invasive treatment options available for treating this symptom. Many guidelines recommend tranexamic acid as first-line nonhormonal treatment, which is well tolerated. Levonorgestrel-IUD is used to treat heavy menstrual bleeding by inhibiting UF cell proliferation. A review by Sangkomkamhang et al. published in 2020 concluded that hormonal IUDs do not reduce uterine fibroids growth and should only be recommended for the treatment of abnormal uterine bleeding. The expulsion rates are also higher in women with distorted uterine cavities⁽⁸⁾. Until recent years, selective progesterone receptor modulators (ulipristal acetate) were used to reduce the size of uterine fibroids, but newer studies reported serious side effects; therefore, in 2020, the European Medical Agency suspended the use of this medication for uterine fibroids. As of now, no selective progesterone receptor modulator is approved for uterine fibroids treatment and, despite initial promising results, the future use is conditioned by high liver toxicity and serious side effects. Combined oral contraceptives, especially a combination of estradiol valerate and dienogest, may be useful to control the bleeding, but the effects on fibroid size remain controversial^(9,10).

The best choice for reducing fibroid size are GnRH antagonists. Fibroid volume reduction is often around 20-50%.  A new generation of GnRH antagonists, such as relugolix and elagolix, proved to be effective in treating heavy menstrual bleeding and in reducing the size of the leiomyomas. These drugs must be associated with add-back therapy to minimize the hypoestrogenism-related side effects. GnRH antagonists with add-back therapy are the best choice for bridging therapy. This strategy is used in patients who need to use temporary medical treatment to stabilize symptoms until a more definitive endpoint is reached. This endpoint may be natural menopause, planned surgery, fertility treatment, postpartum recovery, improvement of anemia, or a time when surgery becomes safer or more acceptable^(11-13).

Surgery is recommended in patients who do not respond to medical treatment or who prefer a faster solution. Myomectomy can be performed either by hysteroscopy or abdominally by different approaches. Women who desire preservation of fertility and uterine sparing benefit from this technique with an increased satisfaction rate. Hysteroscopic myomectomy is indicated in FIGO 0-1 types of uterine fibroids, with symptom improvement in 2-3 months and a low reintervention recurrence at five years after procedure. Abdominal myomectomy improves the quality of life, but studies found no significant improvement of heavy menstrual flow and an increased tendency in symptoms recurrence after three years of follow-up compared to hysterectomy. Hysterectomy remains the last resort and definitive treatment option for women who do not want to get pregnant^(14-16) (Figure 2).

Alternative treatments – other than medical or surgical options – may be suitable for selected patients. Uterine artery embolization (UAE) can be used to treat abnormal uterine bleeding, but patients may experience a recurrence of symptoms over the years. It can be used as bridging therapy or when the patient refuses surgery. A lower risk for blood transfusion and short hospital stay is an advantage when compared to surgery. There is some controversy regarding UAE and a risk of miscarriage and preterm birth, but uterine artery embolization remains a reasonable treatment option⁽¹⁷⁾.

A nonhormonal, nonpharmacological option to treat heavy menstrual bleeding and to decrease fibroid size is a natural compound found in green tea, which is being investigated with recent promising results. Recent studies also mention vitamin D supplementation and D-chiro inositol (DCI)⁽¹⁸⁾.

The reduction of bulk symptoms caused by medium to large size uterine fibroids was also investigated during medical treatment. Until EMA banned the use of ulipristal acetate because of its serious liver toxicity, UPA was the best choice to reduce fibroid volume. Currently, the new generation of GnRH antagonists have been suggested as presurgical treatment to reduce fibroid size. Their use without add-back therapy should be short-termed, and even in longer use, there is a regrowth to pretreatment size after 6-9 months after cessation of therapy. Although efficient in reducing heavy menstrual bleeding related to uterine fibroids, uterine artery embolization was not proven to be very efficient in reducing bulk symptoms⁽¹⁹⁾ (Figure 3).

Management of special situations: coexistence of endometriosis, adenomyosis and fibroids

Uterine fibroids share common symptoms with endometriosis and adenomyosis: dysmenorrhea, pelvic pain and impaired fertility. Endometriosis and UFs are both estrogen-dependent, but have different response to progesterone. Some authors found an association of fibroids with endometriosis and adenomyosis, suggesting there are some common pathways. Lin et al. showed that patients presenting uterine fibroids have a six-fold higher risk of presenting endometriosis compared to controls. Conversely, having endometriosis doubles the risk of having UFs. According to genetic meta-analysis data, these associations may be due to a possible common genetic origin, relating genetic alterations of uterine fibroids to endometriosis, despite presenting different molecular pathways. There are limited data on the association of uterine fibroids with endometriosis and adenomyosis, but acknowledging the concomitant presence of lesions is important to clinicians, because these women may have increased obstetrical risks, and surgical interventions may be hindered by simultaneous lesions^(7,20).

Management of perimenopausal women with uterine fibroids

The incidence of uterine fibroids is increased in perimenopause. In women 40-50 years old, abnormal uterine bleeding is frequently caused by anovulatory cycles, and having uterine fibroids enhances the chance to experience heavy or abnormal menstrual bleeding and anemia. Menopause decreases fibroid size and stops menstrual bleeding, therefore the treatment of fibroid-related symptoms until the onset of menopause should be discussed with the perimenopausal patient. Tumor size reduction can be aimed using short-term medical treatment until menopause. Hormonal replacement therapy in menopausal women with uterine fibroids is not contraindicated. The treatment is individualized based on symptom severity, fibroid size and location, bleeding history, risk factors, menopausal symptoms and quality of life. In women with symptomatic fibroid history, clinicians prefer the lowest effective estrogen dose, with transdermal route, a careful choice of progestogen and periodic reassessment⁽²¹⁾.

Uterine fibroids in pregnancy

High-quality data on the relationship between uterine fibroids and pregnancy outcome are very limited. The prevalence of UFs during pregnancy is 1.6-10.7%, and 10% to 30% of women with uterine fibroids experience complications during pregnancy and the postpartum. Complications are more frequent in women with multiple fibroids, large fibroids (>5 cm) and with fibroids located in the lower uterine segment. Fibroids may contribute to infertility and recurrent miscarriage⁽²²⁾.

Preconception consultation and individualized treatment are very important. Studies report that long-term medical therapies for symptomatic patients seeking fertility often led to adverse effects, and they cause a rebound of symptoms once the medication is stopped, making them generally ineffective. In patients with bleeding submucosal FIGO 0-1 fibroid types, hysteroscopic myomectomy is recommended. For other types, laparoscopic (with or without robotic assistance) or open abdominal myomectomy are used. A systematic review showed that data are insufficient to advise a minimal time interval between myomectomy and conception to prevent uterine rupture. Patients should be informed that uterine rupture can occur anytime during pregnancy^(23,24).

Longitudinal studies showed that up to 71.4% of uterine fibroids increased in size during the first and second trimesters, then stabilized in growth during the second and third trimesters, and reduced in size in the postpartum. The main complications that can occur in pregnancy are red degeneration and torsion. While the first can be managed conservatively, the second requires surgical intervention⁽²⁵⁾.

High-quality data on obstetric complications caused by UFs are limited, but research shows an increased risk of early pregnancy loss, preterm birth, placental abruption, placenta praevia, postpartum hemorrhage, malpresentation, dysfunctional labor and caesarean birth. During pregnancy, myomectomy should not be performed in asymptomatic women due to an increased risk of severe hemorrhage, uterine rupture, pregnancy loss or preterm birth. There are some rare situations when conservative management fails and myomectomy is performed: torsion, severe abdominal compression by large fibroids, rapid fibroid enlargement possible hiding malignancy. Caesarean myomectomy is not recommended^(22,26-30).

In the postpartum, uterine fibroids generally gradually decrease in size, but they should be monitored by ultrasound. In rare situations, a leiomyoma can degenerate and become infected, leading to life-threatening situations like peritonitis and sepsis^(22,31). Pregnant patients with large uncomplicated UFs are generally advised to wait until postpartum and breastfeeding, and have their fibroids routinely monitored before taking a decision about surgery.

Conclusions

Uterine fibroids remain an important health challenge globally and locally. Treatment alternatives are available, and physicians can discuss with patients about a wide range of choices. The last 20 years offered a lot of progress in the medical treatment of primary symptoms of uterine fibroids. Consequently, a tailored approach must weigh medical and surgical interventions with consideration of innovative medical alternatives potentially comparable to surgery. Future studies should concentrate on tailored approach to different types of fibroids. Additionally, more data are needed, and prospective studies on the timing of conception after myomectomy and about fibroid regression after childbirth should be prioritized.

Autor corespondent:   Delia Grădinaru E-mail: dr_deliagradinaru@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.