Uterine fibroids: symptoms, diagnosis, treatment

A uterine fibroid, or leiomyoma, is a benign tumor of the smooth muscle cells of the myometrium, often with a prominent extracellular matrix component. Most fibroids are asymptomatic, but in some patients they cause heavy menstrual bleeding, pelvic pain, pressure on adjacent organs, anemia, and fertility problems. Symptoms depend on the number of fibroids, their size, and their location in the uterine wall according to the FIGO classification system. A modern approach focuses on choosing a treatment that is proportionate to the severity of symptoms, the woman's reproductive plans, and her preferences. [1]

In recent years, effective medical options for controlling bleeding in fibroids have emerged—oral gonadotropin-releasing hormone antagonists in combination with low-dose estrogen and progestogen—as well as improved organ-preserving procedures, including uterine artery embolization, transcervical radiofrequency ablation, and magnetic resonance imaging-guided focused ultrasound. This has expanded the possibilities for personalized treatment and allowed many patients to avoid radical surgery. [2]

There is no screening for myoma in the general population; diagnosis is established upon presentation or as an incidental finding during pelvic ultrasound. Transvaginal and transabdominal ultrasound remain the primary imaging methods; magnetic resonance imaging is used for complex cases, preoperative mapping, and interventional planning. Saline contrast of the uterine cavity during sonohysterography and diagnostic hysteroscopy are helpful if submucosal nodes are suspected. [3]

Treatment decisions require consideration of symptom severity, impact on quality of life, age, somatic risks, pregnancy plans, and the characteristics of each nodule according to the FIGO classification. Current guidelines emphasize shared decision-making and a stepwise approach, ranging from conservative measures to minimally invasive and surgical interventions. [4]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, Tenth Revision, uterine fibroids are coded in block D25 with specifications for location: submucosal, intramural, subserosal, or unspecified. These codes are widely used for statistics, routing, and reimbursement. [5]

The International Classification of Diseases, Eleventh Revision, uses code 2E86.0 for "Uterine Leiomyoma." It covers various locations, including cervical nodes and parasitic leiomyomas. The transition to ICD-11 is proceeding gradually across countries, but the coding structure is already being incorporated into clinical registries. [6]

Table 1. ICD-10 and ICD-11 codes for uterine fibroids

Classifier	Code	Name
ICD-10	D25.0	Submucous uterine leiomyoma
ICD-10	D25.1	Intramural uterine leiomyoma
ICD-10	D25.2	Subserous leiomyoma of the uterus
ICD-10	D25.9	Leiomyoma of the uterus, unspecified
ICD-11	2E86.0	Uterine leiomyoma
[7]

Epidemiology

Uterine fibroids are the most common benign tumor in women of reproductive age. According to clinical reviews and guidelines, by age 50, approximately 70 percent of Caucasian women and 80 percent of women of African descent have developed fibroids. While severe symptoms are less common, they remain a significant cause of anemia and hysterectomy. Peak incidence occurs between the ages of 35 and 54. [8]

Recent large cohorts and reports confirm marked ethnic differences: the risk of diagnosis is higher in some Asian and Hispanic groups than in white women, and in women of African descent, the disease begins earlier and has a more severe course. These differences reflect a combination of genetic, hormonal, metabolic, and sociobehavioral factors. [9]

Global estimates based on epidemiological databases show a moderate increase in age-standardized prevalence and incidence rates from 1990 to 2021, partly due to improved access to ultrasound diagnostics and increased awareness. Age-specific incidence peaks in those aged 30–44 years. [10]

According to sample surveys and insurance registries, the proportion of women with a confirmed diagnosis by a given age varies due to differences in detection methods: lower with clinical diagnosis, higher with ultrasound screening, and highest with histological verification. This should be taken into account when comparing studies. [11]

Table 2. Epidemiology of uterine fibroids

Indicator	Grade
The proportion of women with fibroids by age 50	≈70 percent in white women, ≈80 percent in women of African descent
Peak detection rate	35-54 years old
The highest incidence	30-44 years old
Trend 1990-2021	Slight increase in global indicators
Ethnic differences	Higher risk in certain groups of Asian and Hispanic descent
[12]

Reasons

Myomas are monoclonal smooth muscle cell neoplasms that develop against a background of a combination of genetic, hormonal, and tissue factors. Most myomas harbor somatic mutations in the MED12 gene and rearrangements in the HMGA1 and HMGA2 regions, which affect transcriptional control and proliferation. These molecular features explain the diversity of myoma phenotypes with the same clinical diagnosis. [13]

Myoma growth is supported by estrogens and progesterone through overexpression of the corresponding receptors in the myometrium and stromal component. The hormonal-dependent nature is confirmed by a decrease in the size of the nodes after menopause and during therapy with gonadotropin-releasing hormone analogues. Paracrine interactions between myometrial cells and node stem cells enhance proliferation and accumulation of extracellular matrix. [14]

The local tissue component is also important: regulation of the extracellular matrix, collagen, and proteoglycans alters the mechanical properties of the myometrium, which supports the growth and deformation of the uterine cavity. A low mitotic index is combined with rapid matrix remodeling, which explains the discrepancy between symptoms and classic indicators of cell proliferation. [15]

Hereditary predisposition plays a separate role: in the syndrome of hereditary leiomyomatosis and kidney cancer with mutations of the fumarate hydratase gene, fibroids develop earlier and are more severe, although the proportion of such cases is small compared to sporadic variants. [16]

Risk factors

Risk factors include early menarche, nulliparity, late menopause, excess body weight, a family history of fibroids, and certain dietary factors. These factors are associated with the long-term cumulative effects of endogenous estrogens and progesterone on the myometrium. [17]

Large population-based data indicate a significantly higher risk in women of African descent, an earlier age of onset, and a higher frequency of severe symptoms compared to white women. Increased risk has also been described in some Asian subgroups.[18]

Protective factors include multiple births and later menarche; the use of some hormonal contraceptive methods may reduce the risk, while smoking has been associated with a lower incidence of fibroids in some studies, but is not considered an acceptable "preventive" factor due to health risks. [19]

Certain metabolic and inflammatory conditions, including insulin resistance and hypertension, are associated with greater symptom severity and need for interventions, which are taken into account when planning treatment.[20]

Pathogenesis

The key to nodule growth is hormonal sensitivity and localized molecular transcriptional abnormalities. MED12 mutations disrupt the functioning of the mediator complex, altering the cells' response to steroid hormone signals. Progesterone and estradiol stimulate proliferation and extracellular matrix synthesis and suppress apoptosis. [21]

The phenomenon of mechanotransduction is important: excess collagen and changes in tissue stiffness support proliferative signaling pathways and likely explain the resistance of some nodules to certain types of therapy. This is reflected in imaging, where dense nodules exhibit specific signaling characteristics according to magnetic resonance imaging and ultrasound. [22]

Immune-inflammatory mechanisms are also involved in pathogenesis: local inflammation and cytokine profiles influence angiogenesis and matrix remodeling, which may determine growth rate and symptomatology. These differences partially explain the unequal severity of symptoms in patients with the same nodule size and type. [23]

The interaction of hormonal, genetic, mechanical, and immune factors results in a heterogeneous disease picture—from asymptomatic nodules to severe forms with chronic anemia and infertility. This justifies the need for individualized treatment. [24]

Symptoms

The most common complaints are heavy and prolonged menstrual bleeding, intermenstrual spotting, signs of iron deficiency anemia, pelvic pain, and lower abdominal pressure. Symptoms of urinary and intestinal dysfunction are caused by compression of the bladder and rectum by large subserosal and intramural nodes. [25]

In some patients, myomas manifest as impaired fertility or miscarriage, especially with submucosal and transmural nodes that distort the uterine cavity. However, the association is not absolute and requires careful differential assessment of other causes of infertility. [26]

Pain syndrome may include dysmenorrhea, chronic pelvic pain, and dyspareunia. Severe pain is often associated with degenerative changes within the node, torsion of the subserosal node pedicle, or rapid growth during pregnancy. [27]

Symptoms change over time: nodes can grow, undergo hyaline, cystic or red necrosis, calcify, which changes the clinical picture and approach to treatment. [28]

Forms and stages

The FIGO topographic type of the nodule, which takes into account the nodule's relationship to the endometrium and serosa, is crucial for clinical evaluation and treatment decisions. The types are numbered from 0 to 8, including purely submucosal, intramural, and subserosal variants, as well as transmural nodules of varying depths. This system is accepted worldwide and is used by radiologists, gynecologists, and reproductive specialists. [29]

Type 0 - pedunculated intracavitary node; types 1 and 2 - submucosal with a lesser or greater intramural component; type 3 - completely intramural with contact with the endometrium; type 4 - purely intramural; types 5 and 6 - subserosal with a greater or lesser intramural portion; type 7 - pedunculated subserosal; type 8 - unclassifiable nodes, including cervical. This helps to predict symptoms and choose the approach to treatment. [30]

The size of the nodes is described in centimeters or millimeters, and the volume of the uterus is expressed in milliliters. For multiple nodes, the volume index or the total diameter of the largest nodes is indicated. For dynamic measurements, comparable measurements are used using the same imaging method. [31]

Table 3. FIGO classification of uterine leiomyomas

Type	Brief description
0	Intracavitary on a leg
1	Submucous with intramural portion less than 50 percent
2	Submucous with an intramural portion of 50 percent or more
3	Completely intramural, in contact with the endometrium
4	Completely intramural, without contact with the endometrium
5	Subserous with an intramural portion of 50 percent or more
6	Subserous with intramural portion less than 50 percent
7	Subserous on a stalk
8	Other locations, including the cervix
[32]

Complications and consequences

Chronic iron deficiency anemia is a common consequence of heavy menstrual bleeding, requiring correction of iron deficiency in conjunction with causal treatment of fibroids. Severe anemia may require parenteral iron or blood transfusion. [33]

Large nodes cause compression of adjacent organs, leading to dysuria, nocturia, constipation, pain, and decreased quality of life. In rare cases, acute complications such as torsion of the subserosal node pedicle or node necrosis during pregnancy may occur. [34]

The impact on fertility depends on the location: submucosal and some transmural nodes may reduce the likelihood of implantation and increase the risk of miscarriage; removal of submucosal nodes sometimes improves outcomes. The decision is always individual and requires the exclusion of other causes of infertility. [35]

Long-term risks are low: transformation into sarcoma is extremely rare, and rapid growth alone does not indicate malignancy. However, if the clinical picture and imaging findings are atypical, an MRI evaluation and oncologic alertness are indicated. [36]

Diagnostics

The initial assessment includes a collection of complaints, a menstrual history, an assessment of the impact on quality of life, and a gynecological examination. Laboratory diagnostics are aimed at identifying anemia and iron deficiency, assessing pregnancy if menstruation is delayed, and ruling out coagulopathies if indicated. The decision regarding hormonal testing is made on an individual basis. [37]

The basic imaging method is ultrasound examination of the pelvic organs using transvaginal and, if necessary, transabdominal access. Current reporting protocols recommend describing the number of nodules, maximum dimensions in three projections, distance to the endometrium and serosa, and FIGO type. Saline contrast of the uterine cavity during sonohysterography helps verify submucosal components. [38]

Magnetic resonance imaging is indicated in cases of diagnostic doubt, multiple large nodules, planning myomectomy or embolization, and before focused ultrasound. Magnetic resonance imaging is superior to ultrasound in nodule mapping and assessment of their signal characteristics related to tissue type and treatment response. [39]

Diagnostic hysteroscopy with the option of simultaneous removal of submucosal nodes is indicated in cases of cavity deformation and bleeding symptoms. In most cases, a biopsy is not required if the imaging is typical and there is no suspicion of a malignant process. [40]

Table 4. Instrumental methods for myoma

Method	Strengths	Restrictions	Typical indications
Ultrasound examination	Accessibility, no radiation exposure, primary imaging	Limitations in obesity and multiple nodes	Initial detection, dynamics
Sonohysterography	Excellent visualization of the cavity	Invasiveness, discomfort	Confirmation of submucosal nodes
Magnetic resonance imaging	Precise mapping, tissue characteristics	Cost, availability	Planning of operations and interventions
Hysteroscopy	Direct visualization, removal option	Anesthesia, invasiveness	Diagnosis and treatment of submucosal nodes
[41]

Differential diagnosis

It is important to differentiate myoma from adenomyosis, endometrial polyps, uterine malformations, ovarian tumors, and rare myometrial tumors. A combination of history, clinical examination, and imaging allows for diagnosis in most cases without invasive procedures. [42]

Adenomyosis is often associated with diffuse uterine enlargement, pain, and characteristic magnetic resonance imaging findings. Endometrial polyps appear as focal intracavitary lesions on a thin stalk and are best detected by sonohysterography and hysteroscopy. [43]

Ovarian tumors can mimic subserosal pedunculated nodules; differentiation is aided by visualization of the adnexa and blood flow characteristics. Uterine sarcoma is rare, but atypical growth, necrosis without pregnancy, and atypical signals on magnetic resonance imaging (MRI) indicate oncologic suspicion. [44]

Table 5. Differential diagnosis

State	Distinguishing features	How to confirm
Adenomyosis	Diffuse wall thickening, tenderness, magnetic resonance imaging signs	Magnetic resonance imaging, clinic
Endometrial polyp	Focus in the cavity, thin stalk	Sonohysterography, hysteroscopy
Subserous node on a pedicle against an ovarian tumor	Displacement of appendages, signs of ovarian stroma	Ultrasound examination, magnetic resonance imaging
Sarcoma	Rapid growth, atypical signal, necrosis without pregnancy	Magnetic resonance imaging, histology as indicated
[45]

Treatment

General principles

The choice of strategy depends on the severity of symptoms, fertility plans, the FIGO nodule type, its size, associated pathology, and the patient's preferences. Current guidelines recommend starting with the least invasive methods that provide symptom control and discussing alternatives, including medical therapy, organ-preserving procedures, and hysterectomy when necessary. [46]

Drug therapy

Hormonal contraceptives with a levonorgestrel-containing intrauterine system (IUS), combined hormonal contraceptives, and progestogens reduce blood loss in some patients, especially with small nodes and the absence of significant uterine cavity deformation. Nonsteroidal anti-inflammatory drugs and tranexamic acid are used to control menstrual bleeding. The choice depends on contraindications and preferences. [47]

A key innovation in recent years is oral gonadotropin-releasing hormone antagonists in fixed combinations with low-dose estradiol and norethisterone to prevent hypoestrogenic effects. In the US, combinations of elagolix with estradiol and norethisterone, as well as relugolix with estradiol and norethisterone, have been approved to reduce menstrual bleeding in fibroids. In Europe, linzagolix is indicated for the treatment of moderate to severe fibroid symptoms in women of reproductive age. Duration of treatment is limited due to the risk of decreased bone mineral density. [48]

The drug ulipristal acetate for the treatment of fibroids is no longer available in the European Union: in July 2024, the registration was withdrawn at the request of the authorization holder on commercial grounds, following previous restrictions due to the risk of drug-induced liver injury. This is important to consider when updating treatment regimens. [49]

Table 6. Medication options

Group	Target	Who is it suitable for?	Restrictions
Levonorgestrel-containing system	Reduction of menstrual blood loss	Small nodes without significant deformation	Expulsion is possible in case of severe deformation
Combined hormonal contraceptives and gestagens	Regulation of the cycle and blood loss	Mild to moderate symptoms	Contraindications, individual response
Tranexamic acid and nonsteroidal anti-inflammatory drugs	Control of blood loss and pain	Symptomatic therapy based on the days of menstruation	Does not affect the size of the nodes
Gonadotropin-releasing hormone antagonists with adjunctive therapy	Significant reduction in blood loss	Moderate to severe symptoms	Duration limitation due to bone risks
[50]

Minimally invasive methods

Uterine artery embolization is an effective organ-preserving method for controlling bleeding and pressure symptoms in patients not planning immediate pregnancy. It requires evaluation using magnetic resonance imaging data, a discussion of the risk of post-procedure pain, and the likelihood of repeat interventions in the long term. [51]

Focused ultrasound techniques are used under magnetic resonance imaging (MRI) guidance or with external ultrasound guidance. They do not require incisions and provide reduction in nodule volume and symptomatic improvement in selected patients with suitable nodule characteristics and anatomy. The choice depends on the availability of the technology and compliance with eligibility criteria. [52]

Transcervical radiofrequency ablation with intrauterine ultrasound guidance is an incision-independent method that has demonstrated a sustained reduction in symptom severity and a low rate of re-interventions over several years of follow-up. European guidelines and review publications support its use in selected patients, including those seeking uterine preservation. [53]

Surgical treatment

Hysteroscopic myomectomy is the treatment of choice for submucosal myomectomy types 0-2 with cavity deformation and profuse bleeding. Laparoscopic or open myomectomy is indicated for symptomatic intramural and subserosal myomectomy in patients who wish to preserve fertility. Hysterectomy is considered when organ-preserving approaches are ineffective or reproductive plans are absent, but should not be the first line of treatment solely for bleeding control. [54]

Table 7. Choice of treatment tactics according to clinical situations

Situation	Preferred options
Small nodes, priority is bleeding control	Levonorgestrel-containing system, combined hormonal contraceptives, gonadotropin-releasing hormone antagonists with adjunctive therapy
Deformation of the cavity with bleeding	Hysteroscopic myomectomy
Large intramural nodes, desire for pregnancy	Myomectomy, Discussion of Scar Risks
Symptomatic nodes when surgery is not desired	Uterine artery embolization, focused ultrasound, transcervical radiofrequency ablation
Refractory cases without reproductive plans	Hysterectomy
[55]

Prevention

There is no specific prevention for fibroids, but lifestyle modifications aimed at normalizing body weight and improving metabolic parameters can reduce the severity of symptoms and the need for invasive interventions. Regular monitoring helps to promptly adjust therapy. [56]

Planning a pregnancy with fibroids requires an individual assessment of the location of the nodes and their impact on the uterine cavity. For submucosal nodes, their removal before conception should be considered to improve reproductive outcomes. [57]

Iron deficiency should be identified and treated promptly, especially in cases of heavy menstrual flow. Iron supplementation and correction of vitamin D deficiency, if present, may improve quality of life, although there is no direct proven effect on nodule growth. [58]

Knowledge of modern medications and interventions is important to prevent unnecessary radical surgery. Shared decision-making and discussion of alternatives are part of the prevention of adverse treatment outcomes. [59]

Forecast

In most patients, myomas are benign, with fluctuating size dynamics. After menopause, the nodes typically shrink and symptoms subside. The prognosis for symptom control is favorable with the use of modern medications and minimally invasive techniques. [60]

The risk of reoperation depends on the chosen strategy, age, and reproductive plans. After organ-preserving procedures, growth of remaining nodes is possible; this requires observation and a willingness to take a stepwise approach. [61]

Quality of life indicators are significantly improved after effective control of blood loss and pain. Individualized choice allows for minimization of side effects and preservation of reproductive potential. [62]

FAQ

• Is this a life-threatening disease?

In the vast majority of cases, myomas are benign and not life-threatening. The danger lies not in their transformation, but in complications such as severe anemia or acute pain from torsion of the pedicle. Atypical imaging findings require further investigation. [63]

• Is it possible to cure fibroids without surgery?

Yes, a significant proportion of patients successfully control their symptoms with medication, including modern gonadotropin-releasing hormone antagonists in combination with adjunctive therapy, as well as the levonorgestrel intrauterine system (IUS). The choice depends on the size and location of the nodes and reproductive plans. [64]

• How does fibroid affect pregnancy?

Dependent on the location. Submucosal and some transmural nodes may reduce the likelihood of pregnancy and increase the risk of complications. In some cases, removal of the submucosal node before planned conception improves outcomes. The decision is individual. [65]

• What new minimally invasive techniques are available?

In addition to uterine artery embolization, focused ultrasound and transcervical radiofrequency ablation are used. These techniques allow for reduction of nodule volume and symptom severity without incisions in selected patients. Availability varies by center and equipment. [66]

• Why is ulipristal no longer considered in Europe?

The drug's marketing authorization was revoked in the European Union in 2024 at the request of the authorization holder, following previous restrictions due to the risk of severe drug-induced liver injury. Therefore, current regimens are focusing on other agents. [67]

Additional tables for practice

Table 8. Criteria for choosing a method taking into account childbearing plans

Pregnancy plan	Preferences	The methods under consideration
Pregnancy in the next year	Preservation of the uterus and endometrium	Hysteroscopic myomectomy for submucosal nodes, myomectomy for intramural and subserous nodes; careful assessment of the need for interventions
Delayed pregnancy	Symptom control with options saved	Gonadotropin-releasing hormone antagonists with adjunctive therapy, embolization for strict indications, minimally invasive ablations in selected patients
No plans to have children	Maximum efficiency	Embolization, minimally invasive ablations, hysterectomy for refractory symptoms
[68]

Table 9. Magnetic resonance features influencing the choice of intervention

Sign	Meaning
Low signal on T2-weighted images and homogeneous contrast enhancement	Generally favorable for focused ultrasound
High T2 signal or severe degeneration	May reduce the effectiveness of focused ultrasound and predispose to embolization or myomectomy
Clear mapping of multiple nodes	Helps plan myomectomy and embolization
[69]

Table 10. Assessment of blood loss and anemia

Step	What to do
Clinic	Symptom severity scales, menstrual diary
Laboratory	Complete blood count, ferritin, transferrin saturation
Correction	Oral or parenteral iron preparations as indicated
Etiotropy	Parallel choice of therapy for myoma
[70]

Table 11. Documentation of nodes on ultrasound examination

Parameter	Recommendation
Number and localization	Specify all nodes and their type according to FIGO
Size	Three dimensions of each significant node
Relationship with the endometrium and serosa	Minimum distances
Report	Standardized protocol with total uterine volume
[71]

Table 12. New drug approaches for myoma

Drug and combination	Indication	Restrictions
Elagolix plus estradiol and norethisterone	Heavy bleeding from fibroids in premenopausal women	Duration limitation due to risk of bone loss
Relugolix plus estradiol and norethisterone	Likewise	Duration limit, contraindications
Linzagolix	Moderate and severe symptoms of fibroids in women of reproductive age in Europe	Countrywide availability, bone mass monitoring
[72]