Leiomyoma (Myoma) of the Uterus: Etiology, Classification, Diagnosis, and Treatment

Uterine myoma (or leiomyoma) is a benign hyperplastic lesion of the smooth muscle cells of the uterus or cervix.

Etiology of uterine myoma

The exact pathophysiology of uterine myoma development remains unclear. Studies show that the first myoma cell develops from a single uterine smooth muscle cell (myometrium) that is characterized by deviation from normal cell division signaling pathways.

Myoma is an estrogen-dependent tumor, with the potential to alter estrogen and progesterone receptors compared to the normal surrounding myometrium.

A genetic pathology associated with a mutation in genes regulating smooth muscle cell growth (MED12, HMGA2) has also been identified.

During its growth, myoma squeezes the surrounding structures (myometrium and connective tissue), causing progressive formation of a pseudocapsule rich in collagen fibers, neurofibers, and blood vessels.

Epidemiology

No cases of uterine myoma have been described in pre-pubertal girls. The probability of the disease increases with age and may reach 80% during the reproductive years, with a decreasing incidence at menopause.

Risk factors for developing myoma include:

• Early menarche;
• Obesity;
• Late onset of menopause;
• Family history of uterine myoma;
• Alcohol use.

The risk of developing uterine myoma is reduced in women with:

• Late menarche;
• Regular physical activity;
• who have given birth more than twice.

The effect of smoking on myoma development remains unclear, and more research is needed.

Classification of uterine myoma

3D models of uterine myoma types according to the FIGO classification:

Type 0 – the pedicle node is located in the uterine cavity

Type 1 – less than 50% of the node is located intramurally

Type 2 – more than 50% of the node is located in the muscle layer

Type 3 – nodule located in the myometrium, the edge is adjacent to the endometrium, but does not extend into the uterine cavity

Type 4 – myoma located entirely in the myometrial thickness

Type 5 – less than 50% of the node protrudes into the pelvic cavity

Type 6 – more than 50% of the node is located above the serous layer of the uterus

Type 7 – subserosal nodule on a pedicle, completely located in the pelvic cavity

• Type 8 – other types of myoma (e.g., cervical myoma, broad ligament myoma, and parasitic myoma).

Type 2-5 is a hybrid classification used when the myoma extends from the endometrial cavity to the serosa. It consists of two numbers separated by a hyphen, the first characterizing the relationship between the myoma and the endometrium and the second its relationship with the serous layer.

Anatomy of a uterine myoma

The localization of myoma affects not only the presence of symptoms, but also the tactics of treatment. For this purpose, myomatous nodes are divided into:

• FIGO 0-2 submucosal (submucosal);
• FIGO 3-4 intramural (interstitial);
• FIGO 5-7 subserosal;
• Intraligamentary (interligamentous);
• Also located in the isthmus-neck zone according to FIGO 8.

Clinical picture

Uterine myoma can exist completely asymptomatic and be an incidental finding with any imaging modality.

Common symptoms of uterine leiomyoma include:

• Metrorrhagia;
• Menorrhagia or a combination of the two;
• Abnormal uterine bleeding.

These symptoms are characteristic of myomas with a submucosal component.

Less common symptoms include:

• Dysmenorrhea;
• Dyspareunia;
• Pain in the pelvic region, including the sacrum;
• Pathology of the small and large intestine;
• Symptoms of urinary dysfunction;
• Signs and symptoms associated with anemia.

Myomatous nodes can be a cause of infertility, especially those that deform the uterine cavity or are located on a pedicle in the cavity.Such myomas are to be treated surgically regardless of size and the presence of other symptoms.

Complications of uterine myoma

In addition to anemia and infertility, myomatous nodes can be complicated by degenerative processes and torsion of the stem of the subserosal node with the development of a clinical picture of acute abdomen.

Diagnosis of uterine myoma

1. Collection of obstetric and gynecologic history is necessary to establish menstrual cycle changes, as well as to clarify the history of infertility and/or reproductive losses.
2. Mirror examination with bimanual examination should be performed to exclude vaginal or cervical pathology and to assess the size and shape of the female reproductive organs. When examining in mirrors, it is possible to diagnose the neck-neck localization of myomatous node. In bimanual examination, an asymmetric uterus can indicate myoma and is a reason for the appointment of clarifying studies. Pale skin and conjunctival color should also be evaluated to identify potential secondary symptoms of abnormal uterine bleeding.
3. Radiologic studies:

• Transvaginal ultrasound is the gold standard for diagnosing uterine myoma. A fibroid appears as a dense, well circumscribed, hypoechogenic mass. There is usually varying degrees of shadowing on ultrasound, and calcinates or necrosis may distort echogenicity.
• Hysteroscopy – this method allows better visualization of the nodule in the uterine cavity. The advantage of this method is that it is possible to remove intrauterine neoplasms during the procedure.
• Magnetic resonance imaging (MRI) gives a better idea of the number, size, blood supply and boundaries of the myoma in relation to the pelvis. However, this method should not be favored in routine diagnosis when myoma is suspected. MRI has not been found to differentiate leiomyosarcoma from leiomyoma.

Treatment of uterine myoma (leiomyoma)

When choosing uterine myoma treatment options, it is important to consider the patient’s age, present symptoms, desire to preserve fertility, and the experience of the physician. The location and size of the myoma will determine the treatment options available.

Surveillance: this is the preferred method for women with asymptomatic myomas. Current recommendations do not require periodic surveillance using imaging techniques for female patients.

1. Medication treatment

Drug treatment is primarily aimed at reducing the severity of bleeding and pain symptoms.

• Hormonal contraceptives. This treatment group includes combined oral contraceptives and the intrauterine device (IUD) with levonorgestrel. The levonorgestrel IUD is currently the recommended therapy for symptomatic myoma. It has the advantage of no systemic effects and a low side effect profile. Caution should be exercised when treating myomas that deform the uterine cavity, as the risk of spiral expulsion is increased.
• GnRH agonist: this method, acting on the pituitary gland, reduces the production of sex hormones, thereby reducing hormone-stimulated myoma growth. It has been shown that long-term therapy with GnRH agonists leads to a statistically significant loss of bone mass. Because of this, the use of drugs of this group should be limited to 6 months or less; in case of prolonged treatment, add-back therapy (addition of estrogen/gestagen drugs in cyclic mode or in isolation) should be used.
• Non-steroidal anti-inflammatory drugs (NSAIDs). Anti-inflammatory drugs reduce levels of prostaglandins, which are elevated in women with heavy menstrual bleeding and are responsible for painful cramps during menstruation. However, NSAIDs have not been found to reduce myoma size.
• Tranexamic acid has been approved for the treatment of abnormal uterine bleeding but has not been approved for inhibiting uterine myoma growth.
• Selective progesterone receptor modulators. Short-term use of these drugs resulted in improved quality of life, decreased menstrual bleeding and amenorrhea. Endometrial changes that are benign and not associated with precancerous processes or cancer have been described with drugs in this group.
• Other potential medical treatments include aromatase inhibitors and selective estrogen receptor modulators (SERMs). There is little evidence to support the use of these drugs for the treatment of symptomatic uterine myoma.

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2. Surgical treatment

• Endometrial ablation. It is an alternative to surgery in women whose main complaint is abnormal uterine bleeding. There is a greater risk of procedure failure in the presence of submucosal myoma because it deforms the uterine cavity.
• Uterine artery embolization. A minimally invasive approach for those patients who need to preserve fertility. Reducing the overall blood supply to the uterus reduces local blood flow to the myoma and causes a reduction in bleeding symptoms. The procedure has been shown to be effective for patients with menorrhagia. However, there are limited studies that show the effectiveness of this technique for fertility preservation.
• Myomectomy. An invasive surgical option for those who wish to preserve fertility. This surgery can be performed by laparotomy, laparoscopic or hysteroscopic access. The outcome of the surgery depends largely on the location and size of the myoma. Nevertheless, it can be an effective treatment option for those who want to avoid hysterectomy.
• Myolysis is a minimally invasive procedure aimed at destroying myomas using focused energy delivery such as heat, laser and more recently focused ultrasound surgery with magnetic resonance. Because this method is relatively new, there is currently insufficient clinical evidence to support its long-term efficacy.
• Hysterectomy. If other treatments are ineffective, hysterectomy remains the definitive treatment.