Uterine leiomyoma

Uterine leiomyomas (fibroids) are benign, hormone-sensitive uterine neoplasms. These tumors are classified as either submucosal (beneath the endometrium), intramural (within the muscular uterine wall of the uterus), or subserosal (beneath the peritoneum). Symptoms depend on the location, size, and number of myomas, and include menstrual abnormalities (menorrhagia), features of mass effects (e.g., back/abdominal/pelvic pain or bladder and bowel dysfunction), and infertility. Physical examination and sonohysterography are used to establish the diagnosis. Treatment for symptomatic patients includes surgery (myomectomy or hysterectomy) as well as interventional (uterine artery embolization) and/or medical therapy (GnRH agonists).

• A benign, hormone-sensitive smooth muscle tumor of the uterus
• Can be submucosal, intramural, or subserosal
• Arises from a single myometrial cell (monoclonal growth) and causes:
  • Upregulation of hormone receptors, particularly estrogen and progesterone
  • Excessive production of extracellular matrix (hence "fibroids")
• Results in an overgrowth of smooth muscle cells and connective tissue (often multiple tumors)
• The myometrium also develops vascular changes (e.g., increased arterioles and venules, dilated veins).
• The most common tumor of the female genital tract.

Predisposing factors

• Nulliparity
• Early menarche (< 10 years old)
• Age: 25–45 years
  • Fibroids are largely found in women of reproductive age
  • Influenced by hormones (i.e., estrogen, growth hormone, and progesterone)
  • During menopause, hormone levels begin to decrease and leiomyomas begin to shrink
• Increased incidence in African American individuals
• Obesity
• Family history

References:^[1][2]

Leiomyomas are classified according to their location. ^[3]

• Subserosal leiomyoma: located in the outer uterine wall beneath the peritoneal surface
• Intramural leiomyoma (most common): growing from within the myometrium wall
• Submucosal leiomyoma: located directly below the endometrial layer (uterine mucosa)
• Cervical leiomyoma: located in the cervix
• Diffuse uterine leiomyomatosis: The uterus is grossly enlarged due to the presence of numerous fibroids.

Most women have small, asymptomatic fibroids. Symptoms depend on the number, size, and location of leiomyomas.

• Abnormal menstruation: : hypermenorrhea, heavy menstrual bleeding; , metrorrhagia (possibly associated anemia), dysmenorrhea
• Features of mass effect
  • Enlarged, firm and irregular uterus during bimanual pelvic examination
  • Back or pelvic pain/discomfort
  • Urinary tract or bowel symptoms (e.g., urinary frequency/retention, constipation, features of hydronephrosis)
• Reproductive abnormalities
  • Infertility; (difficulty conceiving and increased risk of miscarriage)
  • Dyspareunia

• Ultrasound (best initial test)
  • Concentric, hypoechoic, heterogeneous tumors
  • Calcifications or cystic areas suggest necrosis
  • Saline-infused sonography: can be used to better visualize submucosal and intramural fibroids
• Hysteroscopy: to assess submucosal fibroids
• MRI: to evaluate the uterus and ovaries for potentially complicated surgical cases and visually differentiate between leiomyomas, adenomyomas, and adenomyosis

References:^[4]

• Macroscopic
  • Grayish-white surface
  • Homogeneous; tissue bundles on cross-section partly in a whorled pattern
  • Some leiomyomas may involve regressive changes: scar formation, calcification, and cysts
• Microscopic: Smooth muscle tissue in a whorled pattern with well-demarcated borders, consisting of monoclonal cells interspersed with connective tissue

References:^[5]

• Uterine fibroids, adenomyosis, and endometriosis may be present simultaneously in the same patient.
• See also endometrial cancer, benign tumors of the endometrium, and differential diagnosis of dysmenorrhea and menorrhagia

The differential diagnoses listed here are not exhaustive.

Treatment should only be considered in symptomatic patients because of the side effects of medical therapy and surgery. The goal is to relieve symptoms. Perimenopausal women warrant expectant management in most cases.

Asymptomatic fibroids

• Do not require treatment
• Frequent follow-ups (approx. every 6–12 months) with pelvic ultrasonography and symptom monitoring
• Patients should be counseled to contact their physician if new symptoms develop.

Symptomatic fibroids

The choice of treatment modality depends on the patient's desire to preserve fertility, other personal preference, comorbidities (e.g., contraindications to surgery), and severity of symptoms.

Postmenopausal patients and those who do not wish to conceive in the future are eligible for all forms of treatment, i.e., medical therapy, interventional therapy, and surgery. The options available to patients who wish to conceive in the future are medical therapy and myomectomy.

Treatment options that preserve fertility

• Medical therapy
  • First-line: drugs to reduce heavy bleeding and manage symptoms
    • Combined oral contraceptive pill and progestin-only contraceptive pill
      • Control bleeding and pain but may promote the growth of leiomyomas
      • Also used as adjuvants to GnRH agonist therapy
    • Progestin-releasing intrauterine device (IUD): controls heavy and painful bleeding but does not treat fibroids themselves (only for fibroids that do not distort the inside of the uterus)
    • Antifibrinolytics (e.g., tranexamic acid)
      • Reduce heavy bleeding
      • Used in patients who do not wish to use hormonal contraceptives
    • NSAIDs: for dysmenorrhea
  • Second-line: drugs that may help reduce tumor size and decrease tumor vascularization
    • Gonadotropin-releasing hormone (GnRH) agonists: e.g., leuprolide, goserelin, nafarelin
      • Optimal treatment prior to surgery; but not suited for long-term monotherapy (> 6 months); due to risk of osteoporosis, hot flushes, depression
      • Decrease size of leiomyomas
      • Suppress growth of new leiomyomas
      • Decrease tumor vascularization
      • Induce amenorrhea and, thereby, improve anemia
      • Leiomyomas recur once therapy is discontinued (rebound growth).
    • GnRH antagonists e.g., oral elagolix, relugolix
    • Androgenic agonists (e.g., danazol): suppress growth of fibroids but have many potential side effects (e.g., acne, edema, hair loss, etc.)
    • Selective progesterone receptor modulators (SPRMs): e.g., ulipristal acetate, mifepristone (currently only approved in Canada and Europe)
• Myomectomy: surgical removal of fibroids
  • Surgery is often preferred in rapidly growing fibroids, recurrent refractory bleeding secondary to medical therapy, and in severe symptoms.
  • Approach
    • Hysteroscopic myomectomy: submucosal fibroids and some intramural fibroids that are primarily intracavitary
    • Abdominal myomectomy (laparoscopic or open incision): subserosal and intramural fibroids

Treatment options that will affect fertility

• Interventional therapy
  • Uterine artery embolization: a percutaneous, radiologic procedure in which an embolic agent is injected into the uterine artery in order to block the blood supply to the fibroid(s)
    • Procedure
      • Injection of polyvinyl alcohol (PVA) into the arteries that supply the fibroid, causing it to shrink
      • 25% of patients require further invasive treatment (e.g., hysterectomy) due to failed embolization or recurrent symptoms
    • Indications
      • Recurrent refractory heavy bleeding and/or severe pain unresponsive to medical treatment
      • Contraindications to surgery or personal preference to avoid surgery
      • No desire to preserve fertility, but wish to preserve the uterus
  • Magnetic resonance-guided focused ultrasound surgery (MRgFUS): a procedure that utilizes MRI and ultrasound waves to destroy fibroids
• Surgery: hysterectomy with/without bilateral salpingo-oophorectomy (definitive treatment) )

• Infertility
• Iron deficiency anemia (due to heavy menstrual bleeding)
• Fibroid torsion
• Thromboembolism
• Very rare: malignant transformation to uterine leiomyosarcoma

We list the most important complications. The selection is not exhaustive.

Uterine leiomyomas during pregnancy

• Elevated concentrations of progestin and estrogen foster the growth of leiomyomas.
• Pain may be caused by:
  • Mass effect
  • Necrosis
  • Peritoneal irritation
• Premature contractions
• Depending on location and size:
  • Fetal malpresentation
  • Fetal growth retardation
  • Prematurity and miscarriages
  • Extrauterine pregnancy
  • Placental abruption
• Cervical leiomyoma: obstruction of the birth canal is an indication for cesarean delivery
• Postpartum: atonic hemorrhages
• Puerperium: fibroid regression accompanied by calcification

References:^[11]