Uterine leiomyoma (Fibroid…)

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][3]

Leiomyomas are classified according to their location within the uterus:

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

References:^[1]

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

1. Abnormal menstruation
   • Hypermenorrhea, menorrhagia, metrorrhagia (possibly associated anemia)
   • Dysmenorrhea
2. 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)
3. Reproductive abnormalities
   • Infertility; (difficulty conceiving and increased risk of miscarriage)
   • Dyspareunia

References:^[1]

• 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][1]

• 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

Differential diagnosis of uterine leiomyoma
Factors	Uterine leiomyoma (fibroids)	Adenomyosis	Endometriosis	Uterine polyps	Uterine leiomyosarcoma [6][7]
Definition	Benign smooth muscle tumors within the uterine wall (submucous, subserous, or in myometrium)	Benign endometrial tissue within the uterine wall	Benign endometrial tissue outside the uterus	Overgrowth of localized endometrial tissue attached to the inner wall of the uterus, usually benign [8]	Rare malignant tumor arising from the smooth muscle cells of the myometrium
Risk factors	Early menarche Nulliparity	Early menarche Increased parity Previous uterine surgery	Retrograde menstruation	Menopause Obesity Hypertension Tamoxifen therapy Lynch syndrome	Menopause
Clinical features	Dysmenorrhea Abnormal bleeding Infertility (difficulty conceiving and increased risk of miscarriage)	Dysmenorrhea Abnormal bleeding Menorrhagia Chronic pelvic pain	Dysmenorrhea Pelvic pain Abnormal bleeding Dyspareunia Dyschezia Infertility	Abnormal bleeding Menorrhagia Postmenopausal bleeding Infertility/difficulty conceiving	Symptoms similar to uterine fibroids Menstrual irregularities Postmenopausal bleeding Pelvic pain
Uterine findings	Irregularly enlarged, firm	Uniformly enlarged	Typically not enlarged	Typically not enlarged	Rapidly enlarging
Pathology	Smooth muscle tissue in a whorled pattern with well-demarcated borders	Irregular distribution of smooth cells and endometrial glandular tissue in the myometrium [9]	Gunshot lesions: black or yellow-brown nodules Chocolate cysts	Pedunculated or sessile Single or multiple Length varies (up to many centimeters in size)	Single lesions with necrosis

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) are necessary to monitor any potential growth.

Symptomatic fibroids

Medical therapy

Preoperative medical therapy may help reduce tumor size and decrease tumor vascularization.

• Hormone therapy
  • Gonadotropin-releasing hormone (GnRH) agonists: e.g., leuprolide, goserelin, nafarelin
    • Optimal treatment prior to surgery; but not suited for long-term monotherapy (> 6 months) because they cause osteoporosis, hot flushes, depression
    • Decrease size of leiomyomas
    • Suppress growth of new leiomyomas
    • Decrease tumor vascularization
    • Induce amenorrhea and thereby improve anemia
    • Leiomyomas grow back once therapy is discontinued (rebound growth)
  • Combined oral contraceptive pill and progestin-only contraceptive pill
    • Usually used as add-ons to GnRH agonist therapy
    • Control bleeding and pain but may promote growth of leiomyomas
  • 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
• Androgenic agonists (e.g., : danazol): suppress growth of fibroids but have many side effects (e.g., acne, edema, hair loss, etc.)
• NSAIDs: : for dysmenorrhea

Interventional therapy

• Uterine fibroid embolization: uterine artery embolization
  • Procedure: injection of polyvinyl alcohol (PVA) into the arteries that supply blood to the fibroid, causing it to shrink; ¼ of patients may require further invasive treatment
  • Indications:
    • Continued heavy bleeding and/or severe pain with insufficient response to medical treatment
    • Contraindications to surgery or personal preference to avoid surgery
    • No wish to conceive in the future

Surgical therapy

• Indications: rapidly growing fibroid, recurrent refractory bleeding: secondary to medical therapy, severe symptoms
• Procedures
  • Myomectomy: excision of subserosal or intramural fibroids (preferred for women planning future pregnancies)
  • Hysterectomy: definitive treatment

References:^[10]

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

References:^[1]

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