Uterine Fibroids (Leiomyomas)

Definition and Overview

Incidence and Epidemiology

• African American women: ~60% incidence by age 35, >80% by age 50
• White women: ~40% by age 35, ~70% by age 50
• Incidence rises sharply with age: 4.3 per 1,000 woman-years at ages 25-29, rising to 22.5 per 1,000 at ages 40-44

Pathophysiology

Hormonal Influence

• Fibroids are rare before puberty, peak during reproductive years, and regress after menopause
• Increased aromatase activity within fibroids drives de novo estradiol production higher than in normal myometrium
• Fibroids have increased concentrations of progesterone receptors A and B vs. normal myometrium
• Highest mitotic counts occur at the peak of progesterone production
• GnRH agonists shrink fibroids, but concurrent progestin prevents size reduction
• RU486 (antiprogestin) blocks estradiol + progesterone-driven fibroid growth in animal models

Factors that increase risk (higher estrogen exposure):

• Obesity, early menarche (<10 years), African American ethnicity, nulliparity

Protective factors (decreased estrogen exposure):

• Smoking, regular exercise, increased parity

Growth Factors

• TGF-β, bFGF - increase smooth muscle proliferation
• EGF, PDGF - increase DNA synthesis
• TGF-β - stimulates extracellular matrix synthesis
• TGF-β, EGF, IGF, prolactin - promote mitogenesis
• bFGF, VEGF - promote angiogenesis

Classification (FIGO System)

Clinical Features and Symptoms

Heavy Menstrual Bleeding (Most Common)

• Submucosal fibroids are most closely associated with menorrhagia
• Enlargement of the uterine cavity and increased endometrial surface area contribute
• Anemia can result from chronic blood loss

Bulk/Pressure Symptoms

• Pelvic pressure, abdominal distension
• Urinary frequency and urgency (improved ~68% after UAE with 35% volume reduction)
• Constipation, hydronephrosis (rare, from ureteric compression)

Pelvic Pain

• Women with fibroids are only slightly more likely to experience pelvic pain than women without
• Fibroid degeneration (hyaline, cystic, calcific, hemorrhagic) can cause acute or subacute pain
• Torsion of a pedunculated subserosal fibroid causes acute pain requiring surgery

Rapid Growth

• In premenopausal women, "rapid uterine growth" almost never indicates sarcoma - only 1 sarcoma found in 371 women (0.26%) operated on for rapid growth

Natural History

• Most fibroids grow slowly: median growth rate ~9% over 12 months (by MRI)
• Multiple fibroids in the same patient can have highly variable growth rates
• After age 35, growth rates decline with age in White women but not in African American women
• ~7% of fibroids regress spontaneously

Investigations

Ultrasound (First-line)

• Most readily available and least costly
• Reliable for uterine volume <375 cc with ≤4 fibroids
• Appearance: symmetrical, well-defined, hypoechoic, heterogeneous masses
• Calcification/hemorrhage → hyperechoic; cystic degeneration → anechoic
• Saline infusion sonography (SIS) better delineates submucosal fibroids

MRI (Gold Standard for Mapping)

• Best for defining number, size, and precise location relative to endometrium and serosa
• Helps plan surgical approach (hysteroscopic vs. laparoscopic vs. open)
• Distinguishing sarcoma: LMSs show increased gadolinium enhancement (increased vascularity); degenerating fibroids show decreased enhancement
• LDH + LDH isoenzyme 3 + Gd-DTPA MRI: reported 100% specificity and diagnostic accuracy for LMS in one study
• Diffusion-weighted imaging (DWI): lower ADC in LMSs vs. degenerating fibroids (sensitivity 100%, specificity 90% in one study - needs further validation)

Fertility

• Submucosal fibroids decrease fertility; removal increases fertility (ongoing pregnancy/live birth rates reduced ~70% by submucosal fibroids distorting the cavity)
• Subserosal fibroids do not affect fertility; removal does not improve it
• Intramural fibroids may slightly decrease fertility; removal does not clearly improve it

Treatment

1. Watchful Waiting

• Appropriate for asymptomatic or mildly symptomatic women
• Average fibroid volume increases ~9%/year (range: -25% to +138%)
• 77% of women in one study had no significant change in symptoms at 1 year
• Particularly appropriate as women approach menopause (limited time for new symptoms; fibroids shrink post-menopause)

2. Medical Therapy

3. Surgical Options

• Indicated for women wishing to preserve fertility or retain uterus
• Safe alternative to hysterectomy even for large fibroids
• Approaches: hysteroscopic (Type 0-2), laparoscopic, robotic, abdominal (open)
• Submucosal fibroids are often removed hysteroscopically
• Uterine rupture risk after myomectomy: ~0.47% (similar to trial of labor after C-section)
• Laparoscopic myomectomy requires meticulous multilayered closure to reduce rupture risk

• Definitive cure; no risk of recurrence
• ~240,000/year in the US for fibroids
• Appropriate when fertility preservation is not desired and symptoms are severe

4. Uterine Artery Embolization (UAE)

• Effective for selected women; occludes arterial supply to fibroids causing ischemic necrosis
• Reduces uterine volume ~35%, significantly improves bleeding and urinary symptoms
• Effects on fertility and early ovarian failure remain unclear - caution in women desiring pregnancy

5. Focused Ultrasound (MRgFUS)

• Non-invasive thermal ablation guided by MRI
• Emerging option for selected symptomatic fibroids

Key Points Summary

1. Fibroids are the most common benign pelvic tumor in women of reproductive age
2. Both estrogen and progesterone drive growth - hence regression after menopause
3. The FIGO 0-8 classification guides treatment decisions
4. Heavy menstrual bleeding + submucosal location = strongest treatment indication
5. Rapid growth does not indicate sarcoma in premenopausal women
6. MRI + LDH isoenzyme 3 can distinguish sarcoma from degenerating fibroid pre-operatively
7. Submucosal fibroids impair fertility; their removal improves outcomes
8. Treatment must be individualized: fertility wishes, symptom severity, fibroid location/size, proximity to menopause