Pathogenesis

● Benign smooth muscle neoplasms originating from myometrium.

● Gross appearance: off-white, whorled; surrounded by thin connective tissue layer →
allows easy surgical removal ("shelling").

● Poor blood supply → frequent ischemia and necrosis → replaced by degenerative

changes (hyaline, calcific, cystic, myxoid, red, fatty).
● Each leiomyoma arises from a single progenitor myocyte.
● Hormone sensitive:
○ High density of estrogen & progesterone receptors.
○ Progesterone = key mitogen; estrogen maintains progesterone receptors.

● Tumors create local hyperestrogenic environment.

● Risk factors: early menarche, obesity, PCOS (sustained estrogen exposure).
● Not induced by combined OCPs or DMPA use.
● Rare sites: cervix, broad ligament, ovary, fallopian tube, vagina, vulva.

Leiomyoma (Fibroid) Classification – FIGO System

Fibroids are categorized numerically based on location relative to the uterine wall.

1. Submucosal Myomas (0–3)

● Originate near the endometrium, grow inward into the uterine cavity.

● Types:

○ Type 0: Pedunculated intracavitary, entirely in cavity.

○ Type 1: <50% intramural extension.

○ Type 2: ≥50% intramural extension.

○ Type 3: 100% intramural but in contact with endometrium (so included in

submucosal group).

2. Intramural Myomas (4)

● Growth centered within the myometrium.
● Type 4: Completely intramural, no contact with endometrium or serosa.

3. Subserosal Myomas (5–7)

● Originate from outer myometrium, grow outward toward serosa.
● Types:

○ Type 5: Subserosal, ≥50% intramural.

○ Type 6: Subserosal, <50% intramural.
 ○ Type 7: Pedunculated subserosal, attached by stalk.

4. Other (8)
● Do not relate to myometrium directly.
● Examples: cervical, broad ligament, parasitic myomas.
● Parasitic fibroids: detach from uterus, reattach to nearby pelvic structures for
vascular supply.
● Transmural fibroids: involve both endometrial & serosal surfaces.
● Rare locations: cervix, broad ligament, ovary, fallopian tube, vagina, vulva.

Symptoms
● Most are asymptomatic; symptoms depend on size & number.
● Bleeding:
○ Heavy menstrual bleeding (HMB) most common.
○ Mechanisms: endometrial vessel vasodilation, altered hemostasis.

● Pressure & pain:

○ Large uterus → urinary frequency, incontinence, constipation.
○ Dysmenorrhea, dyspareunia, chronic pelvic pain.
○ Acute pain → due to degeneration, torsion of pedunculated myoma, or
prolapse.
■ Degeneration: necrosis → acute pain + fever + leukocytosis (mimics
other pelvic pain).
■ Treatment: NSAIDs, analgesics, antipyretics; antibiotics if
differentiation from infection unclear.
■ Pedunculated torsion → surgical excision curative.
 ■ Prolapse → severe cramping, bleeding/discharge; surgical removal
required.

● Fertility:

○ Only 1–3% infertility cases solely due to leiomyomas.

○ Submucous myomas strongly linked to infertility (pregnancy rates improve
after resection).
○ Subserosal tumors not linked; intramural controversial.
○ Risks of myomectomy: adhesions, myometrial defects → uterine rupture risk.
○ No proven reduction in miscarriage risk with surgery.

Diagnosis
● Pelvic exam: uterine enlargement, irregular contour.

● Rule out pregnancy (urine/serum hCG).

● Sonography:
○ TVS = best resolution; TAUS needed for very large uterus.
○ Appearance varies: heterogeneous mass, calcifications (bright), cystic/myxoid
areas (hypoechoic).

● Evaluate cavity for submucous fibroids, polyps, synechiae → SIS, hysteroscopy, or

3D imaging helpful.
● Doppler: leiomyomas = peripheral circumferential vascularity.
○ Differentiates from adenomyosis (central vascularity) and polyps (single
feeder vessel).

● Infertility evaluation: HSG, HyCoSy, hysteroscopy (assess cavity & tubal patency).
● MRI: useful for size, number, location; differentiates fibroids from adenomyosis or
leiomyosarcoma.
● CT: rarely used, except in acute pelvic pain.

Nonsurgical Management
● Observation:
○ Most leiomyomas are slow-growing.
○ Asymptomatic → annual pelvic exam (± sonography).

● Medical therapy:

○ Used for symptom relief (long-term or pre-operative).

○ Often as a bridge to menopause (since fibroids regress postmenopausally).

● Sex steroid hormones:

○ COCs, continuous progestins, DMPA → induce endometrial atrophy,

reduce prostaglandins.
○ LNG-IUS: improves bleeding but higher expulsion rates (10–15%); not for
distorted cavities or very large uteri (>12-week size).
○ Androgens (danazol, gestrinone): shrink fibroids & reduce bleeding but
cause acne, hirsutism → not first-line.
GnRH Receptor Agents
● Types: Agonists (leuprolide, goserelin, triptorelin, nafarelin) and antagonists
(elagolix, relugolix).
● Mechanism: ↓ Estrogen & progesterone → shrink leiomyomas.
○ Agonists: initial flare (↑ LH/FSH for 1 week) → receptor downregulation → ↓
gonadotropins → ↓ estrogen/progesterone.
○ Antagonists: immediate suppression, no flare.

● Effects:

○ ↓ Uterine/leiomyoma volume (35–50%).

○ Amenorrhea in 90–97% by 3 months.
○ Improves anemia when combined with iron.

● Limitations:

○ Regrowth after discontinuation (uterus returns to pretreatment size in 3–6

months).
○ Menopause-like side effects (hot flushes, bone loss up to 6% in 6 months).

● Add-back therapy:

○ Low-dose estrogen + progestin (or SERMs) prevents bone loss & vasomotor
symptoms without negating shrinkage.
○ Typically started 1–3 months after initiation.

● Duration: Not recommended >6 months without add-back.

Selective Progesterone-Receptor Modulators (SPRMs)

● Examples: Ulipristal acetate (UPA).
● Mechanism: Antiprogestin effect in myomas → shrinkage & bleeding control.
● Efficacy: Comparable to leuprolide, but avoids hypoestrogenic side effects & flare.
● Unique effects: PAECs (Progesterone-receptor modulator-associated endometrial
changes) – reversible, not precancerous.

● Limitations:
○ Treatment limited to 12 weeks/course.
○ Liver injury risk → contraindicated in liver disease; requires liver function
monitoring.
○ EMA allows use only preoperatively or if surgery contraindicated.

Nonhormonal Options
● Tranexamic acid (TXA): Reduces HMB (not leiomyoma-specific).
● NSAIDs: May help dysmenorrhea but limited effect on leiomyoma bleeding.
● Aromatase inhibitors (AIs): (letrozole, anastrozole, exemestane) → ↓ estrogen in
myomas, 50% volume reduction in small studies.
○ Side effects: hot flashes, musculoskeletal pain, ovarian stimulation (FSH ↑),
bone/cardiovascular risks uncertain.
 ○ Not FDA-approved; need more evidence.

Uterine Artery Embolization (UAE)

● Procedure: Catheter via femoral artery → embolic particles occlude uterine arteries
→ ischemia & necrosis of fibroids.
● Indications: Alternative to hysterectomy/myomectomy in women not seeking future
fertility.
● Efficacy:

○ High satisfaction, significant symptom relief by 6 months.

○ Faster recovery vs surgery.
○ 28–35% require reintervention (often hysterectomy).

● Complications:

○ Post-embolization syndrome (10–25%): pelvic pain, fever, leukocytosis.

○ Passage of necrotic fibroid tissue (~4%).
○ Groin hematoma, discharge, transient amenorrhea; occasional permanent
amenorrhea (esp. older women).
○ Pregnancy after UAE → ↑ miscarriage, postpartum hemorrhage, cesarean
rates.

MR-Guided Focused Ultrasound (MRgFUS / MR-HIFU)

● Procedure: MR-guided ultrasound beams → heat & necrosis of fibroid tissue.
● Advantages: Non-invasive, outpatient, fertility-sparing, rapid recovery.
● Limitations:
○ Contraindications: pregnancy, malignancy, menopause, calcified myomas,
size >10 cm, uterine >24 weeks, >12 cm depth.
○ Less effective with >4 myomas, adenomyosis, pedunculated fibroids.

● Efficacy:
○ Improves quality of life; 30–70% symptom improvement.
○ Reintervention needed in 13–30% within 1–3 years (higher than UAE).

● Complications: vaginal discharge, fever, hematuria, burns, retained necrotic tissue.

● Pregnancy outcomes: Mostly term births; some placenta previa/retention but no
reported rupture or accreta.

Surgical Management of Leiomyomas

Hysterectomy
● Definitive & most common treatment for women with persistent symptoms.
● Routes: vaginal, abdominal, laparoscopic (depends on patient/uterine factors).
● Best for: symptomatic cervical or broad ligament leiomyomas.
● Outcomes: high satisfaction; superior symptom relief vs conservative options.
● Limitation: risks of major surgery, no fertility preservation.
Myomectomy (uterus-preserving)
● Indications: fertility preservation, refusal of hysterectomy.
● Contraindications: infection, pregnancy, suspected malignancy.
● Pros: uterus preserved, lower risk of injury to adjacent organs.
● Cons: higher recurrence, incomplete symptom relief.
● Techniques:

○ Hysteroscopic: for intracavitary (type 0, 1, ≤3 cm). Quick recovery, less

morbidity.
■ STEP-W criteria guide selection.
■ Risks: incomplete resection (esp. type 2, larger size), perforation, fluid
overload.
■ Reintervention: 15–20%.

○ Laparoscopic/Laparotomy: for subserosal & intramural.

■ Improves pain & HMB in 70–80%.

■ Reintervention: 10–15%.
■ Laparoscopy: less pain, blood loss, adhesions, faster recovery, but
rare uterine rupture in future pregnancy.
■ Limits: size >6–10 cm, >3 tumors, complex locations → need higher
skill.
■ Minilaparotomy: faster but more pain & blood loss vs laparoscopy.
■ Robot-assisted: similar outcomes, but longer, costly, higher recurrence
due to missed tumors.
● Summary: hysteroscopic preferred when possible; MIS favored over laparotomy
when feasible.

Endometrial Ablation
● Used for AUB (including myoma-related).
● Limitations: cavity distortion, length.
● May be effective for submucous myomas ≤3 cm.
● Sometimes used after hysteroscopic resection for HMB control.
● Higher failure rates in myoma patients.

Myolysis & Other Approaches

● Myolysis: direct destruction (RFA, laser, cryotherapy).
○ RFA (Acessa system):
■ Best for myomas <7 cm, uterus <16 weeks.
■ Not for very large (>10 cm), type 0/1, pregnancy, malignancy,
infection, adenomyosis.
■ Outcomes: ~50% symptom improvement; reintervention 11% (3 yrs),
29% (5 yrs).
■ Less blood loss & faster recovery vs myomectomy.
■ Fertility data limited but encouraging.

● Laparoscopic uterine artery occlusion (LUAO): occludes uterine & ovarian

arteries.
 ○ Reintervention: 15% (16 mo), 28% (4 yrs) → similar to UAE.
○ Limited by advanced skills & scarce long-term data.

Rare Manifestations of Leiomyomas

● Vascular/hematologic:
○ DVT risk with very large fibroids (>1000 g).
○ Myomatous erythrocytosis syndrome → ↑ RBC count (from excess
erythropoietin).

● Urologic: urinary retention, hydronephrosis from compression.

● Pseudo-Meigs syndrome: ascites + pleural effusion (resolves after removal).

● Genetic:

○ Hereditary leiomyomatosis & renal cell carcinoma (HLRCC/Reed

syndrome): FH mutation → cutaneous + uterine fibroids + RCC.

● Other rare conditions:

○ Leiomyomatosis: benign but infiltrative, must rule out leiomyosarcoma.

○ Intravenous leiomyomatosis: invades veins up to IVC/heart → requires
extensive surgery.
○ Benign metastasizing leiomyoma: hematogenous spread, often to lungs.
○ Disseminated peritoneal leiomyomatosis (DPL): multiple peritoneal
nodules; linked to pregnancy or COCs.
○ Parasitic leiomyomas: secondary implants after morcellation in MIS.

Hematometra
● Definition: Accumulation of blood in uterus due to outflow obstruction.
● Sites of collection:
○ Vagina = hematocolpos.
○ Cervix = hematotrachelos.
○ Uterus = hematometra.
○ Tubes = hematosalpinx.

● Causes:

○ Congenital anomalies (imperforate hymen, transverse vaginal septum).

○ Acquired: scarring, radiation, hypoestrogenic atrophy, cervical stenosis
(post-conization, ablation), Asherman syndrome, malignancy.

○ Postablation tubal sterilization syndrome (PATSS).

● Clinical: suprapubic/low back pain, pelvic fullness, amenorrhea, urinary

retention/constipation, foul discharge if partial obstruction, pyometra if infected.

● Diagnosis: pelvic exam (enlarged, cystic uterus), sonography (enlarged cavity with
low-level echoes), MRI in unclear cases. Rule out pregnancy (hCG), malignancy
 (Pap, biopsy).

● Management: relieve obstruction & evacuate blood.

○ Cervical dilation (clinic or OR).

○ Hysteroscopy with adhesiolysis if synechiae.

○ Extensive surgery if congenital anomalies.

Adenomyosis
Pathophysiology
● Definition: Uterine enlargement due to ectopic endometrial glands + stroma within
myometrium.

● Forms:

○ Diffuse adenomyosis – scattered foci throughout myometrium.

○ Focal adenomyosis (adenomyoma) – localized nodular form.

● Gross pathology:

○ Globally enlarged uterus (rarely >12-week size).

○ Smooth surface, reddish/soft consistency.
○ Cut surface: spongy/trabeculated, with hemorrhagic foci.

● Theories:

○ Invagination of endometrial basalis into myometrium.

○ Risk factors: prior uterine surgery, estrogen/progesterone influence.

○ ↑ Aromatase expression → ↑ local estrogen (similar to leiomyomas &

endometriosis).

● Difference from endometriosis:

○ Adenomyosis originates from basalis layer.

○ Endometriosis originates from functionalis layer.

● Epidemiology:

○ 20–40% in hysterectomy specimens.

○ 90% occur in parous women.

○ 80% in women 40s–50s.

○ Regresses after menopause.

Clinical Features
● 1/3 of women are symptomatic.
● Common: heavy menstrual bleeding (HMB), dysmenorrhea.
● Occasional: dyspareunia (~10%).
● Symptom severity correlates with number & depth of foci.
● Link with subfertility – unclear, poor-quality data.

Diagnosis
● Preferred imaging:
○ TVS (more accurate than TAS).
○ MRI – equal or slightly superior to TVS; used if inconclusive or distorted
anatomy.

● TVS findings:

○ Asymmetric myometrial wall thickening.

○ Heterogeneous myometrium.
○ Small myometrial cysts (ectopic glands).
○ Striated projections from endometrium into myometrium.
○ Ill-defined endometrial–myometrial border.
○ Globally enlarged uterus.
○ ↑ Vascularity on Doppler.

● Focal adenomyosis vs leiomyoma:

○ Poorly defined margins, elliptical shape, minimal mass effect, lack of

calcification, presence of cysts.

Management Goals: relieve pain & bleeding.

Medical

● NSAIDs: for dysmenorrhea.

● Hormonal options:

○ COCs / progestin-only → induce endometrial atrophy, ↓ prostaglandins.

○ LNG-IUS: effective for HMB but higher expulsion rates.
○ GnRH agonists: effective, but limited by cost + hypoestrogenic effects; useful
for infertility or pre-surgery.
○ Danazol: rarely used (androgenic side effects).

Surgical

● Hysterectomy: definitive treatment.

● Endometrial ablation/resection: option for HMB/dysmenorrhea but higher failure
rates in adenomyosis (up to 19% require hysterectomy within 3 yrs).
● UAE: improves symptoms in many (65–90% short-term relief, some sustained up to
5 yrs).
● MRgFUS: effective for focal adenomyomas (case series)