Uterine

Leiomyoma
Romy Mansour

OBGYN Clerkship
November 2021
Case Presentation

A 30-year-old African American G 0 woman

comes to your office for her annual examination.
During the history assessment, she reports
increased pelvic pressure, constipation, and
worsening menorrhagia with menses. During
menstrual cycles she is using about 10 large pads
per day with her heaviest flow and passing
“quarter sized” blood clots.
Case Presentation

On physical examination, you palpate a non-

tender, irregularly enlarged uterus with a
lumpy-bumpy, firm contour. Her cervix
appears normal, and she has no evidence of
ascites or other abnormal physical findings.
You suspect that she has uterine fibroids.
Case Presentation
Which of the following tests is most commonly used for diagnosis of
uterine fibroids?

a. CT scan
b. Pelvic x-ray
c. Pelvic ultrasound
d. MRI
e. Hysterosalpingogram
Case Presentation
All of the following medical therapies can be used to treat menorrhagia
in women with uterine fibroids except:

a. Combined oral contraceptive pills

b. Antifibrinolytic agent (tranexamic acid)
c. Nonsteroidal anti-inflammatory drugs
d. Progestin only pills
e. Opioid agonists
Case Presentation
Which of the following fibroid locations is most commonly associated
with abnormal vaginal bleeding?

a. Submucosal
b. Intramural
c. Subserosal
d. Pedunculated
e. Parasitic
Case Presentation
All of the following are risk factors for uterine fibroids except:

a. African American heritage

b. Multiparity
c. Early menarche
d. Perimenopause
e. Hypertension
 01 02 03
Definition & Patho- Risk Factors
Outline Epidemiology physiology

04 05 06
FIGO Signs & Diagnosis
Classification Symptoms

07 08 09
Treatment Risks of Uterine References
Morcellation
Table of
Contents

01
DEFINITION &
EPIDEMIOLOGY
Definition & Epidemiology
Uterine leiomyomas are the most common pelvic neoplasm in females
They are estimated to occur in up to 70 % of women by menopause

They are non-cancerous monoclonal tumors (solid) arising from

the smooth muscles cells and fibroblasts of the myometrium

They arise mainly in reproductive-age females

Although they can grow to huge sizes, their malignant potential

is minimal (transformation to leiomyosarcoma is 0.1-0.5 %)
 Definition & Epidemiology
The prevalence rate of uterine leiomyomas is 2-3 times higher among
Black women compared with White women

Myomas are clinically apparent in approx. 12-25 % of

reproductive-age females & noted on pathologic examination in
approx. 80 % of surgically excised uteri *

The prevalence of leiomyomas increases with age during the

reproductive years, and most, but not all, patients have shrinkage after
menopause

The most common indications for hysterectomy are symptomatic

uterine leiomyomas (51.4%), abnormal uterine bleeding (41.7%),
endometriosis (30%), and prolapse (18.2%) **
*Cross-sectional study done in Europe: Downes et. al, 2010 “The burden of uterine fibroids in five European Countries”
** Wright JD, Herzog TJ, Tsui J, Ananth CV, Lewin SN, Lu YS, et al. Nationwide trends in the performance of inpatient hysterectomy in the United States
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02
PATHOPHYSIOLOGY
Table of
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03
RISK FACTORS
• Nulliparity • Increasing parity
• Early menarche (< 10 years old) • Use of combined oral
• Prenatal exposure to hormonal contraceptives
diethylstilbestrol (DES) • Long-acting progestin-only
• Premenopausal status contraceptives
• Obesity • Smoking (?)
• Family History/Genetics • Post-menopausal
• Hypertension
• Diets including high consumption
of beef and red meats
• Alcohol consumption
• Race/ethnicity (Blacks+)
• Chronic stress/major life events
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04
SOME STATISTICS
& FIGO
CLASSIFICATION
 Myomas have a median growth
rate of 35.2% by volume per
year, and small (<2 cm) myomas
grow significantly faster than do
larger ones

Yearly volumetric
increase of 22.8 %

Most Prevalent of all

leiomyomas (58-79 %) Yearly volumetric
increase of 25.1 %
Yearly volumetric increase
of 53.2 %
 In a retrospective study of 145 consecutive cases, Hanafi evaluated those
factors that were associated with recurrence of myomas that were at least 2
cm in greatest diameter and that formed after open myomectomy. At surgery:

Submucous or Subserosal
submucous–intramural myomas
myomas
4% 23%

Intramural or
intramural–subserosal Myomas in all locations
myomas 68% 5%
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05
SIGNS AND
SYMPTOMS
 Signs & Symptoms

Symptoms are related to the number, size, and

location of the myomas

The size of the myomatous uterus is described

in menstrual weeks as with the gravid uterus

The majority of myomas are small and

asymptomatic
Bleeding +++ (most common fibroid symptom)
• Prolonged, heavier periods. May cause anemia
• Submucosal myomas that protrude into the uterine cavity (type 0,1) are most frequently
related to significant heavy menstrual bleeding
• Intramural myomas are associated with heavy or prolonged bleeding
• Subserosal fibroids are not considered a major risk for heavy menstrual bleeding
• Pedunculated submucosal may cause intermenstrual bleeding

Bulk-related symptoms
• Pelvic/rectal pressure (may present as lower back pain), constipation, urinary frequency or
retention, bloating, venous compression…
• Anterior fibroid presses on bladder  bladder symptoms
• Posterior fibroid pushes entire uterus forward  bladder symptoms
• Fibroids that place pressure on rectum  constipation

Pain
• Secondary dysmenorrhea, dyspareunia
Massive Uterine 44 year old nulliparous woman with intramural
Fibroid Resulting fibroid and acute retention of urine. A: T1WI coronal
in Extensive Deep
Venous
screening MR of the pelvis shows the fibroid (white
Thrombosis, arrow) isointense relative to the uterine wall
Compartment (asterix). B: Contrast enhanced SPGR sagittal
Syndrome and screening MR of the pelvis shows enhancement of
Rhabdomyolysis the fibroid (yellow arrow)
Reproductive dysfunction
• Infertility, miscarriage obstetric complications
• Submucosal or intramural  distort uterine cavity  difficulty conceiving + risk of miscarriage
• Impede normal implantation due to their position or poor endometrial receptivity of the
decidua overlying the myoma
• Common cause of size-date discrepancy in pregnancy. May be undetected prior to pregnancy
but will be large than expected in pregnancy due to high estrogen
• Adverse pregnancy outcomes: preterm labor and birth (most common +), placental abruption,
FGR, malpresentation,, spontaneous abortion (intracavitary ++), PPH, obstruction of birth
canal

Pelvic symptoms
• Firm, non-tender, irregularly enlarged (“lumpy bumpy”) or cobblestone uterus felt on physical
exam
RARELY
Fibroid Degeneration (Red Degeneration)
• Edema & hypertrophy or venous thrombus  impede blood supply  hemorrhagic infarction
of the uterine leiomyoma, especially during pregnancy  preterm birth & rarely DIC
• Acute pain, low-grade fever, uterine tenderness on palpation, elevated WBC, peritoneal signs
• Associated with severe infection and torsion of a pedunculated fibroid
• Self-limited responds to NSAIDs

Prolapsed Fibroid
• Submucosal leiomyoma prolapses through cervix
• Presents with a mass, bleeding, possible ulceration or infection

Endocrine Effects (fibroids may secrete ectopic hormones)

• Polycythemia from autonomous production of erythropoietin
• Hypercalcemia from autonomous production of parathyroid hormone-related protein
• Hyperprolactinemia
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06
DIAGNOSIS
Diagnostic Tools
• Medical History
 Heavy or prolonged menstrual bleeding
 Pelvic pain (NOT of acute onset usually)
 Infertility
 Identify risks for sarcoma +++
• Abdominal & Pelvic Examination
 Enlarged, mobile uterus with an irregular contour
• Pelvic Ultrasound
• Transvaginal Ultrasound
• Sonohysterography
• Hysteroscopy
• MRI
• CBC, hCG
Differential Diagnosis
Other causes of Other causes of
Uterine enlargement abnormal bleeding

• Endometrial hyperplasia
• Adenomyosis • Endometrial cancer
• Myometrial Other causes of Pelvic • Uterine sarcoma
hypertrophy Masses • Polyps
• Endometrial cancer • Adenomyosis
• Pregnancy • Endometriosis
• Ovarian cancer
• Tubo-ovarian
abscess
• Endometriosis
Pelvic Ultrasound
• First line study
• 95-100 % sensitivity for detecting myomas < 10 gestational weeks’ size
• Fibroids appear hypoechoic, well-circumscribed, round, with shadowing
• Calcification implies fibroid degenerated
Sonohysterography
• Allows identification of submucosal lesions & intramural myomas that protrude
into the cavity
• Distinguishes between type 0, type 1, and type 2 (in which the % of submucosal
involvement varies)

(A) Sagittal transvaginal sonogram shows hypoechoic

endometrial thickening (arrowheads).
(B) Sagittal sonohysterogram shows submucosal fibroid
with thin overlying endometrium (cursors).
Hysteroscopy
• Evaluation for submucosal or protruding fibroids
• Cannot ascertain depth of penetration if the fibroid is not type 0 (intracavitary)
• Useful to distinguish between type 2 and 3, where there is contact with the
endometrium but there may not be distortion of the endometrial cavity
• Less accurately predicts the size of the myoma compared with ultrasound &
sonohysterography
MRI
• Useful in surgical planning, determining vascularity and degeneration
• Useful in distinguishing between types 4 and 5, in which there is an intramural
component, with or without a submucosal component
• Useful to distinguish between leiomyoma, adenomyosis, and adenomyomas
• Useful before uterine artery embolization
• May help identify features concerning for leiomyosarcoma
Sagittal T2-weighted MRIs
show (A) the intramural
uterine fibroid inside the
myometrium (white arrow);
(B) the submucosal uterine
fibroid projecting
completely into uterine
cavity (white arrow); and
(C) the subserosal uterine
fibroid projecting outward
the uterus (white arrow).
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07
TREATMENT
Medical Surgical
Primarily Treat bulk
addresses symptoms by
bleeding decreasing
symptoms uterine mass
Expectant Management
• Consider if:
Asymptomatic patients
Patient who do not desire intervention
Patients experiencing perimenopausal
symptoms
• Counsel patients to return for follow-up if
symptoms become bothersome or if active
management or pregnancy is desired
Medical Therapy for Bleeding Symptoms
1) GnRH Antagonists with Hormonal Add-Back Therapy
• Compete with endogenous GnRH for pituitary binding sites
• May be considered for treatment of AUB-L for up to 2 years
• Elagolix results in reversible, dose-dependent suppression
of gonadotropins and ovarian sex hormones
• Elagolix (300 mg twice daily) + add back therapy ( 1 mg
estradiol and 0.5 mg norethindrone acetate once daily) is
FDA approved
• Hormonal add-back therapy is indicated to offset
hypoestrogenic effects (hot flushes, increased serum lipid
levels, BMD loss)
Medical Therapy for Bleeding Symptoms
2) Levonorgestrel-Releasing Intrauterine Devices
• 52-mg LNG-IUD
• Reduce menstrual bleeding by inducing endometrial decidualization and
atrophy
• Insufficient evidence to support the use of LNG-IUD for leiomyoma
symptoms other than bleeding
• Rates of IUD expulsion are higher in patients with leiomyomas,
especially in patients with leiomyomas that distord the uterine cavity
Medical Therapy for Bleeding Symptoms
3) Contraceptive Steroid Hormones
• COC & progestin-only pills reduce menstrual blood loss
• LNG-IUD provides a greater reduction in menstrual blood loss
• No evidence to support their use in managing bulk symptoms
Medical Therapy for Bleeding Symptoms
4) Tranexamic Acid
• Anti-fibrinolytic (prevents fibrin degradation)
• Effective treatment for heavy menstrual bleeding
Medical Therapy for Bleeding Symptoms and Uterine
Enlargement
GnRH Agonists with or without Hormonal Add-Back Therapy
• Produce a down-regulation of GnRH receptors
• Recommended for SHORT-TERM treatment for AUB-L and uterine
enlargement associated with leiomyomas, as a bridge to other treatment
strategies
• GnRH agonists  reduction in leiomyoma size and overall size of uterus,
decreased AUB-L and dysmenorrhea, improvement in quality-of-life
measures (days of bleeding, pelvic pressure, urinary frequency…)
Medical Therapy for Bleeding Symptoms and Uterine
Enlargement
GnRH Agonists with or without Hormonal Add-Back Therapy
• Leiomyoma regrowth is observed between 3-9 months after cessation
• Used to reduce uterine volume before surgical therapy  facilitates use of
minimally invasive surgical route
• Use of GnRH agonist  increase in preoperative hemoglobin levels by an
average of 0.88 g/dL
• Because of risk of long-term hypoestrogenic adverse effects:
 6 months treatment without add-back therapy
 12 months treatment with add-back therapy
Uterine Artery Embolization
• Minimally invasive, percutaneous  all myomas (including
intramurals, but NOT pedunculated)
• In patients who desire uterine preservation but no pregnancy
• Significant reduction in leiomyoma and uterine volume (up to 5
years)
• Improved bleeding
• 2-5 x higher rate of re-intervention compared to hysterectomy
or myomectomy
• Lower risk of requiring blood transfusion than other surgical
interventions
• Complications: thromboembolic events, postembolization
syndrome
• Risks: effects on ovarian reserve, risk of pregnancy loss,
cesarean delivery, post-partum hemorrhage
Radiofrequency Ablation

• Can be done by a laparoscopic,

transvaginal, or transcervical
approach
• Uses laparoscopic ultrasound
guidance to induce coagulative
necrosis in the leiomyomas
• Improvements in symptom severity
• Even small (< 1 cm) and hard-to-
access intramural myomas can be
ablated
Focused Ultrasound
• Guided by magnetic resonance
• Uses multiple high-intensity waves to
cause coagulative necrosis of uterine
leiomyomas
• Nonsurgical ablation of leiomyomas,
including intramurals
• Has showed less improvement in
symptoms and higher risk of intervention
than UAE
• Limitations: large body habitus, bowel
obstructing the target myoma, large
fibroid volume (uterine size > 24 weeks),
intracavitary nonenhancing or heavily
calcified myomas
Surgical Management
• Goals of treatment are defined for each patient: desire for uterine preservation,
future fertility, symptoms including bleeding and bulk symptoms
• The most minimally invasive route is recommended when feasible
• GnRH agonists are often used to reduce uterine volume before surgical therapy
• If specimen or uterus is too large to be removed intact, morcellation is required
Myomectomy
• For women who desire uterine preservation or future pregnancy
• Must be counseled about risk of recurrence
• May be performed with hysteroscopic, laparoscopic, robotic-assisted
laparoscopic, or abdominal techniques
• Improvement of quality of life ++
• No evidence to conclude if myomectomy improves AUB-L
• Use of dilute vasopressin during myomectomy  decrease operative blood
loss
• Pregnancy post-myomectomy is influenced by leiomyoma type:
 Submucosal  higher pregnancy rates
 Subserosal & intramural  lower pregnancy rates
Hysteroscopic Myomectomy
Laparoscopic Myomectomy
Isolated submucosal leiomyomas
Type 0, type 1, and some type 2 Symptomatic types 2-8 leiomyomas
(only if < 4 cm in greatest diameter)

Laparotomy
Intramural myomas
Low-transverse cut
Hysterectomy
• Definitive surgical management for AUB-L and
bulk symptoms
• Women who do not desire future childbearing
or do not wish to retain uterus
• Risks if before menopause: cardiovascular,
neurologic, and somatic morbidity + increased
risk of mortality
• Most minimally invasive route is recommended
• Vaginal approach is preferred
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08
RISKS OF
UTERINE
MORCELLATION
Possible spread of unsuspected leiomyosarcoma during hysterectomy or myomectomy in
open/uncontained morcellation using a power morcellator

Risk of unexpected leiomyosarcoma may range from 1 in 770 surgeries to less

than 1 in 10,000 surgeries for presumed leiomyoma

A woman should be evaluated to determine if she is at increased risk of malignancy

of the uterine corpus

Preoperative evaluation includes risk stratification, appropriate use of imaging,

cervical cancer screening, and endometrial tissue sampling

Leiomyosarcoma cannot be reliably diagnosed preoperatively

Abdominal hysterectomy or myomectomy reduce chance of spreading cancer cells, but have
increased morbidity vs minimally invasive approaches
Leiomyosarcoma

• Incidence: 0.36 per 100,000 woman

• Median age at diagnosis: 54 (Range: 48-63)
• Mostly arise de novo 5 from uterine musculature
or the connective tissue of uterine blood vessels,
• Can rarely arise from a pre-existing benign
leiomyoma (incidence of sarcomatous
transformation is reported to be 0.1-0.8%)
Leiomyosarcoma
• Risk factors:
 History of tamoxifen use for more than 5 years
(increased risk of endometrial carcinoma and
leiomyosarcoma)
 History of pelvic irradiation
 Hereditary cancer syndromes (e.g. hereditary
retinoblastoma syndrome, Li fraumeni)
• Uterine size and rapid uterine growth are NOT
associated with an increased risk
Leiomyosarcoma Diagnosis
1 MRI

A diagnostic algorithm with predictive features

including lymphadenopathy, high diffusion-
weighted imaging signal with reference to
endometrium, and low apparent diffusion
coefficient enabled differentiation of malignant
sarcomas from atypical leiomyomas

2 Lactate Dehydrogenase Isoenzyme Testing

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09
REFERENCES
 References
1. ACOG Practice Bulletins (Numbers 781, 228, 810, 800, 822)
2. UpToDate Retrieved from https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-epidemiology-clinical-
features-diagnosis-and-natural history?
search=uterine+leiomyoma&amp;source=search_result&amp;selectedTitle=2~150&amp;usage_type=default&amp;dis
play_rank=2.
3. https://radiopaedia.org/articles/uterine-leiomyosarcoma
4. El Sabeh, M., Saha, S. K., Afrin, S., Islam, M. S., &amp; Borahay, M. A. (2021, May 17). Wnt/β-catenin signaling pathway
in uterine leiomyoma: Role in tumor biology and targeting opportunities. Molecular and Cellular Biochemistry.
Retrieved November 17, 2021, from https://link.springer.com/article/10.1007/s11010-021-04174-6.
5. Wechter, M. E., Stewart, E. A., Myers, E. R., Kho, R. M., & Wu, J. M. (2011, November). Leiomyoma-related
hospitalization and surgery: Prevalence and predicted growth based on population trends. American journal of
obstetrics and gynecology. Retrieved November 17, 2021, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746963/.
6. Duc, N. M., &amp; Huy, H. Q. (2018, April 3). Effect of magnetic resonance imaging characteristics on uterine fibroi:
RMI. Reports in Medical Imaging. Retrieved November 17, 2021, from https://www.dovepress.com/effect-of-magnetic-
resonance-imaging-characteristics-on-uterine-fibroi-peer-reviewed-fulltext-article-RMI.
7. Thompson, M. J., & Carr, B. R. (2016, May 17). Intramural Myomas: To treat or not to treat. International journal of
women's health. Retrieved November 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876842/.