UTERINE LEIOMYOMATA

Uterine Leiomyomata
Benign tumor comprised mostly of
smooth muscle cells

First described by Reinier De Graff 1641

Most common tumor of the female pelvis

Represent 1/3 of all GYN admissions to
hospitals
Incidence
Usually quoted 50% (Underestimate)
Cramer and Patel
100 serial Uteri
Sectioned at 2mm
77 of 100 had myomas
84% had multiple myomas
649 myomas found in all
No difference in incidence within pre or post menopausal uteri
Am J Clin Pathol. 1990 Oct;94(4):435-8
Incidence
More common in African-Americans than white
Torpin et al. investigated 1741 Uteri
Overall incidence 3 times higher in blacks
Also tended to be larger
Also occurred at a younger age
J Obstet Gynecol 1942;44:569
Incidence
Cumulative incidence by age 50, > 80%
for African American and nearly 70% for
Caucasian women.

One in four women have at least one
submucosal fibroid.

Overall prevalence of uterine fibroids
increases with age from 3.3% in women
25-32 to 7.8% in women 33-40 years.
- Baird et al, Am J Obstet Gynecol 2003.
- Borgfeldt et al, Acta Obstet Gynecol Scand 2000.
Etiology
Arise from a single muscle cell (monoclonal).

Proliferate under the influence of sex
hormones, including estrogen, progesterone
& androgens.

Effects of steroids are modulated by local
growth factors.
- Rein et al, Am J Obst Gyne 1995.
- Ichimura et al, Fertil Steril 1998.
- Stewart et al, Obstet Gynec 1998.
- Wer et al, Fertil Steril 2002.
Etiology

Fibroblast growth factor
Vascular endothelial growth factor
Heparin-binding epidermal growth factor
Platelet-derived growth factor
Transforming growth factor
Parathyroid hormone-related protein
Prolactin
GENETIC BASIS ?
Twin studies [3]
First-degree affected relatives [4,5]
Race as risk factor
Hereditary Leiomyomatosis and Renal Cell
Carcinoma (HLRCC) [6]
Cutaneous and uterine leiomyomata
At risk for papillary renal cell carcinoma (women >
men) [7,8]
Women: increased risk of leiomyosarcoma [7,8]
Mutation in fumarate hydratase gene
Etiology
Nevertheless fibroids are both estrogen and
progesterone dependent
Over expressed estrogen and progesterone receptors
within fibroids
Noted to increase in size in high estrogen states
Pregnancy
High-dose OC use
Obesity
Etiology
Risk Factors
Nurses Health Study II
95,061 nurses completed questionnaires in 1989, 1991, 1993
Obesity
Early menarche
Nulliparity
Fertil Steril. 1998 Sep;70(3):432-9
Etiology
Oral Contraceptives
High dose pills have been assoc. with stimulation of
fibroid tumors

Smoking

Presentation
Most fibroids do not cause symptoms.

20-50% experience tumor-related symptoms:

- Menstrual dysfunction
- Bowel and bladder dysfunction
- Bulk effects

Such symptoms, account for up to 35% of all
hysterectomies.
- Lefebvre et al, J Obstet Gynecol Can 2003.
- Myers et al, Agency for Health Care Research and Quality, 2001.
Symptoms
Pelvic Pain
Menstrual
Irregularities
GI complaints
Bladder
complaints
Dyspareunia

Back pain
Leg pain
Vascular
symptoms
Infertility
Asymptomati
c
Diagnosis
History
Bimanual pelvic or abdominal exam
Pelvic ultrasound - most common
MRI, HSG, sonohysterogram,
hysteroscopy
Appearance
Appearance
Appearance

Degenerative Changes
Degenerative changes are reported in
approximately two-thirds of all specimens,
but most of them have no clinical
significance.
1. Hyaline degeneration- It is the most
common
2. Cystic degeneration
3. Mucoid degeneration
4. Fatty degeneration
5. Carneous degeneration
6. Calcification
7. Sarcomatous degeneration(malignant
transformation)
Treatment
Expectant management - most cases
Indications for treatment
Abnormal uterine bleeding, causing anemia
Severe pelvic pain
Large or multiple
Obscuring evaluation of adnexa
Urinary tract symptoms
Postmenopausal or rapid growth
Treatment Choices
Medical therapies
Medroxyprogesterone (Provera)
Danazol
GnRH agonists (nafarelin acetate, Depot Lupron)

Treatment
RU486
Anti-progestin
High affinity to Progesterone and glucocorticoid
receptors
Murphy et al (1995) showed decrease of
volume an average 49%
Recent reviews supports usage, but has been
associated with
Hot flashes
Endometrial hyperplasia
Is not associated with trabecular bone loss
Fertil Steril. 1995 Jul;64(1):187-90
Obstet Gynecol. 2004 Jun;103(6):1331-6
Clin Obstet Gynecol. 1996 Jun;39(2):451-60
Treatment
Gestrinone
Antiestrogen/antiprogesterone
GnRH analogues
Suppresses pituitary mediated secretion of estrogens
Basically treat 3-6 months
Expect 50% reduction of uterine volume
Treatment Choices
Uterine Artery Embolization (UAE)
UAE

Within three months following embolization:
- 45% and 55% reduction in total uterine and myoma
volume.
- Reduction in symptoms in approximately 80% of
women.


long- term data on durability and effects on
fertility and pregnancy outcomes are very limited.
Pron et al, Fertil Steril 2003
Burbank et al, J Am Assoc Gynecol Laparosc 2000
The Elements of the flostat System
U.S. FDA clearance of this device does not include the treatment of uterine leiomyomas
Flostat System
MR guided Focused Ultrasound
Myomectomy
First performed by ?
Myomectomy
First performed by Washington and John Atlee,
1844
May be approached in a variety of ways
Abdominally (open)
Laparoscopic
Hysteroscopic
Primarily for submucosal/intramural fibroids impacting the
endometrial cavity
Vaginal
Primarily for pedunculated submucous fibroids
Myomectomy
Biggest complication is blood loss
Treatment Choices
Hysterectomy
Vaginal
Abdominal
Myolysis
Laparoscopic myolysis,
introduced in 1992.

The procedure of delivering
energy to myomas in an attempt
to desiccate them directly or
disrupt their blood supply.

Uterine fibroids may shrink up to
80% of their total volume
following the procedure.

The integrity and strength of the
uterine wall has not been
determined after this procedure.
Lefebvre et al, J Obstet Gynecol Can 2003
Myolysis
Fertility and pregnancy outcomes after
laparoscopic myolysis remain unknown.

Three cases of uterine rupture during the third
trimester of pregnancy have been reported.

Further research is needed to determine the
efficacy and safety of myolysis.

However, until then it remains an option for
uterine preservation.
Vilos et al, J Am Assoc Gynecol Laparosc 1998
Treatment Choices
Hysterectomy
Vaginal
Abdominal