Download Fibroids for Meds

UTERINE LEIOMYOMATA
BASIM ABU-RAFEA, MD, FRCSC, FACOG
Assistant Professor & Consultant
Obstetrics & Gynecology
Reproductive Endocrinology & Infertility
Advanced Minimally Invasive Gynecologic Surgery
Department of Obstetrics & Gynecology
College of Medicine
King Saud University
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
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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 ?
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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:
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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
• Asymptomatic
Diagnosis
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History
Bimanual pelvic or abdominal exam
Pelvic ultrasound - most common
MRI, HSG, sonohysterogram,
hysteroscopy
Appearance
Appearance
Appearance
Degenerative Changes
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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