Benign Uterine Tumours

Prof Athula Kaluarachchi
11/26/2019 Reproductive Health Module A/L 2013

Objectives
 Describe different types of Benign Uterine tumours
 Discuss possible aetiology of Uterine Fibroids
 Classify Uterine Fibroids
 Explain the pathophysiological basis of uterine fibroids
 Discuss the principles and management options for
uterine fibroids
 Explain the management of other benign uterine
tumours

Benign Uterine Tumours
 Leiomyoma
 Adenomatous Polyps
 Adenomyosis

Leiomyoma(Fibroids)

Incidence
Uterine leiomyomas are the most common
gynaecological tumours and are present in 30% of
women of reproductive age.

Leiomyomata
 Each fibroid arises from a single cell and are
overgrowth of smooth muscle and connective tissue
that are hormone dependent.
 Composed of smooth muscle, fibroblasts and
 Collagen, Elastin and extracellular matrix protein

Classification of Leiomyomata
Submucosal
Submucosal (Intracavitary)
Intramural
Subserosal
Subserosal(Pedunculated)
Cervical

Unknown
Oestrogen dependent –
Not seen before menarche
Regresses after menopause
No hormonal abnormality in women developing fibroids

Age – rare before the age of 20 years
10%-15% over the age of 40 years have fibroids
Parity – common in nulliparous
Race - more common in negros
Familial – increased familial tendency

Symptoms
The majority of fibroids are asymptomatic
and will not require intervention or further
investigations.
Twenty to fifty percent of uterine leiomyomas are
estimated to produce symptoms.

Symptoms
 Depends on
 Site of tumour
 Size of tumour
 Complications – Degeneration, Tortion

Menstrual disorders
Menorrhagia
Metrorrhagia
Dysmenorrhoea
Infertility
Pain
Acute abdominal pain
Constant ache
Dysmenorrhoea Pressure symptoms
Asymptomatic
(50%)
Symptoms of fibromyoma
Urinary Symptoms
Increased frequency
Urinary retention

Menstrual Symptoms
Menorrhagia
The mechanism of fibroid-associated menorrhagia is
unknown.
 possible explanations.
1.Vascular defects,
2.Increased Surface area -Submucous tumours,
3.Impaired endometrial haemostasis
Dysmenorrhoea
(Submucous Fibroids)

Fibroids and infertility
 The impact of fibroids on fertility is controversial.
 Fibroids probably account for only 2% to 3% of
infertility cases.
 No randomized controlled Trials

Fibroids and Infertility
Various theories have been advanced to explain the potential
subfertility effect of fibroids:
1. Dysfunctional uterine contractility,
2. Focal endometrial vascular disturbance,
3. Endometrial inflammation,
4. Secretion of vasoactive substances, or
 The published evidence suggests that submucous fibroids are
more likely to cause subfertility.
 Rarely – Tubal Obstruction

Pain
 Degeneration
 Torsion
 Sarcomatous Change
Urinary Symptoms
 Anterior wall – Increased frequency
 Posterior wall – Urinary retention

Pressure Symptoms
 Due to size
 Location

Symptoms
 Submucous
 Menorrhagia(29 - 59%)
 Dysmenorrhoea
 Intermenstrual bleeding with polyps

Symptoms
 Intramural
 Menorrhagia
 Palpable mass
 Pressure Symptoms
 Retention of Urine(Post wall)
 Increased Frequency of passing urine(ant wall)
 Pain due to degeneration

 Subserous
 Pain due to torsion
 Palpable mass
 Pressure Symptoms

Symptoms - General
Anaemia
Polycythaemia – rarely associated with broad ligament
fibroids

1-Atrophy
2- Degenerations
3-Sarcomatous changes
Secondary Changes - Complications

Type of Degenerative Change
Persaud & Arjoon, Obstet & Gynecol, 1970
0
10
20
30
40
50
60
70
Hya. Myx. Calc. Muc. Cystic Red Fatty Sarc.

4-Torsion
5-Inversion
6-Infection
Other complications of myomas

Pregnancy and Leiomyoma
complications

Pregnancy Complications Due to
Leiomyoma
 Miscarriage
 Malpresentations
 Premature labor
 Pain
 Ineffective uterine
activity in labor
 Premature rupture of
membrane
 Increase operative
deliveries
 Postpartum
hemorrhage
 Inversion of uterus

Investigations
Ultrasound Scan
CT Scan
MRI
MRI - Not for routine use

Investigations- Laparoscopy

Investigations-Hysteroscopy

Management
The type and timing of any intervention should be individualized,
based upon factors such as
 Type and severity of symptoms
 Size of the myoma(s)
 Location of the myoma(s)
 Patient age
 Reproductive plans and obstetrical history
 Rate of growth
Treatment should be individualized

Management
The majority of uterine leiomyomas are
asymptomatic and will not require therapy.

Management Options
Treatment modalities of fibroids include
1. Expectant management
2. Medical Management
3. Surgical Management
4. Radiological Management

Expectant Management
 Indications
 Asymptomatic fibroids
 Fibroids in women who are approaching the menopausal
transition
Prospective studies have found that between 7 to 40 percent of
fibroids regress over six months to three years.. In one
prospective study of 64 women (mean age 44 years) with
fibroids, the average growth rate was 1.2 cm in diameter over 2.5
years (range 0.9 to 6.8 cm)
Risk of transformation to Leomyosarcoma – 0.26%

Medical Management
 Indications
 In Peri-menopausal women whose symptoms are likely to resolve
with the onset of the menopause
 In women who are not suitable for surgery
 In some women receiving fertility treatment
 Pre-operatively to reduce the size of the fibroid and to reduce
menstrual bleeding (Ulipristal Acetate and GnRH analogues)
(Symptomatic management – Will not resolve completely)
 Symptom releif

Tranexaemic Acid
 Antifibrinolytic agent
 For symptomatic management
 Systemic review by Peitsidis et al.
 May reduce fibroid associated menorrhagia
 May reduce perioperative blood loss in
myomectomy
 Depend on the size and location of the fibroid
 Necrosis and infarcts in fibroids have been
reported
Peitsidis P, Koukoulomati A. Tranexamic acid for the management of uterine fibroid tumors: A systematic review
of the current evidence. World J Clin Cases 2014;2:893–98.
Ip PP, Lam KW, Cheung CL, Yeung MC, Pun TC, Chan QK, et al. Tranexamic acid-associated necrosis and
intralesional thrombosis of uterine leiomyomas: a clinicopathologic study of 147 cases emphasizing the
importance of drug-induced necrosis and early infarcts in leiomyomas. Am J Surg Pathol 2007;31:1215–24.

Combined Oral Contraceptive
Pills
 Systemic review by Moroni et al in 2015 on COCs for
treatment of fibroids
 To assess
 Efficacy to reduce menstrual bleeding
 Efficacy to reduce fibroid size
 Effect over quality of life
 Conclusion: Published data for the outcome of
treatment with the COCs is inconclusive
Moroni RM, Martins WP, Dias SV, Vieira CS, Ferriani RA, Nastri CO, Brito LG. Combined
oral contraceptive for treatment of women with uterine fibroids and abnormal
uterine bleeding: a systematic review, Gynecol Obstet Invest. 2015;79(3):145-52.

Danazol
 Danazol has been associated with a reduction in volume
of the fibroid in the order of 20% to 25%.
 Although the long-term response to danazol is poor, it
may offer an advantage in reducing menorrhagia.

Medical Management
 GnRH agonist treatment should be restricted to a 3- to 6-
month interval, following which regrowth of fibroids
usually occurs within 12 weeks.
 Gonadotropin-releasing hormone (GnRH) agonists are
available in nasal spray, subcutaneous injections, and
slow release injections.
 Fibroids may be expected to shrink by up to 50% of
their initial volume within 3 months of therapy.

Selective Progesterone Receptor Modulators -
Mifepristone
 Significant reduction in menstrual blood loss and an
improvement of symptoms
 Change in uterine volume
 Use in treatment of fibroids is currently restricted to
research settings
Tristan M, Orozco LJ, Steed A, Ramírez-Morera A, Stone P. Mifepristone for uterine fibroids. Cochrane Database Syst Rev
2012;(8):CD007687

Levonorgestrel-releasing
Intrauterine System (LNG-IUS)
 Reduces menstrual blood loss by inducing endometrial atrophy
 More effective than COCs in reducing menstrual blood loss and improving
haemoglobin levels
 No change in both uterine and fibroid volume
 Higher device expulsion rates that appear to increase with uterine volume
Kim M, Seong SJ. Clinical applications of levonorgestrel-releasing intrauterine system to gynaecologic diseases. Obstet Gynecol Sci
2013;56:67–75
Sangkomkamhang US, Lumbiganon P, Laopaiboon M, Mol BWJ. Progestogens or progestogen-releasing intrauterine systems for
uterine fibroids. Cochrane Database Syst Rev 2013;(2):CD008994

Ulipristal Acetate
 UPA, a selective progesterone receptor modulator,
has direct effects on fibroids and endometrium. UPA
reduces myoma volume and associated bleeding.
 Short-term use (≤ 3 months) was associated with a
significant reduction in menstrual flow in 90% of
exposed women. The effect was seen as early as 5-
7 days after initiation. It led to a one-third reduction
in fibroid size, an effect that was maintained for up to
6 months.

 Subsequently UPA was tested as extended use (3
months of UPA, then 2 months off UPA, repeated up
to four times). Such use was associated with a
reduction in fibroid size of 54%-67%, no heavy
menstrual bleeding in 67%-81% of women, and
significant improvement in quality of life.

Surgical Management

CONSERVATIVE SURGICAL THERAPIES
 Myomectomy
Laparotomy(Abdominal)
Vaginal
Hysteroscopic
Laparoscopic

Myomectomy
Although myomectomy allows preservation of the
uterus, there is a
1. Higher risk of blood loss and
2. Greater operative time with myomectomy than
with hysterectomy.

 Women should be counselled about the risks of
requiring a hysterectomy at the time of a planned
myomectomy.
 There is a 15% recurrence rate for fibroids a
 10% of women undergoing a myomectomy will
eventually require hysterectomy within 5 to 10 years.
Laparoscopic Myomectomy
1. Reduce hospital stay
2. Improve recovery time.
Myomectomy

Laparoscopic myomectomy
 Uterine rupture during a subsequent pregnancy
has been reported.
 The risk of recurrent myomas may be higher
after a laparoscopic approach, with a 33%
recurrence risk at 27 months.
Most suggest a laparotomy for:
1. Fibroids exceeding 5 cm to 8 cm,
2. Multiple myomas, or
3. When deep intramural leiomyomas are present.

Hysteroscopic Myomectomy
 Hysteroscopic myomectomy is feasible
and very effective, and it should be
considered in women with
1. Symptomatic intracavitary or
2. Submucous narrow-based intrauterine
myomas.

Hysteroscopic Myomectomy
Indications include :
1.Infertility,
2.Repeated pregnancy losses, and
3.Abnormal uterine bleeding.

Selective Uterine Artery
Embolisation
Selective uterine artery embolisation is a
global treatment alternative to
hysterectomy for women with
symptomatic uterine fibroids, in whom
other medical and surgical treatments are
contraindicated, refused, or ineffective.

Selective Uterine Artery
Embolisation
 Ideal candidates for UAE include women with
all of the following characteristics :
 Heavy menstrual bleeding or dysmenorrhea
caused by intramural fibroids
 Premenopausal
 No desire for future pregnancy

Contraindications - UAE
 UAE is absolutely contraindicated in women who
currently have the following conditions:
 ●Asymptomatic fibroids
 ●Pregnancy
 ●Pelvic inflammatory disease
 ●Uterine malignancy

Selective Uterine Artery Occlusion
The most popular approach to uterine
artery occlusion is selective uterine artery
catheterization and embolization.
Eligible women include those with
symptomatic fibroids who wish to avoid
surgical therapy.

Selective Uterine Artery Occlusion
Before undergoing uterine artery
embolization, all women should be
counselled that this procedure is
1. A recent procedure, and
2. Its long-term effects and durability,
including fertility and pregnancy
outcomes, are not yet known.

Myolysis
Myolysis refers to the procedure of
delivering energy to myomas in an attempt
to desiccate them directly or disrupt their
blood supply
Myomata deprived of their blood supply
would presumably shrink or completely
degenerate as they receive less :
nutrients, sex hormones, and growth
factors.

Magnetic resonance guided focused
ultrasound
Magnetic resonance guided focused ultrasound
surgery (MRgFUS; eg, ExAblate 2000) is a more
recent option for the treatment of uterine leiomyomas
in premenopausal women who have completed
childbearing. This noninvasive thermoablative
technique converges multiple waves of ultrasound
energy on a small volume of tissue, which leads to its
thermal destruction, and can be performed as an
outpatient procedure. The maximum size of a
leiomyoma for this procedure is uncertain. It is not
typically size alone that limits treatment, but size,
vascularity, access and other factors.11/26/2019 Reproductive Health Module A/L 2013

Hysterectomy
 The only indications for hysterectomy in a
woman with completely asymptomatic
fibroids are:
1. Abdominally palpable mass
2. Rapidly enlarging fibroids or,
3.When enlarging fibroids raise concerns of
leiomyosarcoma (after menopause).

Hysterectomy - Indications
1.women with acute hemorrhage who do not
respond to other therapies;
2.women who have failed prior minimally
invasive therapy for leiomyomas; and
3. women who have completed childbearing
and have significant symptoms, multiple
leiomyomas, and a desire for a definitive
end to symptomatology.

 Hysterectomy
Laparotomy
Laparoscopic

Endometrial Polyps

Endometrial Polyps
 Localized overgrowths of the endometrial glands and
stroma projecting beyond the endometrial surface
 Peak age incidence is at 40-49 years
 Cause is unknown
but in menopause common in women with HRT and
patient take tomoxifen for ca breast.
 Mostly are asymptomatic, mostly are detected by
sonography.

 Common manifestation is
intermenstrual bleeding in
perimenapause or
postmenapausal bleeding
 Has 3 histological
components:
 Endometrial glands
 Endometrial stroma
 Central vascular channels
Endometrial Polyps

Endometrial Polyps
 Malignant transformation is estimated at 0.5%
 Differential diagnosis:
 Submucous leiomyoma
 Adenomyoma
 Retained products of conception
 Endometrial hyperplasia
 Endometrial carcinoma
 Uterine sarcoma
 Optimal management is removal by Hysteroscopy

Ulipristal Acetate
 Ulipristal acetate is a steroid that reversibly binds to the
progesterone receptor and selectively modulates its activity
 It induces apoptosis of uterine fibroid cells and inhibits
proliferation
 PGL4001 (Ulipristal Acetate) Efficacy Assessment in
Reduction of Symptoms Due to Uterine Leiomyomata
(PEARL I) trial
 PEARL I Trail (5 mg and 10 mg UA were compared with placebo for
13 weeks)
 Both doses of UA were effective in reducing menstrual blood loss
in over 90% of patients after 13 weeks of treatment
 Amenorrhoea was noted within 10 days in 75% of patients
 The median reduction in uterine fibroid volume was 41% and this
reduction was maintained for at least 6 months after
discontinuation of treatment
Donnez J, Tatarchuk TT, Bouchard P, Puscasiu L, Nataliya F, Zakharenko T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl
J Med 2012;366:409–20

PEARL II Trial -Selective Progesterone Receptor
Modulators - Ulipristal Acetate
 PGL4001 (Ulipristal Acetate) Efficacy Assessment in
Reduction of Symptoms Due to Uterine
Leiomyomata (PEARL II) trial,
Evaluated whether daily oral ulipristal acetate (5 mg
or 10 mg) was non inferior to a monthly
intramuscular injection of leuprolide acetate (3.75
mg) in controlling bleeding before planned surgery
for symptomatic fibroids and compared the side-
effect profiles of the two drugs.

Ulipristal Acetate
 PEARL II Trial - (comparison of UA with a GnRH analogue /
Leuprolide)
 No difference in the control of menstrual bleeding
between UA and Leuprolide
 UA was tolerated better and controlled bleeding more
rapidly
 Uterine volume change was greater with Leuprolide
 UA use was associated with benign endometrial changes
termed progesterone-receptor-modulator-associated
endometrial changes
Donnez J, Tomaszewski J, Vázquez F, Bouchard P, Lemieszczuk B, Baró F, et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids.
N Engl J Med 2012;366:421–32

PEARL II - Selective Progesterone Receptor
Modulators - Ulipristal Acetate
 Primary End Point
In the per-protocol population, the proportions of patients with
controlled bleeding at week 13 (PBAC score, <75 for the
preceding 4 weeks) were 90% in the group receiving 5 mg of
ulipristal acetate, 98% in the group receiving 10 mg of ulipristal
acetate, and 89% in the group receiving leuprolide acetate
 Secondary End Points
All treatments reduced the volume of the three largest fibroids,
with median reductions at week 13 of 36% in the group
receiving 5 mg of ulipristal acetate, 42% in the group receiving
10 mg of ulipristal acetate, and 53% in the group receiving
leuprolide acetate (Table 2). Leuprolide acetate was
associated with a significantly greater reduction in uterine
volume (47%) than was either ulipristal group (20 to 22%).

 The PEARL III and the Extension trial -
 studies in which the long-term efficacy and safety of UPA
were evaluated, concretely in four 3-month cycles,
separatedby a two-month off-treatment period. They
showed that 80%of women had a clinically significant
reduction in fibroid volume, and the volume of the three
largest fibroids was reduced by 72% after four courses of
UPA. Moreover, progesteronereceptor modulator associated
endometrial changes (PAEC), observed in previous studies in
approximately 60% of patients, spontaneously reverted
within a few weeks to months after stopping UPA therapy.

Ulipristal Acetate
 PEARL III Trail
 209 patients used 10 mg of UA for 12 weeks and results were similar to those of
PEARL I and II.
 Women received a 3-month open-label course of UPA (10 mg) once daily
immediately followed by double-blind oral NETA (10 mg) once daily or matching
placebo for 10 days allocated randomly in a 1:1 ratio.
 PEARL III Extension
 PEARL III extension study – Up to three further courses of
UPA (and NETA/placebo), each separated by an off-
treatment period including a full menstrual cycle up to the
start of the second menstruation.The use of norethisterone acetate
between courses of UA had no effect on progesterone-receptor-modulator-associated
endometrial changes
Donnez J, Vazquez F, Tomaszewski J, Nouri K, Bouchard P, Fauser BC, et al. Long-term treatment of uterine fibroids with
ulipristal acetate. Fertil Steril 2014;101:1565–73

 PEARL IV
 Women were allocated randomly to receive either 5 or
10 mg/d of oral ulipristal acetate and matching placebos
for two 12-week courses.
 Ulipristal acetate was started during the first 4 days of
menstruation. Treatment courses were separated by a
drug-free interval.
 The second course was commenced with the second off-
treatment menstruation. After the second treatment
course and subsequent menstruation, an end of part I
visit was performed.

PEARL IV
 In the 5- and 10-mg treatment groups (62% and 73% of
patients, respectively) achieved amenorrhea during both
treatment courses. Proportions of patients achieving
controlled bleeding during two treatment courses were >80%.
 Menstruation resumed after each treatment course and was
diminished compared with baseline. After the second
treatment course, median reductions from baseline in fibroid
volume were 54% and 58% for the patients receiving 5 and
10 mg of ulipristal acetate, respectively. Pain and QoL
improved in both groups.
 Ulipristal acetate was well tolerated with less than 5% of
patients discontinuing treatment due to adverse events.

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