Referat

UTERINE MYOMA

dr.

Moderator

DEPARTEMEN OBSTETRI DAN GINEKOLOGI

FAKULTAS KEDOKTERAN UNIVERSITAS SRIWIJAYA
RSPU Dr. MOHAMMAD HOESIN
PALEMBANG
 INTRODUCTION
• Uterine myomas are monoclonal tumors of uterine smooth
muscle cells and consist of a large number of extracellular matrix
containing collagen, fibronectin, and proteoglycans.

• The most common benign uterine tumor

• Incidence  20% -40% in reproductive women

• Classified based on their location to the uterine lining

(subserous, intramural, or submucosal) and can be single or
multiple.
 INTRODUCTION
• In Indonesia, uterine myoma is the second most common tumor.

• Although the pathogenesis is not clearly known, there is

considerable evidence that estrogen and progestogen increase
tumor growth, because uterine myomas rarely appear before
menarche and decrease after menopause.

• Administration of estrogen-progestin is shown to cause myoma

growth during reproductive age.
 INTRODUCTION
• Hysterectomy is considered the only therapy for myoma uteri.

• Currently, several well-known medical therapies are used, both

as an adjuvant therapy and as a primary therapy  hormonal
therapy.

• GnRH agonists and SPRM are the most effective medical

therapies, with the most evidence to support a reduction in
fibroid volume and improvement in symptoms of menstrual
bleeding.
ANATOMY AND PHYSIOLOGY

Fig 1. Anatomy of the Uterus

 ANATOMY AND PHYSIOLOGY
• The uterus consists of three layers of tissue including the
endometrium, myometrium and perimetrium.
• Endometrium has two functional layers, stratum functional and
stratum basal.
• In nonpregnant women, the superficial functional layer which has
glands and blood vessels will be released from the endometrial wall
during menstruation so that only the basal stratum and a portion of
the uterine gland remains. The remaining part is functioning in the
process of regenerating the new functional stratum.
 DEFINITION AND EPIDEMIOLOGY

• Uterine myomas are monoclonal tumors of uterine smooth

muscle cells and consist of a large number of extracellular
matrices containing collagen, fibronectin, and
proteoglycans.
• Prevalence studies in 2009  incidence of uterine myoma
of 4.5% in British women, 4.6% in France, 5.5% in Canada,
6.9% in the United States, 7% in Brazil, 8% in Germany, 9%
Korea, and 9.8% in Italy.
• The average age  33.5 to 36.1 years.
 DEFINITION AND EPIDEMIOLOGY
• In Indonesia, uterine myoma is the second most tumor after
cervical cancer.
• Only 10% of uterine myomas still grow after menopause.
• In research conducted at the General Hospital. Prof. Dr. R. D.
Kandou Manado in the period 1 July 2013 - 1 July 2014 from
medical records  uterine myoma is the second most gynecological
tumor and the most suffering from myoma uteri is the age group
41-50 years.
• Myoma uteri will show a tendency to enlarge during reproductive
age and tend to slow down after menopause.
 ETIOLOGY AND RISK FACTOR
1. Age and ethnic group

2. Menarche age

3. Parity and pregnancy

4. Alcohol consumption and caffeine

5. Others (uterine infections, hormones, metabolism, food, stress, and

environmental factors)
 PATHOPHYSIOLOGY
• Cells proliferate at a moderate level and their growth depends on
estrogen and ovarian steroid progesterone.
• Estrogen estradiol potentially biologically induces PR production
through ER-α.
• PR is very important for myoma tissue response to progesterone
released by the ovary.
• Progesterone and PR are needed for tumor growth, increasing cell
proliferation and survival and increasing extracellular matrix
formation.
 PATHOPHYSIOLOGY

Fig 2. FIGO subclassification system in leiomyomas.

 CLINICAL MANIFESTATION
1. Usually asymptomatic

2. Abnormal uterine bleeding

3. Pelvic pain

4. Incontinence or urinary retention

5. Dispareunia
 DIAGNOSIS
Pelvic examination and vaginal ultrasound

– Transabdominal and transvaginal

ultrasonography is most
commonly used.

– Transvaginal ultrasonography is
more sensitive for the diagnosis
of small myomas.
Fig 3. Transvaginal ultrasound shows a
– Myoma appears as a well-defined large uterine myoma with several
intramural myomas. The largest myoma
solid mass with an uneven (picture above) is in the fundus of the
posterior wall measuring 4.5 × 4 cm.
appearance.
 DIAGNOSIS
MRI

– Provide information about the number of myomas, their size

and location, vascularization, relationship to the endometrial
cavity and the serosal surface and the boundary with normal
myometrium.

– Most sensitive modality for evaluating uterine myomas,

especially for detecting small myomas.

– sensitivity of 88% -93% and specificity of 66% -91%.

 DIAGNOSIS
MRI

Fig 4.
MRI of Myoma. T2-weighted sagittal
midline image
 THERAPY
1. Hormonal Therapy
a. Gonadotropin-releasing hormone (GnRH) analog
b. Antagonis GnRH (GnRHAT)
c. Aromatase inhibitors
d. Combined oral contraceptive
2. Surgical Therapy
a. Histerectomy
b. Myomectomy
c. Uterine fibroid embolization ( UFE)
 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

Agonis GnRH (GnRHSA)

• The most efficient pharmacological treatment for uterine
myoma
• Direct action on the pituitary  down regulation and
desensitization of GnRH receptors  a hypogonadotropic
state with decreased estradiol and progesterone  reduce
uterine myoma volume
• Reduce uterine bleeding, improve hematologic parameters,
manage symptoms of menometrorrhagia, dysmenorrhea, and
pelvic pain, and reduce the size of uterine myomas.
 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

• Cannot be given for a long period of time  side effects

including bone loss, hot flashes, sleep disorders, vaginal
dryness, myalgia, arthralgia, as well as mood and cognition
disorders.
• Using GnRH agonists for three to four months before
myoma surgery reduced uterine volume and myoma size.
• However, the treatment of GnRH agonists is also associated
with histological changes in uterine myomas which can
complicate surgical intervention.
 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

Mechanism of action of GnRHa

 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

Patient characteristic during follow up after GnRHa treatment

(Perrone et al, 2013)
 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

• Lethaby et al (2017), reviewed 17 studies evaluating about the use

of GnRHa (2 months) versus placebo in pre-surgical uterine myoma
patients.

• The result was GnRHSa consistently reduce the uterine volume

compared to control group (uterine volume was 80 cc-570,1 cc in
GnRHa group and 255cc-920 cc in control group)
 THERAPY
Gonadotropin-releasing hormone (GnRH) analog

• Lethaby et al (2017) review 7 studies with 657 patients

• The GnRHa pretreatment was associated with a reduction in the

size of the uterine myoma from 5.7 mL to 155.4 mL (data too
heterogeneous to calculate summary effect sizes).

• In two other trials with the placebo, one reported a significant

difference from the placebo and the other reported no significant
difference.
 THERAPY
Antagonis Gonadotropin-releasing hormone (GnRH)

• The GnRH antagonist is used to suppress FSH and LH secretion by blocking

the pituitary GnRH receptor  estradiol will decrease and lead to
improvements in bleeding patterns and reduction in the size of the
uterine myoma as early as 3 weeks after starting treatment.

• A study reviewed the effects of cetrorelix acetate, for 4 weeks before

surgical treatment in 109 women  a significant reduction in tumor
volume and uterine volume compared with placebo.
 THERAPY
Antagonis Gonadotropin-releasing hormone (GnRH)

• In a smaller open label study, only 19 patients reported

the efficacy of ganirelix, another GnRH antagonist, in
reducing tumor volume and uterine volume over an
average treatment duration of 19 days.

• However, further research is needed on doses and side

effects.
 THERAPY
Aromatase Inhibitors

• Inhibition of the aromatase enzyme inhibiting the

production of estradiol.

• Aromatase inhibitors have been shown to be effective

against myomas in the short term.

• Long term use  bone loss, which requires the use of oral
contraceptives simultaneously.
 THERAPY
Oral Combined Contraceptive

• Estrogen and progesterone treatment, usually with combined oral

contraceptive pills, can control abnormal uterine bleeding (by
suppressing endometrial growth).

• The Levonorgestrel Releasing Intrauterine Device (LNG-IUD) works

at the endometrial level to suppress estrogenic stimulated growth
resulting in thinning endometrial layers, and effective for treating
abnormal uterine bleeding associated with anovulation.
 THERAPY
SPRM

• Four members of the SPRM compound family have been

investigated in phase II clinical trials: mifepristone, asoprisnil,
ulipristal acetate (UPA) and telapristone acetate.
• All have been shown to reduce the size of leiomyomas and
reduce uterine bleeding in a dose-dependent manner.
• UPA compared with placebo and leuprolide acetate (GnRH
agonist) in two randomized trials  uterine bleeding was
controlled in more than 90% of patients who received a UPA
program for three months, and the median time to control
bleeding was shorter in the UPA group (5-7 days) than in the
GnRH agonist group (21 days)
 THERAPY
SPRM

• UPA was also found to have a sustained effect (up to six

months) in women who did not undergo surgery after a
three-month study period. Conversely, those treated with
GnRH agonists got rapid fibroid regrowth
• Safety has also been well documented in pharmacokinetic
studies after several doses.
• The mechanism of action by which SPRM reduces
menstrual blood loss in women with fibroids is still
unknown
 THERAPY
SPRM

New approaches and algorithms, with special emphasis on

infertility
• Key factors that determine the management of uterine
fibroids: patient age, severity of symptoms (pain, bleeding
and infertility), want to maintain the uterus and / or fertility,
localization of fibroids according to FIGO classification and
myoma volume.
• The approach described below is in accordance with the FIGO
classification.
 THERAPY
SPRM

New approaches and algorithms, with special emphasis on

infertility

If there is a type 0 myoma, cut pedicles by

hysteroscopy
 THERAPY
SPRM

New approaches and algorithms, with special emphasis on

infertility

• Medical therapy can be given in one or

two three-month programs.
• In most cases, myoma type 1 responds
to this preoperative therapy and
undergoes regresi size regression
enabling an easier hysteroscopic
approach under better conditions
(hemoglobin recovery).
 THERAPY
SPRM

New approaches and algorithms, with special emphasis on

infertility
• Type 2 or type 2-5 myomas (single or double) distort the
uterine cavity.
• In infertile young women of reproductive age and wanting to
get pregnant, myomas often respond to this preoperative
therapy and experience a decrease in size — allowing a
hysteroscopic approach
THERAPY
 THERAPY
SPRM

Future prospects for medical therapy

• SPRM has opened new avenues for exploring medical therapy
in fibroids, both to treat symptoms and delay or to eliminate
the need for surgery.
 THERAPY
Histerectomy

• In women who have given birth and do not want to have children
anymore, hysterectomy is indicated as a permanent solution for
symptomatic myoma.

• The only indication for hysterectomy in women with truly

asymptomatic myomas is enlarging myomas after menopause,
which raises the concern of leiomyosarcoma, although that is still
very rare.
 THERAPY
Histerectomy

• Myomectomy is an alternative hysterectomy for women who want

to maintain their uterus, regardless of their fertility desires.

• Uterine myoma removal must be considered if it is associated with

heavy menstrual bleeding, pelvic pain, and in some cases
reproductive problems.

• The risk of blood loss is higher and surgery time is longer

• Recurrence rate 15%

 THERAPY
Uterine fibroid embolization ( UFE)

• Embolization is closing the blood vessels that supply tumors with

certain material, so that the tumor will no longer get blood supply,
but still retain the blood vessels that supply healthy uterine
muscles.

• In patients who do not want surgery for some reason, for example,
have not give birth yet but must face the possibility of removal of
the uterus, this therapy can be an option.
 THERAPY
Uterine fibroid embolization ( UFE)

• Embolization is closing the blood vessels that supply tumors with

certain material, so that the tumor will no longer get blood supply,
but still retain the blood vessels that supply healthy uterine
muscles.

• In patients who do not want surgery for some reason, for example,
have not give birth yet but must face the possibility of removal of
the uterus, this therapy can be an option.
 THERAPY
Uterine fibroid embolization ( UFE)

• This is a minimally invasive action. Performed by an

interventional radiology specialist using an
angiography.

• The tumor reduction process occurs gradually, starting

several weeks and continuing between 3 to 12 months.
 SUMMARY
1. Uterine myomas are monoclonal tumors of uterine smooth muscle cells
and consist of a large number of extracellular matrix containing collagen,
fibronectin, and proteoglycans. Uterine myoma is the most common
benign uterine tumor, with an estimated incidence of 20% -40% in
women during their reproductive period. The majority of uterine
myomas are asymptomatic and do not require therapy. However, 20% to
50% are clinically symptomatic, causing abnormal uterine bleeding, iron
deficiency anemia, and reproductive problems that may require
treatment. The diagnosis is made on Ultrasonography and MRI
examination.
 SUMMARY
2. Hysterectomy is considered the only curative solution for uterine
myomas. However, alternative medical treatments that maintain
fertility and avoid invasive surgeries, with high efficacy, and the
desired side effect profile are now available. Currently used several
well-known medical therapies, one of which is hormonal therapy.
Each hormonal therapy has its own level of safety and effectiveness,
and uterine myoma therapy must be adjusted individually
depending on factors such as the patient's age, signs and symptoms,
ongoing reduction in myoma size, and maintenance or increase in
fertility, while minimizing side effects.
 SUMMARY
3. Symptomatic uterine fibroids require surgical and / or medical therapy according to
the severity of symptoms, age, infertility, wanting to maintain the uterus and FIGO
classification. The current strategy mainly involves surgical interventions, such as
hysterectomy, myomectomy with hysteroscopy and myomectomy with laparoscopy
or laparotomy. Hysterectomy provides the most effective treatment for fibroids,
but is not appropriate in many cases. The choice between less invasive techniques
(uterine-saving options such as myomectomy) is guided by the size, number and
location of fibroids and the obstetrician's personal experience and available
equipment. Other surgical techniques, such as laparoscopic cryomyolysis,
thermocagulation or uterine artery occlusion, are rarely used. Non-surgical
interventions, such as the UAE and MRgFUS, are also available but the desire for
future pregnancy is a relative contraindication.
 SUMMARY
4. GnRH agonists have been used to shrink fibroids and restore hemoglobin levels in
symptomatic women, but because of their side effects, they cannot be used for
long periods of time. However, there is now growing evidence of the important role
of progesterone in the pathway in the pathophysiology of uterine fibroids using
SPRM. UPA (a member of the SPRM compound family) has been studied in large
clinical trials and its long-term intermittent administration has been evaluated,
producing promising results for new treatment perspectives. It was found that
more than one three-month UPA course maximizes potential benefits in terms of
bleeding control and fibroid volume reduction. Therefore, depending on age and
symptoms (infertility, bleeding, etc.), SPRM should be considered as an alternative
to surgical therapy, or at least additional to surgery, in some circumstances, as
illustrated in the algorithm.
 SUMMARY
In conclusion, asymptomatic fibroids do not require
treatment after the diagnosis is confirmed by
ultrasonography or MRI. Women must be made aware
of all available treatment options (medical, radiological
and surgical) and why they may or may not be
appropriate. Gynecologists now have new tools in their
new strategies for the management of uterine fibroids.