ADENOMYOSIS

Kanadi Sumapraja
(kanadisuma@yahoo.com)

Division of Reproductive Immuno-endocrinology

Department of Obstetrics and Gynecology
Faculty of Medicine University of Indonesia
 History

First recognized by Rokitansky in 1860 Cytosarcoma

adenoides uterinum
Von Recklinghausen (1896) adenomyomata and
cystadenomata of the uterus and tubal wall
Cullen (1908) describe the differences between
adenomyoma and diffuse adenomyoma
The term of adenomyosis firstly used by Frankl (1925)
Usually unsuspected pre-operatively and the diagnosis is
established by histopathological examination
 Definition

The presence of endometrial glands and

stroma located haphazardly deep within
the myometrium
Ferenczy

The thickness of the uterine wall varies among women

Invagination of basal endometrium Deeply located endometrial glands
surrounded by hypertrophic myometrium,
 Incidence

Varied widely, ranging from 5.7% - 69.6%

No body knows how many exactly
Bird et al (1972) : found 31% from 200 hysterectomy specimens
Lewinski et al (1931); Kistner et al (1964) : performed necropsy
studies and found in around 50%
Correlate strongly with parity 93% of patients are parous
(Owolabi et al 1971 and Vercillini et al 1991)
 Risk Factors (1)

Lower education (OR 1)

Non-smoker (OR 1)
Endometrial hyperplasia (OR 2.5)
Multi-parity (OR 3.1)
One or more spontaneous abortion (OR 1.7)
Heavy menstrual flows (OR 1.7)
Dilatation and curettage (OR 2.2)
Inter-menstrual pelvic pain (OR 1.6)
Dyspareunia (OR 1.4)

Parazzini et al, 1997

 Risk Factors (2)

No correlation with IUD or OC

No correlation with age at first birth and history of induced

abortion
No correlation with age at menarche, menopausal status,
menstrual pattern and duration of flows
Dysmenorrhea was not related

Parazzini et al, 1997

Coexistence with other pathologies

30%

25%

20%

15%

10%

5%

0%
Fibroids Genital Cervical Ca Endom etrial Ovarian Ca Ovarian cyst
prolapse Ca
Vercellini et al, 1996
The difference between myoma vs adenomyosis

Its relationship with the remaining uterine wall

Myoma Adenomyosis

More circumscribed; can be Has no cleavage plane;

enucleated from its pseudo- difficult to be excised
capsule
 Pathophysiology
Results of down growth and invagination of the basalis endometrium
into the myometrium (Ridley, 1968)
 Pathophysiology

HLA

Macrophages

B cells T cells
 Clinical features (1)

Metrorrhagia

Menorrhagia

Dysmenorrhea

About 35% of adenomyotic cases are asymptomatic

Benson & Sneeden, 1958

 Clinical features (2)

Poor contractibility
MENORRHAGIA Compression of the endometrium
Arachidonic acid metabolism
(PGF2a)

Hypercontractility

DYSMENORRHEA
 Clinical features (3)
Auto-immune response

Activation of immune
components

Secretes variety of
cytokines

Over-expression of COX-
2

Prostaglandin increased
Ota et al, 2001
 Clinical features (4)
Late Follicular Mid Secretory
Control
Patients

Ota et al, 1998

 The role of EMI
(Endometrial-Myometrial Interface)

Basal endometrium and

Sub-endometrial myometrium

Sperm transportation, embryo

implantation, placental
development and menstruation

Fertility

Uduwela et al, 2000

 Infertility
the invasion of basal endometrial gland and basal
endometrial stroma into the underlying myometrium

Peristromal muscular cells of the adenomyotic lesions, a muscular

tissue develops that is, in contrast to the archimyometrium with its
circular muscle fibres, irregularly arranged

Presumably responsive to the endocrine and

paracrine stimuli that regulate uterine peristalsis

Increased intra-uterine pressure and

dysperistalsis during late follicular phase Kunz et al, 2005
 Diagnosis

Imaging techniques should aim at three goals :

To diagnose the condition with sufficient sensitivity,

specificity and predictive power in a non-invasive manner
To determine the extent of the pathological zone and the
depth of the infiltration
Follow-up of patients after receiving conservative
management
Hystero-Salphyngography (HSG)

Characteristic finding : multiple spicules 1-4 mm in length

extending from the endometrium to the myometrium
Only 25% patients truly had adenomyosis (low accuracy)
Goldberger, 1949

HSG is no longer used

in the evaluation for
adenomyosis !!!

Dr SM Ascher
 Ultrasound
Trans-abdominal US relatively poor to differentiates between
adenomyosis and uterine myoma

Bohlman et al, 1987; Siedler et al, 1987

Trans-vaginal US is more reliable

Most common finding :
poorly marginated hypo-echogenic and heterogeneous area;
small myometrial cysts;
absence of circular vascularization at the border of the lession
Reinhold et al, 1998
Adenomyosis vs Leiomyoma

Reinhold et al, 1998

 Some important points

Echo texture is not uniform, with poorly defined borders

Minimal mass effect on the endometrium or the serosa
Elliptical shape rather than globular
Lack of edge shadowing
Small myometrial cysts or spaces scattered throughout
myometrium
Echogenic nodules or linear striation radiating out from
the endometrium into the myometrium
Absence of circular vascularization at the border of the
lession
Devlieger et al, 2003
 Treatment options

Definitive treatment HYSTERECTOMY

Conservative treatment

Vessel embolization Hormonal treatment Surgical

 Vessel embolization

Interventional radiological techniques to embolize the

uterine vessels selectively

The reported series are small, and so far no successful

pregnancy was described

Improvement in quality of life in 12 out of 13 patients

Siskin et al, 2001
Uterine artery embolization
 Hormonal treatment (1)

For symptomatic relief :

Progestagens, OCs, Danazol and GnRH analogue

Progestagens MPA 30-50 mg daily

OCs Continuous therapy, withdrawal bleed every

4-6 months
Danazol Minimum dosage of 400 mg daily

GnRH analogue Consider add back therapy if using more

than 6 months or climacteric symptoms
does occur

Wood, 1998
 Hormonal treatment (2)

LNG-IUS can reduce menorrhagia, dysmenorrhea and uterine

size after 12 months
Fedele et al, 1997
BUT Fong and Singh, 1999

No pregnancies have been reported so far

Before After

LNG-IUS reduces VEGF expressions

Laoag-Fernandez et al, 2003
 Hormonal treatment (3)
Danazol loaded IUD also effective in reducing dysmenorrhea
and menorrhagia
Shawki and Igarashi, 2002

Danazol loaded IUD for

adenomyosis patients did not
give any systemic effects

Igarashi et al, 2000

 Hormonal treatment (4)
Eutopic
Ectopic Proliferative Secretory GnRH treated

Adenomyosis Inflammatory response NO over-production Fertilization

Implantation
Ovulation
Estrogen
Kamada et al, 2000
 Surgical (1)

Drugs treatment fail or patients indicate a preference for surgery

Indications for surgery n = 54

Failed medical treatment
OC pill 30
Progestogens 8
Danazol 3
GnRH analogue 5

Patient preference for surgical 8

treatment

Wood, 1998
 Surgical (2)

Uncertainty in defining the site and the extent of

adenomyosis difficult to determine the feasibility
and the accuracy of complete excision

The choice of surgical technique should consider :

The site and extent of disease
The age of the patient
The desire for future pregnancy
The patients desire for certain cure or not
The surgical skill of the gynecologist
 Surgical (3)

Cyto-reductive surgery
Impaired fertility might be due to smooth muscle cell
hyperplasia and hypertrophy secondary to ectopic
endometrial proliferation interfere gamete transportation
and/or implantation process
Removing a relatively poor blood supply tumor
Enhancing immune function of the host
Enhancing the response of remaining tumor to chemotherapy

Kenny et al, 2000

Wang et al, 2000
 Surgical (4)

Microsurgical technique
To avoid extensive injury of the uterus

Initial vasopressin injection

Mid-line incision on the anterior wall
Meticulous coagulation
Continuous irrigation with heparin-containing warm saline
(5000 iu in 500 mL)
Careful excision to prevent uterine cavity damage
Application of an adhesion-prevention barrier
Clearing of the abdominal cavity
Wang et al, 2000
 Surgical (5)

GnRHa as an adjuvant treatment prior or after surgery ?

Prior treatment (n=23) (2+2) After treatment (n=33) (0+4)

Smaller uterine volume

Lesser blood loss intra-operatively
Less post-operative recurrence rate
Lower Ca-125 level
Higher pregnancy rate

Pre-operative treatment :
Decrease the difficulty of surgical procedure; decrease post-operative
symptoms; improve pregnancy rate

Chang et al, 2002