Endometriosis

& Adenomyosis
By R1 Jiratsaya Dankawna 22/07/2020
References
ENDOMETRIO
SIS
 Definition
• Presence of endometrial-like tissue
(glands and/ or stroma) outside the
uterus

• Prevalence 3% to 43% in
asymptomatic women up to 50% in
unexplained fertility patients

Berek & Novak’s Gynecology. 16th edition. 2019.

 Risk factor
• Infertility
• red hair
• Early age at menarche,
• Shorter menstrual cycle length
• Hypermenorrhea
• nulliparity,
• Mullerian anomalies
• Low birth weight
• (Less than 7 pounds)
• Being one of multiple gestation,
• Diethylstilbestrol exposure,
• Endometriosis in first degree relative
• Tall height
• Dioxin or polychlorinated biphenyls
exposure
• A diet high in fat and red meat
• Prior surgeries or medical therapy for
endometriosis
Berek & Novak’s Gynecology. 16th edition. 2019.
 Pathogenesis

• Retrograde menstruation
and implantation
• Coelomic metaplasia

ALLPPT.com
Berek & Novak’s Gynecology. 16th edition. 2019.
Petra A.B., et al. Molecular and Cellular Pathogenesis of Endometriosis. Current Women’s Health Reviews, 2018, 14, 106-16.
 Genetic factor
Genetic factor

• Endometriosis is six to seven times more prevalent

among first-degree relatives of affected women
than in the general population.

• Gene-expression profiling has identified candidate

susceptibility genes relating to implantation failure,
infertility, and progesterone resistance.

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Molecular mechanism

• Compared to normal endometrium, ectopic

endometrial implants produce excessive amounts
of estrogen, prostaglandins, and cytokines.

• Abnormalities intrinsic to the endometrium of

women who develop endometriosis predispose to
cell survival, ectopic implantation, proliferation, and
chronic inflammation.

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Molecular mechanism

• Ectopic endometrium appears even more

resistance to apoptosis

• Resistance to apoptosis may improve the survival

of endometrial cells entering the peritoneal cavity
and also help to explain why ectopic endometrium
is resistant to macrophage-mediated immune
surveillance and clearance.

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Progesterone

17β-hydroxysteroid dehydrogenase ↑

Estradiol Estrone ↑
Normal
woman

COX-2 ↓ Aromatase enzyme ↓

PGE2 ↓
Estrogen production ↓
Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Progesterone ↓ Progesterone resistance

17β-hydroxysteroid dehydrogenase ↓

Estradiol ↑ Estrone ↓

Woman
With Endometriosis

COX-2 ↑ Aromatase enzyme ↑

PGE2 ↑
Estrogen production ↑
Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Epigenetic changes

MMP TNF-α, Integrins

MCP-1,RANTES

VEGF,MDGF,Fibronectin
IL-1, IL-8

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Mechanism of infertility
The pain associated with endometriosis has been attributed
to three primary mechanisms.

The direct and indirect effects of focal bleeding from endometriotic implants

Contents
The action of inflammatory cytokines in the peritoneal cavity

Irritation or direct infiltration of nerves in the pelvic floor

Contents

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Mechanism of infertility
Between 20% - 40% of infertile women have disease

• Distorted adnexal anatomy that inhibits or prevents

ovum capture after ovulation
• Excess production of prostaglandins,
metalloproteinases, cytokines, and chemokinases
resulting in chronic inflammation

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Dysmenorrhea
Signs
Cyclic pelvic pain
And
Symptoms
Dyspareunia

Intestinal complaints

Infertility

Mass
 Vaginal examination
Infiltration or nodules of the vagina,
Uterosacral ligaments, pouch of Douglas

Rectovaginal digital examination

Infiltration or mass involving the rectosigmoidal colon or adnexal masses

Deeply infiltrating endometriosis : Particular form of endometriosis that penetrate >5 mm.
under the peritoneal surface

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 rk e rs
a
Biom
MRI
ag ina l
sv
Tran graphy
ro s co py sono
Lapa iopsy
With b logy
o
01 &hist

Medical technologies
in the diagnosis
Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 Surgical diagnosis
The classic peritoneal implant

• Blue-black “powder burn” lesion

(containing hemosiderin deposits
from entrapped blood) and varying
amounts of surrounding fibrosis

• Typically observed on the ovaries and

on peritoneal surfaces in the Cul-de-
sac, uterosacral ligaments, and
ovarian fossa.
Berek & Novak’s Gynecology. 16 th edition. 2019.
Surgical diagnosis - Laparoscopy
The majority of implants are “Atypical”

• White and opaque

• Red and flame-like or vesicular

Berek & Novak’s Gynecology. 16th edition. 2019.

 Surgical diagnosis - Laparoscopy
• Large endometriomas usually locate on the anterior surface of the ovary
and associate with reaction, pigmentation, and adhesions to the posterior
peritoneum
• Endometrioma features: cyst diameter < 12 cm, adhesion to pelvic
sidewall or broad ligament, on surface of ovary, and tarry, chocolate-colored
fluid content

Berek & Novak’s Gynecology. 16th edition. 2019.

 Surgical diagnosis - Laparoscopy
Microscopic endometriosis
Histologic appearance : endometrial glandular epithelium, surrounded
by stroma in typical lesion and clear vesicle

Consist of endometrial glands and/ or stroma

with or without hemosiderin-laden macrophages

Berek & Novak’s Gynecology. 16th edition. 2019.

Classification and staging systems (ASRM 1996)

American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67:817-821
Classification and staging systems (ASRM 1996)

American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67:817-821
Deep Infiltrating
Endometriosis

Johnson NP, et al. World Endometriosis Society consensus on the classification of endometriosis. Human Reproduction, Vol.32, No.2pp. 315-324, 2017.
Berek & Novak’s Gynecology. 16th edition. 2019.
 Transvaginal sonography
Compared to laparoscopy, transvaginal ultrasound has no value in diagnosing
peritoneal endometriosis, but it is useful in making or excluding the diagnosis of an
ovarian endometrioma

Imaging: Transvaginal ultrasonography can detect ovarian endometriomas

Sensitivity = 90%, specificity = 100%

Ground glass echogenicity of the

cyst fluid, one to four locules and no
solid parts no papillary structures with
detectable blood flow

Clinical gynecologic endocrinology and infertility/ Marc A. Fritz, Leon Speroff. 8 th edition. 2011.
 MRI
MRI has good sensitivity and specificity for the diagnosis of deep
endometriosis and endometriomas
Clinicians should be aware that the usefulness of magnetic resonance
imaging to diagnose peritoneal endometriosis is not well established
(Stratton, et al., 2003)

Berek & Novak’s Gynecology. 16th edition. 2019.

ESHRE Endometriosis Guideline Development Group, 2013.
 CA 125
Serum CA -125 in the diagnosis of endometriosis

Clinicians are recommended not to use biomarkers in endometrial

tissue, menstrual or uterine fluids to diagnose endometriosis
(May,et al.,2011)
Compared with Laparoscopy, measurement of serum CA 125
levels has no value as a diagnostic tool

ESHRE Endometriosis Guideline Development Group, 2013.

Treatment
 Asymptomatic endometriosis

The GDG recommends that clinicians should not routinely perform

surgical excision and ablation for an incidental finding of asymptomatic
endometriosis at the time of surgery, since the natural course of the
disease is not clear

ESHRE Endometriosis Guideline Development Group, 2013.

 Treatment decision
• Age
• Clinical presentation
(Pain, Infertility, mass)
• Symptom severity
• Disease extent and location
• Previous management
• Reproductive desires
• Cost
• Patient preference
• Medication side effects
• Risk of surgical complication
• Treatment available in center
 Treatment goal
• Pain relief
• Avoiding rupture or torsion
• Excluding malignancy
• Preventing symptomatic or expanding
endometriomas
Treatment of endometriosis associated pain

• Empirical treatment
• Medical treatment
• Surgical treatment
• Pre or postoperative medical
treatment
• Non-medical treatment

ESHRE Endometriosis Guideline Development Group, 2013.

 Empirical treatment

The GDG recommends clinicians to counsel women with

symptoms presumed to be due to endometriosis thoroughly,
and to empirically treat with adequate analgesia, combined
hormonal contraceptives or progestagens

ESHRE Endometriosis Guideline Development Group, 2013.

Medical treatment

• Progestagens and anti-progestogens

• GnRH agonist
• Hormonal contraceptives
• Aromatase inhibitors

ESHRE Endometriosis Guideline Development Group, 2013.

Medical treatment

ESHRE Endometriosis Guideline Development Group, 2013.

 Progestagens and anti-progestogens

Side effect : Nausea, weight gain, fluid retention, breast tenderness, irregular bleeding, depression
at higher dose resulting in spinal bone mineral depletion

ESHRE Endometriosis Guideline Development Group, 2013.

 GnRH agonist

Side effect : Bone mineral depletion, hot flashes, progressive vaginal dryness, decrease libido, depression, irritability, fatigue,
headache, changes in skin texture,

ESHRE Endometriosis Guideline Development Group, 2013.

Hormonal contraceptives

ESHRE Endometriosis Guideline Development Group, 2013.

 Aromatase inhibitors

Side effect : Significant bone loss with prolong use, cannot be used alone in premenopausal causing development of multiple
ovarian cyst
ESHRE Endometriosis Guideline Development Group, 2013.
 Treatment of endometriosis associated pain
Medication Leve Side effect Cost
l
1) Progestagen A Weight gain, spotting Dienogest
- Oral progestin (MPA, META,Dienogest) 2,000B/Mo
- DMPA (IM) Reversible bone marrow density 14B/3Mo
- LNG – IUD Suitable for recto-vaginal DIE Less side effect 7,000/5Y

2) Anti - progestogen A Low side effect N/A

- Gestrinone
3) GnRH agonist A Flare up effect, vasomotor symptom 5,000/Mo
- Leuprolide acetate Decrease bone marrow density if more
than 6 months use
4) Oral contraception B
5) Danazol A Irreversible hoarseness N/A
Hyperandrogenism

6) Aromatase inhibitor B Development of multiple ovarian cyst FDA not

- Letrozole approve
Surgical treatment

ESHRE Endometriosis Guideline Development Group, 2013.

Laparotomy and Laparoscopy are equally effective
in the treatment of endometriosis-associated pain

• Laparoscopic surgery is usually associated

with less pain, short hospital stay, quicker
recovery and better cosmetic outcome

ESHRE Endometriosis Guideline Development Group, 2014.

Surgical interruption of pelvic nerve pathways

ESHRE Endometriosis Guideline Development Group, 2013.

Surgery for treatment of pain associated with
Peritoneal endometriosis

ESHRE Endometriosis Guideline Development Group, 2013.

Surgery for treatment of pain associated with
ovarian endometrioma

ESHRE Endometriosis Guideline Development Group, 2013.

Surgery for treatment of pain associated
with deep endometriosis

ESHRE Endometriosis Guideline Development Group, 2013.

 Comparison
Peritoneal Ovarian Deep
Endometriosis Endometrioma Endometriosis
Both ablation and Cystectomy Surgical removal
excision

ESHRE Endometriosis Guideline Development Group, 2013.

Hysterectomy for endometriosis
associated pain

ESHRE Endometriosis Guideline Development Group, 2013.

Adhesion prevention after
endometriosis surgery

ESHRE Endometriosis Guideline Development Group, 2013.

Preoperative hormonal therapies
for treatment of endometriosis
associated pain

ESHRE Endometriosis Guideline Development Group, 2013.

 Postoperative hormonal
therapies for treatment of
endometriosis associated pain

ESHRE Endometriosis Guideline Development Group, 2013.

 Treatment of pain associated
with extragenital endometriosis

ESHRE Endometriosis Guideline Development Group, 2013.

Treatment of endometriosis
associated infertility
 Hormonal therapies for
treatment of endometriosis-
associated infertility

ESHRE Endometriosis Guideline Development Group, 2013.

Menopause in women with endometriosis

ESHRE Endometriosis Guideline Development Group, 2013.

ADENOMYOSI
S
 Definition
• Presence of endometrial stroma
and glands within the myometrium
• Usually older than 40 years,
increasing parity, early menarche
and shorter menstrual cycles

• Adenomyosis, endometriosis and

uterine leiomyomas frequently
coexist

Berek & Novak’s Gynecology. 16th edition. 2019.

 Classic symptoms
Signs
• Excessively heavy or prolonged
And menstrual bleeding
Symptoms • Progressive dysmenorrhea
• Dyspareunia

Signs
• Uterus typically diffusely enlarge
• Usually less than 14 cm in size
• Often soft and tender, particularly at the
time of menses.

Berek & Novak’s Gynecology. 16th edition. 2019.

• Diffuse adenomyosis
Ectopic growth of the endometrium into the myometrium with diffuse widening of
endometrial myometrial junctional zone

• Focal adenomyosis
Ectopic growth of the endometrium into the myometrium with focal widening of
endometrial myometrial junctional zone can be found with pelvic or ovarian
endometrioma
 Diagnosis
• Adenomyosis is clinical diagnosis.
• Definitive diagnosis can only be made histologically
• Imaging studies including pelvic ultrasound or MRI are not
definitive
• Transvaginal ultrasound : accuracy rate 68%-86%
• Accuracy decrease in coexist fibroids, focal adenomyosis

Berek & Novak’s Gynecology. 16th edition. 2019.

 Management

Medical Surgical treatment

• NSAIDS • Hysterectomy
• Hormonal contraceptives
(definitive treatment of choice)
• Menstrual suppression using
oral, intrauterine, or injected
progestins or GnRH agonists

Berek & Novak’s Gynecology. 16th edition. 2019.

 Indication for surgery
• Pressure symptoms
• Abnormal uterine bleeding causing anemia
• Excessively enlarged uterine size (>12 weeks gestation)
• Fail medication
 Medical treatment of Adenomyosis
Administration Dose Frequency
Medroxyprogesterone acetate (10B) PO 20-100mg Daily

Dienogest (76B) PO 2mg Daily

Megestrol acetate PO 40mg Daily
Lynestrenol PO 10mg Daily
Dydrogesterone PO 20-30mg Daily
Depot medroxyprogesterone acetate IM 150mg 3 months
(14B/3mo)
Gestrinone PO 1.25/2.5mg Twice weekly
Danazol PO 400mg Daily
Leuprolide SC 500mg Daily
Leuprolide (5,532B) IM 3.75mg Monthly
Goserelin SC 3.6mg Monthly

Buserelin IN 300mcg Daily

SC 200mcg Daily

Nafarelin IN 200mcg Daily

Triptorelin IM 3.75mg Monthly
Levonorgestrel (6,000B/5yr) IUD Release 20mcg/d -

Anastrozole PO 1mg Daily

Letrozole PO 2.5mg Daily
 Take home message

• Sign and symptoms

• Examination
• Suitable treatment : Medication, Surgery
• Infertility
THANK YOU
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