Update on Endometriosis - Grampians Medicare Local

Report
Update on Endometriosis
Grampians Medicare Local
2nd September, BHS
Russell Dalton
Ballarat IVF
Ballarat Endometriosis Clinic
Obstetrics & Gynaecology Ballarat
The Aim today..
 Young women with possible endometriosis
 Older women with suspected endometriosis
 What to look for.
 Treatment options & rationale for these
 Aromatase inhibitors
 The role of endometriosis in subfertility
 The future of endometriosis treatment
Endometriosis
 Common condition 2-10 % of women
 Presents: varying stages of reproductive life
 Later presentation , tends to be more severe
 Ectopic endometrium,




Pelvis, mainly in dependent areas.
Peritoneal cavity
Rarely other locations,
Rarely in oestrogenised males
Endometriosis images
 Micro
Endometriosis:
what happens?
 Theories:
 In situ development: coelomic metaplasia
 Induction theory: differentiation of mesenchymal cells
 Transplantation Theory: implantation of retrograde
menstruation
 Need a process of:
 Survival of detached cells, attachment & invasion of
peritoneum,
 Proliferation & Neo-vascularization
Why does it happen?
 Endometriosis cells : marked resistance to Apoptosis
 Role of CD 1347 cell membrane glycoprotein controlling cell
migration & Cadherin lack ( Inhibits cell spread)
 Matrix metallo-proteinases ( disrupt intercellular bonds)
 Vascular &epithelial growth factors, cytokines, growth factors
(VEGF) released by abnormally functioning leucocytes
 Genetics: Clear familial association
 6-7x more prevalent in first degree relatives of affected women
 ?disease of Epigenetic origins increasing evidence
Endometriosis- The cost
 Major burden on Health services
 Annual Healthcare costs (US) :$2801 per patient
 Loss of productivity
(US) $1023 per patient
 Significant adverse influence on QOL & rates of
depression.
 Contributor in 50% of couples with infertility
Endometriosis-Presenting
symptoms
 Pelvic pain
 Dysmenorrhea
 Pain related to function of pelvic organs
 Bloating
 Psychological sequelae.
 Subfertility / Infertility
Endometriosis in Young
women
 Difficult clinical challenge.
 Often generalized Gynae symptoms:
 Pain, irregular bleeding, bloating, headaches, lethargy
 What is normal?
 Other influences on symptoms:

puberty, relationships etc
 Is something else going on ?
Endo in Young women
 Clinical assessment:
 Appropriate history including sexual history
 NB Ballarat 40% higher teen mum rate than Vic
average)
 More specifically related to menstrual cycle, more
likely to be endometriosis
 Physical examination: limited due to age etc
 Ultrasound : TA Sensitivity - limited
 Exclude other causes – sepsis, IBD other bowel
pathology,
Endo in Younger women.
Treatment Principles
 Our Goal:




Minimize symptoms & side effects
Stay out of Emergency Department
Stay off codeine/Narcotic based analgesia
Have High QOL / emotional well being scores
 Suppression of ovulation
Ovulation Suppression
 via continuous hormonal regimen
 Reduces endometriosis activity
 Controls cyclical, dysmenorrhea.
 Options:
 OCP, Depo, Nuva Ring.
 Only standard preparations apart from GnRH
analogues
 2 Microlut/day
 Need to use combinations of other medications if
alternatives needed
Endometriosis & Mirena
 Shown to reduce dysmenorrhea but not
dyspareunia
 Doesn’t suppress ovulation
 Need equivalent of 50mcg levonorgestrol/day
 So : Mirena(20 + microlut 30)
Often used in conjunction with laparoscopy

Difficult insertion in nulliparous
 Additional benefit with associated Adenomyosis
Endometriosis & Implanon
 Observational study & small RCT
 improvement of symptoms





Dysmenorrhea
Dyspareunia
Non menstrual pelvic pain
Similar to Depo for 12/12 ( Ovulation suppression)
? Double dose Implanon
Endo in Younger Women
 Treatment of pain:
 Analgesics
 NSAIDS: best for Gynaecological pain. Prob best for endo
 Paracetamol /Codeine /doxylamine
 Exercise: Consistent reduction in pain scores
 Diet & Vitamins
 Vegetarian diet, Increased dairy intake
 Fich oilB1, B 6 :
 Vitamin D starting 5 days pre menstrually
Endo in younger women:
Pyschological support
 CBT & Psychology.
 General support: Clinician support, encourage
compliance& continuous hormonal regimen.
 Endometriosis Nurse: email, text &phone support
 Allay concerns regarding side effects
 Often treatment regimens require changing
Endometriosis in younger
women
 When to perform a laparoscopy:




Complex symptoms
Poor response.
Ultrasound abnormalities.
Abnormalities on examination (can be limited)
 Findings are often mild endometriosis,
 Occasional localised disease able to be excised.
 Small biopsy required to confirm diagnosis
Miliary pattern
Endometriosis
 Insert pic
Post Laparoscopy
Management
 Change of OCP:
 more progestagenic
 Norinyl 1 +/- additional norethisterone
 Other OCP
 Zoladex GnRH analogues
 ? Aromatase inhibitors + OCP / progestagens
 Nurse/ Clinician support.
Endometriosis on older
women ( 30yrs +)
 CAN present as younger women do.
 BUT usually more extensive/infiltrating
 Elucidate localizing symptoms.
 Ipsilateral dysmenorrhea & dyspareunia
 Menstrual related dyschezia & sacral pain.
 Bowel dysfunction
 Generalized intermenstrual pelvic pain
 Intermenstrual bleeding &menorrhagia
 (?associated adenomyosis)
Endo in older women (
30yrs +)
 What to look for on examination.
 Localized tenderness in the posterior & lateral
fornix
 Positioning of the cervix
 Deviation laterally
 Nodularity /crimping of the vagina
 Mobility & tenderness of the uterus
 ?associated Adenomyosis
Endometriosis in the
posterior fornix
Endo in older womenUltrasound Assessment
 Look at pelvic organs, fibroids,
cysts/endometriomata, endometrial, myometrial
pathology
 AND parametrial & pelvic side wall characteristics
 Increased & discordant uterosacral & parametrial
echoes
 Pouch of Douglas peritoneal thickening
 Rectosigmoid- cervicouterine tethering
 Rectovaginal space tethering
CA 125
 CA 125 cell surface antigen from derivatives of
coelomic epith.
 Not a sensitive test, but often elevated, esp with
endometriomas & more advanced disease
 Other causes: menstruation, ovulation, Infection,
fibroids, pregnancy, Ovarian cancer
 Older the patient, more careful consideration of
elevated level
Management
 Same principles as for younger women
 Ovulation suppression
 Stable hormonal environment
 Analgesia
 May need combination therapy
 Consider earlier surgical intervention for associated
abnormalities on clinical/ultrasound examination
Endometrioma
 Invagination of ovarian serosal endometriosis
 - Damage ovaries
 80% associated with Pouch Endometriosis.
 Surgical treatment requires care
 Diff Diagnosis: Functional cyst, Dermoid.
 Confirm with trial of OCP suppression
Endometrioma
 Add US & lapy image
Bowel involvement
usually bowel symptoms
 Show lapy image
Bowel Involvement
 Initial planning laparoscopy: EUA, Images
 Combined Gynae & Colorectal surgical approach.
 Often Zoladex to reduce volume & inflammation
 Bowel prep, preop planning(nurse), consult x 2
 Strict systematic approach to surgery.
 Disc excision,or segmental bowel resection, often
“ultralow” anastamosis
 Careful resection back to normal tissue
Complex endometriosis
surgery

Endometriosis &
Aromatase
 Converts Androgen to Oestrogen
 Aromatase inappropriately expressed in eutopic
endometrium & endometroisis
High levels of expression in endometriomas.
Facilitates local production of Oestrogen.
>> stimulates proliferation of endometriosis deposits
New Agent for
Endometriosis
 Aromatase inhibitors:
 Anastrazole, Letrozole. (off label)
 For those with refractory pain& minimal visible
disease.
 Add to current regimens
 In combination with OCP or progestagen
 Can be used in conjunction with Zoladex
 Significant reduction in pain scores
 Note: Bone loss Risk : Ca. Vit D supps .
Subfertility:
What is normal Conception
rate?
 Age influenced.
 Life plans
 Other fertility factors
 Male factor
 Lifestyle Obesity, Smoking,
 Ovulation.
 12 month definition is fairly blunt instrument
25-30 yr old Healthy
couple fecundability
Endometriosis &
subfertility
 Strong association. 40 -50% with subfertility
 (OGB :70%of fertility pts have endometriosis)
 Often have minimal pain.
 Many couples have a number of contributing factors
 Need to optimize each factor.
 Older the woman more important to correct
contributing factors
Endometriosis contributes
to subfertility
 Distortion of pelvic structures
 Ovarian damage ( reduced reserve)
 Abnormal Eutopic endometrium
 Impaired fertilization (inflammatory mediators)
 Poor oocyte quality
 -Better pregnancy with normal donor eggs
 -Worse rates from endometriosis egg donors
Outcomes of Interventions:
Natural attempts
200 couples planning pregnancy
• 60% of pregnancies occur in
3 cycles of Rx
No. Pregnancies(cumulative)
180
160
• 70% in 5 cycles of treatment
140
• Any intervention has similar
shaped curve
Number pregnant
120
100
No. Pregnancies(cumulative)
80
60
40
20
0
1
2
3
4
5
6
7
8
Cycle Number (mths)
9
10
11
12
Fertility Treatment options
 Expectant
 Younger woman, couple desires
 Surgery
 Excision deposits, tubal patency, endometrial biopsy
 Ovulation induction with IUI
 Letrozole, FSH, Clomiphene
 IVF.
 Fertilization outside pelvis, embryo selection
Effects of Endometriosis on
treatment outcomes
 Subfertile couples with endometriosis have lower
pregnancy rates.
 Compared to male factor, tubal factor, idiopathic
 Due to:
functional, proteomic abnormalities in Eutopic
endometrium
 Ongoing adverse effects of endometriosis on pelvic
environment. Via inflammatory mediators
 Reduced oocyte quality

 Adverse effect correlates with severity, and age
Results of treatment on
Endometriosis related fertility
 Complex interpretation of influence of each
component.

Surgical studies
 Heterogeneous disease pattern
 Inter patient variation & variable surgical techniques.
 Different thresholds for intervention
 Often multifactorial infertility
 Age variations
Overall, we can say..
 Natural conception can still be pursued

Ovulation induction + IUI improves pregnancy rates
 2-3 cycles only
 Excision surgery for mild-moderate reduces time to pregnancy.


Improves implantation rates
Improves natural conception rates.
 Treatment of Endometriomas reduces oocyte yield, but increases
natural conception rates & reduces infection rates from IVF,
 “Long down regulation” with Zoladex prior to IVF improves
pregnancy rates in women with severe endometriosis
The Future of
Endometriosis treatment
 Immunologically based Therapy influencing
Leucocyte function
Chemokine receptor 1 antagonist ( CCR-1)
 Anti Nerve growth factor ( ANGF)
 Endometriosis as an epigenetic disease
 Hypermethylation of promoter genes cause aberrant
expression esp of aromatase & cadherin 1
 Histone DeaCetylase Inhibitors ( HDACI s) may reverse
hypermethylation : (Valproate)
Summary
 Endometriosis is a common condition.
 Young women: mild , use hormonal therapy
 Older women; look for localizing symptoms
 Ovulation suppression –range of options
 Significant influence on fertility
 Surgical management can be technically complex
requiring multidisciplinary approach.

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