Update on Endometriosis - Grampians Medicare Local
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Transcript Update on Endometriosis - Grampians Medicare Local
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.