Update on Endometriosis - Grampians Medicare Local
Update on Endometriosis - Grampians Medicare Local
Update on Endometriosis
Grampians Medicare Local
2nd September, BHS
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
The role of endometriosis in subfertility
The future of endometriosis treatment
Common condition 2-10 % of women
Presents: varying stages of reproductive life
Later presentation , tends to be more severe
Pelvis, mainly in dependent areas.
Rarely other locations,
Rarely in oestrogenised males
In situ development: coelomic metaplasia
Induction theory: differentiation of mesenchymal cells
Transplantation Theory: implantation of retrograde
Need a process of:
Survival of detached cells, attachment & invasion of
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
Contributor in 50% of couples with infertility
Pain related to function of pelvic organs
Subfertility / Infertility
Endometriosis in Young
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
Appropriate history including sexual history
NB Ballarat 40% higher teen mum rate than Vic
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
Endo in Younger women.
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
via continuous hormonal regimen
Reduces endometriosis activity
Controls cyclical, dysmenorrhea.
OCP, Depo, Nuva Ring.
Only standard preparations apart from GnRH
Need to use combinations of other medications if
Endometriosis & Mirena
Shown to reduce dysmenorrhea but not
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
Non menstrual pelvic pain
Similar to Depo for 12/12 ( Ovulation suppression)
? Double dose Implanon
Endo in Younger Women
Treatment of pain:
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:
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
When to perform a laparoscopy:
Abnormalities on examination (can be limited)
Findings are often mild endometriosis,
Occasional localised disease able to be excised.
Small biopsy required to confirm diagnosis
Change of OCP:
Norinyl 1 +/- additional norethisterone
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.
Generalized intermenstrual pelvic pain
Intermenstrual bleeding &menorrhagia
Endo in older women (
What to look for on examination.
Localized tenderness in the posterior & lateral
Positioning of the cervix
Nodularity /crimping of the vagina
Mobility & tenderness of the uterus
Endometriosis in the
Endo in older womenUltrasound Assessment
Look at pelvic organs, fibroids,
cysts/endometriomata, endometrial, myometrial
AND parametrial & pelvic side wall characteristics
Increased & discordant uterosacral & parametrial
Pouch of Douglas peritoneal thickening
Rectosigmoid- cervicouterine tethering
Rectovaginal space tethering
CA 125 cell surface antigen from derivatives of
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
Same principles as for younger women
Stable hormonal environment
May need combination therapy
Consider earlier surgical intervention for associated
abnormalities on clinical/ultrasound examination
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
Add US & lapy image
usually bowel symptoms
Show lapy image
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
Careful resection back to normal tissue
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
Anastrazole, Letrozole. (off label)
For those with refractory pain& minimal visible
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 .
What is normal Conception
Other fertility factors
Lifestyle Obesity, Smoking,
12 month definition is fairly blunt instrument
25-30 yr old Healthy
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
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:
200 couples planning pregnancy
• 60% of pregnancies occur in
3 cycles of Rx
• 70% in 5 cycles of treatment
• Any intervention has similar
Cycle Number (mths)
Fertility Treatment options
Younger woman, couple desires
Excision deposits, tubal patency, endometrial biopsy
Ovulation induction with IUI
Letrozole, FSH, Clomiphene
Fertilization outside pelvis, embryo selection
Effects of Endometriosis on
Subfertile couples with endometriosis have lower
Compared to male factor, tubal factor, idiopathic
functional, proteomic abnormalities in Eutopic
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
Heterogeneous disease pattern
Inter patient variation & variable surgical techniques.
Different thresholds for intervention
Often multifactorial infertility
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
Immunologically based Therapy influencing
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)
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.