This document discusses various treatment options for endometriosis. It covers medical treatments like NSAIDs, combined oral contraceptives, progestagens, GnRH agonists, and aromatase inhibitors. Surgical treatments include ablation/excision of endometriotic lesions, cystectomy, and hysterectomy for severe cases. Adjuvant procedures like presacral neurectomy and LUNA are also mentioned. Recurrent endometriosis and extra-pelvic endometriosis involving the urinary tract, intestines, and abdominal wall are briefly covered. Novel treatments under investigation include Elagolix, dienogest, SERMs, and SPERMs.

1. Endometriosis
Presentor- Dr. Kajal Gupta
Moderator- Dr. Ankita nigam

3. Pain management -Medical treatment
Mainstay-- Medical therapy
 NSAIDs-
 eg. Naproxen, ibuprofen, mefenamic acid ( cox inhibitors)
 Estrogen-progestin contraceptives mild cases
 ocps in a cyclical or continuous manner
 Progestagens
 LNG IUS
 Dinogest – dose 2mg once daily for 12-24 months
 GnRH agonists  severe pelvic pain.
 Danazole

4.  Functional dysmenorrhea
 Neuromodulators (e.g., anti-depressants, selective serotonin uptake
inhibitors or anticonvulsants)
 Tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
 selective serotonin uptake inhibitors (e.g., duloxetine)
 anticonvulsants (e.g., gabapentin and pregabalin)

5.  I ST LINE: LOW DOSE OCP’S WITH NSAIDS AS NEEDED
 II LINE:PROGESTINS(START WITH ORAL DOSING,CONSIDER SWITCHING
TO LEVONORGESTEROL IUD OR DEPO IF TOLERATED
 III LINE: GnRH AGONIST WITH IMMEDIATE ADD BACK THERAPY

7. Combined oral contraceptives- continuous
or cyclical administrations
 Dose- 30-35 mg of ethinyl oestradiol used continuously
 Episodic Breakthrough bleeding is common
 Supplemental estrogen (Conjugated estrogens 1.25 mg or micronized
estradiol 2.0 mg daily for 7-10 days is used to control episodic
breakthrough bleeding.

8. Progestagens
 Progestins - an antiproliferative effect by causing initial
decidualisation of endometrial tissue followed by atrophy.
 In high doses inhibit pituitary gonadotropic secretion and ovulation
inducing amenorrhea.
 considered as a first choice for the treatment of endometriosis.
 Medroxyprogesterone acetate (MPA) – at a dose of 30 mg/day
and increasing the dose based on the clinical response and
bleeding patterns.

9. Gestrinone
 androgenic, anti-progestagenic, anti-oestrogenic and anti-
gonadotropic properties.
 dose - 2.5 mg twice a week.
 side effects are dose-dependent and include nausea, muscle
cramps, and androgenic effects such as weight gain, acne,
seborrhoea, oily hair/skin, and irreversible voice changes.
 Pregnancy is contraindicated while taking gestrinone because of
the risk of masculinisation of the foetus.

10. Gonadotropin releasing hormone agonists
 GnRH agonists bind to pituitary GnRH receptors and initially
stimulate LH and FSH synthesis and prolonged stimulation
causes down regulation of gonadotrophic activity.
 reversible state of pseudo menopause.
 Eg. leuprorelin buserelin, nafarelin, histrelin, goserelin,
deslorelin, and tryptorelin.
 intramuscularly, subcutaneously, or intranasally administered
 Add back therapy - can be achieved by progestagens only
including norethisterone 1.2 mg, norethindrone acetate 5 mg

11. Danazole
 Causes steroidogenesis, increase metabolic clearance of
oestradiol and progesterone, and interacts with endometrial
androgen and progesterone receptors.
 Dose - 400 mg daily (200 mg twice a day).
 weight gain, fluid retention, acne, oily skin, hirsutism, hot
flushes, atrophic vaginitis, reduced breast size,
 reduced libido, fatigue, nausea, muscle cramps, emotional
instability and Deepening of the voice

12. Aromatase inhibitors
 Supress estrogen production in periphery and endometric tissues as well
as ovary.
 Used in management of pain associated endometriosis.
 Includes Anastarzole (1 mg daily) and Letrozole( 2.5 mg daily)
 S/E: Multiple ovarian cysts in premenopausal women and bone loss
 use in combination with GnRH agonist or norethindrone acetate (5 mg
daily) in premenopausal women to avoid complications.

13. Surgical treatment
 If medical treatment fails
 TOC for moderate or severe endometriosis associated pain
 Performed via laparoscopy or laparotomy.
 Conservative includes
1)Ablation of endometriotic deposits
2)Cyst drainage excision of lesion
3)Laser vaporisation
4)Cystectomy
5)Nerve ablation
 Curative : Oophorectomy and Hysterectomy with B/L salpingo-
oophorectomy

14. Adjuvant procedures
 Adjuvant presacral neurectomy and laparoscopic uterosacral nerve
ablation (LUNA) advocated for management of dysmenorrhoea and severe
central pelvic pain unresponsive to medical or surgical treatment.
 Presacral neurectomy involves interrupting sympathetic innervation of
uterus at level of superior hypogastric plexus
 LUNA involves destruction of midportion of uterosacral ligments.
 Operative complications and postoperative bowel or bladder dysfunction
are uncommon.

15. Other therapies
 Accupuncture
 Physiotherapy, massage
 Excercise
 Transcutaneous Electrical Nerve Stimulation (TENS)
 Nutrition – eg. Omega 3 fatty acids, vitamin D supplement, fish oil,
antioxidants

16. Eshre recommendation

17. Novel treatment for endometriosis
 Elagolix
 Oral medication
 GnRH receptor antagonist suppreses estrogen and progesterone
 decrease inflammation and the proliferation of endometrial
tissue
a tablet for oral use in 150-mg or 200-mg
S/E- change in menstrual pattern.
C/I- pregnancy, osteoporosis

18. Dienogest
 Dienogest is a fourth- generation progestin of 19- nortestosterone
derivative.
 It is well tolerated with no androgenic glucocorticoid activity. Has
antiandrogenic properties
 Dose 2mg once daily for 12-24months
 Mechanism- binds progesterone receptor, had potent progestogenic
effect.
 Increaese progesterone receptor expression
 Decreases proinflammatory cytokines.
 Inhibition of gonadotropin secretion- reduction in endogenous
production of estradiol

19. SERM- Selective estrogen receptor
modulator
 Non-steroidal anti-estrogens bind to ERs, can act as either
estrogen agonists or antagonists, depending on the target tissue.
 Have estrogen antagonist activity on the endometrium but agonist
activity on bone and circulating lipoproteins.
 Role yet to be studied in humans.
 raloxifene- decrease volume of implants in dose dependent
manner in animal studies.

20. SPERM- Selective progesterone receptor
modulator
 Can act as either agonists or antagonists of progestogenic activity,
depending on the target tissue.
 Suppress endometrial proliferation selectively in the presence of an
estrogenic environment, allowing the treatment of endometriotic
implants without the side effects of systemic estrogen deprivation.
 Role yet to studied in humans.

21. Antioxidants-Vitamin C,Vitamin E
Tumor Necrosis Factors- inhibitors
Matrix Metalloproteinase Inhibitors
Immunomodulators
Green Tea
Stem Cells Therapy
Gene therapy

22.  Pentoxiphylline could change the immune cell function by
inhibition of Cytokine and TNF-alpha secretion. (Cochrane review
2009)
 VEGF- C suggested to be an effective factor for significant
reduction in endometriotic implants after Pentoxiphylline
administration (Vlahos et al. 2010)
 Another immunomodulator Etanercept (ETA) has promising
reductive effect equal to Letrazol in early investigation (Ceyhan et
al. 2011)

23. Recurrent endometriosis
 Spontaneous resolution occurs in about 20% of endometriosis
stage I-II.
 Residual disease- persistence of symptoms or reappearance of
symptoms within 3 months .
 Recurrence usually appears after 3 months .
 Incidence-6-30% in various studies.
 Depends on- age, stage of disease, prior treatment, completeness
of surgery, extent of peritoneal disease.
 Usually presents as chronic pelvic pain , dysmenorrhea

24.  Diagnosis- rising CA-125,TVS, MRI, laparoscopy.
Treatment-
 Pain killers
 Hormones- progesterones, OCPs, GnRH analogues
 Conservative surgery-
Indicated if medical therapy fails or contraindicated or intolerable
side effects.
Cystectomy/ adhesiolysis may be an option after IVF fails..
 Postoperative hormone therapy delays recurrence but does not
reduce the recurrence.
 LNG IUCD- reduces recurrences post surgery & role is being
studied in recurrent disease.
 Hysterectomy with bilateral salphigo oophorectomy

25. Extra‐pelvic endometriosis
 Rare type of endometriosis
 Occurs in a distant site from gynecological organs including bladder,
intestine, appendix, surgical scars, umbilicus, hernia sacs, lung, kidney,
and extremities.”
 Endometriosis can be found in almost any tissue in the body apart from
the spleen.
 Symptoms will depend on the site of the disease. Cyclicity of symptoms is
usually present
 Diagnosis is usually made by histological confirmation

26. Intestinal endometriosis
 Bowel endometriosis is present in 5-40% of patients with pelvic
endometriosis.
 Rectum and sigmoid are the most common sites (up to 95% of
cases)
 5-20% of the cases have appendix endometriosis
 Endometriosis of the small intestine is rare.
 Symptoms- chronic abdominal pelvic pain, dyschezia,
dysmenorrhoea, dyspareunia, tenesmus, constipation or
diarrhoea and rectal bleeding
 Diagnosis- laparoscopy, MRI, contrast studies or
rectosigmoidoscopy
 Surgical - Appendicular endometriosis is usually treated by
appendicectomy.

27. Urinary tract endometriosis
 Urinary tract endometriosis is found in 1-4% of women with pelvic
endometriosis
 80-90% of these are on the bladder and the rest are ureteral
endometriosis.
 Endometriosis of the kidney is extremely rare
 Ureteral endometriosis may cause obstruction and functional loss of a
kidney without causing symptoms (i.e. silent kidney).
 The majority of ureteral endometriosis lesions are extrinsic, lesions within
the wall of the ureters are less common.
 symptoms of bladder endometriosis - cyclical suprapubic pain, dysuria,
frequency and haematuria. Ureteral endometriosis is mostly
asymptomatic but may cause low back pain, haematuria and recurrent
urinary tract infections.

28.  Pelvic and abdominal ultrasonography, computerised tomography
or MRI, intravenous urography and cystoscopy with biopsy -
bladder endometriosis.
 Surgical treatment for bladder endometriosis - excision of the
lesion and primary closure of the bladder wall.
 Ureteral lesions may be excised after stenting the ureter
 In the presence of intrinsic lesions or significant obstruction
segmental excision with end-to-end anastomosis or
reimplantation of ureter.

29. Abdominal wall and perineal
endometriosis
 Endometriotic lesions at the site of previous surgical scars,
umbilicus or inguinal canal.
 lesions are located within the scar of gynaecological operations,
particularly hysterotomy, caesarean sections or episiotomy.
 Lesions are dark red-blue or brown, tender nodules.
 become more painful during menstruation and occasionally
associated with cyclical bleeding from these lesions.
 Diagnosis is usually by history and clinical examination and
treatment is by complete excision of the nodule.

30. Thoracic endometriosis
 Endometriotic lesions of the pleura, lung parenchyma and the
diaphragmatic surface present with pneumothorax,
haemothorax, haemoptysis, chest pain and dyspnoea.
 The symptoms are cyclical and tend to start within 24-48 hours
after the onset of menstruation
 Women with pleural disease frequently associated with pelvic
endometriosis, it almost always affects the right side.
 The right to left ratio being 9:1.
 The lung parenchyma is a bilateral disease.

31.  Diagnosis- chest X-ray, computerised tomography or MRI,
thoracoscopy, thoracotomy for pleural/diaphragmatic disease and
bronchoscopy for pulmonary disease.
 Medical, surgical or combination treatment options are used.
 pneumothorax or haemothorax managed by insertion of a chest
tube drain.
 In cases of recurrent pneumothorax or haemothorax chemical
pleurodesis, pleural abrasion or pleurectomy may be helpful.
 Persistent haemoptysis due to parenchymal lesions may be
treated by lobectomy, segmentectomy or rarely
tracheobronchoscpic laser ablation

32. Endometriosis in adolescence

33.  Ultrasonography - initial imaging modality
 Family history of endometriosis among the first degree relatives increases
the risk by 7-fold to 10-fold.
 two thirds of adolescent girls with chronic pelvic pain or dysmenorrhea
unresponsive to hormonal therapies and NSAIDs will be diagnosed with
endometriosis at the time of diagnostic laparoscopy.

34. Laproscopy in adolescence endometriosis
 In adolescents, endometriotic lesions are typically clear or red .
 These clear or red endometriotic lesions are more metabolically active and
are associated with greater prostaglandin production.

35. Cont.
 Lesions suspicious of endometriosis should be sampled and biopsied, and
visible lesions should be destroyed, ablated, or excised at the time of initial
laparoscopy.
 ACOG does not recommend “peritoneal stripping” in adolescents based
on theoretical concerns (eg, adhesion formation contributing to bowel
obstruction or infertility, or both, and persistent pain).

36. Treatment for endometriosis in
adolescence
 First-line therapy for adolescents endometriosis includes
 suppressive hormonal therapy using a continuous combined hormonal
contraceptive, a progestin-only agent, or 52 mg of LNG-IUS.
 Patients with pain refractory to conservative surgical therapy and
suppressive hormonal therapy - benefit from at least 6 months of GnRH
agonist therapy

37. Endometriosis and menopause
 most women with endometriosis experience regression of disease after
menopause.
 women with a history of endometriosis may experience worsening of
symptoms and reactivation of residual disease with the use of hormone
therapies aimed at relieving postmenopausal complaints.
 incidence of endometriosis in postmenopausal women is approx. 4%.
 first line treatment for endometriosis in postmenopausal patients is
surgical

38. Infertility management in endometriosis,
what’s new
 Surgery for endometriosis – including endometriomas– does not improve
ART outcome.
 Pre IVF surgery may actually cause more harm by impairing ovarian
reserve.
 ART does not worsen endometriosis symptoms and has no impact on
ovarian endometriomas or deep infiltrating endometriosis
 Surgery before ART may be done for colorectal endometriosis.
 The indication for surgery in the case of infertility associated with
endometriosis is for enhancing the chances of conceiving naturally in the
12-18month after surgery.

39. How IVF in endometriosis different
 Oocyte and embryo quality- similar – endometriosis does not markedly
affect folliculogenesis and embryo development in the context of IVF.
 Implantation rate in frozen cycle – similar
 Risk of infection in presence of endometrioma

40. ART
 IVF for women with infertility and endometriosis stage III/IV
 Can be offered for stage I/II, especially when other treatment have failed.
 Including those who have been diagnosed with endometrioma
 Do a laparoscopic surgery for endometriosis before IVF when
 Ovarian cyst has features of malignancy
 Patient has severe endometrioisis associated pain
 May be done for endometrioma - whether this improves outcome is not known

41. ART IN ENDOMETRIOSIS ASSOCIATED
INFERTILITY

42. Intrauterine insemination (IUI)
 Intrauerine insemination is effective in improving fertility in minimal and
mild endometriosis.
 In infertile women with ASRM stage I/II endometriosis, clinician may
perform IUI with controlled ovarian stimulation, instead of expectant
management , as it increases birth rate,
 The value of IUI in infertile women with rASRM stage III/IV endometriosis
with tubal patency is uncertain, the use of IUI with ovarian stimulation
could be considered.

43. Intrauterine insemination in endometriosis