Endometriosis

Question 1

differential diagnosis for endometriosis

Answer 1

• Pelvic pain- ectopic pregnancy, PID, intersittial cystitis, adenomyosis, ovarian neoplasms , pelvic adhesions, IBS, colon cancer, diverticular disease
• Dysmenorrhea-adenomyosis, primary dysmenorrhea, uterine leiomyomas
• Dyspareunia- vulvovaginal atrophy
• Infertility-hormonal imbalance, inadequate sperm etc.
• Bowel symptoms—IBS, inflammatory bowel disease

Question 2

definition of endometriosus

Answer 2

• Endometriosis is defined as the presence of endometrial glands and storm at extrauterine sites
  
  • Usually located in the pelvis
  • But can occur nearly anywhere in the body
• Common, benign, chronic, estrogen-dependent disorder
• Maintenance of the implants are dependent on the presence of ovarian steroids
• Therefore, diagnosis is commonly made during the active reproductive period
  
  • 25-35 years old most common
  • Uncommon on pre/post monarchal girls
  • Rare in post menopausal women NOT taking estrogen
  • This is a very important thing to remember because it plays a role in diagnosis and treatment

Question 3

common sites for endometriosis

Answer 3

• Most common sites include ovaries, anterior and posterior cul-de-sac, posterior broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon, appendix and round ligaments.
• Rarely it has been reported in the breast, pancreas, liver, gallbladder, kidney, urethra, lung, spleen

Question 4

epidemiology

Answer 4

• Prevalence in general population is difficult to determine because symptoms are diverse, nonspecific some are asymptomatic
  
  • 12-32% of women of reproductive age undergoing laparoscopy to determine the cause of pelvic pain
  • 9-50% of women undergoing laparoscopy for infertility
  • 50% of teenagers undergoing laparoscopy for evaluation for chronic pelvic pain or dysmenorrhea
• Higher rates in taller, thinner, body habits and lower BMI
• More common in Caucasian and Asian women
• But some estimates of prevalence based on visualization of pelvic organs include the following
• The role of socio-economic status tends to be controversial. Tends to be dx more in higher scission economic classes—delayed pregnancy as a risk factor? Greater access to medical care?

Question 5

pathogenesis

Answer 5

• Leading theories
  
  • Retrograde menstruation/ Implantation theory
  • Hematogenous / lymphatic spread
  • Coelomic metaplasia
  • Direct transplantation
  • Combo?
• There are the leading theories for how one may develop endometriosis. But they are controversial and neither of them can fully explain how endometriosis develops or explain why there is such a variation in the sites that are affected, the extent to which damage is done etc.

Question 6

retrograde menstruation theory

Answer 6

• Endometrial tissue reflux into the fallopian tubes and implant on neighboring structures
  
  • Supported by increase incidence in women with genital tract obstructions that prevent expulsion of menses into the vagina
  • However, there are women who have endometriosis but no genital tract obstruction
  • Does not explain how endometriosis gets into other sites

Question 7

hematogenous or lymphatic spread theory

Answer 7

• Spread to outside location by dissemination of endometrial cells through lymphatics and blood vessels
  
  • Helps explain causes of endometriosis to areas outside the pelvis
    
    • breast, pancreas, liver, gallbladder, kidney/urethra, extremities, vertebrae, bone, peripheral nerves, lung, diaphragm, CNS, nose, aorta
  • No evidence of endometrial tissue on blood samples

Question 8

coelomic metaplasia theory

Answer 8

• Coelomic (peritoneal) cavity contains undifferentiated cells or cells capable of dedifferentiating into endometrial tissue
  
  • Based on embryologic studies demonstrating that all pelvic organs, including the endometrium, are derived from cells lining the coelomic cavity
    
    • explains causes in non menstruating women (turner’s syndrome or absent uterus)
    • doesn’t explain how it ends up in organs not in the pelvis

Question 9

direct transplantation theory

Answer 9

• Spreads from direct transfer of endometrial tissue
  
  • Explains less common locations like episiotomy scars, abdominal incision, c-section scars etc.

Question 10

combination

Question 11

genetics

Answer 11

• 7% likelihood of developing endometriosis if you have a first degree relative affected
• Concordance in twins
• There is some link but it is not that strong of a link like you would expect in breast cancer risk, pCOS etc. 1% in unrelated

Question 12

clinical presentation

Answer 12

• Pelvic pain
• Severe dysmenorrhea
• Dyspareunia
• Infertility
• Asymptomatic
• Constipation/diarrhea
• Bowel pain
• Ovarian mass/tumor
• Dysuria
• Combination of symptoms
• It’s a wide rang of symptoms it can be anything from extreme pain—periods that are so painful they are having to miss school or work/going to the ER/ even passing out due to pain to being asymptomatic—being discovered only incidentally on imaging, while undergoing laparoscopy or post mortem.
• Many symptoms of endometriosis overlaps with other conditions—PID, interstitial cystitis is et. and this is why there is a delay in diagnosis—some report delays of 10-20 years!
• Clinical presentation does NOT always correlate to severity of diagnostic findings
  
  • Size of the implants can vary from being microscopic to large masses, but the stage of the disease does not correlate very well to the extensiveness of the disease. This is one of the reasons why it is so hard to diagnose.

Question 13

appearance and size of implants are variable

Answer 13

• Superficial implants to pelvic masses to cyst-like structures
• Stage 1: minimal disease—isolated implants and no significant adhesions
• Stage 2: mild enometriosis, superficial implants less than 5 cm in aggreagte, scattered on the peritoneum and ovaries. no significant adhesions
• Stage 3: moderate disease exhibits multiple implants, bother superficial and invasive, Peritubal and periovarian adhesions
• Stage 4: severe disease, multiple superficial and deep implants, including large ovarian endometrioma. filmy and sense adhesions are usually present

Question 14

endometriomas

Answer 14

• “Chocolate cysts”
• Contains blood, fluid, menstrual debris
• Differentiated by hemorrhagic cysts because it is lined with endometrial epithelium, storm and glands
• Detected on imaging (US, CT, MRI)
• The appearance varies a lot as you can tell from these slides, not just in color but in shape. Also sometimes the disease is microscopic and there are no visible lesions but when you do pathology you see endometrial tissue.
• If you see an endometrioma, youre automatically a stage 4

Question 15

pathology of endometriomas

Answer 15

• Microscopic appearance:
  
  • Similar to that of endometrium in the uterine cavity
  • Endometrial glands and stroma
  • Overtime implants will containing fibrous tissue, blood and form cysts

Question 16

clinical presentation of endometriomas

Answer 16

• Pelvic pain
• Severe dysmenorrhea
• Dyspareunia
• Infertility
• Asymptomatic
• Constipation/diarrhea
• Bowel pain
• Ovarian mass/tumor
• Dysuria
• Combination of symptoms
• So now lets go back to clinically speaking, what is important for us to know? Lets go back to the clinical presentation. As complex as endometriosis is it’s important to know how it “typically” manifests. Many symptoms of endometriosis overlaps with other conditions—PID, interstitial cystitis is et. and this is why there is a delay in diagnosis—some report delays of 10-20 years!
• Gold standard = confirmation on pathology via surgery (open or laproscope) or if you had an endometrioma on US or imaging

Question 17

dysmenorrhea and pelvic pain

Answer 17

• “Typically “dull or crampy that begins 1-2 days before menses and can persists during and a few days after, chronic
• Onset usually several years after menarche in contrast with primary dysmenorrhea which often begins with menarche
• Pathophysiology???
  
  • Expanding of endometrial tissue in confined spaces
  • Increase in cytokines, inflammatory factors
  • Neighboring nerve irritations
• However can be sharp, focal or diffuse
• secondary dysmenorrhea, adenomyosis, uterine fibroids
• There’s a few theories around that try to explain the pathophysiology of why we experience pain…and though they are good they do not explain why some have symptoms and others don’t

Question 18

dyspareunia

Answer 18

• “Typically” deep dyspareunia
• Pain during vaginal intercourse with deep penetration rather than at the introits or superficial pain limited to the vagina
• secondary dysmenorrhea, adenomyosis, uterine fibroids

Question 19

Bladder or bowel symptoms

Answer 19

• “Typically” presents as urinary frequency during menses, urinary urgency, suprapubic pain at micturition or urinary retention
• “Typically” presents as diarrhea, constipation, dyschezia, and bowel cramping

Question 20

the presenting sx in 1/4 of women with endometriosis

Answer 20

• Infertility is the presenting symptom in ~ 1/4 of women with endometriosis
  
  • may be due to pelvic adhesions, distortion of pelvic anatomy, prevent normal tubo-ovarian function, encase ovary implants can even destroy ovarian and tubal tissues but occlusions are rare
  • But some women who have normal anatomy and mild disease also have infertility issues. So how it causes infertility is not 100% clear as well. There are several theories out there but I do not have time to go over them today because I want to go over what you will typically encounter in the clinic.

Question 21

physical exam for endometriosis

Answer 21

• Typically a normal exam!
  
  • Tenderness when palpating posterior vaginal fornix
  • Lateral displacement of the cervix
  • Localized tenderness or palpable tener nodule in the posterior cul-de-sac or uterosacral ligaments
  • Tender, enlarged adenxal mass —> endometrioma
  • Pain with movement of the uterus
  • Retroverted or retroflexed uterus

Question 22

labs in endometriosis

Answer 22

• No clinically useful labs for diagnosis
  
  • Some studies being done on CA 125
  • Consider doing a cervical culture to rule out pelvic infection

Question 23

imaging in endometriosis

Answer 23

• Pelvic ultrasound is suggested
  
  • Rarely helpful in making a diagnosis or determining extent of disease
  • BUT can detect some findings that can suggest the diagnosis
    
    • Endometrioma
    • Rectovaginal or bladder nodule

Question 24

confirmation of endometriosis diagnosis

Answer 24

• Diagnostic laparoscopy is performed to confirm a diagnosis of endometriosis
  
  • You may have a high suspicion of endometriosis but unless lesions are seen grossly of via pathology you cannot confirm endometriosis. It is a diagnosis that is confirmed only surgically and with a histologic confirmation of a lesion.
  • Exceptions are visualization of an ovarian endometrioma on imaging or if you see a lesion on physical exam

Question 25

how can a presumptive diagnosis be made?

Answer 25

• Presumptive diagnosis can be based on classic pattern of symptoms and the exclusion of other etiologies
  
  • And a clinical dx is sufficient to initiate therapy

Question 26

treatment of endometriosis

Answer 26

NSAIDS, Estrogen-progestin contraceptives, progestin only contraception, orlissa (GnRH agonist), Depo-lupron (GnRH agonist), Letrozole (aromatase inhibitor), Danazol (androgen)

Question 27

treatment with NSAIDs

Answer 27

• Ibuprofen 400-600mg Q4-6 hours is a good start
• For women attempting conception, we avoid selective COX-2 inhibitors (celecoxib, rofecoxib, and valdecoxib) as some studies indicate these drugs can prevent or delay ovulation
• Ibuprofen 400-600mg Q4-6 hours. And I find that starting the NSAIDS a day before their symptoms typically starts seems to help (i.e. if they get cramping the day before their period then starting the NSAIDS 2 days before their period)

Question 28

treatment with hormonal birth control

Answer 28

• Estrogen-Progestin Contraceptives
  
  • First line treatment for most women
  • Includes NuvaRing and Orthoevra Patches
  • Can be used long term
  • Preferably a monophasic pill, can also do continuous to skip periods (do not take placebo pills and start new pack)
• Progestin Only Contraception
  
  • POP
  • If contraindication to COC can do a progesterone only pill; Norethindrone 0.35mg. If no improvement can switch to change to norethidrone acetate 5mg
  • Needs to be taken daily around the same time (3 hour window)
  • Nexplanon (68mg Etonogestrel, 3 years)
  • Levonogestrel IUD (Levonogestrel aka Mirena IUD)
  • Depo-provera (medroxyprogesterone acetate 150mg)
• If patient has contraindication to estrogen can give POP (norethindrone 0.35) with NSAIDS
• Continuous hormonal contraceptives so as to avoid that hormone free period to prevent bleeding and pain. Can use any monophonic pill or can do the seasonal and seasonique which come prepared for 3 month continuous pills. Based on patient preference, availability and cost.
• Patient follow up in 3 months
• If no improvement with NSAIDS and OCP
  
  • Continue NSAIDS but consider changing type of OCP
  • POP change to norethidrone acetate 5mg
  • Consider depot medroxyprogesterone acetate 150mg IM

Question 29

treatment with GnRH antagonist

Answer 29

• Decreases GnRH and FSH/LH secretion, decreases stimulation of ovaries
• Still need to be on a contraceptive
• MODERATE PAIN, or no response to previous therapies or recurrent symptoms
  
  • GnRH agonist with add-back (Depo-Lupron)
    
    • add-back helps decrease hypoestrogenic effects (hot flashes, night sweats etc.) and preserves bone density
    • the “add-back” is progesterone

Question 30

treatment with aromatase inhibitors

Answer 30

• Aromatase is the enzyme that catalyzes a key aromatization step in the synthesis of estrogen. Aromatase inhibitors block the production of estrogen or block the action of estrogen on receptors
• Reserved for women who continue to have refractory symptoms despite GnRH agonist treatment
• Less data on long-term use

Question 31

treatment with androgens

Answer 31

• Danazol is an attenuated androgen and a progestin and works to inhibit cellular activity in endometriosis lesions.
• Can cause weight gain and permanently change a woman’s voice pitch and should not be used in professional singers or speech therapists

Question 32

what to do if there is no response to treatment, refractory symptoms, endometrioma or masses seen on imaging or exam

Answer 32

• Laparoscopy for diagnosis and treatment
• Benefits should out weight the risk
• Counsel patients on recurrence rates
  
  • 10% in 3 years
  • 35% in 5 years
• Patients who need treatment for infertility should be referred to a specialist