Endometriosis Flashcards
What is endometriosis?
The presence of endometrial tissue outside of the uterus (usually limited to the pelvic area)
Can result in pain and/or infertility
What is the prevalence of endometriosis?
Affects 10% of women of reproductive age
Up to 50% of women experiencing infertility
Affects 70-80% of women experiencing chronic pelvic pain
What are some hypothesis for endometriosis?
- Retrograde Menstruation Theory
- Immunologic Theory
- Coelomic metaplasia theory
- Vascular/lymphatic theory
What are the details of the retrograde menstruation theory for endometriosis?
Endometrium shedding during menses flows back through the fallopian tubes and becomes implanted on organs/tissues in the pelvic area
What are the details of the immunologic theory for endometriosis?
An underlying immunologic disorder is responsible and endometrial tissue is able to evade the immune system
How does endometriosis progress?
Endometrial tissue (inside and outside the uterus) is dependent on estrogen for growth stimulation.
Since estrogen levels fluctuate during the menstrual cycle, the endometriosis also grows and bleeds similar to uterine lining
Aromatose is present in lesions, contributing to more estrogen
Estrogen stimulation also has a pro-inflammatory effect, which contributes to pain
What is the impact of endometriosis on pain?
Inflammation due to immune responses causing increased levels of pro-inflammatory cytokines
Neuropathic pain from endometrial growth impinging on nerve fibres
Central sensitization due to persistent pain (increased pain perception)
Bleeding from endometrial tissues causes pain
What are the hallmark factors associated with endometriosis?
- Genetic predisposition
- Estrogen dependence
- Progesterone resistance
- Inflammation
What are some risk factors associated with developing endometriosis?
- European descent
- 1st degree maternal relative with endometriosis
- Not having children (nulliparity)
- Early menarche (under 10yo)
- Short menstrual cycle (less than 28 days)
- Heavy menses (more than 5-6 days)
What are some symptoms associated with endometriosis?
Pain (non-cyclic) and subfertility are the main symptoms associated with endometriosis
Other symptoms:
- Dysmenorrhea
- chronic pelvic pain
- Dyspareunia (painful sex)
- Painful defecation/urination
- Lower back pain
What is the goal of treatment for endometriosis?
No cure, so treatment is geared towards management
Relieve symptoms and improve fertility are goals of therapy
What are the first-line pharmacotherapeutic options for endometriosis treatment?
Hormonal therapies (CHC and progestins)
These are considered first-line because they have fewer ADRs and cost less than later treatments
What is the goal of hormonal treatments for endometriosis?
- Supress the menstrual cycle
- Create amenorrhea
- Stop ovulation if that process is painful
How does hormonal therapy help with endometriosis?
By supressing ovulation and implant growth, they supress hormone levels and regulate the menstrual cycle (reduced pain)
The estrogen used in hormonal therapy is less active vs. endogenous forms of estrogen and the progestin component helps prevent a rise in estradiol
This treatment option is ideal for patients who do not want to get pregnant anytime soon
What is the role of progestin in endometriosis?
They help prevent the rise in estradiol, without estrogen related stimulation of endometriotic growth, and induce a hypoestrogenic environment (reduce growth of endometrial tissue)
How long should each treatment option be tried before switching to an alternate?
A minimum of a 3 month trial should be tried prior to moving on to subsequent treatment options
What is the utility of NSAIDs in endometriosis therapy?
Lack of high quality evidence assessing efficacy
Appropriate 1st line choice if symptoms are mild and pt does not want to take hormonal contraception
Can use intermittently or continuously
What are some non-NSAID options for analgesia in endometriosis?
Acetaminophen (for milder symptoms)
Narcotic analgesics (in very severe situations)
What is the utility of GnRH agonists in endometriosis treatment?
They are synthetic analogues of human GnRH and they cause increased release of LH and FSH
ex. Lupron
They help down-regulate the hypothalamic-pituitary-ovarian (HPO) axis by limiting the release of endogenous GnRH and resulting in a hypoestrogenic state (causing endometrial atrophy and amenorrhea)
What are some side effects associated with GnRH agonists?
Due to hypoestrogenic state induced by GnRH agonists, patients experience menopause-like symptoms
Bone loss
Vasomotor symptoms (hot flashes, night sweats, vaginal dryness)
Headaches/migraine
Mood swings
Rule out pregnancy before use
How can side effects from GnRH agonists be managed?
Add-back treatments (low dose estrogen and/or progestin therapy, not combined OCP)
This does not effect efficacy of GnRH agonist due to estrogen threshold effect
This is the reccomended approach to using GnRH due to fewer ADRs while maintaining good efficacy
What is an example of a GnRH antagonist used to treat endometriosis?
Elagolix (Orlissa)
How do GnRH antagonists work to treat endometriosis?
Competitively bind to GnRH and causes rapid, dose-dependent hypoestrogenic state
Start at lower to dose to minimize risk of decreases in BMD
Begin at time of menstruation, patients should use an effective method of contraception not containing estrogen
What are some side effects seen with GnRH antagonists?
Similar to GnRH agonists due to hypoestrogenic state
Dose-dependent increase in total cholesterol, LDL, TG and decrease in BMD
Rule out pregnancy
What are some examples of aromatase inhibitors used in the treatment of endometriosis?
Anastrozole, letrozole, exemestane
What is the MOA of aromatase inhibitors in the treatment of endometriosis?
Aromatase is involved in the creation of estrogen in the body, so by inhibiting this enzyme, a hypoestrogenic state can be acheived
lower evidence (not the best option for endometriosis)
What are some symptoms associated with aromatase inhibitors?
Similar to GnRH agonists, but less severe
What is the role of Danazol in the treatment of endometriosis?
80-90% acheive symptomatic improvement, but not preferred due to androgenic ADRs (voice changes, weight gain, hair growth)
Which patient groups is surgical management for endometriosis reccomended?
For those who are infertile and desire pregnancy and are not responding to pharmacologic therapies
When should a patient stop drug therapies for endometriosis before conceiving?
1 month after d/c medical therapy
Endometriosis tends to go into remission with pregnancy, but may reoccur after childbirth
What are some potential causes of infertility-associated endometriosis?
- Changes in characteristics of peritoneal fluid
- Extensive scarring from endometrial lesions distorts pelvic anatomy causing mechanical obstruction
- Autoimmune mechanisms
- Increased concentrations of inflammatory cells (hostile to sperm/embryo)
- Increased uterine perstaltic activity
- Irregular menstrual cycle
How is infertility-associated endometriosis managed?
- Watchful waiting
- NSAIDs for pain relief
- COnservational surgery (minimal endometriosis)
- Ovarian stimulation or in-vitro fertilization
