Endometriosis Flashcards
Endometriosis is defined as…
The presence of endometrial tissue outside of the uterus; can present anywhere, but commonly limited to pelvic area
Ovaries, fallopian tubes
Cause of endometriosis is likely due to…
Multiple factors
Retrograde menstruation theory tries to explain endometriosis via…
When the endometrium is shed during menstruation it may flow back through the fallopian tubes, and becomes implanted on organs/tissues in the pelvic area.
Some people will experience this and do not have endometriosis
Immunologic theory tries to explain endometriosis via…
Underlying immunologic disorder - endometrial tissue able to evade immune system
Immunologic theory is supported by the presence of…
Labwork?
Abnormal B & T cell function
Altered level of cytokines + IL’s present in endometrial lesions
Coelomic metaplasia theory tries to explain endometriosis via…
Lesions developing when cells covering peritoneum undergo metaplasia (normal peritoneal tissue transforms via metaplastic transition to ectopic endometrial-like tissue)
Vascular/Lymphatic theory tries to explain endometriosis via…
Endometrial cells spread to distant locations via lymphatic system, or vascular pathways
____ is present in endometrial lesions, leading to ____
Enzyme ???
Aromatase; leading to increased estrogen
Patients with endometriosis usually have ____ progesterone receptors. This is linked to estrogen because…
Decreased progesterone receptors. Progesterone cannot antagonize effects of estrogen
Overall, there is ____ estrogen in endometriosis
Increased
Stimulation of estrogen promotes…
Proliferation of endometriotic lesions
Inflammation
Leading to pain
Repetitive cycles of bleeding and inflammation may lead to…
Adhesions and scarring on adjacent tissues
Endometriosis involves increases in inflammation via…
Immune responses to endometrial lesions
Stimulation of COX-2 via estrogen
Endometriosis can cause neuropathic pain because…
Endometrial lesions may compress on nerve fibers or adjacent structures
Central sensitization can occur in endometriosis because…
Persistent pain can alter response to stimuli (increasing pain perception)
Does severity of pain or symptoms correlate with degree of endometriosis?
No
Neither does degree of bleeding or other symptoms.
Hallmarks of endometriosis pathophysiology include…
Genetic predisposition
Estrogen dependent
Progesterone resistance
Inflammation
Progression of endometriosis may…
Remain stable
Regress
Progress
Approximately 1/3 each
Common risk factors for endometriosis include…
1st degree relative
Not having children
Early menarche (before 10)
Short monthly cycle
Heavy menses
Symptoms of endometriosis are ____ and vary from person to person.
Unpredictable
1/3 can be asymptomatic
The two major sx’s of endometriosis are…
Pain
Sub/infertility
Pain in endometriosis can manifest as…
Dysmenorrhea
Chronic pelvic pain
Dyspareunia
Painful defecation or urination
Lower back pain
Chronic pelvic pain = non-cyclical abdominal and pelvic pain longer than 6 months
Nature of pain in endometriosis can be ____ or ____. It often occurs with the ____, but can occur ____
Intermittent or constant. Often occurs with menstrual cycle, but can occur anytime in cycle
Other symptoms of endometriosis include…
GI issues (urinary disturbances, constipation, diarrhea)
Abdominal bloating
Premenstrual spotting, heavy, irregular bleeding
Fatigue
Signs of endometriosis include…
Not symptoms
Pelvic mass
Pelvic/adnexal tenderness
Subfertility
Endometriosis should be suspected in women complaining of…
Subfertility
Dysmenorrhea
Dyspareunia
Chronic pelvic pain
Diagnosis of endometriosis is based on…
Thorough history
Physical exam
Imaging assessments
Treatment of endometriosis is aimed at…
Management of the condition
The goals of treatment will vary depending on the person’s desired outcomes, but usually revolves around…
Relieving symptoms
Improving fertility
1st line pharmacotherapy for pain-associated endometriosis is…
Hormonal therapies (CHC, progestins)
NSAIDs for dysmenorrhea
CHC helps with endometriosis by…
Suppressing ovulation and growth of implants
Decrease hormone levels, and keep menstrual cycle regular, shorter, and lighter
Trials showed clinically significant decrease in endo-related pain
Also has benefit of contraception
The goals of hormonal therapy in pain-associated endometriosis is to…
Suppress the menstrual cycle + hormonal fluctuations
Create amenorrhea
Stop ovulation if that process is painful
Progestins can come in the following dosage forms:
Oral
IM
Intrauterine (IUD)
Subdermal implant
If someone refutes that estrogen stimulates endometrial growth and CHC should not be used, we should say…
The estrogen used in CHC has less estrogenic activity than endogenous estradiol
Progestin also helps prevent rise in estradiol
CHC’s can be used ____ or ____. Some evidence favours ____ because…
Cyclically or continuously - some evidence favours continuous use to provoke amenorrhea
CHC evidence is primarily with ____, but…
OCP’s - but patch or vaginal ring are options as well and should work as well
Benefit of CHC’s compared to alternative hormonal options is primarily…
Better tolerability - safer, can be used long-term
Progestin-only tx in endometriosis MOA is to…
Prevent rise in estradiol, without estrogen related stimulation of endometriotic growth - induces hypoestrogenic environment
Progestin-only tx compared to CHC has ____ efficacy.
Similar efficacy - to other hormonal therapies
Recall some of the AE’s of CHC’s, such as…
Breast tenderness
Headache
Nausea
Weight gain
Mood changes
Breakthrough bleeding
DVT risk
Recall AE’s of progestins, such as…
Breakthrough bleeding
Weight gain/fluid retention
Mood changes
Headache
Depot progestins may cause issues such as…
Delaying return in ovulation
Decreased BMD with prolonged use
Dienogest progestins may cause issues such as…
May be detrimental to BMD
Associated with less anti-androgenic effects
Requires non-hormonal contraception
IUS’s progestin therapy may cause potential issues such as…
Risk of expulsion
Long-term effect on BMD unknown
An adequate trial for pain control should be…
A minimum of 3 months - prior to trying other pain control options
NSAID’s may help with endometriosis pain via…
Interfering with prostaglandin synthesis (which is overexpressed in endometrial lesions)
NSAID’s may be an appropriate 1st choice for endometriosis related pain if…
Symptoms are mild
Patient wants a non-hormonal treatment option
Could NSAID’s be used in conjunction with hormonal treatment options?
Yes, this would be appropriate
NSAID’s can be used ____ or __
Intermittently or continuously
Continuous is good if pain is constant
NSAID precautions with continuous use is primarily…
GI and renal dysfunction
Reactive airway disease
MOA of gonadotropin-releasing hormone (GnRH) agonists is to…
Bind to GnRH receptors in pituitary, initially causing increased release of LH/FSH. Long half-life eventually causes down regulation of HPO axis
hypothalamic-pituitary-ovarian axis
Down-regulation of HPO axis will…
Prevent release of endogenous GnRH from hypothalamus, blocking release of FSH/LH - results in hypoestrogenic state, endometrial atrophy, amenorrhea
GnRH agonists will likely cause ____ in pain + endometriosis symptoms due to…
Increase in pain symptoms in 1st month - increase in estrogen due to increase in LH/FSH
Product monographs recommend this duration of treatment for GnRH drugs…
Up to 6 months - Mainly involving BMD concerns, and not studied beyond 1 year
Once GnRH agonists down-regulate the HPO axis, estrogen becomes ____
Decreased - patient will be in hypoestrogenic state, which induces endometrial atrophy and amenorrhea
Hypoestrogenic AE’s with GnRH agonists may lead to…
Vasomotor symptoms (hot flashes, night sweats, vaginal dryness, insomnia, decreased libido)
Bone loss
Headache/migraine
Mood swings
Alterations in bleeding patterns
The antagonists seem to have better tolerability compared to the agonists.
AE’s with GnRH drugs are analogous to…
Menopause symptoms
To counter bone loss and vasomotor symptoms with GnRH agonists, this should be added…
Low dose estrogen +/- progestin
Could likely be done with the antagonists as well but has not been clearly studied yet.
Low dose estrogen +/- progestin is able to maintain efficacy of GnRH agonists while decreasing likelihood of AE’s. It is theorized that this is possible due to…
Presence of an estrogen threshold effect; not enough estrogen to stimulate growths but enough to help with AE’s
A GnRH receptor antagonist MOA is to…
Competitively bind to GnRH in pituitary and suppress gonadotropins - causes rapid, reversible, dose-dependent hypoestrogenic state
Efficacy between a GnRH antagonist and agonist is…
Similar - both induce the hypoestrogenic state which causes endometrial atrophy and amenorrhea
Tolerability between a GnRH antagonist and agonist is…
The antagonist avoids initial worsening of symptoms compared to the agonist, and may have better tolerability of AE’s.
When a patient is taking drugs that affect GnRH, this is required…
An effective method of contraception not containing estrogen - they do not fully suppress ovulation
Often recommended to start when menstruation begins to help rule out pregnancy
AE’s with GnRH antagonists are…
Similar to the agonists
Hypoestrogenic - hot flashes, night sweats, insomnia, nausea, amenorrhea, mood swings
Alterations in bleeding patterns
Dose-dependent: increases in TC, LDL, TG, decrease in BMD
Efficacy of GnRH antagonists are ____, but it is important to consider that tolerability is also _____
Dose-related
The three aromatase inhibitors are…
Anastrozole
Letrozole
Exemestane
Aromatase is a key enzyme involved in…
Conversion of adrenal androgens to estrogens
Inhibition of aromatase will…
Lower overall estrogen
Efficacy of aromatase inhibitors…
Show some evidence that they may help pain alone, or in combination with CHC’s, progestins, and GnRH agonists.
Not a whole lot of evidence available
Notable AE’s with aromatase inhibitors include…
Lower estrogen - hot flashes, vaginal dryness, headache, nausea, diarrhea
Long-term use may impact BMD (add back tx with CHC or progestins)
Hypoestrogenic AE’s are less than GnRH agonists
Danazol could be used for endometriosis symptoms by its MOA:
Inducing a pseudomenopausal state via increasing androgen levels + decreasing estrogen levels = anovulation, amenorrhea, atrophy of endometrial tissue
Suppresses production of LH + FSH
Efficacy of danazol was ____, however usage is no longer supported due to…
High efficacy - no longer used due to androgenic AE’s (voice change, weight gain, hair growth, acne, lipids…)
Surgical management is an option for patients who…
Are infertile and desire pregnancy
Or not responding to pharmacologic therapies
Conservational treatment with surgery is…
Laparoscopy
Benefit of laproscopy for fertility has shown…
Improvement in those with minimal/mild endometriosis
Benefit of laparoscopy for pain has shown…
Some improvement but recurrence of pain in ~50% 5 yrs post-surgery. May consider repeat surgery or long-term hormonal suppression to reduce risk of recurrent pain
A hysterectomy +/- oophorectomy also involves…
Removal of all visible endometriosis
With a hysterectomy, a patient will likely experience ____ and will potentially need…
Menopause symptoms - hormonal therapy
It is generally recommened to wait ____ after discontinuation of endometriosis pharmacotherapy before trying to conceive
1 month
Endometriosis generally enters ____ with pregnancy
Remission
Estrogen is being suppressed
There are multiple proposed theories to explain infertility associated with endometriosis, such as…
Extensive scarring
Autoimmune mechanisms (inflammatory cells)
Menstrual cycle irregularities
Increased uterine peristalsis activity
Management options for infertility associated endometriosis include…
Watchful waiting
NSAID’s for pain relief (d/c once pregnancy achieved)
Conservational surgery
Use of reproductive technologies
