Block 2 Lecture 3 -- Endometriosis and Amenorrhea Flashcards
What are the theories for causation of endometriosis?
1) retrograde menstrual flow
2) vascular/lymphatic spread
3) immunologic disorder
Where are usual locations of lesions from endometriosis?
usually restricted to pelvic cavity
- ovaries
- fallopian tubes
- intestines
- bladder/uterus
Why do some endometriosis patients experience pain with intercourse and/or bowel movements?
adhesions form between organs and restrict movement of organs
How is endometriosis classified? What does the classification mean?
Stage I - IV
- relates to severity
- does not relate to pain, infertility, or prognosis
What is the primary choice for restoring fertility in endometriosis?
laparoscopic surgical treatment
What is the only solution to ondometriosis?
ovarectomy +/- hysterectomy
What are the GnRH agonists?
Leuprolide IM
Goserelin SQ
Nafarelin IN
What is the MoA of danazol?
weakly androgenic steroid that suppresses FSH/LH release; slightly immunosuppressive
What proportion of reproductive women are affected by endometriosis?
6-10%
What are the symptoms of endometriosis?
1) chronic acyclic or cyclic pelvic pain
+/- dyspareunia
+/- dysmenorrhea
What are the considerations of laparoscopic surgical treatment for endometriosis?
best results for tx, but:
– 20% recurrence after 2 years, increasing after that
What are the therapeutic classes indicated for endometriosis treatment?
1) NSAIDs or CHC
2) progestins
3) GnRH agonists
4) Danazol
What are the therapeutic classes indicated for PMS treatment?
1) antidepressants (SSRIs, TCAs, venlafaxine)
2) GnRH agonists or oral/depot contraceptives
3) diuretics
What is the definition of amenorrhea?
absence of menses
Define primary amenorrhea:
no previous menses
Define secondary amenorrhea:
no menses for 6 months
What is the most common cause of amenorrhea
unrecognized pregnancy
Which form of amenorrhea (primary/secondary) is more common – give percentage.
secondary = 4% of women
– also more common if
What are the 3 general categories of amenorrhea?
1) HT/pituitary suppression
2) anovulatory amenorrhea (PCOS, ovarian tumors, CAH)
3) POI
What are causes of hyperprolactinemia?
1) OCs
2) antipsychotics (DAr blockers = haldol, risperidone, chlorpromazine)
3) antidepressants (TCAs, SSRIs)
4) opiates, H2RAs
What is defined as hyperprolactinemia?
PRL = 100+ ng/mL
– indicates prolactinoma
Describe feedback loop of PRL release.
– HT makes DA
1) PRL from pituitary
2) PRL stimulates DA release from HT
3) DA inhibits PRL (pituitary) and GnRH (HT)
How is menorrhagia defined?
excessive bleeding
- 80+ mL
- or 7+ days
What are the characteristics of PCOS?
1) menstrual abnormalities
2) infertility
3) hyperandrogenism
4) obesity, esp. abdominal
5) symptoms of t2dm
6) acanthosis nigricans
7) U/S shows polycystic ovaries
What is acanthosis nigricans?
dark skin at neck, groin, and axillae
What are menstrual symptoms of PCOS?
1) amenorrhea
2) menorrhagia
3) acyclic anovulatory bleeding
Why does anovulatory bleeding occur in PCOS?
CL does not form = no progesterone = unopposed estradiol
– endometrial hypertropy leads to necrosis and irregular bleeding
What are risk factors for PCOS?
1) f/h (25-50% prevalence)
2) central obesity
What is the cause of PCOS?
genetic, but underlying defect unknown
Describe hormonal abnormalities in PCOS.
1) LH greater than FSH
2) flat-line LH, slight fluctuation in FSH
3) E 2x greater than P
4) decreased SHBG = elevated FREE T
Describe role of adipose in PCOS.
converts androgen into estrone
What is the function of leutinizing hormone?
1) stimulate androstenedione production in ovaries
2) surge converts follicle into corpus luteum
What are estrone’s effects on the pituitary?
increased LH release
What are the goals of therapy in PCOS?
1) reduce ovarian androgen secretion, restore hormonal cycle
2) reduce insulin resistance
PCOS increases risk for these diseases.
1) T2DM/metabolic syndrome
2) dyslipidemia
3) CV disease
What are treatment classes for PCOS?
1) COCs (progestin only may be appropriate)
2) Metformin/TZDs
3) glucocorticoids or spironolactone/flutamide for anti-androgenic activity
4) clomiphene or metformin for infertility
What are the FDA-approved PCOS treatments?
1) COCs
2) metformin
How is POI defined?
in women less than 40 yo…
- sex steroid deficiency
- amenorrhea
- infertility
POI increases your risk for what other diseases?
osteoporosis, CVD
When is the usual onset of POI?
after establishment of menses
- after d/c COCs
- post-partum
How is POI diagnosed?
1) 4+ months of amenorrhea
2) FSH = 40+ IU/L
What are symptoms of POI?
- 50%: oligomenorrhea or anovulatory bleeding
- vasomotor sxs
- mood changes
What are causes of POI?
autoimmune diseases, genetic defects
- Turner Syndrome
- Fragile X
What percentage of POI patients get pregnant?
5-10%
What are causes of HT/pituitary suppression?
1) pituitary disease/tumor
2) idiopathic
3) anorexia
4) low-body fat (exercise, weight loss)
5) obesity
6) hyper/hypothyroid
7) hyper-PRL
What are causes of anovulatory amenorrhea?
PCOS
ovarian tumor
CAH (excessive androgen)
What are causes of POI?
1) genetic
2) autoimmune
3) idiopathic
What are the hormone changes present in POI?
low E, high FSH
What are ADRs of danazol?
androgenic:
- - weight gain
- - acne
- - vasomotor sxs
- - hirsutism
- - more LDL
What are C/I’s of danazol?
hyperlipidemia, liver disease
TERATOGEN
What are ADRs of GnRH analogs?
- 5% bone loss over 6 months (reversible)
- vasomotor sxs
- insomnia
- vaginal dryness
What are special counseling points of GnRH agonists?
1) supplement with Ca (500-1000 mg/day) + exercise
2) add-back E/P/BP therapy can limit ADRs
What is the MoA of GnRH agonists in endometriosis
inhibit FSH/LH to establish anovulatory state
What is the MoA of progestins in endometriosis?
establish anovulatory state with amenorrhea
What is the MoA of CHCs in endometriosis?
cyclic: hypoestrogenic
continuous: anovulatory; suppress menstruation; prolonged infertility
What is the black-box warning on progestins?
2-year limit (BMD)
How is hypothalamic amenorrhea treated?
estrogens +/- progestins
– OCs, CEE, E patch
How is hyper-PRL amenorrhea treated?
cabergoline 2 x/week
Why are spironolactone/flutamide used in PCOS?
used with COCs
- neither FDA approved
- used to antagonize androgen receptor
Why are glucocorticoids used in PCOS?
low-dose qhs suppresses adrenal androgens
- does not restore fertility
- not FDA approved
What are the progesterone-only options in PCOS?
1) oral medroxyprogesterone (po x 12-14 days)
- - no contraception
- - not FDA approved
2) levonorgestrel IUD
- - contraception
When are progestins contraindicated in PCOS?
breast/cervical/uterine/vaginal cancer
thrombembolic disease
stroke
When might progesterone-only tx be advantageous in PCOS?
if menorrhagic
– amenorrhea likely in 6 months
What progestin is preferred in PCOS?
desogestrel (least androgenic)
Why are COCs used in PCOS?
1) restore hormonal cycle
2) increase SHBG to decrease free T
3) reduce ovarian hormone production
What is clomiphene’s moa?
estrogen receptor antagonist to increase FSH and LH to stimulate ovulation
– acts on HT to increase GnRH pulses
How is clomiphene dosed?
50 mg/day x 5 days beginning on days 3-5
- after MPA to induce withdrawal bleed
- up to 250 mg/day
How is POI treated?
- low-dose E increasing to 1.25 mg/day CEE
- progestin for 12-14 days
- +/- T for BMD/libido
Why is low-dose E used in POI?
to re-establish baseline ovarian function
– does not prevent ovulation: you already have elevated FSH/LH
