Block 2 Lecture 3 -- Endometriosis and Amenorrhea Flashcards by Drew Spargo

What are the theories for causation of endometriosis?

1) retrograde menstrual flow
2) vascular/lymphatic spread
3) immunologic disorder

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Where are usual locations of lesions from endometriosis?

usually restricted to pelvic cavity

- ovaries
- fallopian tubes
- intestines
- bladder/uterus

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Why do some endometriosis patients experience pain with intercourse and/or bowel movements?

adhesions form between organs and restrict movement of organs

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How is endometriosis classified? What does the classification mean?

Stage I - IV

- relates to severity
- does not relate to pain, infertility, or prognosis

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What is the primary choice for restoring fertility in endometriosis?

laparoscopic surgical treatment

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What is the only solution to ondometriosis?

ovarectomy +/- hysterectomy

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What are the GnRH agonists?

Leuprolide IM
Goserelin SQ
Nafarelin IN

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What is the MoA of danazol?

weakly androgenic steroid that suppresses FSH/LH release; slightly immunosuppressive

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What proportion of reproductive women are affected by endometriosis?

6-10%

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What are the symptoms of endometriosis?

1) chronic acyclic or cyclic pelvic pain
+/- dyspareunia
+/- dysmenorrhea

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What are the considerations of laparoscopic surgical treatment for endometriosis?

best results for tx, but:

– 20% recurrence after 2 years, increasing after that

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What are the therapeutic classes indicated for endometriosis treatment?

1) NSAIDs or CHC
2) progestins
3) GnRH agonists
4) Danazol

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What are the therapeutic classes indicated for PMS treatment?

1) antidepressants (SSRIs, TCAs, venlafaxine)
2) GnRH agonists or oral/depot contraceptives
3) diuretics

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What is the definition of amenorrhea?

absence of menses

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Define primary amenorrhea:

no previous menses

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Define secondary amenorrhea:

no menses for 6 months

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What is the most common cause of amenorrhea

unrecognized pregnancy

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Which form of amenorrhea (primary/secondary) is more common – give percentage.

secondary = 4% of women

– also more common if

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What are the 3 general categories of amenorrhea?

1) HT/pituitary suppression
2) anovulatory amenorrhea (PCOS, ovarian tumors, CAH)
3) POI

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What are causes of hyperprolactinemia?

1) OCs
2) antipsychotics (DAr blockers = haldol, risperidone, chlorpromazine)
3) antidepressants (TCAs, SSRIs)
4) opiates, H2RAs

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What is defined as hyperprolactinemia?

PRL = 100+ ng/mL

– indicates prolactinoma

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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)

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How is menorrhagia defined?

excessive bleeding

- 80+ mL
- or 7+ days

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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

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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