PB#136: Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction Flashcards by Gordon Skeoch

Physiologic reason behind AUB occurring 2/2 ovulatory dysfunction

Effects of chronic unopposed estrogen on endometrium

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PALM (structural causes) classification of AUB

Polyp (AUB-P), adeno (AUB-A), leiomyoma (AUB-L), malignancy/hyperplasia (AUB-M)

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Subclassification of AUB-L

AUB-Lsm (submucosal myoma), AUB-Lo (other myoma)

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COEIN (nonstructural causes) classification of AUB

Coagulopathy (AUB-C), ovulatory dysfunction (AUB-O), endometrial (AUB-E), iatrogenic (AUB-I), not yet classified (AUB-N)

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Duration of most ovulatory menstrual cycles; normal duration of flow

21-35 days; 5 days (w/ most blood loss occurring within first 3 days)

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Median age of menarche; typical range of cycle duration and duration of flow for such pts

12.43 y/o; 21-45 days and <7 days

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Is it normal for cycle length to vary if cycles are ovulatory?

Yes, by a few days per month

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At what point in reproductive lifespan does menstrual cycle vary more?

Approaching menopause

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How are ovary and endometrium coordinated during an ovulatory cycle?

Selection/Ovulation of mature oocyte coordinated w/ process that results in growth/differentiation of endometrium

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General steps of normal ovulatory cycle (4)

Follicle develops > ovulation > corpus luteum develops > luteolysis

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Effect of normal ovulatory cycle on endometrium

Endometrium sequentially exposed to ovarian production of estrogen alone, followed by combo of estrogen and progesterone, then withdrawal of estrogen and progesterone at end of cycle

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Steps of endometrial progression during normal ovulatory cycle (4)

Proliferation > secretory change > shedding > repair

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Meds that could potentially impair coagulation process during repair of blood vessels at time of menstruation (3)

Warfarin, ASA, clopidogrel

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Effect of absence of ovulation on endometrium

Corpus luteum does not develop and ovary fails to secrete progesterone, resulting in continual endometrial proliferation w/o progesterone-withdrawal-induced shedding and bleeding

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Clinical result of absence of regular ovulation

Noncyclic, unpredictable bleeding of inconsistent volume

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Description of endometrium that develops in milieu of unopposed estrogen

Fragile, vascular, lacking sufficient stromal support; as a result, one area of bleeding begins to heal while another area begins to slough, resulting in erratic bleeding patterns

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Phases of reproductive lifespan associated w/ physiologic AUB-O (2)

Puberty, menopause

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Why does puberty result in AUB-O?

Immature HPO axis does not develop the necessary hormonal feedback to result in ovulation and subsequent stable endometrium

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Why does perimenopause result in AUB-O?

Progressive oocyte depletion and abnormal follicular development lead to anovulatory cycles

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Physiologic causes of anovulation (4)

Adolescence, perimenopause, lactation, pregnancy

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Pathologic causes of anovulation (8)

Hyperandrogenic anovulation (ie PCOS, CAH, androgen-producing tumors), hypothalamic dysfunction (ie 2/2 anorexia), hyperprolactinemia, thyroid disease, primary pituitary disease, POI, iatrogenic (ie 2/2 radiation/chemotx), meds

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Menstrual sxs that pts w/ AUB-O typically do NOT experience (3)

Breast discomfort, increased mucoid vaginal discharge, premenstrual cramping

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If cycles vary by more than this many days, they are likely anovulatory

> 10 days

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What should be considered if medical tx fails to resolve bleeding though to be resulting from anovulation (2)?

Anatomic causes (including malignancy/hyperplasia), coagulopathy

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Recommended assessment for AUB, thought to be AUB-O (6)

hCG for sexually active pts (even s/p TL); sensitive hCG testing (to exclude trophoblastic disease in pts who were recently pregnant); TSH (to exclude hypothyroidism/hyperthyroidism); PRL (and, if elevated, repeated in fasting state); EMB (in pts w/ risk factors for hyperplasia/malignancy); SIS/hysteroscopy/TVUS (to r/o anatomic abnormality)

Most frequent cause of AUB-O in pts during first 12-18 months after menarche

Immaturity of HPO axis

Time s/p menarche at which cycles typically normalize

Third year s/p menarche (60-80% of cycle are 21-34 days long, regardless of age at menarche)

Which adolescent pts achieve regular ovulation sooner?

Pts w/ earlier menarche (since time after menarche to normalization of cycles is the same regardless of age at menarche)

Increasing contributor to anovulatory cycles among teens

Adolescent obesity

General risk for endometrial hyperplasia/malignancy among adolescent pts w/ AUB

Extremely low

Most common bleeding disorder in women

vWD

Percent risk of coagulopathy in adolescent pts who require hospitalization (w/ Hgb <10) or transfusion

20-30%

Conditions to r/o in initial workup of adolescent pt w/ AUB (3)

Pregnancy, sexual trauma, STIs

Physical signs/sxs to inquire about to r/o PCOS/hyperandrogenism (2)

Acne, hirsutism

Initial lab testing for adolescent pts w/ AUB (2)

hCG, CBC (and if plts are normal, consider further testing for coagulopathy when significant bleeding/anemia present)

Goals of tx for AUB in adolescent pts (4)

Halt AUB, prevent recurrence, avert morbidity, improve QoL

Adjuvant tx for pts w/ AUB and w/ evidence of IDA

PO iron tx (and if refractory, referred to heme for poss IV iron tx)

Signs/Sxs of PCOS (3)

Noncyclic bleeding, hyperandrogenic signs, characteristic ovarian appearance of US

Important comorbid condition for many pts w/ PCOS

Obesity

Condition to consider in high-risk pts aged 19-39 y/o w/ AUB-O (especially w/ inadequate response to medical tx)

Hyperplasia/malignancy

Condition that must be ruled out in pts aged 40+ y/o w/ AUB

Hyperplasia/malignancy

Definition of perimenopause; mean age of menopause

Onset of cycle irregularity to 1 year s/p LMP; 51.4 y/o

Factor that lowers age of menopause, and by how much

Smoking, by 1.74 years

Average duration of menopausal transition (menstrual irregularity)

4 years

Are cycles always unpredictable during perimenopause?

No, they can fluctuate between predictable ovulatory bleeding and erratic AUB-O

Condition that must be excluded in all perimenopausal pts (until 1 full year s/p LMP)

Pregnancy

First-line tx for perimenopausal pts w/ AUB w/o contraindications, and why

CHCs (rather than HRT), as it provides pregnancy prevention + menstrual control + alleviation of perimenopausal sxs

Does premenopausal HRT provide menstrual regularity; does premenopausal HRT provide contraception?

No; no

Incidence of endometrial cancer in pts <20 y/o

0.2/100,000

Clinical hx typically seen in adolescent pts w/ endometrial cancer

2-3 years of AUB and obesity

Incidence of endometrial cancer for pts 20-34 y/o; incidence of endometrial cancer for pts 35-44 y/o

1.6%; 6.2%

Risk factors for endometrial cancer in pts <40 y/o (5)

Nulliparity, HTN, BMI >30, irregular menstruation, fam hx

Incidence of endometrial cancer in pts 40-50 y/o; incidence of endometrial cancer in pts 70-74 y/o

13.6-24 cases per 100,000 pt-years; 87.3 cases per 100,000 pt-years

Features of endometrial cancer seen more frequently in pts <45 y/o (3)

Lower rate of advanced-stage disease, higher degree of tumor differentiation, better prognosis

Recommended testing for all pts >45 y/o w/ suspected AUB-O

EMB (after pregnancy is excluded)

Is management for pts w/ AUB-O medical or surgical?

Medical, as underlying issue is endocrinologic (unless medical tx fails, is contraindicated, is not tolerated, or pt has concomitant intracavitary lesions)

Classes of first-line medical tx options for AUB-O

CHCs, progestin-only therapies

Progestin-only therapies for pts w/ AUB-O (5)

LNG-IUD, Provera, Megace, norethindrone, depo

Benefits of both CHCs and progestin-only therapies re AUB-O (2)

Thinning endometrium, endometrial protection)

Benefit of cyclic CHC use

Induction of regular withdrawal bleeding, improving abnormal menstruation patterns and physiologic functioning

Preferred CHCs for pts w/ AUB-O

CHCs w/ 20-35micrograms ethinyl estradiol

When is hospitalization (+/- high-dose estrogen) indicated for pts w/ AUB (3)?

Hemodynamic instability, intolerance of outpt regimen, clinically symptomatic

Benefits of extended-cycle oral contraceptive regimens (3)

Permits resolution of anemia, emotional recovery from acute bleeding, additional imaging/consultations if needed

Is cyclic or continuous dosing preferred for adolescent pts following resolution of anemia?

Either is appropriate, as per pt preference

What clotting factors have CHCs been shown to increase (2)?

Factor VIII, vWF

Physiologic benefit of CHCs for pts w/ hyperandrogenic sxs associated w/ PCOS

Suppress ovarian/adrenal androgen production and increase SHBG, further reducing bioavailable androgens, ultimately improving sxs (ie hirsutism, acne)

Lifestyle changes strongly advised in overweight anovulatory pts (2)

Weight loss, increased exercise (w/ evidence showing return to ovulatory cycles w/ sustained weight reduction)

Theory for why weight loss improves anovulatory cycles

Thought to decrease serum testosterone concentration and resumption of ovulation

Tx options for late perimenopausal pt w/ AUB (4)

Cyclic progestin tx, low-dose OCPs, LNG-IUD, cyclic hormonal tx

Benefits of hormonal tx for late perimenopausal pts w/ AUB (2)

Menstrual control, endometrial protection

Does cyclic progestin tx or cyclic hormonal tx provide contraception?

No (though they do provide relief from perimenopausal sxs)

Percentage of pts receiving combined continuous estrogen + cyclic progesterone therapy who experience cyclic menstrual bleeding as well as reduction in vasomotor sxs

86%

Satisfaction rate at 48 month f/u among obese perimenopausal pts w/ AUB w/ LNG-IUD in place

75%

Positive features seen w/ longer use of LNG-IUD (2)

Decreased menstrual bleeding, amenorrhea

Surgical tx options for AUB-O (2)

Endometrial ablation, hyst

Disadvantages of endometrial ablation (2)

Reduces ability to detect/dx future endometrial cancer, does not serve as contraception

Long-term complications of endometrial ablation (7)

Post-ablation Asherman syndrome, synechiae, cervical stenosis, contracture of endometrium, strictures, endometrial distortion, delay in detection of endometrial cancer

Effect of endometrial ablation on endometrial surveillance methods (ie EMB, hysteroscopy, TVUS, SIS)

May be compromised

Percentage of cases of endometrial cancer found after endometrial ablation that were stage I at dx; interval range from endometrial ablation to endometrial cancer

76.5%; 2 weeks to 10 years

What should be done if satisfactory endometrial evaluation cannot be collected s/p ablation?

Hyst

Which AUB pts reported better improvement in QoL between those undergoing hyst and those treated w/ LNG-IUD

Equivalent

Which endometrial surveillance method is preferred for pts w/ AUB-O; why (3)?

Office EMB; less invasive, safer, less expensive

Factors that influence sensitivity of office EMB (7)

Type of lesion present (focal vs diffuse), pathologic dx (intracavitary fibroid/polyp), size of lesion, presence of uterine malformation, volume of path, surface area of endometrial cavity, number of lesions

Additional info that EMB can provide

Hormonal status of endometrium

Rate of sampling failure of EMB

0-54%

Percent of endometrium that EMB typically samples (and range reported)

4% (0-12%)

Percentage of postmenopausal pts w/ insufficient office EMB result that had uterine pathology; percentage of postmenopausal pts w/ insufficient office EMB result that had malignancy

20%; 3%

Sensitivity of office EMB for detecting polyps/fibroids; sensitivity of office EMB for diagnosing hyperplasia

0.1; 0.33

Features of lesions more likely to be missed w/ office EMB (2)

Focal, encompass small surface area

Benefits of hysteroscopy over other methods of endometrial surveillance (3)

Affords full visualization of endometrial cavity and endocervix, allows for targeted bx, more accurate dx of atrophy/ hyperplasia/polyps/fibroids/cancer

Likelihood of endometrial cancer dx after neg hysteroscopy

0.4-0.5%

Pts for whom TVUS generally not recommended

Non-sexually active pts

Between TAUS and TVUS, which is more sensitive in evaluation of endometrium?

TVUS (though TAUS can still be used to evaluate other structural abnormalities)

Ideal timing of TVUS, and why

Day 4-6 of cycle, when endometrium is thinnest

Is endometrial thickness useful for determining management in anovulatory pts w/o a cycle?

Typical endometrial thickness range during proliferative phase; typical endometrial thickness range during secretory phase

4-8mm; 8-14mm

Should endometrial thickness alone be used to exclude benign endometrial path in premenopausal pts; why?

No; this would miss 1 in 6 intracavitary lesions

Sensitivity of SIS in evaluating uterus/endometrium for pathology; NPV of SIS in evaluating uterus/endometrium for pathology

96-100%; 94-100%