PB#136: Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction Flashcards
Physiologic reason behind AUB occurring 2/2 ovulatory dysfunction
Effects of chronic unopposed estrogen on endometrium
PALM (structural causes) classification of AUB
Polyp (AUB-P), adeno (AUB-A), leiomyoma (AUB-L), malignancy/hyperplasia (AUB-M)
Subclassification of AUB-L
AUB-Lsm (submucosal myoma), AUB-Lo (other myoma)
COEIN (nonstructural causes) classification of AUB
Coagulopathy (AUB-C), ovulatory dysfunction (AUB-O), endometrial (AUB-E), iatrogenic (AUB-I), not yet classified (AUB-N)
Duration of most ovulatory menstrual cycles; normal duration of flow
21-35 days; 5 days (w/ most blood loss occurring within first 3 days)
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
Is it normal for cycle length to vary if cycles are ovulatory?
Yes, by a few days per month
At what point in reproductive lifespan does menstrual cycle vary more?
Approaching menopause
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
General steps of normal ovulatory cycle (4)
Follicle develops > ovulation > corpus luteum develops > luteolysis
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
Steps of endometrial progression during normal ovulatory cycle (4)
Proliferation > secretory change > shedding > repair
Meds that could potentially impair coagulation process during repair of blood vessels at time of menstruation (3)
Warfarin, ASA, clopidogrel
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
Clinical result of absence of regular ovulation
Noncyclic, unpredictable bleeding of inconsistent volume
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
Phases of reproductive lifespan associated w/ physiologic AUB-O (2)
Puberty, menopause
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
Why does perimenopause result in AUB-O?
Progressive oocyte depletion and abnormal follicular development lead to anovulatory cycles
Physiologic causes of anovulation (4)
Adolescence, perimenopause, lactation, pregnancy
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
Menstrual sxs that pts w/ AUB-O typically do NOT experience (3)
Breast discomfort, increased mucoid vaginal discharge, premenstrual cramping
If cycles vary by more than this many days, they are likely anovulatory
> 10 days
What should be considered if medical tx fails to resolve bleeding though to be resulting from anovulation (2)?
Anatomic causes (including malignancy/hyperplasia), coagulopathy
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?
No
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%
