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- 2. © 2016 Virginia Mason Medical Center Case #1 38yo woman presents due to abnormally heavy menstrual flow. Typical menses: q28 days, 5 days in duration, and “normal” flow. Now: significantly increased flow, duration 10 days. Associated lower abdominal cramping and mild dizziness. Condoms for contraception. Meds: none PMH: GERD. Two normal vaginal deliveries. BMI 27. FHx: Mother with GERD, father with DM Soc: lives with two daughters. No new sexual partners. 2
- 3. © 2016 Virginia Mason Medical Center Case #1 Exam: BP 108/72, HR 88, RR 14 Gen: well-appearing, sitting comfortably Skin: no pallor GU: Normal external genitalia, no lesions. Frank blood present in vaginal vault. Cervix pink without discharge, no visible polyps. Bimanual exam: Difficult to palpate uterus, not grossly enlarged. No palpable adnexal masses. No cervical motion tenderness. 3
- 4. © 2016 Virginia Mason Medical Center Definitions • Normal menses: every 24-38 days, up to 8 days in length • Abnormal uterine bleeding (AUB) per ACOG: • intermenstrual • post-coital • heavier than normal flow • menstrual cycles longer than 38 days or shorter than 24 days • post-menopausal, any volume • AUB represents 33% of all outpatient GYN visits 4
- 5. © 2016 Virginia Mason Medical Center Menstrual cycle 5 Image adapted from: Physiology of the Normal Menstrual Cycle. UpToDate.
- 6. © 2016 Virginia Mason Medical Center Back to Case #1 38yo woman presents due to abnormally heavy menstrual flow. Now: significantly increased flow, duration 10 days. Associated lower abdominal cramping and mild dizziness. Condoms for contraception Meds/PMH/FHx/Soc: unremarkable Vitals: normal Gen: well-appearing, sitting comfortably, no pallor GU: Normal external genitalia, no lesions. Frank blood present in vaginal vault. Cervix pink without discharge, no visible polyps. Bimanual exam: Difficult to palpate uterus, not grossly enlarged. No palpable adnexal masses. No cervical motion tenderness. 6
- 7. © 2016 Virginia Mason Medical Center AUB Classification System • Polyp • Adenomyosis • Leiomyoma • Malignancy & hyperplasia • Coagulopathy • Ovulatory dysfunction • Endometrial • Iatrogenic • Not yet classified 7
- 8. © 2016 Virginia Mason Medical Center Case #1 Initial labs/imaging? A. Hemoglobin, pelvic ultrasound B. TSH, prolactin C. hCG, CBC, TSH D. No testing, ask her to follow up in one month E. Endometrial biopsy 8
- 9. © 2016 Virginia Mason Medical Center Case #1 Initial labs/imaging? A. Hemoglobin, pelvic ultrasound B. TSH, prolactin C. hCG, CBC, TSH D. No testing, ask her to follow up in one month E. Endometrial biopsy 9
- 10. © 2016 Virginia Mason Medical Center Case #1 hCG negative TSH 0.9 (normal) Pap normal 1 year ago. No history of abnormal paps CBC: Hb 10.5 (was 12 six months ago) NOW WHAT? 10
- 11. © 2016 Virginia Mason Medical Center Treat Heavy Menstrual Bleeding 1. Control bleeding 2. Treat anemia - High-dose oral estrogen - Premarin 2.5mg QID until bleeding subsides (<25 days) - Follow with progesterone 10mg x 10 days - Levonorgestrel-releasing IUD (Mirena) - Estrogen-progestin contraceptives (monophasic) - Ideally contains 35mcg ethinyl estradiol - Medroxyprogesterone acetate - 20mg TID x 7 days - Tranexamic acid (antifibrinolytic) - 1.3g PO TID x 5 days 11
- 12. © 2016 Virginia Mason Medical Center Case #1 Through shared decision making, you and your patient decide on a course of progesterone. You prescribe medroxyprogesterone acetate 20mg TID x 7 days and ask her to follow up in 10 days. Your patient returns ten days later after completing her PO progesterone course and is still bleeding, though less than a week ago. POC Hb is 10.4. 12
- 13. © 2016 Virginia Mason Medical Center Indications for Pelvic Imaging - Any abnormal exam findings, such as enlarged or globular uterus - Persistent symptoms despite treatment (with normal exam) But what are we looking for with ultrasound? Leiomyomas Polyps 13
- 14. © 2016 Virginia Mason Medical Center Case #1 You appropriately refer her for pelvic ultrasound. Pelvic ultrasound shows: Left-sided hypoechoic, well-circumscribed round submucosal mass 14 Image adapted from: Uterine Leiomyomas (Fibroids): Epidemiology, Clinical Features, Diagnosis, and Natural History. UpToDate.
- 15. © 2016 Virginia Mason Medical Center Treatment Symptomatic submucosal fibroids: -Least invasive: watchful waiting, Mirena -Hysteroscopic or laparoscopic myomectomy -Abdominal myomectomy if location not amenable to hysteroscopy and significant symptoms -Other options: uterine artery embolization, hysterectomy 15 Image adapted from: Intrauterine Contraception: Background and Device Types. UpToDate.
- 16. © 2016 Virginia Mason Medical Center Case #2 43yo woman with history of diabetes, presenting for intermenstrual bleeding. Typical menses q28 days, duration 6 days. Now having spotting between periods, sometimes but not always associated with intercourse. No new pain, vaginal discharge, GI symptoms. Monogamous with male partner No prior STIs or abnormal paps FHx: Mother went through menopause age 50, father with DM Meds: metformin 16
- 17. © 2016 Virginia Mason Medical Center Case #2 Exam: Normal vital signs Abdominal exam: benign GU: Normal external genitalia, no lesions. Cervix pink with minimal whitish discharge. Single area of erythematous lobular tissue at 12 o'clock on cervix, approx 1cm diameter, easily friable on Pap testing. Bimanual exam: no cervical motion tenderness no adnexal masses 17
- 18. © 2016 Virginia Mason Medical Center Case #2 You order appropriate initial labs as you learned from your other patient. hCG: negative CBC: normal TSH: normal Gonorrhea/chlamydia: negative Pap: LSIL with (+) HPV 18
- 19. © 2016 Virginia Mason Medical Center Case #2 19 Most appropriate next step in management? A. Pelvic ultrasound B. Discharge home with 1 month follow up C. Oral contraceptives D. Endometrial biopsy E. Refer for colposcopy + polypectomy
- 20. © 2016 Virginia Mason Medical Center Case #2 20 Most appropriate next step in management? A. Pelvic ultrasound B. Discharge home with 1 month follow up C. Oral contraceptives D. Endometrial biopsy E. Refer for colposcopy + polypectomy
- 21. © 2016 Virginia Mason Medical Center Case #2 21 Your patient returns two months later for discussion of her diabetes. Her intermenstrual bleeding has stopped after polypectomy and colposcopy. If it recurs, your plan: - Consider trial of medical therapy, TVUS - Referral to gynecology for endometrial sampling
- 22. © 2016 Virginia Mason Medical Center Endometrial Sampling: AUB 22 right lung nodules and infiltrates Postmenopausal: any vaginal bleeding 45yo to menopause: frequent (< q21 days), heavy, prolonged, intermenstrual < 45yo: persistent AUB with one of: - unopposed estrogen exposure (chronic ovulatory dysfunction, obesity) - failed medical management of bleeding - high risk for endometrial cancer
- 23. © 2016 Virginia Mason Medical Center Other tests to consider 23 Test Context Androgen levels AUB + hirsutism or virilization FSH or LH AUB in < 40yo + menopausal symptoms Suspected hypothalamic dysfunction Coagulation studies (PT, PTT) Heavy menses since menarche AUB with + family history Easy bruising or prolonged bleeding
- 24. © 2016 Virginia Mason Medical Center Case #3 53yo woman presents for annual appointment, mentions she has had some vaginal bleeding intermittently for the last two months. LMP 2 years ago. PMH: HTN, hypothyroidism Meds: losartan, levothyroxine FHx: mother with osteoporosis, father with HTN Exam: normal vitals, GU exam unremarkable 24
- 25. © 2016 Virginia Mason Medical Center Case #3 Most appropriate next step(s) in management? A. hCG, TSH, CBC B. Don’t worry about it, postmenopausal bleeding is normal C. CBC, TSH, endometrial biopsy D. Pelvic ultrasound, endometrial biopsy E. Hysterectomy 25
- 26. © 2016 Virginia Mason Medical Center Case #3 Most appropriate next step (s) in management? A. hCG, TSH, CBC B. Don’t worry about it, postmenopausal bleeding is normal C. CBC, TSH, endometrial biopsy D. Pelvic ultrasound, endometrial biopsy E. Hysterectomy 26
- 27. © 2016 Virginia Mason Medical Center Case #3 After some discussion, she strongly prefers to pursue transvaginal ultrasound rather than biopsy. Her ultrasound shows an endometrial stripe < 4mm. Does she need an endometrial biopsy? 27 Image adapted from: Evaluation of the Endometrium for Malignant or Premalignant Disease. UpToDate.
- 28. © 2016 Virginia Mason Medical Center MKSAP 166 A 40-year-old woman is evaluated for intermittent heavy vaginal bleeding for the past year. Her menses had been regular until the past 2 years, when they became irregular and would sometimes skip for several months. Her last period was 3 months ago and lasted for almost 3 weeks. Menarche occurred when she was age 12 years. She has never been pregnant and is not currently sexually active. Her most recent cervical cancer screening was 2 years ago. Medical history is otherwise unremarkable, and she takes no medications. On physical examination, vital signs are normal. BMI is 29. The general medical examination is unremarkable, as is the pelvic examination. A urine pregnancy test is negative. 28
- 29. © 2016 Virginia Mason Medical Center MKSAP 166 A 40yo woman has intermittent heavy vaginal bleeding x 1 yr. Menses previously regular until past 2 yrs -> irregular, unpredictable. LMP 3 mos ago, lasted 3 wks. Menarche: 12yo. Nulliparous. Not sexually active. Last pap 2 yrs ago. No PMH, no meds. Exam: BMI is 29. Exam, including GU, normal. Urine hCG negative. Which of the following is most appropriate diagnostic test? A. Endometrial biopsy B. Follicle-stimulating hormone level C. Serum hCG level D. Transvaginal ultrasound 29
- 30. © 2016 Virginia Mason Medical Center MKSAP 166 A 40yo woman has intermittent heavy vaginal bleeding x 1 yr. Menses previously regular until past 2 yrs -> irregular, unpredictable. LMP 3 mos ago, lasted 3 weeks. Menarche: 12yo. Nulliparous. Not sexually active. Last pap 2 yrs ago. No PMH, no meds. Exam: BMI is 29. Exam, including GU, normal. Urine hCG negative. Which of the following is most appropriate diagnostic test? A. Endometrial biopsy B. Follicle-stimulating hormone level C. Serum hCG level D. Transvaginal ultrasound 30
- 31. © 2016 Virginia Mason Medical Center MKSAP 166 A 40yo woman has intermittent heavy vaginal bleeding x 1 yr. Menses previously regular until past 2 yrs -> irregular, unpredictable. LMP 3 mos ago, lasted 3 weeks. Menarche: 12yo. Nulliparous. Not sexually active. Last pap 2 yrs ago. No PMH, no meds. Exam: BMI is 29. Exam, including GU, normal. Urine hCG negative. Which of the following is most appropriate diagnostic test? A. Endometrial biopsy B. Follicle-stimulating hormone level C. Serum hCG level D. Transvaginal ultrasound 31
- 32. © 2016 Virginia Mason Medical Center Key Points: AUB - Rule out pregnancy - Risk stratify for endometrial malignancy - Pre-menopausal women: consider fibroids, cervicitis, endometrial polyps, medications (especially contraception!) - Post-menopausal women: get that endometrial biopsy or transvaginal ultrasound 32
- 33. © 2016 Virginia Mason Medical Center References Natural history of uterine polyps and leiomyomata. DeWaay DJ, Syrop CH, Nygaard IE, Davis WA, Van Voorhis BJ. Obstet Gynecol. 2002;100(1):3. Diagnosis of abnormal uterine bleeding in reproductive-aged women. American College of Obstetricians and Gynecologists Practice Bulletin.. Obstetrics and Gynecology. 2012; 120: 197-206. Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Committee Opinion No. 557. American College of Obstetricians and Gynecologists. Obstetrics and Gynecology 2013;121:891–896. Abnormal Uterine Bleeding. Albers JR, Hull SK, Wesley RM. American Family Physician. 2004; 69(8): 1915-1926. Abnormal Uterine Bleeding in Premenopausal Women. Wouk N and Helton M. American Family Physician. 2019; 99(7): 435-443. American College of Physicians. MKSAP : Medical Knowledge Self-Assessment Program XVII. Philadelphia, PA :American College of Physicians, 2017. Physiology of the Normal Menstrual Cycle. Welt C. 2019. KA Martin (Ed.), UpToDate. Retrieved May 1, 2019, from https://www.uptodate.com/contents/physiology-of-the-normal-menstrual-cycle. Uterine Leiomyomas (Fibroids): Epidemiology, Clinical Features, Diagnosis, and Natural History. Stewart EA, Laughlin-Tommaso SK. 2019. In Falk SJ (Ed.), UpToDate. Retrieved May 1, 2019, from https://www.uptodate.com/contents/uterine-leiomyomas-fibroids-epidemiology-clinical-features- diagnosis-and-natural-history. Intrauterine Contraception: Background and Device Types. Madden T. 2019. In Eckler K (Ed.). UpToDate. Retrieved May 1, 2019, from https://www.uptodate.com/contents/intrauterine- contraception-background-and-device-types. Evaluation of the Endometrium for Malignant or Premalignant Disease. Feldman S. 2019. in Falk SJ (Ed.). UpToDate. Retrieved May 1, 2019, from https://www.uptodate.com/contents/evaluation-of-the- endometrium-for-malignant-or-premalignant-disease. American College of Physicians. “Women’s Health.” Medical Knowledge Self-Assessment Program XVII. Ed. Karen Mauck. Philadelphia. 2015. 33
- 34. © 2016 Virginia Mason Medical Center 34
Editor's Notes
- Title your presentation “Noon Conference” Prevents inadvertently giving away the case.
- Soaking through tampon q3 hours Anovulatory pre-menopausal bleeding: Unpredictable Variable volume and duration – absence of normal cyclic progesterone Estrogen-mediated endometrium proliferates excessively -> endometrial instability, erratic bleeding Higher risk of uterine cancer
- Think about definitions…
- Women with normal volume of menstrual blood loss tend to: Change pads/tampons > q3 hours Use fewer than 21 pads/tampons per cycle Seldom need to change pad/tampon overnight Have clots < 1 inch in diameter Are not anemic
- Ovulatory pre-menopausal bleeding: Previously known as menorrhagia Normal, regular intervals BUT excessive volume or duration Estrogen-mediated endometrial proliferation, produce progesterone, slough endometrium at progesterone withdrawal Anovulatory pre-menopausal bleeding: Unpredictable Variable volume and duration – absence of normal cyclic progesterone Estrogen-mediated endometrial proliferation excessively -> endometrial instability, erratic bleeding Higher risk of uterine cancer
- From FIGO PALM = visually objective structural criteria COEIN = unrelated to structural anomalies, tend to be more endocrine Polyps: endometrial or cervical canal Adenomyosis: endometrial-type glands within myometrium Malig: endometrial or uterine hyperplasia/carcinoma/sarcoma Ovulatory dysfxn: psychological stress; weight loss or gain; excessive exercise; medications that affect dopamine metabolism; or endocrine abnl affecting hypothalamic-pituitary-ovarian axis, (hyperPRL, thyroid, PCOS) Endometrial: endometritis, local endometrial hemostasis d/o, sometimes dx of exclusion Iatrogenic: contraceptive method side effect, menopausal HRT, psychotropic meds, antiepileptic meds NYC: poorly defined, extremely rare ( AVM, problems post-C section) AUB replaces prior confusing terms: menorrhagia, menometrorrhagia, oligomenorrhea
- Thyroid – typically oligomenorrhea (long cycles) or amenorrhea Hyperprolactinemia – anovulatory bleeding (irregular pattern), anemorrhea, galactorrhea 50% unknown source This is after you have confirmed GU tract as source of bleeding. (rule out GI, urinary, etc)
- Thyroid – typically oligomenorrhea (long cycles) or amenorrhea Hyperprolactinemia – anovulatory bleeding (irregular pattern), amenorrhea, galactorrhea 50% unknown Bonus points: make sure cervical cancer screening up to date
- How to treat continued uterine bleeding?
- PO estrogen: < 25 day duration; BID for moderate bleeding; s/e: N/V Combined OCPs: cascading regimen: 5 pills 1st day, 4 pills next, etc. continue 1 pill daily for at least 1 week after bleeding stops, then 2-3 days w/o pills to allow withdrawal bleed Progesterone: usually more helpful for anovulatory bleeding; most effective with thickened endometrium - Tranexamic acid is FDA approved but pricey - NSAIDs can also be used due to high concentrations of prostaglandins in endometrium – mechanism poorly understood - Endometrial ablation if no future pregnancy desired All have contraindication for VTE, breast cancer (except TXA) Hemodynamically unstable: - Uterine curettage, intrauterine tamponade - IV conjugated equine estrogen 25mg IV q6hr x 24 hr (contraindications VTE, breast cancer, liver dz)
- You are unable to talk her out of her opposition to OCPs and an IUD. Indications for pelvic imaging?
- Consider sonohysterography or hysteroscopy if suspicious for endometrial polyps or submucosal leiomyomas.
- Failed medical therapy Consistent with fibroid
- 7-40% of fibroids regress over 6 months to 3 years Typically regress at menopause OCPs seem to have little effect on submucosal leiomyomas May do expectant management if minimal symptoms, no significant anemia
- Intermenstrual bleeding
- Transvaginal ultrasound to measure endometrial thickness can be alternative to endometrial sampling in women with postmenopausal bleeding, NOT in premenopausal women.
- Transvaginal ultrasound to measure endometrial thickness can be alternative to endometrial sampling in women with postmenopausal bleeding, NOT in premenopausal women. ASCCP: Age 30-64, HPV (+) and LSIL -> colposcopy
- Polypectomy – successful excision of polyp seen at 12 o’clock Colposcopy -> CIN I Consistent with Pap results Plan: repeat co-testing in 1 year Transvaginal ultrasound to measure endometrial thickness can be alternative to endometrial sampling in women with postmenopausal bleeding, NOT in premenopausal women.
- High risk for endometrial cancer: Tamoxifen tx, Lynch syndrome, Cowden syndrome, nulliparity, obesity - six months of unopposed estrogen therapy substantially increases the risk of endometrial hyperplasia in menopausal women, it is reasonable to consider six months or more of AUB-O as “persistent” Lynch: germline mutation in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) -> higher risk of CRC, endometrial cancer Cowden: loss of function germline mutation in PTEN gene -> oncogenesis -> risk of hamartomatous tumors, breast cancer, non-medullary thyroid cancer, endometrial cancer, CRC Liver and kidney disease represent other rare causes of anovulation and cause AUB by more than one mechanism. Liver disease can affect estrogen metabolism, synthesis of coagulation factors, and cause thrombocytopenia, thereby potentially leading to both anovulation and bleeding diathesis. Chronic renal disease is associated with both hypothalamic-pituitary-gonadal and platelet dysfunction.
- Hirsutism: male-pattern body and facial hair Virilization: deep voice, temporal balding, breast atrophy, clitoromegaly Androgen levels – PCOS FSH or LH – Primary ovarian insufficiency Coagulation studies – fibrinogen and TT optional, bleeding time neither sensitive nor specific – not indicated
- Post-menopausal bleeding 10% of patients with postmenopausal bleeding have endometrial malignancy Perimenopausal bleeding: Increased anovulatory bleeding Typically changes in intermenstrual period Highly variable, lasting 4-8 years
- Postmenopausal bleeding: ALWAYS abnormal ALWAYS requires further evaluation
- Postmenopausal bleeding: ALWAYS abnormal ALWAYS requires further evaluation Can do either pelvic ultrasound OR endometrial biopsy; don’t have to do both depending on US results
- NO she does not need biopsy if endometrial stripe < or = to 4mm. Long arrow = cervix Arrowheads = thickness of endometrial stripe
- Objective: evaluate anovulatory bleeding in premenopausal woman Bleeding: irregular, unpredictable, suggestive of anovulatory pattern. In women with prolonged anovulation, there is loss of normal hormonal flux with exposure to unopposed estrogen without the normal endometrial protective effect of progesterone. This increases the risk for endometrial hyperplasia and endometrial malignancy. FSH: can be used to confirm menopausal status if no menses x 12 mos, but single level can be misleading in perimenopausal period. Serum hCG: no further diagnostic value added – urine preg is sensitive TVUS: not useful in premenopausal woman with AUB, unless suspect structural uterine abnormality
- Objective: evaluate anovulatory bleeding in premenopausal woman Bleeding: irregular, unpredictable, suggestive of anovulatory pattern. In women with prolonged anovulation, there is loss of normal hormonal flux with exposure to unopposed estrogen without the normal endometrial protective effect of progesterone. This increases the risk for endometrial hyperplasia and endometrial malignancy. FSH: can be used to confirm menopausal status if no menses x 12 mos, but single level can be misleading in perimenopausal period. Serum hCG: no further diagnostic value added – urine preg is sensitive TVUS: not useful in premenopausal woman with AUB, unless suspect structural uterine abnormality