A Practical Approach to Abnormal Uterine Bleeding

Educational Objectives

The goal of this program is to improve the management of abnormal uterine bleeding (AUB). After hearing and assimilating this program, the clinician will be better able to:

1. Recognize the common causes of AUB.
2. Diagnose AUB based on patient age, bleeding patterns, diagnostic testing, and imaging.
3. Compare options for medical management of AUB.
4. Employ surgical management for treatment of select causes of AUB.

Summary

Causes of Abnormal Uterine Bleeding (AUB)

Classification: the International Federation of Gynecology and Obstetrics (FIGO) Working Group on Menstrual Disorders (Munro et al, 2011) divided AUB into heavy menstrual bleeding (HMB) or intermenstrual bleeding (IMB); FIGO delineated structural and nonstructural causes of AUB with the acronym PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy or hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not yet classified)

Endometrial polyps: present in 10% to 30% of women with AUB; risk factors include increasing age, obesity, and tamoxifen use; risk for malignancy is ≈5% in patients who are postmenopausal, ≈4.1% in patients with symptoms, and 5% to 6% in patients who are postmenopausal and symptomatic; tamoxifen use significantly increases the risk for malignancy; small polyps have a high rate of spontaneous regression; removal is indicated with presence of symptoms or risk for malignancy

Adenomyosis: infiltration of stromal and glandular endometrial tissue within the myometrium; present in 20% to 30% of patients with AUB; surgical diagnosis; symptoms widely vary but include AUB, dysmenorrhea, or infertility; risk factors include increased parity and prior uterine surgeries; ultrasonography (US) findings include global uterine enlargement, cystic spaces in the myometrium, asymmetric wall thickening, heterogeneous myometrium, or obscured junctional zone

Leiomyoma (ie, fibroids): present in ≤85% of women; symptoms include heavy menstruation, pelvic pressure, and dysmenorrhea; a genetic basis is likely; diagnosis is made through physical examination (findings include a bulky or irregular smooth-walled uterus); diagnostic confirmation is through transvaginal ultrasonography (TVUS; gold standard for diagnosis; magnetic resonance imaging [MRI] is generally reserved for surgical planning); fibroids are the most common reason for hysterectomy; subserosal fibroids are least likely to cause AUB or HMB, followed by intramural fibroids and submucosal fibroids (most likely to cause HMB)

Age-based differential diagnosis (DD)

Adolescents: consider anovulation (most common; secondary to immaturity of the hypothalamic-pituitary-gonadal axis), polycystic ovary syndrome (PCOS), oral contraceptive pills (OCPs; missed pills or breakthrough bleeding), pregnancy-related bleeding, infectious causes (eg, pelvic inflammatory disease), coagulopathy (≤20%), and tumors (rare)

Patients ≤39 yr of age: ovulatory problems are less likely in this age group, while structural causes are most likely; consider pregnancy-related causes, fibroids, adenomyosis, polyps, and coagulopathy; AUB can also occur secondary to anovulatory cycles, contraceptive side effects, endometrial hyperplasia or malignancy, and other reproductive tract malignancies (RTM)

Patients 40 yr of age to menopause: AUB can be caused by anovulation (because of declining ovarian function with age); DD includes polyps, endometrial atrophy (postmenopausal), hyperplasia, carcinoma, and trauma

DD based on bleeding pattern: heavy, prolonged, regular bleeding — this pattern rules out ovulatory dysfunction and polyps (usually cause irregular, intermenstrual, or postmenopausal bleeding); bleeding can be caused by, eg, fibroids, adenomyosis, coagulopathy; heavy irregular bleeding — occurs with, eg, estrogen excess (eg, PCOS), pregnancy-related, infections, adenomyosis, polyps, endometrial hyperplasia, RTM; regular intermenstrual bleeding — can be caused by physiologic midcycle spotting that occurs because of a postovulatory drop in estrogen levels; consider polyps, carcinoma, and trauma

Evaluation of AUB

History and physical examination: determine age of menarche, plus heaviness and pattern of bleeding; adolescent patients may not need an initial pelvic examination, though the examination is important for older women; perform speculum and bimanual examinations

Laboratory testing: order pregnancy testing; for HMB, order complete blood count and coagulation testing; ensure that cervical cancer screening is up to date; perform biopsy for suspect lesions; consider liver function testing and thyroid-stimulating hormone levels; order prolactin level in a patient with oligomenorrhea; order serum testosterone, dehydroepiandrosterone sulfate, and 17-hydroxyprogesterone levels in a patient with symptoms of anovulation and excess androgens (eg, PCOS); order chlamydia testing for patients who are sexually active; hemostatic disorders — screen for bleeding disorders, then order additional testing if needed; test patients with history of HMB since menarche, postpartum hemorrhage, surgery-related bleeding, bleeding associated with dental treatment, unexplained monthly bruising or nose bleeds, frequent gum bleeding, or family history of bleeding symptoms or a known bleeding disorder; order peripheral blood smear and coagulation testing; order von Willebrand factor antigen testing and ristocetin cofactor assay to test for von Willebrand disease (most common bleeding disorder); check factor VIII levels; check blood type; consult hematology

Imaging: recommended for evaluation of an abnormal clinical examination, under suspicion of a structural lesion, or with persistent symptoms despite treatment; TVUS is the gold standard, while MRI is generally reserved for surgical planning

Endometrial biopsy (EMB): the decision to perform EMB is based on the risk for hyperplasia or malignancy (with unopposed estrogen); according to the American College of Obstetricians and Gynecologists (ACOG) 2012 Practice Bulletin, order US with enhanced risk for a structural abnormality; perform office EMB with enhanced risk for hyperplasia or malignancy; presume anovulatory bleeding or an endometrial factor without enhanced risk for structural abnormality, hyperplasia, or malignancy, and treat without US or EMB; EMB is recommended for patients >45 yr old with AUB, a long history of unopposed estrogen exposure (eg, morbid obesity, PCOS) at any age, failure of medical management, persistent AUB, and patients with AUB during tamoxifen treatment

Treatment of AUB

General recommendations: consider patient preference and the most likely diagnosis; avoid hormonal therapy in patients trying to conceive; avoid combined OCPs in patients for whom estrogen is contraindicated (eg, uncontrolled hypertension, history of venous thromboembolic event [VTE], migraine headaches in women >35 yr of age); very few contraindications exist against the use of progestins; initiate iron therapy for patients with anemia

Nonsteroidal anti-inflammatory drugs (NSAIDs): indicated for regular HMB in patients who do not wish to receive hormonal therapy; continuously dosed during menstruation (eg, ibuprofen 3-4 times daily, naproxen twice daily) with 20% to 25% efficacy in reduction of MB; adverse effects limited to the gastrointestinal system

Hormonal therapy: combined OCPs — reduce MB by ≈50%; dosed daily; moderately decrease blood loss; side effects are related to hormones; moderately effective for contraception (typical-use pregnancy rate of 5%-8%); depot medroxyprogesterone acetate (DMPA) — continuous injectable progestin dosed every 3 mo; >60% effective for HMB; may cause amenorrhea; can be administered to patients in whom estrogen-containing contraceptives are contraindicated; typical-use pregnancy rate of 0.3%; levonorgestrel-releasing intrauterine device (LNG-IUD) — highly effective for HMB; approved by the United States Food and Drug Administration (FDA; 5 yr for HMB and 8 yr for contraception); may cause amenorrhea; hormonal side effects are rare; highly effective for contraception (typical-use pregnancy rate of ≈0.1%); oral progesterone therapy — administer norethindrone acetate once or twice daily; oral progesterone therapy may be effective for regular HMB with continuous use, or if taken during cycle days 5 to 26 (21 days), rather than for 10 to 14 days (effective for irregular [anovulatory] bleeding but ineffective for regular HMB); oral medroxyprogesterone acetate can be dosed 10 to 40 mg daily

Tranexamic acid (Lysteda): prescribe when NSAIDs are ineffective for patients who do not desire hormonal therapy; 1300 mg is administered 3 times daily for maximum of 5 days during menstruation; an antifibrinolytic drug which reduces MB by ≈50%; approved by the FDA; risk for VTE is not increased among patients with HMB and bleeding disorders who take tranexamic acid in conjunction with OCPs; prescribed for postpartum hemorrhage; may be prophylactically prescribed for patients undergoing C-section; evidence does not show significantly increased incidence of VTEs during the intrapartum or postpartum periods

52-mg LNG-IUDs (Liletta, Mirena): have greater efficacy than lower-dose LNG-IUDs (Kyleena, Skyla) for treatment of HMB; reduce bleeding by 74% to 97% after 3 mo; studies have demonstrated superior efficacy compared with NSAIDs, tranexamic acid, combined OCPs, and DMPA; studies have demonstrated similar efficacy compared with endometrial ablation; per review of multiple randomized controlled trials, therapeutic effects are similar after 2 yr vs endometrial ablation; may reduce uterine volume and fibroid size in women with HMB due to fibroids, though risk for IUD expulsion is increased with uterine cavity distortion; Kingman et al (2004) demonstrated an amenorrhea rate of ≈56% and improvement in MB in 100% of patients following IUD insertion in women with HMB due to inherited bleeding disorders

Surgical management: endometrial ablation — success rate is 70% to 90%; amenorrhea is achieved in 15% to 35% of patients; >90% patient satisfaction and success rates and ≈50% rate for amenorrhea are noted in studies of patients >40 yr; failure rate is higher in younger patients (≈27% at 5 yr, and ≈12% require subsequent hysterectomy), secondary to increased time to menopause; uterine artery or fibroid embolization — improves symptoms in 80% to 90% of patients; complication rates are low; can be performed for patients (in outpatient settings) who prefer to avoid surgery or general anesthesia or have poor surgical candidacy; myomectomy — performed when fibroids cause AUB and for patients who desire to retain childbearing ability; radiofrequency ablation of fibroids — laparoscopic procedure, with good postsurgical outcomes and pregnancy rates

Hysterectomy: performed for definitive management or when other treatments fail; a minimally invasive procedure with high patient satisfaction rates

Endometrial thickness and need for biopsy: endometrial thickness of ≤4 mm on US reduces likelihood for cancer to 1%; a postmenopausal female patient with endometrial thickness >4 mm on US does not need biopsy if bleeding is absent

Readings

Bergeron C, Laberge PY, Boutin A, et al. Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis. Hum Reprod Update. 2020;26(2):302-311. doi:10.1093/humupd/dmz051. View Article; Committee on Practice Bulletins — Gynecology. Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012;120(1):197-206. doi:10.1097/AOG.0b013e318262e320. View Article; Gupta J, Kai J, Middleton L, et al. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. N Engl J Med. 2013;368(2):128-37. doi:10.1056/NEJMoa1204724. View Article; Kingman CE, Kadir RA, Lee CA, et al. The use of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders. BJOG. 2004;111(12):1425-1428. doi:10.1111/j.1471-0528.2004.00305.x. View Article; Kwon CS, Abu-Alnadi ND. Updates on the surgical approach to fibroids: The importance of radiofrequency ablation. Semin Intervent Radiol. 2023;40(4):335-341. Published 2023 Aug 10. doi:10.1055/s-0043-1770734. View Article; Lauring JR, Lehman EB, Deimling TA, et al. Combined hormonal contraception use in reproductive-age women with contraindications to estrogen use. Am J Obstet Gynecol. 2016;215(3):330.e1-330.e3307. doi:10.1016/j.ajog.2016.03.047. View Article; Lee H, Cronk N. Are cyclical progestogens effective in treating heavy menstrual bleeding?. Evidence-Based Practice. 2021 June;24(6):p 23-24. DOI: 10.1097/EBP.0000000000001074. View Article; Munro MG, Critchley HO, Broder MS, et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3-13. doi:10.1016/j.ijgo.2010.11.011. View Article; Options for prevention and management of menstrual bleeding in adolescent patients undergoing cancer treatment: ACOG Committee Opinion, number 817. Obstet Gynecol. 2021;137(1):e7-e15. doi: 10.1097/AOG.0000000000004209. View Article; Ranjan S, Kumar H, Gore C, et al. Histopathological pattern of endometrial biopsies in patients with abnormal uterine bleeding. Medical Journal of Dr D.Y. Patil Vidyapeeth. 2023;16(4):599-604. doi:10.4103/mjdrdypu.mjdrdypu_653_21. View Article; Schatz F, Guzeloglu-Kayisli O, Arlier S, et al. The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. Hum Reprod Update. 2016;22(4):497-515. doi:10.1093/humupd/dmw004. View Article; Wheeler KC, Goldstein SR. Transvaginal ultrasound for the diagnosis of abnormal uterine bleeding. Clin Obstet Gynecol. 2017;60(1):11-17. doi:10.1097/GRF.0000000000000257. View Article.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Karjane is a consultant for Organon and a trainer for Nexplanon. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Karjane was recorded at the Health of Women 2023, held virtually May 18-19, 2023, and presented by the Virginia Commonwealth University Institute for Women's Health. For information on upcoming CME activities from this presenter, please visit https://vcu.cloud-cme.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.50 CE contact hours.

Lecture ID:

FP714801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.