Evaluation and Management of Abnormal Uterine Bleeding

Educational Objectives

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

1. Differentiate between structural and nonstructural causes of AUB.
2. Use appropriate imaging modalities for the detection of intracavitary lesions in patients with AUB.
3. Select appropriate interventions for the medical management of AUB.

Summary

Definition: abnormal uterine bleeding (AUB) is bleeding from the uterine corpus that is abnormal in regularity, volume, frequency, and duration, and occurs in the absence of pregnancy; the American College of Obstetrics and Gynecology defines heavy menstrual bleeding as heavy bleeding during menses; bleeding may occur between periods more often than every 21 days; amenorrhea is bleeding less frequent than every 35 days

Etiology: PALM refers to structural causes of bleeding, ie, polyps, adenomyosis, leiomyomas or fibroids, malignancy; COIEN refers to nonstructural causes, ie, coagulopathies, ovulatory dysfunction, iatrogenic and endometrial causes, and not yet classified

Structural causes: endometrial polyps — benign overgrowths in the lining of the uterus; polyps are common among women of reproductive and postmenopausal age; adenomyosis — occurs when the ectopic endometrium grows into the myometrium; can be focal or diffuse; presents with heavy menstrual bleeding and dysmenorrhea; diagnosed using transvaginal ultrasonography (TVUS) or magnetic resonance imaging (MRI); definitive diagnosis is made after hysterectomy; one wall of the uterus may appear thicker than the other wall; associated with Venetian blind sign (shutter blind effect) on ultrasonography; leiomyomas or fibroids — benign growths that affect ≈66% of women; common in African American women; composed of smooth muscle cells and fibroblasts; most patients are asymptomatic; some patients may experience prolonged or heavy menstrual bleeding; large fibroids may cause abdominal enlargement, bloating, pelvic pressure, urinary frequency, or constipation

Endometrial hyperplasia (EH): occurs when the endometrial glands exceed the amount of endometrial stroma; EH with atypia refers to the presence of atypical cells within the endometrial glands; old terminology — simple hyperplasia with and without atypia, and complex hyperplasia with and without atypia; new terminology — EH with and without atypia; EH with atypia is called endometrial intraepithelial neoplasia and requires definitive management

Nonstructural causes: coagulopathies — patients have abnormal hemostasis, leading to excessive menstrual blood loss; ≤13% of women with heavy menstrual bleeding may have some variant of von Willebrand disease; ≤20% of women may have an underlying coagulation disorder; screening is important; acquired coagulopathies include leukemia, liver failure medication, and chemotherapy; ovulatory dysfunction — associated with issues involving the hypothalamic pituitary ovarian axis which causes anovulation; physiologic causes of anovulation include adolescence, perimenopause, lactation, and pregnancy; pathologic causes include polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia; the withdrawal of progesterone causes the endometrium to shed and results in menstruation; in the absence of progesterone, the endometrial lining keeps building; the lining is fragile and eventually leads to heavy, painful bleeding; endometrial and iatrogenic causes — endometrial causes include infection and pelvic inflammatory disease; these are diagnoses of exclusion; iatrogenic causes include hormonal contraception and anticoagulants

Evaluation: history-taking — involves classification of menstrual bleeding patterns, assessment of severity, pain, family or personal history of AUB, and history of bleeding issues; screen the patient for underlying bleeding disorders; obtain history of medications (eg, warfarin, heparin, enoxaparin, birth control agents); obtain history relevant to conditions, eg, excessive bleeding since menarche, postpartum bleeding, surgery-relating bleeding; frequent bruising and nose bleeding may indicate underlying bleeding disorder; referral to a hematologist is important; examination — evaluate signs of excessive weight (body mass index [BMI]) and PCOS (eg, hirsutism, acne); assess for signs of thyroid disease (eg, goiter, thyroid nodules) and insulin resistance (eg, acanthosis nigricans); signs of bleeding disorder include bruises, petechiae, and skin pallor; pelvic and bimanual examination are required

Laboratory testing: includes pregnancy test (age appropriate), complete blood cell counts, thyrotropin, and prolactin; it is advisable to repeat prolactin levels if elevated at the first instance; consider obtaining a Pap smear and screening for sexually transmitted infections (STI); coagulation tests (partial thromboplastin time) and tests for von Willebrand disease may also be considered

Imaging: required in cases of abnormal physical examination findings; TVUS is commonly used; MRI is another option; TVUS is sensitive but not specific for the detection of intracavitary lesions, eg, fibroids, polyps; sonohysterography (SHG) is more sensitive for such lesions; other options are in-office hysteroscopy or hysteroscopy in the operating room (OR); SHG — a small catheter is inserted into the uterus and saline solution is injected to distend it, which can be helpful for identifying abnormalities, eg, fibroids, that may not be visible on regular ultrasonography

Tissue sampling: endometrial biopsy is recommended for patients <45 yr of age with risk factors for endometrial cancer, eg, history of unopposed estrogen exposure (obesity, PCOS), evidence of chronic anovulation; biopsy is also recommended for young patients unresponsive to medical treatment having persistent bleeding; hysteroscopy with directed sampling or dilation and curettage in the OR may also be performed; endometrial biopsy is accurate for detecting endometrial cancer; if the patient has persistent symptoms despite negative biopsy, the adequacy of the specimen must be ascertained; imaging with biopsy ensures adequate specimen retrieval; these examinations can be uncomfortable to the patient (hysteroscopy may be planned in the OR); a tenaculum is helpful for examination and sampling; endometrial thickness is relevant only for postmenopausal patients; patients with endometrial thickness of ≥4 mm with postmenopausal bleeding require biopsy; patients of African American descent may have disease at smaller cutoff

Management: patients with suspected adenomyosis are treated with nonsteroidal anti-inflammatory drugs for dysmenorrhea and hormonal contraceptives; hysterectomy is a definitive therapy; for patients with evidence of hyperplasia or malignancy, referral to a gynecologic oncologist is advised; EH without atypia is managed with progestin therapy, especially if the patient desires future fertility or is not a good candidate for surgery; EH with atypia or cancer requires definitive management

Fibroids: asymptomatic fibroids do not require specific management; evidence on complimentary therapy (eg, acupuncture, herbal preparations) is sparse; medical therapy (eg, hormonal contraceptives pills, tranexamic acid [TXA], levonorgestrel intrauterine device) must address bleeding symptoms; gonadotropin-releasing hormone (GnRH) agonists, eg, leuprorelin, may be used; a combination of elagolix, estradiol, and norethindrone (Oriahnn) is used to manage symptoms of fibroids; these agents may cause menopausal symptoms for which estrogen and progesterone may be required; GnRH agonists can be used only for 2 yr as a bridge to another therapy; combination of relugolix, estradiol, and norethisterone (Myfembree) is used for fibroids and endometriosis; surgical options — myomectomy is indicated in patients who wish to retain fertility but is associated with risk for relapse; hysterectomy is recommended if the patient does not wish to retain fertility; interventional therapy — includes injection of an embolic material into the blood vessels feeding the fibroid; patients may experience pain after the procedure as the fibroid regresses in size; radiofrequency ablation is typically performed laparoscopically

Anovulatory bleeding: medical therapy is preferred over surgical management; patients may opt for nonhormonal therapy; regular exercise and maintenance of a normal BMI is helpful; TXA can help with AUB and may be taken on the day of menses; exercise caution if the patient has a history of thromboembolism; TXA is useful for patients who are trying to conceive; combined hormonal contraceptives can reduce menstrual blood loss by ≤96% after 1 yr; GnRH agonists may be tried; progestins may cause irregular vaginal bleeding, bloating, and nausea; norethisterone (eg, Aygestin, Lyza, Ortho Micronor) can be given daily or for 5 to 10 days every month to induce withdrawal bleeding; drospirenone (Slynd; 4 mg daily) has antiangiogenic properties and is beneficial for patients with PCOS; micronized progesterone (a natural progesterone) can be administered as an oral medication or vaginal gel to induce withdrawal bleeding in patients with anovulation

Diagnostic considerations based on age: menarche to 18 yr — pregnancy, sexual trauma, STI, PCOS, and bleeding disorder; reproductive age — pregnancy, fibroids, polyps anovulatory cycles, iatrogenic causes, and EH; age >40 yr — anovulatory cycles, EH, cancer, and endometrial atrophy

Acute abnormal bleeding: assess hemodynamic stability; patients may need intravenous (IV) fluids, blood transfusion or clotting factors; identify possible etiology; IV estrogen is approved by the US Food and Drug Administration for the treatment of acute abnormal bleeding; combined oral contraceptives may be given (start with a monophasic pill containing 35 μg estrogen thrice daily for 7 days or as a tapered regimen; may cause nausea and bloating); oral progestins can be given at a maximum dose of 20 mg thrice daily for 7 days; TXA can be given orally for 5 days or as IV; surgical management may be required in some cases; endometrial ablation is recommended for patients who are not good candidates for surgery; hysterectomy is used as definitive therapy

Readings

Chandra V, Kim JJ, Benbrook DM, et al. Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol. 2016 Jan;27(1):e8. doi: 10.3802/jgo.2016.27.e8. Epub 2015 Dec 1. PMID: 26463434; PMCID: PMC4695458; Fraser IS, Critchley HO, Broder M, et al. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):383-390. doi:10.1055/s-0031-1287662; Heil S, Nasrullah A. I saw the Venetian blind sign. Clin Imaging. 2024;106:110050. doi:10.1016/j.clinimag.2023.110050; Hill S, Shetty MK. Abnormal uterine bleeding in reproductive age women: Role of imaging in the diagnosis and management. Semin Ultrasound CT MR. 2023;44(6):511-518. doi:10.1053/j.sult.2023.10.002; Jain V, Chodankar RR, Maybin JA, et al. Uterine bleeding: How understanding endometrial physiology underpins menstrual health. Nat Rev Endocrinol. 2022;18(5):290-308. doi:10.1038/s41574-021-00629-4; Khafaga A, Goldstein SR. Abnormal uterine bleeding. Obstet Gynecol Clin North Am. 2019;46(4):595-605. doi:10.1016/j.ogc.2019.07.001; Lebduska E, Beshear D, Spataro BM. Abnormal uterine bleeding. Med Clin North Am. 2023;107(2):235-246. doi:10.1016/j.mcna.2022.10.014; Munro MG, Critchley HOD, Fraser IS. FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions [published correction appears in Int J Gynaecol Obstet. 2019 Feb;144(2):237]. Int J Gynaecol Obstet. 2018;143(3):393-408. doi:10.1002/ijgo.12666; Wouk N, Helton M. Abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2019;99(7):435-443; Yaşa C, Güngör Uğurlucan F. Approach to abnormal uterine bleeding in adolescents. J Clin Res Pediatr Endocrinol. 2020;12(Suppl 1):1-6. doi:10.4274/jcrpe.galenos.2019.2019.S0200.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Strickland was recorded at the Women’s Health Conference, held February 8-9, 2024, in Greenville, NC, and presented by Brody School of Medicine at East Carolina University and UNC Eshelman School of Pharmacy in association with Eastern Area Health Education Center. For more information about upcoming CME activities from this presenter, please visit easterahec.net. 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 1.25 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 1.25 CE contact hours.

Lecture ID:

OB711301

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.