Assessment & management

carcinoma. Hysterectomy may be needed when sig- nificant abnormal persists, despite medical and minimally invasive treatments, and when cancer is diagnosed. Abnormal uterine bleeding Terminology and classifications for abnormal uterine bleeding in reproductive-aged women Two systems created by the International Federation of Gynecology and Obstetrics (FIGO) standardize terminol- utilizing the PALM-COEIN system ogy and provide a systematic approach to the evaluation By Barbara A. Dehn, NP, FAANP, NCMP of AUB in reproductive-aged women. The FIGO System 1 includes four parameters of menstrual bleeding with terminology and definitions for bleeding that fall outside In this article, the author discusses how the PALM- of the normal for these parameters, which are regularity, COEIN classification system helps clinicians group frequency, duration, and volume (Table 1).4 FIGO System various causes of abnormal uterine bleeding into 2, the PALM-COEIN classification system, was created structural and nonstructural etiologies, allowing as- by FIGO to classify and separate the causes of AUB into 5 sessment and management to be more specifically structural and nonstructural etiologies. The first part employed by nurse practitioners to offer women the of the acronym, PALM, succinctly defines the common structural causes as polyps, , most effective treatments. (fibroids), and malignancy/hyperplasia. The second part of the acronym, COEIN, defines the nonstructural causes as coagulopathy, ovulatory dysfunction, endometrial, iat- rogenic, and not yet classified. PALM-COEIN terminology helps healthcare providers base differential diagnoses omen’s health nurse practitioners and treatment options on systematic assessment using Wfrequently provide care for reproductive-aged women knowledge about the etiologies and common signs and who have abnormal uterine bleeding (AUB), which symptoms for each potential one (Table 2).1,5,6 comprises heavy periods, intermittent bleeding, and pro- longed bleeding. It is estimated that 1.4 million women Assessment of abnormal uterine bleeding will experience AUB in the United States each year. This The clinician begins the workup of AUB with a complete includes an estimated 50% of women in perimenopause history, including a detailed focus on menstrual history, who have an increased incidence of polyps, fibroids, and sexual history, current uterine bleeding pattern, any associ- , leading to AUB.1 AUB accounts for as much ated pain, contraception, medication use (including herbal as one-third of all gynecologic visits.2 remedies), other excessive bleeding, family history of AUB The impact of AUB on a woman’s quality of life can or other bleeding problems, and risk factors for cancer of be significant. In fact, over half of women with heavy reproductive tract organs. Any description of a change in and/or prolonged menstrual bleeding report that their menses that leads to a disruption in a woman’s usual life- periods interfere with their lives as compared to the style and interferes with her quality of life is relevant. response by women with lighter cycles.3 Work and The clinician conducts a comprehensive physical ex- school absences as well as loss of productivity can oc- amination to include assessment for significant weight cur. AUB can interfere with sexual relationships. Many change, signs of androgen excess (eg, hirsutism, acne, women lose sleep from frequent trips to the bathroom alopecia), thyroid enlargement/nodules, and signs that during the night to change their menstrual protection. may suggest a bleeding disorder (eg, petechiae, ecchy- Others experience more severe blood loss resulting in mosis). A pelvic examination with speculum and biman- anemia. Most AUB can be managed medically or with ual examination is included for all adult women with minimally invasive treatments. When bleeding is par- AUB. Clinical judgment should be used regarding the ticularly heavy or prolonged, a blood transfusion may extent of pelvic examination for younger adolescents be required to correct severe anemia. AUB may be a who have never had sexual intercourse and may be lim- symptom of and endometrial ited to an external inspection. It is critical in reproduc-

24 February 2020 Women’s Healthcare NPWomensHealthcare.com tive-aged women with AUB to rule out with a sensitive urine HCG [human chorionic gonadotropin] Table 1. AUB terminology with definitions4 test. Other common initial laboratory testing depen- dent on characteristics of the AUB, age of the woman, Parameter Terminology/definition for bleeding outside and history and physical examination findings are a of normal parameter complete blood count, thyroid-stimulating hormone test, and screening per current recom- Regularity Irregular menstrual bleeding: a range of varying lengths 1,2,6 mendation. When anemia is identified, a ferritin (variance > 17 days) of bleeding-free intervals within level provides an indirect measurement of iron stores.1 90-day period If indicated by history or physical examination findings, Frequency Frequent menstrual bleeding: > 4 episodes in 90-day a test for Chlamydia trachomatis should also be consid- period (does not include ) 1,2,6 Infrequent menstrual bleeding: 1–2 episodes in 90-day ered. When ovulatory dysfunction is suspected, ad- period ditional hormonal tests such as follicle-stimulating hor- : no bleeding in 90-day period 1,6 mone, , and prolactin levels may be helpful. Duration Prolonged menstrual bleeding: > 8 days of bleeding on Tests for a coagulopathy are indicated for all ado- regular basis lescents with (HMB) and Volume HMB: excessive menstrual blood loss that interferes for women with frequent epistaxis or gum bleeding, with physical, emotional, social, and material quality of life easy bruising, postpartum hemorrhage, and bleeding HPMB: less common than HMB of normal duration associated with dental work.7 Approximately 5% to Irregular Intermenstrual bleeding: irregular episodes of bleeding 24% of women with a long history of HMB since ado- nonmenstrual occurring between otherwise regular menstrual periods lescence will have a coagulopathy such as von Wille- bleeding (often light and short but may be prolonged and heavy) brand disease. Initial screening when a coagulopathy : bleeding during or immediately after sexual intercourse is suspected should include complete blood count AUB, abnormal uterine bleeding; HMB, heavy menstrual bleeding; HPMB, heavy and with platelets, prothrombin time, an activated partial prolonged menstrual bleeding. thromboplastin time, and fibrinogen. Depending on the results of these initial tests, specific tests for von Wille- brand disease and factor VIII may be indicated.7,8 Table 2. PALM-COEIN1,5,6

Imaging PALM – Structural causes of AUB Several imaging modalities are available to assist with di- P – endometrial and endocervical; may cause intermenstrual bleeding agnosis depending on history and physical examination A Adenomyosis – may cause HMB and/or PMB findings. These include transvaginal ultrasound, sono- L Leiomyoma (fibroids) – may cause HMB or PMB hysterography, and magnetic resonance imaging (MRI). M Malignancy/hyperplasia – AUB is most common symptom of endometrial Transvaginal ultrasound is useful to evaluate abnormal cancer; bleeding patterns are variable findings on bimanual examination or if an adequate ex- COEIN – Nonstructural causes of AUB amination cannot be completed due to obesity or pain. C size and shape and ovaries can be assessed, the Coagulopathy – spectrum of systemic disorders of hemostasis associated with HMB and/or PMB (eg, clotting factor deficiencies, platelet dysfunction, von latter for size, masses, and presence of multiple follicular Willebrand disease, use of anticoagulants) cysts consistent with polycystic ovary syndrome (PCOS). O Ovulatory dysfunction – includes a variety of endocrine disorders (eg, Endometrial thickness can also be assessed, but it is not polycystic ovary syndrome, other androgen excess, thyroid disorders, considered helpful in the evaluation of premenopausal hyperprolactinemia); may have irregular menses, HMB, and/or PMB women with AUB because thickness normally varies E Endometrial – likely due to vasoconstriction disorders, inflammation, infection, throughout the .2 Use of saline-infused HMB associated with predictable ovulatory cycles ultrasound and sonohysterography separates the lateral I Iatrogenic – a variety of medications and devices that act on the walls of the uterus to better detect intracavitary lesions can cause AUB (eg, IUDs, , tamoxifen, tricyclic such as fibroids or polyps. Routine use of MRI is not rec- antidepressants, some antipsychotics) ommended but may be helpful to guide treatment deci- N Not yet classified – poorly understood conditions and rare disorders (eg, arteriovenous malformations) sions when there are multiple myomas.2 Hysteroscopy allows a clinician to directly visualize the AUB, abnormal uterine bleeding; HMB, heavy menstrual bleeding; IUD, lining of the uterus using a small scope. Until recently, ; PMB, postmenopausal bleeding.

NPWomensHealthcare.com February 2020 Women’s Healthcare 25 hysteroscopy was only performed in outpatient or in- of bleeding in a woman of reproductive age, who is patient surgery centers, but newer devices can be used not pregnant, that is of sufficient quantity to require in an office setting.9 With hysteroscopy, clinicians can immediate intervention to prevent further blood loss.5 evaluate the uterine cavity for polyps, features of adeno- Patients with hemodynamic instability, defined as hy- myosis, and the presence of submucosal fibroids. Hys- potension, orthostatic vital signs, and tachycardia with teroscopes with multiple channels can be utilized to pass a hemoglobin level of 10 g/dL or less or those with he- instruments through to eradicate and remove polyps moglobin levels below 7 g/dL, should be hospitalized.12 and fibroids, as well as to obtain samples of the endome- Acute AUB management usually includes high-dose es- trium to assess for endometrial glands and stroma within trogen either intravenously or orally or tranexamic acid the , which may signal adenomyosis. intravenously or orally. Intrauterine tamponade with a catheter infused with 30 mL of fluid may also be used.1 Endometrial tissue sampling Iron supplementation should be initiated for identified Although infrequent, especially in reproductive-aged anemia with follow-up hemoglobin/hematocrit and fer- women, the possibility of endometrial hyperplasia and ritin levels to monitor return of appropriate iron stores. carcinoma must be considered. Endometrial tissue sampling is indicated for all women with AUB older Pharmacologic treatment options for than age 45 years, younger women with a history of un- chronic AUB opposed or increased estrogen exposure such as may Chronic AUB is defined as uterine bleeding that is abnor- be seen with obesity, PCOS, or any condition causing mal in duration, volume, and/or frequency and has been anovulation, and for women who continue to have AUB present for the majority of the last 6 months.5 This does despite medical treatment.10 not mean, however, that treatment should not begin as Women younger than age 45 years, with new onset of soon as the woman identifies a change that is significant AUB and an endometrial stripe that measures over 8 mm to her. or with persistent AUB for 6 months or more and an en- When considering the treatment options for chronic dometrial stripe greater than 3 mm, should have an endo- AUB, it’s imperative to assess the woman’s desire for metrial biopsy to rule out hyperplasia and carcinoma.10,11 fertility at the current time and in the future. Treatment options that also provide contraception include the 52-mg levonorgestrel-releasing intrauterine system, combination oral contraceptives that may be taken Chronic AUB is defined cyclically or in extended or continuous regimens, depot medroxyprogesterone acetate, and the etonogestrel as uterine bleeding subdermal implant. These methods have been shown to be effective at reducing bleeding in women with that is in adenomyosis, , coagulopathies, ovulatory abnormal dysfunction such as PCOS, and endometrial disor- ders.1,13 Other noncontraceptive progestins such as cy- duration, volume, and/ clic medroxyprogesterone acetate and oral micronized can be used for treatment of anovulatory or frequency and has been bleeding.1,14 All of these methods also help to protect women with unopposed estrogen exposure from en- present for the majority of dometrial hyperplasia. None of these methods resolve any underlying structural or hormonal causes for HMB. the last 6 months. Women with chronic AUB related to ovulatory dysfunc- tion who desire a pregnancy in the near future should be referred to a fertility specialist. For women with ovulatory heavy and/or prolonged Management of AUB menstrual bleeding who prefer not to take hormones The goal of treatment for acute or chronic AUB is to or who are considering a pregnancy, over-the-counter reduce blood loss at the time and in the future and to nonsteroidal anti-inflammatory drugs (NSAIDs) and correct anemia. Acute AUB is defined as an episode tranexamic acid are treatment options.1,6,14 NSAIDs

26 February 2020 Women’s Healthcare NPWomensHealthcare.com started up to 3 days prior to menses or at the onset of Women who have AUB from menses may reduce the amount of bleeding and any discomfort and cramping. Tranexamic acid is an antifi- brinolytic medication taken 3 times each day for 5 days endometrial polyps during menses.14 Tranexamic acid should not be used and/or leiomyoma who also in combination with estrogen-containing contraception and is contraindicated in women with a history of or risk for thrombosis. wish to preserve their A GnRH agonist, such as leuprolide acetate, nafarelin acetate, or goserelin acetate may be used short term, fertility and avoid especially for women with HMB related to leiomyomas, to suppress ovarian function and induce amenorrhea, hysterectomy may be promoting a rise in hemoglobin and reduction in the size of the leiomyomas prior to surgical intervention. candidates for minimally invasive Treatment with GnRH agonists is limited to 6 months because of an increased risk for osteoporosis with estro- tissue removal. gen suppression. If treatment is longer than 6 months, concomitant therapy with low doses of estrogen and progesterone are recommended to prevent bone loss.15 accreta, preterm delivery, intrauterine growth restric- tion, intrauterine fetal demise, and uterine rupture.18 Minimally invasive treatment options Women who have AUB from endometrial polyps and/or Uterine artery embolization leiomyoma who also wish to preserve their fertility and Uterine artery embolization is a minimally invasive proce- avoid hysterectomy may be candidates for minimally dure that shrinks uterine fibroids. During the procedure, invasive tissue removal. Hysteroscopic techniques have an interventional radiologist identifies the blood vessels evolved and are known as “see-and-treat,” where the that lead to the specific fibroid and injects clot-forming surgeon can look inside the uterus and remove abnormal particles into them. Over time, the fibroid, deprived of its tissue at the same time. blood supply, shrinks in size.19 To perform hysteroscopic polypectomy and myo- mectomy, instruments are inserted into a hysteroscope Dilation and curettage and utilize tiny rotary or reciprocating cutters to shave While dilation and curettage may be employed with off segments of submucosal fibroids while an inte- other modalities to help evacuate the tissue and blood grated suction device removes the tissue fragments. within the uterus, when utilized by itself, it is inadequate These have become the gold standard of treatment, and will only provide temporary relief.11 with success rates in the range of 85% to 95%.16 Hysterectomy Endometrial ablation In the past, hysterectomy was one of the most common For women who have completed childbearing, endome- surgical procedures in the United States.19 As more min- trial ablation removes a thin layer of the endometrium, imally invasive treatment options have been utilized to utilizing instruments that are passed through the treat AUB, the number of open hysterectomies has de- into the uterine cavity. The procedure is low risk and clined and robotic-assisted laparoscopic hysterectomies efficient, with a short recovery time and no incision, and have become more common due to reduced postoper- has a 98% reduction in bleeding at 12 months and 65% ative side effects. Although hysterectomy remains the amenorrhea rates at 3 years.17 most effective treatment, it also carries the highest risks, Although endometrial ablation may cause infertil- requires the longest recovery time, and can impact a ity, it’s recommended that reproductive-aged women woman’s mood, self-image, and sexual response, which who are sexually active continue to use contraception is why this option should be reserved for women who after an ablation because that do occur have failed other options and who have been appropri- can have serious consequences. Some of these conse- ately counseled.20 quences are: , , placenta

NPWomensHealthcare.com February 2020 Women’s Healthcare 27 Implications for practice 10. Shifren JL, Gass ML; NAMS Recommendations for The clinician who understands normal and abnormal Clinical Care of Midlife Women Working Group. The North American Society recommenda- parameters for menstrual bleeding can utilize PALM- tions for clinical care of midlife women. Menopause. COEIN to guide assessment that includes history, physical 2014;21(10):1038-1062. examination, laboratory tests, imaging studies, and other 11. ACOG committee opinion no. 557: Management of diagnostic procedures to work through differential diag- acute abnormal uterine bleeding in nonpregnant repro- noses and determine the cause for AUB. Shared decision ductive-aged women. Obstet Gynecol. 2013;121(4):891- making between clinician and patient for management 896. of AUB revolves around diagnosis, the impact of bleeding 12. Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti on her quality of life, extent of anemia, her fertility desire, KM. Diagnosis and management of endometrial hyper- and any risks for a cancerous or precancerous cause. = plasia. J Minim Invasive Gynecol. 2012;19(5):562-571. 13. Lethaby A, Hussain M, Rishworth JR, Rees MC. Proges- terone or -releasing intrauterine systems for Barbara A. Dehn is a women’s health nurse practi- heavy menstrual bleeding. Cochrane Database Syst Rev. tioner with the El Camino Women’s Medical Group 2015;(4):CD002126. in Mountain View, California. She is a member of 14. Bitzer J, Heikinheimo O, Nelson AL, Calaf-Alsina J, Fra- our Editorial Advisory Board. The author states that ser IS. Medical management of heavy menstrual bleed- she does not have a financial interest in or other ing: a comprehensive review of the literature. Obstet Gynecol Surv. 2015;70(2):115-130. relationship with any commercial product named in 15. Lethaby A, Puscasiu L, Vollenhoven B. Preoperative this article. medical therapy before surgery for uterine fibroids. Cochrane Database Syst Rev. 2017;11:CD000547. References 16. Tanos V, Berry KE, Frist M, Campo R, DeWilde 1. Marnach ML, Laughlin-Tommaso SK. Evaluation and RL. Prevention and management of complications management of abnormal uterine bleeding. Mayo Clinic in laparoscopic myomectomy. Biomed Res Int. Proc. 2019;94(2):326-335. 2018;2018:8250952. 2. Committee on Practice Bulletins—Gynecology. Prac- 17. Gimpelson RJ. Ten-year literature review of global tice bulletin no. 128: diagnosis of abnormal uterine endometrial ablation with the NovaSure® device. Int J bleeding in reproductive-aged women. Obstet Gynecol. Womens Health. 2014;6:269-280. 2012;120(1):197-206. 18. Kohn JR, Shamshirsaz AA, Popek E, et al. Pregnancy 3. Brito LG, Panobianco MS, Sabino-de-Freitas MM, et al. after endometrial ablation: a systematic review. BJOG. Uterine leiomyoma: understanding the impact of symp- 2018;125(1):43-53. toms on womens’ lives. Reprod Health. 2014;11(1):10. 19. Kohi MP, Spies JB. Updates on uterine artery emboliza- 4. Frasier IS, Critchley HO, Broder M, Munro MG. The tion. Semin Intervent Radiol. 2018;35(1):48-55. FIGO recommendations on terminologies and defini- 20. Rodrigues RC, Rodrigues MRK, Freitas NO, Rudge tions for normal and abnormal uterine bleeding. Semin MVC, Lima SAM. Quality of life in patients who un- Reprod Med. 2011;29(5):383-390. dergo conventional or robotic-assisted total laparo- 5. Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO scopic hysterectomy: protocol for a systematic review Working Group on Menstrual Disorders. FIGO classi- of randomized controlled trials. Medicine (Baltimore). fication system (PALM-COEIN) for causes of abnormal 2019;98(23):e15974. uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3-13. 6. Wouk N, Helton M. Abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2019;99(7):435-443. 7. Elmaog˘ulları S, Aycan Z. Abnormal uterine bleed- ing in adolescents. J Clin Res Pediatr Endocrinol. 2018;10(3):191-197. 8. Gray SH. Menstrual disorders. Pediatr Rev. 2013;34(1):6-17. 9. Kolhe S. Management of abnormal uterine bleeding - focus on ambulatory hysteroscopy. Int J Womens Health. 2018;10:127-136.

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