Approach to abnormal uterine bleeding in reproductive-aged patients: Clinical sciences

Abnormal uterine bleeding, or AUB, is a common problem for reproductive-aged patients. In general, normal menses has a duration of 5 days with a cycle length between 21 and 35 days, with no bleeding in between cycles, while the volume differs between individuals. AUB is defined as menstrual bleeding that deviates from normal duration, regularity, frequency, or volume. The International Federation of Gynecology and Obstetrics has established a classification system for AUB that defines it by bleeding pattern and etiology, and has replaced historical terms for abnormal bleeding, such as menorrhagia, metrorrhagia, and polymenorrhea. The two bleeding patterns include Heavy Menstrual Bleeding and Intermenstrual Bleeding.

The etiologies can be remembered with the mnemonic PALM-COEIN. PALM includes structural causes of AUB: Polyp, Adenomyosis, Leiomyoma, and Malignancy. COEIN includes nonstructural causes: Coagulopathy, Ovulatory Dysfunction, Endometrial, Iatrogenic, and Not yet classified. Keep in mind that PALM-COEIN refers only to gynecological causes of AUB, not pregnancy-related ones.

The first step in evaluating a reproductive-aged patient who presents with AUB is to perform a CABCDE assessment to determine if they are stable or unstable. If the patient is unstable, control life-threatening hemorrhage, which may include IV hormonal therapy or surgical intervention. Also, stabilize the airway, breathing, and circulation; obtain IV access and monitor vitals.

On the flip side, if the patient is stable, the first step is to obtain a focused history and physical exam, as well as an hCG to assess for pregnancy.

If the hCG test is positive, the patient is pregnant. Any vaginal bleeding during pregnancy is abnormal and potentially dangerous, so be sure to evaluate immediately for life-threatening conditions, such as an ectopic pregnancy.

On the other hand, if hCG is negative, assess for non-pregnancy related causes of AUB. For this, you’ll need to obtain a pelvic ultrasound to evaluate the uterus and adnexa. If ultrasound demonstrates abnormal uterine findings, assess for structural causes of abnormal bleeding. Keep in mind that pregnancy doesn’t exclude these conditions, but they’re unlikely to be a source of abnormal bleeding during pregnancy.

Let’s start with polyps, which is the “P” in PALM-COEIN. The history may include postcoital spotting or intermenstrual bleeding. Physical examination will reveal a normal uterine size and shape, and there might be a soft polypoid mass at the cervical os. As for the ultrasound, you’ll see no myometrial pathology, but it may demonstrate a thickened asymmetric endometrial lining that’s suggestive of an endometrial polyp.

While endocervical polyps can be seen on physical examination, endometrial polyps can be delineated with sonohysterogram or hysteroscopy. Sonohysterogram involves injecting a small amount of saline into the uterine cavity during ultrasonography, while hysteroscopy involves placing a hysteroscope into the uterus for direct visualization. If there’s an echogenic mass or lesion within the endometrial cavity, that’s endometrial polyp. For both endocervical and endometrial polyps you should perform a directed excisional biopsy or polypectomy. This will not only treat the patient’s bleeding, but histologic evaluation can provide definitive diagnosis. With benign histology, you can make the diagnosis of endocervical or endometrial polyp. Even though these polyps are frequently benign in reproductive-age patients, be sure to closely follow the results in case it comes back with hyperplasia or malignancy.

Next, let’s assess for adenomyosis, the “A” in our mnemonic. In this case, the patient may report heavy vaginal bleeding or dysmenorrhea, and physical exam will demonstrate a diffusely enlarged, globular, and tender uterus. Ultrasound will show a heterogeneous myometrium, asymmetric myometrial thickness, and myometrial cysts. With these findings, the presumptive diagnosis is adenomyosis.

Let’s move on to “L”, leiomyomas. The patient’s history may include heavy vaginal bleeding, as well as pelvic pain and pressure, while the physical exam might reveal an enlarged uterus with an irregular contour. If ultrasound findings demonstrate one or more myometrial masses, you can diagnose leiomyoma.

Here’s a high-yield fact! Leiomyomas arise from the myometrium. Leiomyomas that grow into the endometrium or endometrial cavity, known as submucosal leiomyomas, are very likely to cause abnormal bleeding. On the other hand, intramural myomas, which are confined to the myometrium; or subserosal myomas, which extend into the pelvic cavity, are much less likely to cause AUB. Sometimes ultrasound doesn’t clearly delineate between submucosal and intramural myomas, so a sonohysterogram or hysteroscopy can be performed to clarify the location.

Next is endometrial malignancy, the “M” in our mnemonic. When considering malignancy, it’s important to obtain a history that addresses risk factors for endometrial hyperplasia or carcinoma. These risk factors include age greater than 45, chronic anovulation, unopposed estrogen, and obesity. Physical examination is usually unremarkable, while ultrasound will show an absence of myometrial abnormalities, but may demonstrate a thickened heterogeneous endometrial lining.

Here’s a clinical pearl! Endometrial thickness varies significantly throughout the menstrual cycle and is most abundant just prior to menstruation, so keep the patient’s last known menstrual period in mind when interpreting the ultrasound.

A thickened endometrium in a premenopausal patient is not necessarily abnormal, but if you have concerns, consider a repeat scan in a different phase of their cycle. On the other hand, a thickened endometrium is definitely concerning for malignancy in postmenopausal patients who are symptomatic.

Alright, if the patient has one or more risk factors for endometrial hyperplasia or carcinoma, endometrial sampling is indicated. This can be done with a blind endometrial biopsy, which involves inserting a pipelle catheter into the uterus and collecting an endometrial sample. The other option is to perform a hysteroscopy and directed biopsies. The decision to perform one or the other is determined by factors like the availability of resources and the patient's medical comorbidities.

If the biopsy demonstrates crowding of the endometrial glands within the stroma and possibly shows nuclear atypia, the diagnosis is endometrial intraepithelial neoplasia, previously known as endometrial hyperplasia with or without atypia.