# Abnormal Uterine Bleeding: Evaluation and Management

## Overview

Abnormal uterine bleeding is one of the most common gynecologic complaints in primary care, affecting up to 30% of reproductive-age women. A systematic approach using the PALM-COEIN classification guides evaluation and management while avoiding unnecessary procedures.

## Definitions

Abnormal uterine bleeding encompasses any deviation from normal menstrual cycle parameters, including frequency, regularity, duration, and volume. Normal menses occur every 24 to 38 days, last 4 to 8 days, and involve blood loss below 80 mL. Heavy menstrual bleeding, which replaces the older term "menorrhagia," is defined as excessive blood loss that interferes with quality of life. Intermenstrual bleeding, replacing "metrorrhagia," refers to bleeding between expected menses. Amenorrhea is the absence of menses for 3 cycles or 6 months. Postmenopausal bleeding, defined as any bleeding occurring more than 12 months after the last menstrual period, requires endometrial evaluation to exclude malignancy.

## PALM-COEIN Classification (FIGO)

| Category | Cause | Key Features | Primary Diagnostic Approach |
|----------|-------|--------------|----------------------------|
| P | Polyp | Intermenstrual bleeding; usually benign | TVUS, saline infusion sonohysterography |
| A | Adenomyosis | Dysmenorrhea + HMB; globular uterus | TVUS or MRI |
| L | Leiomyoma | Submucosal most likely to cause AUB | TVUS; subclassify by location |
| M | Malignancy/hyperplasia | Postmenopausal bleeding; risk factors | Endometrial biopsy |
| C | Coagulopathy | HMB since menarche; easy bruising | vWF, platelet studies |
| O | Ovulatory dysfunction | Irregular cycles; PCOS, thyroid disease | TSH, prolactin, androgens |
| E | Endometrial | Diagnosis of exclusion | After ruling out other causes |
| I | Iatrogenic | OCP, anticoagulants, IUD, tamoxifen | Medication review |
| N | Not yet classified | AVM, cesarean scar defect | Specialized imaging |

### Structural Causes (PALM)

The structural causes of AUB include polyps (endometrial or endocervical, usually benign but capable of harboring hyperplasia or malignancy), adenomyosis (endometrial glands within the myometrium, presenting with dysmenorrhea and heavy menstrual bleeding, diagnosed via MRI or transvaginal ultrasound showing a globular uterus with heterogeneous myometrium), leiomyoma (subclassified by location as submucosal, intramural, or subserosal, with submucosal fibroids being the most likely to cause AUB), and malignancy and hyperplasia (endometrial cancer and hyperplasia, which must be excluded in appropriate clinical scenarios).

### Non-Structural Causes (COEIN)

Non-structural causes include coagulopathy (von Willebrand disease as the most common inherited bleeding disorder, platelet disorders, and anticoagulant use), ovulatory dysfunction (PCOS, thyroid disease, hyperprolactinemia, hypothalamic amenorrhea, and perimenopause), endometrial causes (primary disorders of endometrial hemostasis, which are a diagnosis of exclusion), iatrogenic causes (hormonal contraceptives, anticoagulants, IUDs, SSRIs, and tamoxifen), and not yet classified causes (including rare entities such as arteriovenous malformations and cesarean scar defects).

## Initial Evaluation

### History

The history should establish the menstrual pattern including frequency, duration, and volume (noting whether the patient soaks through pads or tampons hourly or passes clots larger than 2.5 cm). Associated symptoms such as dysmenorrhea, dyspareunia, and pelvic pain or pressure should be elicited. Sexual history, contraceptive use, and the possibility of pregnancy are essential. Medications including anticoagulants, hormonal therapies, and supplements should be reviewed. A bleeding history covering easy bruising, epistaxis, bleeding with dental procedures, and family history of bleeding disorders helps screen for coagulopathy. Heavy menstrual bleeding present since menarche is particularly suggestive of an underlying bleeding disorder.

### Physical Examination

The examination begins with vital signs to assess hemodynamic stability. Abdominal examination evaluates for masses and tenderness. Speculum examination identifies cervical lesions, vaginal bleeding sources, and confirms a uterine origin. Bimanual examination assesses uterine size, shape, tenderness, and adnexal masses.

### Laboratory Workup

A pregnancy test should always be obtained in reproductive-age women. CBC assesses for anemia. TSH screens for thyroid dysfunction. Coagulation studies including PT, PTT, von Willebrand factor antigen, and ristocetin cofactor should be considered when heavy menstrual bleeding has been present since menarche or the history is suggestive. Prolactin is appropriate if oligomenorrhea or amenorrhea is present. Ferritin should be checked even when hemoglobin is normal, as iron stores may be depleted. FSH and estradiol are considered when perimenopause or premature ovarian insufficiency is suspected. An endocrine workup for PCOS including testosterone and DHEA-S is indicated when appropriate.

### Imaging

Transvaginal ultrasound is the first-line imaging modality, evaluating endometrial thickness, fibroids, and ovarian pathology. Saline infusion sonohysterography is superior to standard ultrasound for detecting intracavitary lesions such as polyps and submucosal fibroids. MRI is useful for adenomyosis and preoperative fibroid mapping but is not a first-line study.

### Endometrial Biopsy

Endometrial biopsy is indicated in women aged 45 or older with AUB, in women under 45 with risk factors such as obesity, PCOS, chronic anovulation, tamoxifen use, or failed medical therapy, in any postmenopausal bleeding, and when endometrial thickness exceeds 4 mm on transvaginal ultrasound in postmenopausal women. Office-based pipelle aspiration has sensitivity exceeding 90% for endometrial cancer. If an inadequate sample is obtained, saline infusion sonohysterography or hysteroscopy with directed biopsy should be considered.

## Management by Etiology

### Acute Heavy Bleeding (Hemodynamically Significant)

Acute management options include IV conjugated equine estrogen at 25 mg every 4 to 6 hours for up to 24 hours, or high-dose oral combined OCP using a monophasic pill with 35 mcg ethinyl estradiol taken one pill three times daily for 7 days followed by a taper. Tranexamic acid at 1 to 1.3 grams IV or 1.3 grams orally three times daily can be added. Intrauterine balloon tamponade using a Foley catheter is considered if the patient is unresponsive to medical management. Dilation and curettage is reserved for cases where medical management fails. Transfusion and correction of coagulopathy are provided as needed.

### Medical Management (Chronic AUB)

#### Hormonal Options

Combined oral contraceptives regulate cycles and reduce bleeding by 40 to 50%, serving as first-line therapy for AUB from ovulatory dysfunction. The levonorgestrel IUD (Mirena or Liletta) is the most effective medical therapy, reducing bleeding by 70 to 95%, and is considered first-line for heavy menstrual bleeding in many guidelines. Oral progestins can be used cyclically (medroxyprogesterone 10 mg on days 16 through 25 for anovulatory bleeding) or continuously (norethindrone acetate 5 to 15 mg daily for continuous suppression). Depot medroxyprogesterone acetate may cause amenorrhea and is useful when adherence is a concern. GnRH agonists and antagonists are used short-term preoperatively to reduce fibroid size and control bleeding, with elagolix and relugolix with add-back therapy available for longer-term use.

#### Non-Hormonal Options

Tranexamic acid at 1.3 grams orally three times daily during menses (days 1 through 5) reduces bleeding by 30 to 50%, though concurrent use with combined hormonal contraceptives should be avoided. NSAIDs such as naproxen at 500 mg twice daily or mefenamic acid at 500 mg three times daily during menses reduce bleeding by 20 to 40% and simultaneously treat dysmenorrhea. Iron supplementation with ferrous sulfate at 325 mg daily or every other day should be provided to treat iron deficiency even when hemoglobin remains normal.

### Surgical Management

Polypectomy via hysteroscopic removal is indicated for symptomatic polyps. Myomectomy is appropriate for fibroids in women desiring fertility, with the approach determined by fibroid location: hysteroscopic for submucosal, laparoscopic or open for intramural and subserosal. Endometrial ablation is reserved for women with completed childbearing and is not recommended when endometrial hyperplasia or malignancy is suspected. Uterine artery embolization is an alternative to surgery for fibroids but is contraindicated when future pregnancy is desired. Hysterectomy provides definitive treatment and is indicated for refractory AUB, significant structural pathology, or malignancy.

## Special Populations

### Adolescents

AUB is common in the first 2 to 3 years after menarche due to anovulation from an immature hypothalamic-pituitary-ovarian axis. Screening for bleeding disorders is important, as 20% of adolescents with heavy menstrual bleeding have an underlying coagulopathy. Hormonal management is preferred, and endometrial biopsy is rarely needed.

### Perimenopause

Anovulatory cycles become increasingly common during perimenopause. Hyperplasia and malignancy must be excluded with endometrial biopsy when risk factors are present. The LNG-IUD is effective for both contraception and AUB management in this population.

### Postmenopausal Bleeding

Postmenopausal bleeding always requires evaluation to exclude endometrial cancer, which has a 10% prevalence in this setting. Transvaginal ultrasound is performed first: an endometrial stripe below 4 mm has a negative predictive value exceeding 99% for cancer. If the stripe measures 4 mm or above, or bleeding persists, endometrial biopsy or hysteroscopy is indicated.

<image>The PALM-COEIN classification system displayed as a diagnostic framework with structural causes (Polyp, Adenomyosis, Leiomyoma, Malignancy) on one side and non-structural causes (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not classified) on the other, with key clinical features and diagnostic approaches for each category.</image>

<image>A stepwise evaluation algorithm for abnormal uterine bleeding starting with pregnancy test and CBC, branching by age and risk factors to determine need for imaging (TVUS, SIS) and endometrial biopsy, with decision points for medical versus surgical management based on findings.</image>

<image>Ultrasound images comparing normal endometrium, endometrial polyp, submucosal fibroid, and thickened endometrium suggestive of hyperplasia, with annotations showing measurement technique for endometrial thickness and criteria for biopsy referral.</image>

## Clinical Pearls

A pregnancy test should always be performed in reproductive-age women with AUB, regardless of reported sexual history or contraceptive use. The LNG-IUD is the most effective medical therapy for heavy menstrual bleeding, reducing blood loss by 70 to 95%, and is first-line in many guidelines. Adolescents with heavy menstrual bleeding since menarche should be screened for von Willebrand disease and other coagulopathies, as the prevalence reaches 20% in this population. Postmenopausal bleeding is endometrial cancer until proven otherwise; a thin endometrial stripe below 4 mm on transvaginal ultrasound has excellent negative predictive value but does not completely exclude cancer. Tranexamic acid is an effective non-hormonal option that can be combined with hormonal therapy, though combining it with estrogen-containing contraceptives should be avoided due to theoretical thrombotic risk. Iron deficiency can be present even with a normal hemoglobin, and ferritin should be checked in women with heavy periods. Anovulatory bleeding in perimenopause is common but still requires endometrial biopsy if risk factors for hyperplasia are present. Endometrial biopsy with a pipelle has sensitivity exceeding 90% for cancer but can miss focal lesions; if clinical suspicion remains high after a negative biopsy, hysteroscopy should be pursued.

## References

- Munro MG et al. The FIGO Classification of Causes of AUB (PALM-COEIN). Int J Gynecol Obstet. 2018
- ACOG Practice Bulletin No. 128: Diagnosis of Abnormal Uterine Bleeding. Obstet Gynecol. 2012 (reaffirmed 2022)
- Lethaby A et al. Levonorgestrel-Releasing Intrauterine System for Heavy Menstrual Bleeding. Cochrane Database Syst Rev. 2015
- ACOG Committee Opinion: Screening and Management of Bleeding Disorders in Adolescents. 2019
- Clarke MA et al. Endometrial Thickness and Cancer Risk Among Postmenopausal Women. JAMA Intern Med. 2018