# Abnormal Uterine Bleeding: PALM-COEIN Classification and Workup

## Definitions

Abnormal uterine bleeding (AUB) encompasses any variation from the normal menstrual cycle, including changes in regularity, frequency, duration, or volume. Normal menstrual parameters include a cycle frequency of 24 to 38 days, regularity with cycle-to-cycle variation of 7 to 9 days or less, duration of 8 days or less, and volume of 5 to 80 mL per cycle (though subjective assessment is often used clinically). Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that interferes with quality of life and replaces the older term "menorrhagia." Intermenstrual bleeding refers to bleeding between menses, replacing "metrorrhagia." Postmenopausal bleeding (PMB) is any bleeding occurring after 12 months of amenorrhea.

## FIGO PALM-COEIN Classification

### Structural Causes (PALM)

The structural causes include polyp (P), referring to endometrial or endocervical polyps; adenomyosis (A), in which endometrial glands are present within the myometrium; leiomyoma (L), subdivided into submucosal (SM) fibroids that directly affect the endometrial cavity and other (O) fibroids that are intramural or subserosal; and malignancy and hyperplasia (M), encompassing endometrial cancer, endometrial hyperplasia, and cervical cancer.

| PALM (Structural) | Category | Examples |
|---|---|---|
| P - Polyp | Endometrial/endocervical polyps | Focal intracavitary growths |
| A - Adenomyosis | Endometrial glands in myometrium | Diffuse or focal |
| L - Leiomyoma | SM (submucosal) or O (other) | Fibroids by FIGO classification |
| M - Malignancy/Hyperplasia | Endometrial cancer, hyperplasia, cervical cancer | Tissue diagnosis required |

### Non-Structural Causes (COEIN)

The non-structural causes include coagulopathy (C), such as von Willebrand disease, platelet disorders, and anticoagulant therapy; ovulatory dysfunction (O), including anovulation from PCOS, hypothalamic causes, thyroid dysfunction, and perimenopause; endometrial (E), referring to primary endometrial disorders of hemostasis, inflammation (endometritis), or vasculogenesis; iatrogenic (I), from hormonal contraceptives, anticoagulants, IUDs, or tamoxifen; and not yet classified (N), covering rare causes such as arteriovenous malformations.

| COEIN (Non-Structural) | Category | Examples |
|---|---|---|
| C - Coagulopathy | Bleeding disorders | von Willebrand disease, platelet disorders, anticoagulants |
| O - Ovulatory dysfunction | Anovulation | PCOS, hypothalamic, thyroid, perimenopause |
| E - Endometrial | Primary endometrial dysfunction | Chronic endometritis, hemostatic disorders |
| I - Iatrogenic | Medication-related | Hormonal contraceptives, anticoagulants, tamoxifen |
| N - Not yet classified | Rare causes | AVM, myometrial hypertrophy |

<image>PALM-COEIN classification system displayed as a visual grid with structural causes on one side (Polyp, Adenomyosis, Leiomyoma subdivided into submucosal and other, Malignancy) and non-structural causes on the other (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified), with representative illustrations for each category</image>

## Evaluation

### History

A thorough history covers the menstrual pattern including frequency, duration, and volume (number of pads or tampons, presence of clots, flooding episodes). The onset, duration, and progression of AUB are documented. Associated symptoms such as pain, pressure, and dyspareunia are explored. Sexual history, contraception use, and pregnancy status (which must always be ruled out) are assessed. Bleeding history including easy bruising, mucosal bleeding, and family history of bleeding disorders is important. Current medications, particularly anticoagulants, hormonal therapy, NSAIDs, and herbal supplements, are reviewed. Medical conditions including thyroid disease, liver disease, renal disease, and PCOS are considered. A structured bleeding assessment tool can help screen for coagulopathy.

### Physical Exam

Vital signs are assessed for evidence of anemia. Abdominal exam evaluates for mass or tenderness. Speculum exam identifies cervical lesions, cervical polyps, and the source of bleeding. Bimanual exam assesses uterine size, shape, and tenderness as well as adnexal masses. Cervical cytology is obtained if due.

### Laboratory Studies

A pregnancy test is performed in all reproductive-age women. A CBC assesses for anemia and thrombocytopenia. Ferritin and iron studies evaluate for iron deficiency, which is common with heavy menstrual bleeding. TSH screens for thyroid dysfunction. Coagulation studies are obtained when coagulopathy is suspected, especially in adolescents with heavy menstrual bleeding at menarche; the panel includes von Willebrand factor antigen, ristocetin cofactor, factor VIII activity, PT/INR, PTT, and platelet count. Prolactin, FSH, and LH are checked if amenorrhea or oligomenorrhea is present. Endometrial sampling is performed based on specific indications outlined below.

### Imaging

#### Transvaginal Ultrasound (TVUS)

TVUS is the first-line imaging modality for AUB evaluation. It assesses endometrial thickness, uterine size, fibroids, adnexal masses, and features of adenomyosis. For postmenopausal women with bleeding, an endometrial thickness of 4 mm or less has a 99% negative predictive value for cancer. In premenopausal women, endometrial thickness varies with the cycle phase, and there is no reliable cutoff for cancer.

#### Saline Infusion Sonohysterography (SIS)

SIS is superior to TVUS for detecting intracavitary lesions such as polyps and submucosal fibroids. Saline is infused through a catheter into the uterine cavity during TVUS, delineating focal versus diffuse endometrial pathology. It should be performed in the follicular phase (days 4 to 10) to minimize false-positive findings.

#### MRI

MRI provides excellent characterization of adenomyosis and is valuable for fibroid mapping before myomectomy. It is not a routine first-line study for AUB.

### Endometrial Sampling

#### Indications

Endometrial sampling is indicated for all women aged 45 or older with AUB. It is also indicated for women under 45 with AUB who have risk factors for endometrial cancer, including obesity, PCOS, chronic anovulation, tamoxifen use, diabetes, or family history of endometrial or colon cancer. Postmenopausal bleeding with endometrial thickness greater than 4 mm (or any PMB with high clinical suspicion) warrants sampling. Failed medical management of AUB and persistent intermenstrual bleeding are additional indications.

#### Methods

Office endometrial biopsy using a Pipelle device is the first-line method, with a sensitivity of 90 to 98% for cancer. Hysteroscopy with directed biopsy is the gold standard for focal lesions and is performed when office biopsy is insufficient or negative despite persistent symptoms. Dilation and curettage is reserved for situations where office biopsy cannot be performed, such as cervical stenosis.

<image>Diagnostic algorithm for abnormal uterine bleeding: starting with pregnancy test and CBC, then TVUS for structural assessment, decision point for endometrial sampling based on age and risk factors, SIS if focal lesion suspected, and hysteroscopy for definitive evaluation of intracavitary pathology</image>

## Management by Etiology

### Polyps (AUB-P)

Hysteroscopic polypectomy is performed for symptomatic polyps. Pathology review is essential, as 1 to 3% of polyps harbor malignancy, with risk increasing with age, size greater than 1.5 cm, and postmenopausal status. Small asymptomatic polyps may be observed in premenopausal women.

### Adenomyosis (AUB-A)

Medical management with a levonorgestrel IUD is first-line, with combined hormonal contraceptives and GnRH agonists or antagonists as alternatives. Hysterectomy is the definitive surgical treatment.

### Leiomyoma (AUB-L)

Submucosal fibroids are treated with hysteroscopic myomectomy. Other fibroids are managed with medical therapy, uterine artery embolization, myomectomy, or hysterectomy depending on symptoms and fertility plans.

### Malignancy and Hyperplasia (AUB-M)

Endometrial hyperplasia without atypia is treated with progestin therapy, including cyclic medroxyprogesterone acetate, continuous progestins, or a levonorgestrel IUD. Atypical endometrial hyperplasia warrants hysterectomy (28 to 43% have concurrent cancer), though progestin therapy with close surveillance may be offered if fertility is desired. Endometrial cancer requires staging surgery and adjuvant therapy.

### Coagulopathy (AUB-C)

Up to 13 to 20% of women with heavy menstrual bleeding have an underlying bleeding disorder, with von Willebrand disease being the most common (affecting 1% of the population). Treatment includes hormonal management with combined oral contraceptives or a levonorgestrel IUD, desmopressin (DDAVP) for von Willebrand disease, tranexamic acid, and factor replacement. Hematology referral is indicated for confirmed coagulopathy.

### Ovulatory Dysfunction (AUB-O)

Ovulatory dysfunction is the most common cause of AUB in adolescents and perimenopausal women. Anovulatory cycles produce unopposed estrogen stimulation of the endometrium followed by irregular shedding. Treatment involves combined oral contraceptives for cycle regulation, endometrial thinning, and bleeding reduction; cyclic progestins (medroxyprogesterone 10 mg for 10 to 14 days per month); a levonorgestrel IUD for long-term management; and addressing the underlying cause such as PCOS or thyroid dysfunction.

### Endometrial (AUB-E)

Primary endometrial hemostatic dysfunction may present as AUB with no identifiable structural or hormonal cause. Chronic endometritis is diagnosed by the presence of plasma cells on biopsy using CD138 staining and is treated with doxycycline 100 mg twice daily for 14 days. Tranexamic acid, an antifibrinolytic agent given at 1,300 mg three times daily during menses, reduces blood loss by 40 to 50%. NSAIDs such as mefenamic acid and naproxen reduce prostaglandin-mediated bleeding by 20 to 40%.

### Iatrogenic (AUB-I)

Breakthrough bleeding on hormonal contraception is common in the first 3 months and typically improves with time. Anticoagulant-related bleeding requires regimen adjustment in consultation with the prescribing physician. Tamoxifen use warrants endometrial evaluation if bleeding occurs, as polyps are a common finding.

## Medical Management Summary

### Hormonal Options

Combined hormonal contraceptives are first-line for many causes of AUB and reduce menstrual blood loss by 40 to 50%. The levonorgestrel IUD (Mirena or Liletta) is the most effective medical treatment for heavy menstrual bleeding, reducing blood loss by 70 to 90% and serving as an alternative to hysterectomy. Cyclic progestins (medroxyprogesterone, norethindrone) are effective for anovulatory bleeding. GnRH agonists such as leuprolide produce temporary amenorrhea and are useful for preoperative fibroid shrinkage, though add-back therapy is needed for use beyond 6 months. Oral GnRH antagonists (elagolix, relugolix-estradiol-norethindrone) represent a newer option for fibroids and endometriosis with integrated add-back therapy.

### Non-Hormonal Options

Tranexamic acid at 1,300 mg three times daily for up to 5 days during menses is effective. NSAIDs reduce prostaglandin-mediated bleeding. Iron supplementation, either oral or intravenous (ferric carboxymaltose, iron sucrose), addresses iron deficiency anemia secondary to heavy menstrual bleeding.

## Clinical Pearls

The PALM-COEIN system should be used systematically for every AUB evaluation. Patients often have more than one contributing cause.

The levonorgestrel IUD is the most effective medical treatment for heavy menstrual bleeding and should be offered before proceeding to surgical options.

Up to 20% of adolescents presenting with heavy menstrual bleeding at menarche have an underlying bleeding disorder. Screen for coagulopathy in this population.

Endometrial biopsy is indicated in all women aged 45 or older with AUB and in younger women with risk factors for endometrial cancer.

Tranexamic acid is an effective non-hormonal option that can be used in combination with hormonal therapy. There is a theoretical venous thromboembolism risk when combined with combined oral contraceptives, though the real-world risk is likely low.

SIS is superior to standard TVUS for detecting intracavitary pathology (polyps, submucosal fibroids) and should be used when TVUS is inconclusive or shows thickened endometrium.

Chronic endometritis is an underrecognized cause of AUB. Consider endometrial biopsy with CD138 staining in refractory cases.

<image>Treatment algorithm for heavy menstrual bleeding organized by desire for fertility: fertility desired (NSAIDs, tranexamic acid, combined OCPs, LNG-IUD) versus fertility not desired (LNG-IUD, endometrial ablation, hysteroscopic resection of focal lesions, hysterectomy for refractory cases), with medical options tried before surgical intervention</image>

## References

- ACOG Practice Bulletin No. 128: Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women (2012)
- ACOG Committee Opinion No. 557: Management of Acute Abnormal Uterine Bleeding in Nonpregnant Reproductive-Aged Women (2013)
- Munro MG et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding. Int J Gynaecol Obstet. 2011;113:3-13
- NICE Guideline NG88: Heavy Menstrual Bleeding: Assessment and Management (2018, updated 2021)
- Gupta J et al. Levonorgestrel-releasing intrauterine system versus medical therapy for menorrhagia. N Engl J Med. 2013;368:128-137
- James AH. Von Willebrand disease in women. J Thromb Haemost. 2009;7 Suppl 1:61-65