Lifecycle Approach to Abnormal Uterine Bleeding

Abnormal uterine bleeding (AUB) is experienced by nearly one-third of patients with a uterus and is commonly addressed in the primary care setting. Abnormal uterine bleeding, defined as deviations from the normal regularity, frequency, heaviness, or duration of flow, may be disruptive to daily life and often leads to secondary complications such as anemia and infertility. Causes and presentations of AUB vary across the lifecycle and the International Federation of Gynecology and Obstetrics System 2 mnemonic PALM-COEIN can assist in understanding both the structural and non-structural etiologies of abnormal uterine bleeding.

Key points

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Abnormal Uterine Bleeding (AUB) describes bleeding that deviates from the typical regularity, frequency, heaviness, or duration of flow in a patient’s menstrual cycle.
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Sensitivity to the patient’s story coupled with a thorough history is essential to prevent misdiagnosis and mitigate barriers to treatment.
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Causes of AUB can be classified using the PALM-COIEN mnemonic.
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The most common causes of AUB include ovulatory and anovulatory patterns.
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Treatment of AUB is based on age and cause and frequently includes hormonal therapy.

Abbreviations

AUB	abnormal uterine bleeding
CBC	complete blood count
COC	combined oral contraceptive pill
FIGO	International Federation of Gynecology and Obstetrics
hCG	human chorionic gonadotropin
HPO	hypothalamic-pituitary-ovarian axis
HRT	hormone replacement therapy
IUD	intrauterine device
PALM-COEIN	polyps, adenomyosis, leiomyomas, malignancy, coagulopathies, ovulatory dysfunction, endometrial disorders, iatrogenic, and not yet classified
PCOS	polycystic ovary syndrome
PT	prothrombin time
PTT	partial thromboplastin time
TSH	thyroid-stimulating hormone
TVUS	transvaginal ultrasound
US	ultrasound

Introduction

Abnormal uterine bleeding (AUB) is experienced by nearly one-third of patients with a uterus and is commonly addressed in the primary care setting ( Fig. 1 ). The definition and presentation of AUB varies through the life cycle depending on the expected menstrual patterns of each age group. Generally, AUB is defined as deviations from the normal regularity, frequency, heaviness, or duration of flow. ^, The severity of AUB can range from annoyance to emergent; however, it is universally disruptive to daily life and often leads to secondary complications such as anemia and infertility. ^, Factors that delay a patient presenting for treatment include lack of knowledge around normal menstrual cycles, fear of discussing a “taboo” subject, and negative experiences with health care professionals. ^, In addition to patience in exploring the history, ruling out nonhormonal causes, and performing a physical examination and appropriate testing, understanding the pathophysiology of the menstrual cycle is key to successfully managing AUB. Abnormal uterine bleeding can be classified into structural and nonstructural etiologies using the International Federation of Gynecology and Obstetrics (FIGO) System 2 acronym PALM-COEIN, described in Tables 1–3 . The PALM (polyps, adenomyosis, leiomyomas, and malignancy) designation describes structural causes of AUB and the COEIN (coagulopathies, ovulatory dysfunction, endometrial disorders, iatrogenic, and not yet classified) describes nonstructural causes of AUB.

Table 1

Abnormal uterine bleeding – polyps, adenomyosis, leiomyomas, malignancy, coagulopathies, ovulatory dysfunction, endometrial disorders, iatrogenic, and not yet classified (PALM COEIN) mnemonic

Differential Diagnosis	Clinical History	Initial Work-Up
PALM (structural causes)
P olyps	May cause postcoital bleeding, intermenstrual spotting. Cervical polyps may be seen on examination.	Pelvic examination ^a& pelvic ultrasound
A denomyosis	Heavy menstrual bleeding, painful menses, and chronic pelvic pain may be present. An enlarged, boggy, tender uterus may be felt on examination.	Pelvic examination & US or MRI
L eiomyomas	Heavy or prolonged menstrual bleeding, bulk-related symptoms such as pelvic pressure and pain, and reproductive dysfunction such as infertility or miscarriage may be present. Uterus may feel enlarged on examination.	Pelvic examination & US
M alignancy	Risk factors for endometrial neoplasia include older age and exposure to unopposed estrogen and chronic disease (eg: obesity, anovulation, PCOS, estrogen replacement therapy, tamoxifen, HTN, DM).	Pelvic examination & US, pap smear, endometrial biopsy in patients > 45 y or in patients w/risks for endometrial neoplasia
COEIN (non-structural causes)
Coagulopathies VWD Thrombocytopenia Platelet function disorders Clotting factor deficiencies	• Family hx of abnormal bleeding or bleeding disorder • Personal hx of heavy menstrual bleeding since menarche, frequent bruising, bleeding gums, epistaxis, postpartum hemorrhage, or bleeding with surgical and dental procedures	CBC, PT/PTT, fibrinogen VWD: VWF Ag, VWF functional assay, Factor 8 activity Platelet function testing – consult hematology
Ovulatory Dysfunction Immature HPO axis, Relative energy deficience in sport, Eating disorder, obesity, primary ovarian insufficiency Endocrine Disorders: PCOS, thyroid disease, adrenal insufficiency, Cushing’s, nonclassic CAH, hyperprolactinemia	• Hx of eating disorder • Primary ovarian insufficiency: Hot flashes, vaginal dryness, bone loss/osteoporosis • PCOS, nonclassic CAH: hirsutism, excessive acne, male pattern baldness • Cushing’s: Resistant HTN, osteoporosis, striae, proximal myopathy	• TSH, prolactin, urine hCG • PCOS: check androgen levels if diagnosis unclear • Primary ovarian insufficiency: check FSH, estradiol • Cushing’s: Check cortisol
Endometrial disorders Endometriosis Endometritis	• Family hx of endometriosis • Personal hx of chronic pelvic pain, severe dysmenorrhea, dyspareunia, bowel/bladder dysfunction • Risk factors for pelvic inflammatory disease	Pelvic examination to check for cervical motion tenderness, uterine tenderness, chlamydia/gonorrhea/trichomoniasis laboratorys
Iatrogenic Hormonal contraception, anticoagulants, steroids, antipsychotics, antidepressants, tamoxifen	• Hx of irregular hormonal contraceptive use • Hx of recent contraceptive initiation • Hx of taking SSRIs, TCAs, antipsychotics	Consider pelvic examination or TVUS to ensure IUD is in place
Not yet classified Cesarean scar defect, arteriovenous malformations	• Hx of postmenstrual spotting • AUB refractory to hormonal management	Pelvic US AVM: US w/dopplers

DM, diabetes mellitus; HTN, hypertension; hx, history; SSRI, selective serotonin reuptake inhibitor; VWD, Von Willebrand disease; VWF, Von Willebrand factor.

a Pelvic examination should include a speculum and bimanual examination. It’s important to examine all potential bleeding sites, including the vagina, cervix, urethra, perineum, and anus. Pelvic examination can be deferred in adolescents if the patient is not sexually active, trauma and infection is not suspected, and response to initial treatment is adequate.

Table 2

Medical management of abnormal uterine bleeding

Drug	Dose	Notes
Acute Bleeding
Conjugated equine estrogen	2.5 mg orally every 6 h for 21 d or 25 mg IV every 4-6 h for 24 h	Follow treatment with a progestin to provoke withdrawal bleeding; do not use in patients at increased risk of thrombosis
Estrogen-progestin oral contraceptives	1 monophasic pill containing 35 mcg of ethinyl estradiol orally 3 times daily for 7 d	Do not use in patients at increased risk of thrombosis
Norethindrone acetate	5–10 mg one to four times a day for 5–10 d	Used for treatment in patients with contraindications to estrogen
Medroxyprogesterone acetate	10–20 mg three times a day for 5–10 d	Used for treatment in patients with contraindications to estrogen
Tranexamic acid	1300 mg three times daily for up to 5 d	Do not use in patients at increased risk of thrombosis
Chronic Bleeding
Medroxyprogesterone acetate (Depo Provera)	150 mg IM or 104 mg subq every 13 wk or 5–20 mg pills per day in 1–3 divided doses	Irregular bleeding is common in first 3 mo of using Depo-Provera injection but ∼ 50% of patients become amenorrheic after 12 mo of use
Estrogen-progestin oral contraceptives	1 monophasic pill containing 35 mcg of ethinyl estradiol daily	Other routes (transdermal patch, intravaginal ring) are likely also effective
Levonorgestrel	52 mg IUD	Irregular bleeding is common in the first 3 mo of use, but ∼20% of patients become amenorrheic after 12 mo of use
Norethindrone	5–15 mg per day in 1–3 divided doses	Continuous use is preferred due to increased efficacy and patient adherence
Tranexamic Acid	1300 mg three times daily for up to 5 d during monthly menstruation	Do not use in patients at increased risk of thrombosis
Nonsteroidal antiinflammatory drugs	Naproxen 500 mg orally 2 times daily or ibuprofen 600–800 mg every 6–8 h	Administer only while patient is bleeding; do not use in patients with coagulopathy