Abnormal uterine bleeding

ACRONYMS AND DEFINITIONS

ACOG - American College of Obstetricians and Gynecologists

Cyclical bleeding - menstrual bleeding that occurs at a predictable time interval

Menorrhagia - bleeding exceeding 8 days’ duration or heavy enough to interfere with a woman’s quality of life

Metrorrhagia - bleeding at irregular intervals, particularly between expected menstrual periods

Noncyclical bleeding - menstrual bleeding that occurs at an unpredictable or irregular interval

Oligomenorrhea - infrequent menstrual periods

Polymenorrhea - menstrual cycles that are shorter than 21 days

PREVALENCE

Abnormal uterine bleeding affects approximately one-third of women throughout their lifetime. Abnormal uterine bleeding may refer to heavy menstrual bleeding, bleeding at irregular intervals, or a combination of the two. [3]

CAUSES AND SYMPTOMS

Overview

The tables below list some causes of heavy cyclical bleeding and noncyclical bleeding
Bleeding patterns can provide clues to the underlying pathology, but they are not specific, and in many cases, different patterns may coexist

Refernces [1,2,3]
Heavy Cyclical Bleeding
Cause	Comments
Adenomyosis	Adenomyosis is a condition where the glandular tissue of the endometrium grows into the underlying uterine muscle On exam, the uterus may be enlarged or lobular
Anticoagulant use	Anticoagulants may promote heavy menstrual bleeding. See Factor Xa inhibitors, warfarin, and direct thrombin inhibitors.
Coagulation disorders	Coagulopathy (particularly Von Willebrand disease) may cause heavy bleeding Signs of coagulopathy include heavy bleeding since menarche, easy bruising, and prolonged mucosal surface bleeding See coagulopathy screening for recommendations on who to screen
Copper IUD	The copper IUD may cause heavier and longer menstrual bleeding See copper IUD for more
Leiomyoma (fibroids)	Fibroids are noncancerous growths of the uterus On exam, the uterus may be enlarged or lobular May be treated with uterine artery embolization

Refernces [1,2,3]
Noncyclical Bleeding
Cause	Comments
Cervical polyp	May cause postcoital bleeding
Cervicitis	Cervicitis is an infection of the cervix Most common causes are chlamydia and gonorrhea. Mycoplasma genitalium has also been implicated. May cause postcoital bleeding
Endometrial hyperplasia	More common in perimenopausal and early postmenopausal women Obesity, PCOS, and chronic anovulation are also risk factors
Endometrial polyp	May cause intermenstrual bleeding Larger polyps may be seen on uterine ultrasound May be removed with hysteroscopy
Endometritis	Endometritis is an infection of the uterine cavity Most common causes are chlamydia and gonorrhea. Mycoplasma genitalium has also been implicated. May cause intermenstrual bleeding
Hormonal contraceptives	Hormonal contraceptives are a very common cause of irregular bleeding See oral contraceptives and birth control methods
Hyperprolactinemia	Hyperprolactinemia may present as amenorrhea or oligomenorrhea. Galactorrhea may also be present. Hyperprolactinemia may occur from a pituitary adenoma, or it may be drug-induced (see antipsychotics for more)
Kidney disease	Kidney disease may cause irregular menses. In end-stage renal disease, amenorrhea is common.
Malignancy (endometrial, cervical, vaginal)	May cause postcoital bleeding
Menarche	Menarche is the onset of menstruation. It typically occurs between 12 and 13 years of age (median 12.43 years). During the first 2 - 3 years after menarche, irregular menstrual cycles are common
Perimenopause	Perimenopause is the beginning of menopause, and it occurs at a median age of 47 years Menstrual cycles often become irregular during perimenopause (see menopause for more)
Polycystic ovary syndrome	PCOS is a common cause of noncyclical menses Hirsutism may be present Measure serum testosterone level. See treatment recommendations for more.
Thyroid disease	Both hyper- and hypothyroidism can affect menstrual patterns Amenorrhea and oligomenorrhea are seen in hyperthyroidism, and increased bleeding is common in hypothyroidism

MENORRHAGIA WORKUP

References [1]
ACOG recommendations for working up menorrhagia
All patients CBC Blood type cross and match (if bleeding is severe) Pregnancy test
Most patients Pelvic ultrasound Pelvic exam with PAP smear
Patients at risk for coagulopathy (see coagulopathy screening below) activated Partial Thromboplastin Time (aPTT) Prothrombin time (PT-INR) Testing for von Willebrand disease Fibrinogen
Women ≥ 45 years old Endometrial biopsy
Other considerations in appropriate patients Thyroid testing Iron studies Liver function tests Chlamydia testing

COAGULOPATHY SCREENING

References [1]
ACOG recommendations for coagulopathy screening in menorrhagia
Screen patients for coagulopathy if they meet any 1 of the following 3 criteria:
1. Heavy menstrual bleeding since menarche
2. One of the following: Postpartum hemorrhage Surgery-related bleeding Bleeding with dental work
3. Two or more of the following: Bruising, 1 - 2 times per month Nosebleed, 1 - 2 times per month Frequent gum bleeding Family history of bleeding problems
Initial lab testing CBC activated Partial Thromboplastin Time (aPTT) Prothrombin time (PT-INR) Testing for von Willebrand disease Fibrinogen

TREATMENT

References [1]
ACOG recommendations for acute treatment of uncontrolled bleeding
Conjugated estrogens injection (Premarin®) Dosing: 25 mg IV every 4 - 6 hours for 24 hours Other Shown to stop bleeding within 8 hours in 72% of patients May cause significant nausea. Give with nausea medication. See female hormone medications for more
Monophasic OCP with 35 mcg of ethinyl estradiol Dosing: One tablet three times a day for 7 days Other Shown to stop bleeding in 88% of patients May cause significant nausea. Give with nausea medication. See oral contraceptive chart for more
Medroxyprogesterone (Provera®) Dosing: 20 mg three times a day for 7 days Other Shown to stop bleeding in 76% of patients May cause significant nausea. Give with nausea medication. See female hormone medications for more
Tranexamic acid (Lysteda®) Dosing Oral: 1.3 grams three times a day for 5 days IV: 10 mg/kg (max 600 mg/dose) every 8 hours for 5 days Other Tranexamic acid binds plasminogen and prevents it from dissolving fibrin Contraindicated in women at increased risk for venous or arterial thromboembolism See the Lysteda® PI for full prescribing information

Chronic treatment

Oral contraceptives
Medroxyprogesterone shot
Mirena® IUD
Tranexamic acid (Lysteda®)

Dosed as two 650 mg tablets (1300 mg) three times a day for 5 days during monthly menstruation
See Lysteda® PI for more

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Oriahnn®

Combination of estradiol/norethindrone acetate and elagolix which is a GnRH receptor antagonist
Approved for use up to 24 months
See Oriahnn® PI for more

Myfembree®

Combination of estradiol/norethindrone acetate and relugolix which is a GnRH receptor antagonist
Approved for use up to 24 months
See Myfembree® PI for more

Endometrial ablation
Uterine artery embolization for fibroids
Hysterectomy

BIBLIOGRAPHY

1 - PMID 26254516 - ACOG GL
2 - PMID 2034248 - NEJM review
3 - PMID 31070673 - Abnormal Uterine Bleeding in Reproductive-AgeWomen, JAMA (2019)

ABNORMAL UTERINE BLEEDING