Basics
Description
- Bleeding beyond the range of normal menses, with "normal" defined as duration of 2-8 days, occurring every 21-40 days, with blood loss of 20-80 mL/cycle
- May vary in presentation from heavy, long menses followed by long periods of amenorrhea to short, heavy menses occurring every 1-2 weeks
- In teens, dysfunctional uterine bleeding (DUB) most commonly results from anovulatory cycles, which are secondary to an immature hypothalamic-pituitary-ovarian axis.
Epidemiology
- DUB commonly occurs within the first 2 years of menarche when >50% of cycles are anovulatory.
- Later age at menarche associated with longer duration of anovulation
- Most females who experience anovulatory cycles do not develop DUB.
Risk Factors
Genetics
Patients with disorders, such as blood dyscrasias and polycystic ovary syndrome (PCOS), usually have familial histories of similar disorders.
Pathophysiology
- Anovulation (failure to ovulate) results in corpus luteum absence.
- Without the secretory effect of progesterone from the corpus luteum, endometrial proliferation continues because of unopposed estrogen.
- The thickened endometrium eventually outgrows support from the basal endometrium, resulting in sloughing of the highest endometrial levels. Alternatively, cyclic estrogen withdrawal may occur, which will lead to sloughing of the endometrium in the absence of progesterone.
- As subsequent levels of endometrium are shed, bleeding increases. Profuse bleeding may result when the basal endometrium is exposed.
Diagnosis
History
- Abnormal bleeding
- Assess the amount of bleeding, and confirm if it is vaginal bleeding.
- Important to know when bleeding began and some estimate of blood loss to know if the patient is at risk for anemia or hemodynamic instability
- The pattern of DUB in relation to the menstrual cycle can help guide the diagnostic workup.
- Normal cyclic intervals with increased bleeding during each cycle may suggest a bleeding disorder.
- Normal intervals with bleeding between cycles may suggest infection or foreign body.
- Abnormal intervals with no cycle regularity may suggest anovulatory cycles or endocrinopathy or be a side effect of hormonal contraception.
- Increased time lapse between menarche and onset of DUB lessens the likelihood of anovulatory cycles.
- Teens with chronic diseases and active health problems may have prolonged anovulatory cycles.
- Easy bruisability, epistaxis, and/or bleeding gums may be suggestive of a bleeding disorder.
- A family history of thyroid disease, bleeding disorder, PCOS, or DUB will help guide the laboratory workup.
- Personal and immediate family history of thromboembolism or known familial risk factors
- Ask about sexual activity and abuse in a safe, confidential setting.
Physical Exam
- Often normal in patients with DUB
- Assess vital signs, including orthostatic BPs, for signs of cardiac instability resulting from severe blood loss.
- Skin or mucosal pallor, elevated heart rate, or flow murmur may be indicative of anemic state.
- Assess sexual maturity rating (SMR, or Tanner stage). Menarche usually does not occur before SMR 3, so bleeding before this stage suggests a nonmenstrual source of bleeding.
- Look for signs of androgen excess (e.g., hirsutism, acne), which may be reflective of disrupted ovulatory function.
- Bitemporal hemianopsia is suggestive of a pituitary adenoma leading to hyperprolactinemia.
- Hyperprolactinemia can result in anovulation.
- Only 1/3 of adolescents with hyperprolactinemia will experience galactorrhea.
- Assess for evidence of thyroid disease, hematologic disorder (e.g., bruising, petechiae), or systemic disease (e.g., poor nutritional status).
- Speculum-assisted pelvic examination may help determine source of bleeding. Bimanual examination is helpful in assessing ovarian or uterine masses, cervical motion or adnexal tenderness, and uterine sizing.
Diagnostic Tests & Interpretation
Lab
- Obtain urine or serum human chorionic gonadotropin (β-hCG), regardless of sexual history. Urine hCG testing can reliably detect pregnancy as early as 2 weeks postconception; however, it may be positive for up to 2 weeks following a miscarriage or abortion.
- CBC: Degree of anemia guides treatment plan. Assess for thrombocytopenia. In the setting of acute blood loss, a normal hemoglobin may be falsely reassuring. It is wise to recheck hemoglobin after IV hydration, as decreases may be dramatic.
- For Chlamydia trachomatis and Neisseria gonorrhoeae, obtain cervical cultures or use nucleic acid amplification tests (NAATs) (e.g., PCR or LCR) on urine, vaginal, or cervical swabs. Be careful to check with laboratory or NAAT manufacturers' information regarding reliability with blood in sample and based on collection site.
- Wet mount or vaginal swab may be unreliable but should be attempted for presence of WBCs and Trichomonas. In some labs, Trichomonas vaginalis antigen tests may be available.
- Consider prolactin level and thyroid function tests (TSH, T4): Hyperprolactinemia may have several causes, including pituitary microadenoma, and result in amenorrhea or DUB.
- Prothrombin and partial thromboplastin time, von Willebrand factor: to assess for hematologic causes of bleeding
- Androgen levels, including testosterone (total and free), dehydroepiandrosterone sulfate (DHEAS), androstenedione: Abnormal levels are supportive of PCOS or other hyperandrogenic state.
Imaging
- Pelvic ultrasound
- Indicated when pregnancy is suspected (ectopic or intrauterine)
- Consider when a pelvic mass is felt, uterine anomaly is being considered, or bimanual examination cannot be completed
- MRI of the pelvis: Indicated for patients with a suspected pelvic mass when ultrasonography does not clearly define the anatomy
Alert
Pitfalls
- Neglecting to perform pregnancy testing in an adolescent who denies sexual activity
- Neglecting to reassess hemoglobin concentration after volume expansion
Differential Diagnosis
Although most cases of abnormal uterine bleeding in adolescents can be attributed to anovulatory cycles, it is important to rule out underlying and alternate causes of irregular or heavy bleeding.
- Pregnancy: should be considered and ruled out in every patient, regardless of patient's reported sexual history
- Ectopic pregnancy
- Threatened abortion, incomplete abortion
- Placenta previa
- Hydatidiform mole
- Infection
- Vaginitis (e.g., trichomoniasis)
- Cervicitis or endometritis (e.g., gonorrhea or chlamydia)
- Pelvic inflammatory disease
- Hematologic conditions
- Thrombocytopenia (e.g., immune thrombocytopenic purpura [ITP], leukemia)
- Platelet dysfunction
- Coagulation defect (e.g., von Willebrand disease)
- Endocrinologic disorders
- Hyper- or hypothyroidism
- Hyperprolactinemia
- PCOS
- Adrenal disorders
- Trauma: laceration to vagina or cervix
- Foreign body: usually associated with strong, foul odor
- Medications
- Direct effect on hemostasis (e.g., Coumadin, chemotherapeutic agents)
- Hormonal effects (e.g., oral contraceptives, Depo-Provera, other exogenous steroid hormones)
- Systemic disease
- Disruption of hypothalamic-pituitary-ovarian axis
- Other examples include systemic lupus erythematosus and chronic renal failure.
- Primary gynecologic disorders
- Endometriosis
- Uterine polyps, submucosal myomas
- Hemangioma, arteriovenous malformation
Treatment
General Measures
- For mild DUB (inconvenient, unpredictable bleeding, and the patient has a normal hemoglobin in setting of hemodynamic stability)
- Reassurance until ovulatory cycles resume. Encourage maintenance of a menstrual calendar, with follow-up in 3-6 months.
- Iron supplementation
- If anxiety is unresponsive to reassurance, hormonal therapy with a daily combined oral contraceptive pill (OCP), 1 tablet daily, should be considered to regulate menstrual cycle; if estrogen is contraindicated, may use progesterone-only pill, medroxyprogesterone acetate 5-10 mg/24 h PO for 10-14 days every month
- For mild to moderate DUB, a progestin-containing intrauterine device may be indicated.
- For moderate DUB (irregular, prolonged, heavy bleeding with a hemoglobin >10 g/dL)
- Hormonal therapy, as described previously; may start OCP containing 35 mcg of ethinyl estradiol twice a day until bleeding stops, then taper to once a day
- Menstrual calendar with follow-up every 1-3 months
- For severe DUB (i.e., heavy, prolonged bleeding with a hemoglobin <10 g/dL), treatment depends on the presence of active bleeding.
- If no active bleeding, hemodynamically stable patients can be started on daily OCPs and iron supplementation, with follow-up in 1-2 months.
- In the presence of active bleeding: Hormonal therapy using combined OCP containing higher dose of estrogen (50 mcg ethinyl estradiol)-1 pill q.i.d. until bleeding stops, followed by pill taper (q.i.d. for 4 days, t.i.d. for 3 days, b.i.d. for 2 weeks, then 1 pill daily); switch to lower dose pill (30-35 mcg) after taper is complete.
- Hospitalization of patient during treatment if with severe anemia (hemoglobin <7 g/dL), if hemodynamically unstable, or with compliance concerns; blood transfusion as necessary
- If patient is unstable or unable to tolerate oral pill regimen, can give IV conjugated estrogen q4h for 24 hours to stop bleeding. Add PO or IM progesterone as soon as possible.
- Iron replacement
- Dilation and curettage rarely necessary; may be needed if hormonal therapy fails
- Possible side effects
- Estrogen, given in high doses, will cause nausea and/or vomiting. An appropriate antiemetic should be used for prophylaxis against these symptoms.
- High-dose estrogen may have vascular side effects and should be used with caution in patients particularly at risk for vascular events (e.g., patients with a history of lupus, stroke, or thrombotic phenomena and those who smoke cigarettes). In these cases, consult a gynecologist or adolescent medicine specialist for an alternative progesterone-only therapy.
Alert
Pitfalls
- Neglecting to provide both estrogen and progesterone in a timely fashion
- Neglecting to adequately assess or mediate risk for thromboembolic event related to estrogen therapy
- Neglecting to consider a retained foreign body (e.g., tampon)
Inpatient Considerations
Initial Stabilization
If DUB is attributed to anovulatory cycles, or if a complete workup fails to yield a diagnosis, treatment is guided by the severity of DUB and the presence of active bleeding.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
When to expect improvement
- Bleeding usually tapers after the first few doses of hormone therapy.
- After 6-12 months, if patient does not wish to remain on OCPs, a trial off medication might reveal normal ovulatory cycles.
- Ongoing follow-up with an adolescent medicine or adolescent gynecologist may be warranted.
Prognosis
DUB persists for 2 years in 60% of patients, 4 years in 50%, and up to 10 years in 30%.
Complications
Mild to severe anemia resulting from blood loss
Additional Reading
- Hickey M, Higham JM, Fraser I. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev. 2012;9:CD001895. [View Abstract]
- LaCour DE, Long DN, Perlman SE. Dysfunctional uterine bleeding in adolescent females associated with endocrine causes and medical conditions. J Pediatr Adolesc Gynecol. 2010;23(2):62-70. [View Abstract]
- Levine LJ, Catallozzi M, Schwarz DF. An adolescent with vaginal bleeding. Pediatr Case Rev. 2003;3(2):83-90. [View Abstract]
Codes
ICD09
- 626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
- 626.5 Ovulation bleeding
- 626.9 Unspecified disorders of menstruation and other abnormal bleeding from female genital tract
- 626.2 Excessive or frequent menstruation
ICD10
- N93.8 Other specified abnormal uterine and vaginal bleeding
- N92.3 Ovulation bleeding
- N93.9 Abnormal uterine and vaginal bleeding, unspecified
- N92.1 Excessive and frequent menstruation with irregular cycle
- N92.0 Excessive and frequent menstruation with regular cycle
SNOMED
- 19155002 Dysfunctional uterine bleeding (finding)
- 27585009 Anovular menstruation (finding)
- 237134002 Ovulatory dysfunctional bleeding (finding)
- 444560000 Oligoovulatory dysfunctional uterine bleeding (finding)
FAQ
- Q: If most girls have anovulatory cycles, why do only some present with DUB?
- A: Most girls do have irregular menstrual cycles during the first 2 years after menarche. However, in most, the negative-feedback system of estrogen leads to cyclic endometrial shedding in an anovulatory pattern.
- Q: If DUB from anovulatory cycles is caused by lack of progesterone, why does the initial treatment of severe DUB with active bleeding involve large doses of estrogen?
- A: Estrogen has procoagulation effects that promote hemostasis (e.g., effects on platelet aggregation and levels of fibrinogen and clotting factors). In addition, severe DUB may lead to an exposed endometrial base that bleeds profusely; for progesterone to exhibit its secretory effects, the endometrium in that area must be restored by estrogen.
- Q: When hormonal therapy fails, and the basal endometrium continues to bleed, how does a dilation and curettage act as the final treatment?
- A: The curettage removes any remaining bleeding vessels and stimulates local prostaglandins to create a uterine contracture that inhibits bleeding. This procedure is rarely needed in adolescent patients, as they usually respond to hormonal therapy.