Uterine Bleeding

1. Official reprint from UpToDate
www.uptodate.com ©2015 UpToDate
Author
Nirupama K De Silva, MD
Section Editors
Amy B Middleman, MD, MPH, MS Ed
Mitchell Geffner, MD
Deputy Editor
Mary M Torchia, MD
Abnormal uterine bleeding in adolescents: Differential diagnosis and approach
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2015. | This topic last updated: Nov 18, 2014.
INTRODUCTION — Menstrual cycles are often irregular in the first months after menarche. According to a study
by the World Health Organization, the median length of the first cycle after menarche was 34 days, with 38
percent of the cycles exceeding 40 days and 7 percent occurring less than 20 days apart [1]. Menstrual
disorders and abnormal uterine bleeding (AUB) are among the most frequent gynecologic complaints of
adolescents [2,3]. Abnormal uterine bleeding (AUB) refers to bleeding that is excessive or occurs outside of
normal cyclic menstruation [4]. AUB is described by a variety of terms and may be caused by a number of
genital and nongenital tract diseases, systemic disorders, and medications (table 1). (See "Differential diagnosis
of genital tract bleeding in women".)
Most cases of AUB in adolescents are caused by anovulatory cycles during the first 12 to 18 months after
menarche, which is related to immaturity of the hypothalamic­pituitary­ovarian axis [4,5]. Other common causes
include pregnancy, infection, the use of hormonal contraceptives, stress (psychogenic or exercise induced),
bleeding disorders, and endocrine disorders (eg, hypothyroidism, polycystic ovary syndrome) [4].
The treatment for these disorders ranges from observation to pharmacologic and/or surgical therapy. Potential
sequelae of AUB include anemia [6] and endometrial cancer [7,8]. With appropriate management of the
underlying problem, these sequelae may be prevented. Thus, it is crucial to establish the correct diagnosis
before any therapy is administered [9].
The evaluation of AUB in adolescents will be discussed here. The management of AUB in adolescents is
discussed separately, as is the evaluation of AUB in premenopausal women. (See "Abnormal uterine bleeding in
adolescents: Management" and "Approach to abnormal uterine bleeding in nonpregnant reproductive­age
women".)
GENERAL APPROACH — The differential diagnosis of genital tract bleeding in adolescents is similar to that in
adult women (table 1). However, the most common causes vary according to age (table 2). In adolescents in
particular, disorders of pregnancy and the possibility of pelvic infection should be considered early in the
evaluation [10]. It is essential to rule out pregnancy in the adolescent, regardless of the stated sexual history.
This is especially important in those adolescents who present with unexplained vaginal bleeding [11]. (See
"Ectopic pregnancy: Clinical manifestations and diagnosis" and "Clinical features and diagnosis of pelvic
inflammatory disease".)
Once pregnancy has been excluded, it is helpful to determine whether the bleeding is cyclic (regular) or acyclic
(irregular) in nature. The differential diagnosis varies accordingly. As an example, anovulatory bleeding is the
most common cause of excessive menstrual flow in adolescents with irregular bleeding, whereas blood
dyscrasias and structural anomalies (eg, polyps, fibroids) are more common in those with cyclic bleeding.
As a general rule, bleeding that is preceded by premenstrual symptoms (breast tenderness, water weight gain,
mood swings, or abnormal cramping) is ovulatory [9]. In contrast, heavy bleeding that occurs irregularly is
usually anovulatory. However, many patients are between these extremes, and determination of the ovulatory
status may be difficult.
Common causes of abnormal uterine bleeding in adolescents can be grouped into four patterns:
®
®

2. (See "Abnormal uterine bleeding in adolescents: Definition and evaluation", section on 'Terminology'.)
Characterization into one of these patterns may be difficult because of the range of variability in cycles during
the first one to two years postmenarche and the difficulty in quantifying volume of flow. In addition, the causative
conditions may overlap categories or present atypically. Nevertheless, the categorization scheme is helpful in
narrowing the differential diagnosis and directing the additional laboratory evaluation.
AMENORRHEA — Amenorrhea is the absence of menses, which may be primary or secondary. Although there
are several unique causes of primary amenorrhea (eg, congenital abnormalities in Müllerian development or
urogenital sinus development), all causes of secondary amenorrhea also can cause primary disease. The most
common cause of amenorrhea in a female of reproductive age is pregnancy. (See "Pregnancy in adolescents",
section on 'Diagnosis of pregnancy'.)
Primary — Primary amenorrhea is commonly defined as the absence of menarche by age 15 years. The 95
percentile for menarche in North America is 14.5 years [12,13]. The causes, evaluation, and treatment of
primary amenorrhea are discussed in detail separately. (See "Etiology, diagnosis, and treatment of primary
amenorrhea" and "Evaluation of oligomenorrhea in adolescence".)
Secondary — Secondary amenorrhea is defined as the absence of menses for more than three cycles or six
months in women who previously had menses [14]. In adolescents, it is uncommon for girls to remain without
their menses for >90 days (the 95 percentile for cycle length). Thus, adolescents without menses for 90 days
warrant an evaluation [15]. Once pregnancy is excluded, a step­wise endocrinologic evaluation can be
considered. If labs are normal, a progesterone challenge (such as micronized oral progesterone [200 mg] for 12
days) or a trial of hormonal contraception may be necessary to reestablish menses. (See "Etiology, diagnosis,
and treatment of secondary amenorrhea" and "Evaluation of oligomenorrhea in adolescence".)
IRREGULAR BLEEDING
Anovulatory uterine bleeding — In adolescents, during the first 12 to 18 months after menarche and in the
absence of pregnancy, the most common cause of irregular menstrual bleeding is anovulation due to an
immature hypothalamic­pituitary­ovarian axis [4,5]. This condition is a normal finding in the first few years after
menarche, but all other pathologic diagnoses must be ruled out (table 3). (See "Approach to abnormal uterine
bleeding in nonpregnant reproductive­age women", section on 'History'.)
Every young adolescent female is prone to anovulatory cycles in which the endometrium lacks the stabilizing
effect of progesterone. In such cycles, the endometrium becomes excessively thickened. It breaks down and
sloughs when estrogen is withdrawn (estrogen­withdrawal bleeding) or when it becomes unstable (estrogen­
breakthrough bleeding) [16,17]. (See "Abnormal uterine bleeding in adolescents: Definition and evaluation",
section on 'Normal menstrual cycle'.)
Adolescents with regular menses have cyclic estrogen secretion that permits orderly growth and shedding of the
endometrium (on account of hormone withdrawal), even in the absence of ovulation. In addition, the secretion of
progesterone associated with the occasional ovulatory cycle in these adolescents helps to stabilize endometrial
growth and permits more complete shedding [10].
In contrast, adolescents with anovulatory bleeding appear to have delayed maturation of normal negative
feedback cyclicity [18]. In these girls, rising levels of estrogen do not cause suppression of follicle­stimulating
hormone (FSH) [19]. Estrogen secretion is sustained, and the concentration of FSH is increased relative to that
of luteinizing hormone (LH). In these girls with sustained acyclic estrogen secretion, the endometrium
proliferates beyond estrogen's ability to maintain its integrity. Bleeding occurs when the endometrium becomes
Amenorrhea●
Irregular bleeding●
Heavy menstrual bleeding●
Intermenstrual bleeding●
th
th

3. unstable (estrogen­breakthrough bleeding) and continues until estrogen­induced repair takes place [16,17].
Episodes of amenorrhea may be followed by sudden and substantial hemorrhage [17].
Other causes of irregular menses must be excluded before a diagnosis of anovulatory bleeding can be made. In
girls in whom a diagnosis of anovulatory bleeding is considered, additional evaluation may include FSH, LH,
thyroid­stimulating hormone (TSH), and prolactin on day three of the menstrual cycle (by convention, the first
day of menses is day one of the cycle, even in girls with irregular cycles). Although the concentrations of LH and
FSH vary throughout the cycle (figure 1), they are most reproducible on day three, when they are at their lowest
concentrations. If day three happens to fall on a weekend, the blood may be drawn on day four or five. Free and
total testosterone and dehydroepiandrosterone sulfate (DHEA sulfate) should be obtained if signs of
hyperandrogenism are present (see 'Polycystic ovary syndrome' below). If all pathologic causes are ruled out,
and the patient is not bothered by irregular menses, anovulatory bleeding may be managed expectantly for the
first few years after menarche.
Polycystic ovary syndrome — Polycystic ovary syndrome (PCOS) is a common cause of abnormal bleeding in
the adolescent with chronic anovulation [19]. The diagnosis of PCOS is based upon clinical and biochemical
criteria. It should be pursued in all adolescents with obesity, menstrual irregularity, insulin resistance, and/or
signs of hyperandrogenism (hirsutism, acne, clitoromegaly) [20]. Because signs of hyperandrogenism are not
invariably present, PCOS also should be considered in girls with prolonged menstrual irregularity and/or
severely anovulatory bleeding, even in the absence of hirsutism or acne. (See "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents".)
If PCOS is a consideration, other causes of hyperandrogenism and other causes of irregular menses must be
ruled out. These include congenital adrenal hyperplasia (CAH), tumors of the ovary or adrenal gland, Cushing
syndrome, hyperprolactinemia, and thyroid dysfunction. The differential diagnosis and evaluation of
hyperandrogenism in adolescents is discussed in detail separately. (See "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents".)
Other causes — Other hormonal causes of irregular bleeding in adolescents include hypothyroidism and
hyperprolactinemia [21]. The causes of hyperprolactinemia are discussed separately but include pituitary tumors
and certain medications (eg, metoclopramide and methyldopa). (See "Causes of hyperprolactinemia".)
Psychologic or exercise­induced stress and eating disorders with large weight loss may cause acute anovulation
in adolescents. However, these disorders are typically associated with a hypoestrogenic state and amenorrhea.
(See "Etiology, diagnosis, and treatment of primary amenorrhea" and "Etiology, diagnosis, and treatment of
secondary amenorrhea".)
Finally, intermenstrual bleeding related to bacterial or viral infections of the vulva, vagina, or cervix may give an
adolescent the false impression that her menses are "irregular". (See 'Intermenstrual bleeding' below.)
EXCESSIVE MENSTRUAL BLEEDING — Excessive menstrual flow may be excessive in its duration (>7 days)
or its volume (>80 mL/cycle). Unfortunately, neither patients nor clinicians can accurately estimate the amount of
blood loss. Heavy menstrual bleeding in the adolescent typically occurs at irregular intervals, indicating that it is
anovulatory. (See 'Irregular bleeding' above and "Abnormal uterine bleeding in adolescents: Definition and
evaluation", section on 'History'.)
Bleeding disorders — Heavy menstrual bleeding that occurs at regular intervals or at the onset of menses is
often related to a bleeding diathesis and less commonly to systemic illness or structural lesions [22­28]. Inherited
bleeding disorders should be considered in the differential diagnosis of all patients presenting with heavy
menstrual bleeding [29]. In retrospective studies, the prevalence of bleeding disorders among adolescents
hospitalized for heavy menstrual bleeding ranges from 5 to 28 percent [22,24­27]. In one series of 59
adolescents who were hospitalized with acute heavy menstrual bleeding and in whom genital tract pathology
had been excluded, an underlying coagulopathy was present in approximately one­fifth overall, one­third of
those requiring a transfusion, and one­half presenting at menarche [22].

4. Coagulation disorders among adolescents with heavy menstrual bleeding include von Willebrand disease,
immune thrombocytopenia (ITP), platelet dysfunction, and thrombocytopenia secondary to malignancy or
treatment for malignancy (ie, chemotherapy or hematopoietic stem cell transplantation) [21­26,28]. Bleeding
diathesis in adolescents also may be related to the use of medications such as anticoagulant or platelet
inhibitors. These disorders are discussed separately. (See "Clinical presentation and diagnosis of von
Willebrand disease" and "Immune thrombocytopenia (ITP) in children: Clinical manifestations and diagnosis"
and "Congenital and acquired disorders of platelet function".)
Excessive bleeding should prompt an evaluation of hematologic status. The minimum laboratory evaluation
should include [29]:
We consider the diagnosis of a bleeding dyscrasia in adolescents who present with extremely heavy first
menses, bleeding requiring blood transfusion, and patients with refractory heavy menstrual bleeding and
concomitant anemia. In such patients, the secondary evaluation also should include a von Willebrand panel (ie,
plasma von Willebrand factor (VWF) antigen; plasma VWF activity (ristocetin cofactor activity); and factor VIII
activity) [29,30]. It is important that the von Willebrand panel be obtained when the patient is not taking
hormones, because exogenous estrogen may elevate VWF into the normal range [31]. Thus, the panel should
be obtained at the time of presentation or after exogenous estrogen has been discontinued for seven days. It is
also important to obtain blood group typing since blood group O is associated with lower levels of VWF, and to
consult with a hematologist if the levels are low. (See "Abnormal uterine bleeding in adolescents: Management"
and "Clinical presentation and diagnosis of von Willebrand disease".) If a bleeding disorder is considered,
consultation with a hematologist is warranted.
Other causes — Less common causes of heavy menstrual bleeding in adolescents include systemic illness,
endocrine disorders, and structural lesions. Systemic illness may affect ovarian or liver function, causing
abnormalities in ovulation or coagulation, respectively. Examples include diabetes mellitus, systemic lupus
erythematosus, renal failure, malignancy, and myelodysplasia. Hypothyroidism and hyperthyroidism may cause
heavy menses, as well as anovulatory cycles. Structural lesions that cause heavy menstrual bleeding in
adolescents include cervical polyps and uterine leiomyomas (fibroids). (See 'Irregular bleeding' above and
"Clinical manifestations of hypothyroidism" and "Congenital cervical anomalies and benign cervical lesions".)
In adolescents with heavy menstrual bleeding in whom a bleeding diathesis has been excluded, additional
laboratory evaluation may include:
INTERMENSTRUAL BLEEDING
Exogenous hormones — Exogenous hormone administration (eg, hormonal contraception) is a common cause
of abnormal uterine bleeding in adolescents. Intermenstrual bleeding is a common side effect of oral
contraceptives, depot medroxyprogesterone acetate, the contraceptive patch [32], and the ring, implant, and
intrauterine devices. Bleeding may occur if these medications are not taken as prescribed or as a side effect of
these medications. Thus, it is important to ask detailed questions about how medicines are taken or used. (See
"Risks and side effects associated with estrogen­progestin contraceptives", section on 'Breakthrough bleeding'
and "Overview of contraception".)
Complete blood count with platelets and examination of the peripheral blood smear and ferritin to detect
anemia or thrombocytopenia
●
Coagulation panel (activated partial thromboplastin time (aPTT) and prothrombin time (PT))●
Measurement of serum TSH to exclude thyroid abnormalities●
Evaluation for chronic or systemic diseases as warranted by the history and physical examination●
Pelvic ultrasonography (if it has not already been performed) to exclude structural causes, such as fibroids,
polyps, and/or ovarian tumors
●

5. Infection — Sexually active adolescents who have a history of acute vaginal bleeding unrelated to menses
should be assessed for cervicitis related to sexually transmitted infections. This also applies for girls who have
been sexually abused. The prevalence of C. trachomatis in women with AUB is underestimated [33]. (See
"Sexually transmitted diseases: Overview of issues specific to adolescents" and "Clinical features and diagnosis
of pelvic inflammatory disease".)
Other causes — Other causes of intermenstrual bleeding in adolescents include cervical polyps, ectropion
(particularly in girls with cystic fibrosis [10]), foreign bodies (retained tampons are most common among
adolescents), trauma, and certain medications (eg, anticoagulants). (See "Congenital cervical anomalies and
benign cervical lesions" and "Evaluation of sexual abuse in children and adolescents".)
Less common causes of nonuterine genital tract bleeding in adolescents are discussed separately. (See
"Differential diagnosis of genital tract bleeding in women".)
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SUMMARY AND RECOMMENDATIONS — The initial evaluation of all adolescents with AUB should include
exclusion of pregnancy, assessment of hemodynamic status (blood pressure, heart rate), and hemoglobin or
hematocrit and platelet count to evaluate the presence of anemia or thrombocytopenia. The additional
evaluation depends upon findings from the history and physical examination:
th th
th th
Basics topic (see "Patient information: Absent or irregular periods (The Basics)")●
Beyond the Basics topic (see "Patient information: Absent or irregular periods (Beyond the Basics)")●
The approach to amenorrhea is discussed separately. (See "Etiology, diagnosis, and treatment of primary
amenorrhea" and "Etiology, diagnosis, and treatment of secondary amenorrhea".)
●
Anovulatory bleeding accounts for the majority of abnormal uterine bleeding in adolescents; however, other
pathologic causes of bleeding must be excluded (table 3).
●
Obesity and/or signs of hyperandrogenism (eg, hirsutism, acne, clitoromegaly) in girls with AUB should
prompt evaluation for PCOS. This typically includes total and free testosterone and DHEA sulfate;
additional testing may be necessary to exclude other causes of hyperandrogenism (eg, prolactin, TSH,
cortisol). (See "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents".)
●
A progesterone challenge can be performed in girls with chronic anovulatory cycles to evaluate response
to endogenous estrogen. In addition, progesterone or hormonal contraception is an important component
in the management of prolonged anovulatory bleeding. (See "Abnormal uterine bleeding in adolescents:
Management" and "Endometrial carcinoma: Epidemiology and risk factors".)
●
Bleeding disorders should be considered in all adolescents with AUB who present with extremely heavy
first menses, bleeding requiring blood transfusion, and patients with refractory heavy menstrual bleeding
and concomitant anemia. (See "Approach to the child with bleeding symptoms".)
●

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Topic 114 Version 16.0
Sexually transmitted infections and pelvic inflammatory disease should be considered in all sexually active
(or sexually abused) adolescents who complain of irregular, intermenstrual, or postcoital bleeding. (See
"Sexually transmitted diseases: Overview of issues specific to adolescents".)
●

7. GRAPHICS
Causes of abnormal uterine bleeding in the adolescent girl
Anovulatory uterine bleeding
Pregnancy­related problems
Threatened, spontaneous, incomplete, missed
abortion
Problems with termination procedures
Ectopic pregnancy
Gestational trophoblastic disease
Infection
Pelvic inflammatory disease
Endometritis
Cervicitis
Vaginitis
Vaginal abnormalities
Carcinoma
Lacerations
Cervical problems
Cervicitis
Polyp
Hemangioma
Carcinoma
Uterine problems
Submucous myoma
Congenital anomalies
Polyp
Carcinoma
Intrauterine device
Intermenstrual bleeding
Ovulatory bleeding
Blood dyscrasia
Thrombocytopenia
Clotting disorders
Liver disease
Endocrine disorders
Anovulatory bleeding
Thyroid disease
Adrenal disorders
Hyperprolactinemia
Polycystic ovary syndrome
Ovarian failure
Ovarian problems
Cyst
Tumor
Endometriosis
Trauma
Foreign body
Systemic disease
Diabetes mellitus
Renal disease
Systemic lupus erythematosus
Medications
Hormonal
Anticoagulants, platelet inhibitors
Androgens, spironolactone
Antipsychotics
Adapted from: Emans SJ. Dysfunctional uterine bleeding. In: Pediatric and Adolescent Gynecology, 5th
ed, Emans SJ, Laufer MR (Eds), Lippincott Williams & Wilkins, Philadelphia 2005. p.270.
Graphic 62751 Version 4.0

8. Usual causes of abnormal genital bleeding in women by age group
Neonates
Estrogen withdrawal
Premenarchal
Foreign body
Trauma, including sexual abuse
Infection
Urethral prolapse
Sarcoma botryoides
Ovarian tumor
Precocious puberty
Early postmenarche
Ovulatory dysfunction (hypothalamic
immaturity)
Bleeding diathesis
Stress (psychogenic, exercise induced)
Pregnancy
Infection
Reproductive­age
Ovulatory dysfunction
Pregnancy
Cancer
Polyps, leiomyomas, adenomyosis
Infection
Endocrine dysfunction (polycystic ovary
syndrome, thyroid, hyperprolactinemia)
Bleeding diathesis
Medication related (eg, hormonal
contraception)
Menopausal transition
Anovulation
Polyps, fibroids, adenomyosis
Cancer
Menopause
Endometrial atrophy
Cancer
Postmenopausal hormone therapy
Adapted from: APGO educational series on women's health issues. Clinical management of abnormal
uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.
Graphic 61684 Version 5.0

9. Causes of anovulatory genital tract bleeding in adolescents
Age­related
Immature hypothalamic­pituitary­ovarian
axis at the onset of menarche
Decline in ovarian function during
menopause
Systemic illness and neoplasms
Hypothyroidism and hyperthyroidism
Chronic liver and renal disease
Hypercortisolism (Cushing syndrome)
Polycystic ovary syndrome
Prolactinoma
Empty sella syndrome
Pituitary infarction after postpartum
hemorrhage (Sheehan syndrome)
Adrenal and ovarian tumors
Tumors infiltrating the hypothalamus
Medications
Oral contraceptives
Progestins
Antipsychotic drugs
Corticosteroids
Chemotherapeutic agents
Other
Sudden weight loss
Stress
Intense exercise
Graphic 78931 Version 4.0

10. Hormonal changes during normal menstrual cycle
Sequential changes in the serum concentrations of the hormones released from the
pituitary (FSH and LH; left panel) and from the ovaries (estrogen and progesterone;
right panel) during the normal menstrual cycle. By convention, the first day of
menses is day 1 of the cycle (shown here as day ­14). The cycle is then divided into
two phases: the follicular phase is from the onset of menses until the LH surge (day
0); and the luteal phase is from the peak of the LH surge until the next menses. To
convert serum estradiol values to pmol/L, multiply by 3.67, and to convert serum
progesterone values to nmol/L, multiply by 3.18.
Graphic 72415 Version 1.0