Dysfunctional uterine bleeding (DUB) is the most common cause of
abnormal vaginal bleeding during a woman's reproductive years. The
diagnosis of DUB should be used only when other organic and
structural causes for abnormal vaginal bleeding have been ruled out.
A normal menstrual cycle occurs every 21-35 days with menstruation
for 2-7 days. The average blood loss is 35-150 mL total, which
represents 8 or fewer soaked pads per day with usually no more than
2 heavy days.
During the normal menstrual cycle, the first day corresponds to the
first day of menses. The menstrual phase usually lasts 4 days and
involves the disintegration and sloughing of the functionalis layer
of the endometrium. The proliferation (follicular) phase extends
from day 5 to day 14 of the typical cycle. It is marked by
endometrial proliferation brought on by estrogen stimulation. The
estrogen is produced by the developing ovarian follicles under the
influence of follicle-stimulating hormone (FSH). Cellular
proliferation of the endometrium is marked, and the length and
convolutedness of the spiral arteries increases. This phase ends as
estrogen production peaks, triggering the FSH and luteinizing
hormone (LH) surge.
Rupture of the ovarian follicle follows, with release of the ovum
(ovulation). The secretory (luteal) phase is marked by production of
progesterone and less potent estrogens by the corpus luteum. It
extends from day 15 to day 28 of the typical cycle. The functionalis
layer of the endometrium increases in thickness, and the stroma
becomes edematous. If pregnancy does not occur, the estrogen and
progesterone feedback to the hypothalamus, and FSH and LH production
falls. The spiral arteries become coiled and have decreased flow. At
the end of the cycle, they alternately contract and relax, causing a
breakdown of the functionalis layer and menses to begin.
Approximately 90% of DUB results from anovulation, and 10% occur
with ovulatory cycles. During an anovulatory cycle, the corpus
luteum fails to form, which causes failure of normal cyclical
progesterone secretion. This results in continuous unopposed
production of estradiol, stimulating overgrowth of the endometrium.
Without progesterone, the endometrium proliferates and eventually
outgrows its blood supply, leading to necrosis. The end result is
overproduction of uterine blood flow.
In ovulatory DUB, prolonged progesterone secretion causes irregular
shedding of the endometrium. This probably is related to a constant
low level of estrogen that is around the bleeding threshold. This
causes portions of the endometrium to degenerate and results in
spotting. Progesterone causes the enzymatic conversion of estradiol
to estrone, a less potent estrogen. The changes in the endometrium
remain secretory within the glands. Patients who exhibit these
symptoms in the reproductive years often have ovulatory cycles or
secondary reasons for altered hypothalamic function (eg, polycystic
Dysfunctional bleeding from the uterus can be described as follows:
* Menorrhagia - Prolonged (>7 d) or excessive (>80 mL daily) uterine
bleeding occurring at regular intervals
* Metrorrhagia - Uterine bleeding occurring at irregular and more
frequent than normal intervals
* Menometrorrhagia - Prolonged or excessive uterine bleeding
occurring at irregular and more frequent than normal intervals
* Intermenstrual bleeding (spotting) - Uterine bleeding of variable
amounts occurring between regular menstrual periods
* Polymenorrhea - Uterine bleeding occurring at regular intervals of
less than 21 days
* Oligomenorrhea - Uterine bleeding occurring at intervals of 35
days to 6 months
* Amenorrhea - No uterine bleeding for 6 months or longer
The major categories of DUB include the following:
* Estrogen breakthrough bleeding
* Estrogen withdrawal bleeding
* Progestin breakthrough bleeding
As many as 10% of women with normal ovulatory cycles reportedly have
experienced DUB. Obese females tend to have irregularities in their
menstrual cycles due to nonovarian endogenous production of estrogen
often related to their degree of adipose tissue. This usually
results in prolonged cycles of amenorrhea that alternate with cycles
of metrorrhagia or menometrorrhagia.
No cultural predilection is present with this disease state.
However, note that countries, including the United States, that have
a large population of female athletes have more recognition of this
entity. In athletes, a loss of the LH surge, as well as, a luteal
phase deficiency tends to be present. This is characterized by a
shortened luteal phase from insufficient progesterone production or
effect. This inadequate progesterone stimulation may be coexistent
with high, low, or normal estrogen levels and often results in
similar problems in anovulatory cycles such as amenorrhea.
Morbidity is related to the amount of blood loss at the time of
menstruation, which occasionally is severe enough to cause
Although, DUB in itself is rarely fatal, distinguishing this
presentation from that of endometrial cancer is important.
Development of endometrial cancer is related to estrogen stimulation
and endometrial hyperplasia. Symptoms include postmenopausal
bleeding, which is usually considered cancer until proven otherwise.
DUB has no predilection for race; however, black women have a higher
incidence of leiomyomas and higher levels of estrogen. As a result,
they are prone to experiencing more episodes of abnormal vaginal
DUB is most common at the extreme ages of a woman's reproductive
years, either at the beginning or near the end, but it may occur at
any time during her reproductive life.
* Most severe cases of DUB occur in adolescent girls during the
first 18 months after the onset of menstruation, when their immature
hypothalamic-pituitary axis may fail to respond to estrogen and
progesterone, resulting in anovulation.
* In the perimenopausal period, DUB may be an early manifestation of
ovarian failure causing decreased hormone levels or responsiveness
to hormones, thus also leading to anovulatory cycles. In patients
who are 40 years or older, the number and quality of ovarian
follicles diminishes. Follicles continue to develop but do not
produce enough estrogen in response to FSH to trigger ovulation. The
estrogen that is produced usually results in late-cycle estrogen
* Patients often present with complaints of amenorrhea,
oligomenorrhea, menorrhagia, or metrorrhagia. Ask patients to
compare the number of pads or tampons used per day in a normal
menstrual cycle to the number used at the time of presentation. The
average tampon holds 5 mL of blood; the average pad holds 5-15 mL of
* Occasionally, bleeding is profuse with associated signs and
symptoms of hypovolemia, including hypotension, tachycardia,
diaphoresis, and pallor. These patients usually do not have vaginal
or pelvic pain associated with bleeding episodes, and other systemic
symptoms rarely are noted unless vaginal bleeding has an organic
* A reproductive history should always be obtained, including the
* Menstrual regularity
* Last menstrual period (LMP), including flow and duration
* Gravida and para
* Previous abortion or recent termination of pregnancy
* Contraceptive use
* Questions about medical history should include the following:
* Signs and symptoms of hypovolemia
* Diabetes mellitus
* Hypothyroidism, hyperthyroidism
* Liver disease
* Medication usage, including exogenous hormones, anticoagulants,
aspirin, anticonvulsants, and antibiotics
* Alternative and complementary medicine modalities, such as herbs
* Initial evaluation should be directed at assessing patient's
volume status and degree of anemia. Examine for pallor and absence
of conjunctival vessels to gauge anemia.
* Patients who are hemodynamically stable require a pelvic speculum
and bimanual examination to define the etiology of vaginal bleeding.
The examination should look for the following:
* Trauma to the vaginal walls or cervix
* Retained foreign body
* Cervical or vaginal laceration
* Bleeding from the cervical os
* Uterine or ovarian structural abnormalities may be noted on
bimanual examination, but a negative examination is insensitive for
* Patients with hematologic pathology also may have cutaneous
evidence of bleeding diathesis. Physical findings include petechiae,
purpura, and mucosal bleeding (eg, gums) in addition to vaginal
* Patients with liver disease that has resulted in a coagulopathy
may manifest additional symptomatology because of abnormal hepatic
function. Evaluate patients for spider angioma, palmar erythema,
splenomegaly, ascites, jaundice, and asterixis.
* Women with polycystic ovary disease present with signs of
hyperandrogenism, including hirsutism, obesity, and palpable
* Hyperactive and hypoactive thyroid can cause menstrual
irregularities. Patients may have varying degrees of characteristic
vital sign abnormalities, eye findings, tremors, changes in skin
texture, and weight change. Goiter may be present.
* Multiple organic pathologies can present as abnormal vaginal
bleeding, including thrombocytopenia, hypothyroidism,
hyperthyroidism, Cushing disease, liver disease, hypertension,
diabetes mellitus, and adrenal disorders.
* Pregnancy may be associated with vaginal bleeding that the patient
may report as "abnormal" for her in terms of timing, amount, or
* Trauma to the cervix, vulva, or vagina may cause abnormal
* Carcinomas of the vagina, cervix, uterus, and ovaries always must
be considered in patients with the appropriate history and physical
* Other causes of DUB include structural disorders, such as
functional ovarian cysts, cervicitis, endometritis, salpingitis, and
* Polycystic ovary disease, vaginal infection, polyps, ectopic
pregnancy, hydatidiform mole, blood dyscrasias, excessive weight
gain, increased exercise performance, or stress may also contribute
* Breakthrough bleeding may occur in patients taking oral
contraceptives that have inadequate doses of estrogen and progestin
for the patient.
* Intermenstrual bleeding may occur secondary to missed pills,
varied ingestion times, and drug interactions.
* The most common drug interactions with OCPs occur with
phenobarbital, carbamazepine, some penicillins, tetracycline, and
* Breakthrough bleeding can indicate reduced birth control
efficiency; therefore, advise using additional birth control methods
until the next menstrual cycle begins.
* An iatrogenic cause of DUB is the use of progestin-only compounds
for birth control. Medroxyprogesterone acetate (Depo-Provera), a
long-acting injection given every 3 months, inhibits ovulation. An
adverse effect of this drug is prolonged uterine breakthrough
bleeding; this may continue after discontinuation of the drug
because of persistent anovulation. The Norplant system (surgically
implanted levonorgestrel), which acts to block some but not all
ovulatory cycles, has the same adverse effects as Depo-Provera.
* Contraceptive intrauterine devices (IUDs) can cause variable
vaginal bleeding for the first few cycles after placement and
intermittent spotting subsequently. The progesterone impregnated IUD
(Mirena) is associated with less menometrorrhagia and usually
results in secondary amenorrhea.