Background:
Dysfunctional uterine bleeding (DUB) is irregular uterine bleeding that occurs in the absence of
pathology or medical illness. It reflects a disruption in the normal cyclic pattern of ovulatory
hormonal stimulation to the endometrial lining. The bleeding is unpredictable in many ways.
It might be excessively heavy or light, prolonged, frequent, or random.
This condition usually is associated with anovulatory menstrual cycles but also can present in patients
with oligo-ovulation. DUB occurs without recognizable pelvic pathology, general medical disease,
or pregnancy. It is a diagnosis of exclusion.
Pathophysiology:
Patients with DUB have lost cyclic endometrial stimulation that arises from the ovulatory cycle.
As a result, these patients have constant, noncycling estrogen levels that stimulate endometrial growth.
Proliferation without periodic shedding causes the endometrium to outgrow its blood supply.
The tissue breaks down and sloughs from the uterus. Subsequent healing of the endometrium is irregular and dyssynchronous.
Chronic stimulation by low levels of estrogen will result in infrequent, light DUB. Chronic stimulation from higher levels
of estrogen will lead to episodes of frequent, heavy bleeding.
Frequency:
DUB is a common diagnosis, making up 5-10% of cases in the outpatient clinic setting.
Patients who experience repetitive episodes might experience significant consequences.
Frequent uterine bleeding will increase the risk for iron deficiency anemia.
Flow can be copious enough to require hospitalization for fluid management, transfusion, or intravenous hormone therapy.
Chronic unopposed estrogenic stimulation of the endometrial lining increases the risk of both
endometrial hyperplasia and endometrial carcinoma. Timely and appropriate management will prevent most of these problems.
Many individuals with DUB are exposed to unnecessary surgical intervention, such as repeated uterine curettage, endometrial
ablative therapy, or hysterectomy. Adequate workup and a trial of medical therapy should be completed first.
Age:
Because most cases are associated with anovulatory menstrual cycles, adolescents and perimenopausal women are particularly vulnerable.
About 20% of affected individuals are in the adolescent age group, and 50% of affected individuals are aged 40-50 years.
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:
- 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
History:
- Patients often present with complaints of amenorrhea, oligomenorrhea, menorrhagia, or metrorrhagia.
- 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 cause. Suspect dysfunctional
uterine bleeding (DUB) when a patient presents with unpredictable or episodic heavy or light bleeding despite a normal pelvic examination.
- Patients who report irregular menses since menarche may have polycystic ovarian syndrome (PCOS). PCOS is characterized
by anovulation or oligo-ovulation and hyperandrogenism. These patients often present with unpredictable cycles and/or
infertility, hirsutism with or without hyperinsulinemia, and obesity.
- 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 blood.
- 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 cause.
Physical:
A complete physical examination should begin with assessment of hemodynamic stability (vital signs)
and proceed with evaluation of the following:
- Obesity (BMI)
- Signs of androgen excess (hirsutism, acne)
- Thyroid enlargement or manifestations of hyperthyroidism or hypothyroidism.
- Galactorrhea (may suggest hyperprolactinemia) – secretion of milk from the nipple
A careful gynecologic examination, including Papanicolaou test (Pap smear) and sexually transmitted disease
(STD) screening, is warranted.
The hallmark of DUB is a negative pelvic examination despite the clinical history. In such cases,
management might rest on a clinical diagnosis.
- Rule out the presence of uterine fibroids or polyps.
- Rule out endometrial hyperplasia or carcinoma.
Causes:
In ovulatory cycles, progesterone production from the corpus luteum converts estrogen primed proliferative
endometrium to secretory endometrium, which sloughs predictably in a cyclic fashion if pregnancy does not occur.
Heavy but regular uterine bleeding implies ovulatory bleeding and should not be diagnosed as DUB. Subtle disturbances
in endometrial tissue mechanisms, other forms of uterine pathology, or systemic causes might be implicated.
Anovulatory cycles are associated with a variety of bleeding manifestations. Estrogen withdrawal bleeding and
estrogen breakthrough bleeding are the most common spontaneous patterns encountered in clinical practice.
Iatrogenically induced anovulatory uterine bleeding might occur during treatment with oral contraceptives,
progestin-only preparations, or postmenopausal steroid replacement therapy.
Estrogen breakthrough bleeding:
- o Anovulatory cycles have no corpus luteal formation. Progesterone is not produced.
The endometrium continues to proliferate under the influence of unopposed estrogen.
- o Eventually, this out-of-phase endometrium is shed in an irregular manner that might be prolonged and heavy.
This pattern is known as estrogen breakthrough bleeding and occurs in the absence of estrogen decline.
Estrogen withdrawal bleeding:
- This frequently occurs in women approaching the end of reproductive life.
- In older women, the mean length of menstrual cycle is shortened significantly due to aberrant follicular recruitment,
resulting in a shortened proliferative phase. Ovarian follicles in these women secrete less estradiol. Fluctuating estradiol
levels might lead to insufficient endometrial proliferation with irregular menstrual shedding. This bleeding might
be experienced as light, irregular spotting.
- Eventually, the duration of the luteal phase shortens, and, finally, ovulation stops. Dyssynchronous endometrial
histology with irregular menstrual shedding and eventual amenorrhea result.
Oral contraceptives, progestin-only preparations, or postmenopausal steroid replacement therapy:
- Treatment with oral contraceptives, progestin-only preparations, or postmenopausal steroid replacement therapy might be
associated with iatrogenically induced uterine bleeding.
- Intermittent bleeding of variable duration can occur with progestin-only oral contraceptives, depo-medroxyprogesterone,
and depo-levonorgestrel.
- Progesterone withdrawal bleeding can occur if the endometrium initially has been primed with endogenous or exogenous
estrogen, exposed to progestin,
and then withdrawn from progestin. Such a pattern is seen in cyclic hormonal replacement therapy.
Adolescents:
- o The primary defect in the anovulatory bleeding of adolescents is failure to mount an ovulatory luteinizing hormone
(LH) surge in response to rising estradiol levels. Failure occurs secondary to delayed maturation of the
hypothalamic-pituitary axis. Because a corpus luteum is not formed, progesterone levels remain low.
- o The existing estrogen primed endometrium does not become secretory. Instead, the endometrium continues to
proliferate under the influence of unopposed estrogen. Eventually, this out-of-phase endometrium is shed in an
irregular manner that might be prolonged and heavy, such as that seen in estrogen breakthrough bleeding.
Climacteric:
- Anovulatory bleeding in menopausal transition is related to declining ovarian follicular function.
- Estradiol levels will vary with the quality and state of follicular recruitment and growth.
- Bleeding might be light or heavy depending on the individual cycle response.
Treatment:
Treatment of DUB depends on the cause of the bleeding and the age of the patient.
When the underlying cause of the disorder is known, that disorder is treated. Otherwise the goal of treatment is to
relieve the symptoms to a degree that uterine bleeding does not interfere with a woman's normal activities or cause anemia.
Generally the first approach to controlling DUB is to balance the hormones.
In our office we use progesterone therapy along with Omega-3’s.
When bleeding cannot be controlled by hormone treatment, surgery may be necessary. Dilation and curettage
sometimes relieves the symptoms of DUB. If that fails, endometrial ablation removes the uterine lining,
but preserves a woman's uterus. This procedure is sometimes be used instead of hysterectomy. However, as it
affects the uterus, it can only be used when a woman has completed her childbearing years. The prescription of
iron is also important to decrease the risk of anemia.
Until the 1980s, hysterectomy often was used to treat heavy uterine bleeding. Today hysterectomy is used less
frequently to treat DUB, and then only after other methods of controlling the symptoms have failed.
Key Terms
Dilation and curettage (D and C)
A procedure performed under anesthesia during which the cervix is dilated, and tissue lining the uterus is scraped out
with a metal spoon-shaped instrument or a suction tube. The procedure can be either diagnostic, or to remove polyps.
Endometrial biopsy
The removal of tissue either by suction or scraping of samples of tissue from the uterus. The cervix is not dilated.
The procedure has a lower rate of diagnostic accuracy than a D and C, but can be done as an office procedure under local anesthesia.
Endometrial cancer
Cancer of the inner mucous membrane of the uterus.
Fibroids, or fibroid tumors
Fibroid tumors are non-cancerous (benign) growths in the uterus.
They occur in 30-40% of women over age 40, and do not need to be removed unless
they are causing symptoms that interfere with a woman's normal activities.
Hypothyroidism
A disorder in which the thyroid gland produces too little thyroid hormone causing a
decrease in the rate of metabolism with associated effects on the reproductive system.
Menstrual cycle
The menstrual cycle is the female body's monthly pattern of preparing for a possible pregnancy.
The uterus grows a new lining called the endometrium; one of the ovaries releases an egg; and then,
if the egg is not fertilized by sperm, the endometrium sheds from the uterus as a menstrual period.
Days 1 to 6:
The thickened lining of the uterus (endometrium) is shed, causing menstrual bleeding.
Day 1 of the cycle is the first day of menstrual bleeding.
Days 7 to 14 (the follicular phase):
The lining of the uterus thickens to prepare for pregnancy. An egg (usually one each month) becomes ready to be
released inside a sac (follicle) on the surface of an ovary.
Days 15 to 28 (the luteal phase)
The egg is released (ovulation).
- If the egg is fertilized by sperm, it may attach to (implant in) the lining of the uterus, and pregnancy begins.
- If the egg is not fertilized or does not implant, the lining of the uterus is shed during the menstrual period,
and the cycle starts again.
What is Hysteroscopy?
Hysteroscopy uses a hysteroscope, which is a thin telescope that is inserted through the cervix into the uterus.
Modern hysteroscopes are so thin that they can fit through the cervix with minimal or no dilation. Although hysteroscopy
dates back to 1869, gynecologists were slow to adopt hysteroscopy. Because the inside of the uterus is a potential cavity,
like a collapsed air dome, it is necessary to fill (distend) it with either a liquid or a gas (carbon dioxide) in order to see.
Diagnostic hysteroscopy and simple operative hysteroscopy can usually be done in an office setting.
More complex operative hysteroscopy procedures are done in an operating room setting.
View through a hysteroscope
This is a view through a hysteroscope during office hysteroscopy of the inside of a uterus with two
fibroids (myomas) on the back wall. The upper portion of the photograph shows the top of the uterus, which is normal.
Fibroids like this can cause severe cramping (dysmenorrhea), heavy menstrual periods (menorrhagia) and bleeding between
periods (metrorrhagia.) This was quickly and accurately diagnosed by hysteroscopy.
These myomas can be removed using a special kind of hysteroscope called a resectoscope.
What is Operative Hysteroscopy?
During diagnostic hysteroscopy the hysteroscope is used just to observe the endometrial cavity (inside of the uterus.)
During operative hysteroscopy a type of hysteroscope is used that has channels in which it is possible to insert very thin instruments.
These instruments can be used to remove polyps, to cut adhesions, and do other procedures.
Problems with the Uterus
Fibroids
Approximately 30% of women have fibroid tumors. The medical term for fibroids is leiomyoma, or myoma.
These growths are almost always benign, and most of the time do not cause symptoms. Fibroids typically grow
larger as a woman ages, and usually decreases in size after menopause. They can range in size from pea-size to
larger than a grapefruit. Often a uterus will grow many fibroids.
Polyps
Endometrial polyps are growths in the lining of the uterus that are very common, and usually benign.
They usually hang from the lining of the uterus like figs, but at times can be rather flat. Polyps may
result from long-term estrogen stimulation such as occurs from extended periods of not ovulating or
from taking estrogen hormones without any progesterone.
Adenomyosis
When the lining of the uterus grows into the wall of the uterus, the condition is called adenomyosis.
Normally, when the endometrium sheds during a menstrual period the blood is free to drain out through the cervix.
When the lining goes into the muscle some of the blood may be trapped. When extensive, this may cause severe cramps and heavy bleeding.
This can cause the walls of the uterus to thicken and the uterus to become enlarged. Often an enlarged uterus from adenomyosis is misdiagnosed
as being from fibroids. Since the treatment of adenomyosis may be different from fibroids, this common error can lead to inappropriate treatment.
Usually ultrasound can tell whether a uterus is enlarged from fibroids or from adenomyosis.
