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Case 9

Unexplained Vaginal Bleeding

A 38-year-old woman presents to the emergency room complaining of heavy vaginal bleeding that
has persisted for 1 week. She feels weak and dizzy. The patient states that her last menstrual period
was 10 weeks ago. She was last seen by her gynecologist 2 years ago.

What are potential causes of this patients bleeding?
What further history should be obtained?
Abnormal vaginal bleeding is one of the most common gynecologic complaints, whether in the office,
over the phone, or in the emergency room. This patient has symptoms of acute blood loss (i.e., weakness,
dizziness), which is most likely secondary to the presumed uterine bleeding. When considering the causes
of this type of bleeding, they can be loosely grouped into hormonal causes (associated with irregular
menses) and structural causes (conditions that cause heavy bleeding). It is important to remember that
hormonal and structural conditions can coexist and therefore all causes must be evaluated. Therefore, the
differential diagnosis for this type of bleeding in this patient includes the following:
1. Pregnancy. Pregnancy must be considered in all women of reproductive age. This patients last
menstrual period was 10 weeks ago. There is no information about the regularity of her menstrual cycles,
so it is unclear if it is unusual for her to go 10 weeks without bleeding. If she is pregnant, then significant
blood loss can occur with a miscarriage, especially if late in the first or early second trimester. An ectopic
pregnancy is unlikely in this scenario.
2. Anovulation. Anovulatory bleeding can be extremely heavy. Unlike regular menstrual bleeding when
the whole menstrual lining sheds in a synchronous fashion, anovulatory bleeding represents shedding from

isolated areas in an irregular pattern. Again, if we knew what this patients regular menstrual pattern was,
it would help. A long history of anovulation puts the patient at risk of developing endometrial hyperplasia,
which, if left untreated, can develop into endometrial cancer over time. Even though this patient is young,
endometrial hyperplasia and cancer could present this way.
3. Fibroids. Fibroids can cause very heavy bleeding such as this patient is experiencing. The last menstrual
period of 10 weeks ago suggests a hormonal cause of the bleeding, but coexisting fibroids cannot be
excluded. Also, there is no information about how heavily she normally bleeds with her menses.
Endometrial polyps can also present with extremely heavy bleeding similar to fibroids, but again, if a
polyp was the only cause for the bleeding, the menstrual period would not be delayed.
4. Cancer. Endometrial cancer was already considered above. Cervical cancer must be considered. The
patient was not seen by her gynecologist for 2 years and there is no information about her previous Pap
smears. If her last Pap was 2 years ago and was normal, then cervical cancer would be unlikely. This
presentation is not typical for cervical cancer.
5. Hematologic disorders such as leukemia and idiopathic thrombocytopenia (ITP) are rare but distinct
possibilities for heavy vaginal bleeding. The 10-week delay from the last menses is not consistent with this
diagnosis. If ITP were the cause, it would be more likely to manifest at about the time of menarche.
6. Hormonally active tumor. Granulosa cell tumor produces estrogen and can lead to irregular bleeding
and heavy menses. Typically, the history of irregular bleeding would be relatively recent. Androgenproducing tumors can also lead to irregular bleeding, but are usually accompanied by signs of androgen
excess such as hirsutism and virilization.
7. Endometritis. Endometritis can cause abnormal or heavy bleeding, but this patients presentation is

On further questioning, the patient states that for the past few years she has had irregular cycles
ranging from 30 to 90 days. Prior to that her cycles were regular. She attributed this change to her
60-lb. weight gain. She usually bleeds for 3 to 12 days, but never this heavily. Occasionally she has
spotting between her menses. She had a pregnancy 10 years ago, which ended in spontaneous
abortion. She has never used contraception and has engaged in unprotected intercourse since her
last menstrual period. The patient gives no history of easy bruising or abnormal bleeding from her
gums or from cuts. She says that she thinks her uterus may be enlarged.

What is the significance of the patients pattern of menstrual cycles?
The additional history helps to narrow the diagnosis. Her history of irregular menses for the past few
years suggests anovulatory or unopposed estrogen bleeding as a good possibility. A 60-lb. weight gain
can be associated with irregular menstrual cycles, especially in a woman with PCOS who at a lower
weight has more regular menses. Any woman with the varied menstrual cycle lengths described by this
patient is not ovulating regularly and may not be ovulating at all. With anovulatory cycles, prolonged
heavy bleeding is the result of unopposed estrogen continuously stimulating the endometrium. This
condition can lead to a hyperplastic, sometimes atypical, and occasionally neoplastic endometrium. This
history makes anovulation, endometrial hyperplasia, and endometrial cancer most likely. The history of
the uterus being larger brings up the possibility of pregnancy and fibroids, depending on how long the
symptoms have been present. Bleeding from endometrial polyps, endometritis, or submucous myomas
still must be considered possibilities, especially with a history of an enlarged uterus. A bleeding diathesis
cannot be ruled out from the history alone, but is less likely given the lack of abnormal bruising or
bleeding history. It is doubtful that cervical cancer is the cause of bleeding in this patient given the history.

Physical examination of the patient shows a well-nourished, well-developed female in mild distress,
with no evidence of bruising and no petechiae. Her vital signs show a pulse of 90 and a blood
pressure of 110/65 prone, and a pulse of 110 and pressure of 90/45 standing. Abdominal
examination shows a firm, irregular suprapelvic mass, just palpable above the symphysis. Pelvic
examination reveals a firm, smooth cervix that appears slightly open, with a steady stream of blood
coming through the os. The uterus is firm, irregular, and the size of a 12-week gestation, with
presumed lateral and fundal myomas; it is not possible to palpate the adnexa accurately due to the
enlarged uterus. A urine pregnancy test is negative, and the complete blood count shows a
hemoglobin of 5.6 g/dL, a white cell count of 9600 with a normal differential, and a normal platelet
count. Prothrombin time (PT) and partial thromboplastin time (PTT) are normal.

Which diagnoses are less likely based on the physical examination finding?
Which diagnostic studies should be performed now?
What would be the initial therapy for this patient?
The physical examination and few laboratory findings help to direct the clinicians thinking about this
case. The low hemoglobin level certainly indicates significant blood loss and explains the patients
weakness and dizziness. ITP, leukemia, and other hematologic problems are excluded by the laboratory
findings. The negative pregnancy test is not absolute, but a pregnancy advanced enough to give this kind
of clinical picture certainly should show up on a urine test. Pathologic conditions of the endometrium
(i.e., endometritis, hyperplasia, carcinoma, polyps, or submucous myomas) cannot be diagnosed by a
physical examination without sampling the endometrium. The combination of myomas and unopposed

estrogen bleeding is a likely possibility, because a woman can bleed significantly from either of these
causes without the other. An ovarian tumor still is a possibility, because the enlarged, irregular uterus
prevented an accurate examination of the ovaries. At this point, it is important to stop the bleeding and
make a diagnosis.

Based on the suspicion that unopposed estrogen is partly responsible for the bleeding and with the
need to stop the bleeding as quickly as possible, the emergency room physician decides on a course
of intravenous estrogen. However, realizing the need to sample the endometrium before any
hormone manipulation, the physician first performs an endometrial biopsy, sampling all four
quadrants of the uterus. After completing the biopsy and beginning an IV infusion of 25 mg of
conjugated estrogen, the physician sends the patient for pelvic ultrasound. The ultrasound report
notes an enlarged uterus with multiple subserous myomas, an endometrial cavity with markedly
thickened endometrium, and a left ovary that is 4 cm 4 cm 5 cm and solid.

What is learned from the ultrasound report?
What are some of the causes of unopposed estrogen secretion?
Now the pieces of the diagnostic puzzle are falling into place. The pelvic ultrasound is very helpful
because it demonstrates an ovarian mass and subserous myomas. Because of the subserosal position of
the myomas, they are less likely to contribute to the bleeding. Submucosal myomas are more often
associated with heavy bleeding. The thickened endometrium probably is the result of prolonged
unopposed estrogen stimulation. Without the biopsy report, endometrial pathology cannot be ruled out,
although endometritis seems unlikely at this point. The finding of an ovarian mass suggests a cause for the

unopposed estrogen secretion, the endometrial thickening, and the abnormal bleeding. A granulosa cell
tumor-secreting estrogen could be responsible for all of these clinical features.

The patient is admitted to the hospital with an order to infuse 25 mg of conjugated estrogen every
4 hours. By the third dose, the bleeding has stopped and the patient is started on a daily dose of
progestin. Her hemoglobin is rechecked and is stable at 5 g/dL. She is short of breath with the
slightest exertion and has a constant headache. Decision is made to transfuse 2 units of packed red
blood cells. The endometrial biopsy report shows simple endometrial hyperplasia without atypia.
The patient is started on progestin to treat the hyperplasia and daily iron. She is then scheduled
for a laparoscopy and left salpingo-oophorectomy for presumed hormone-secreting tumor.

Why is estrogen used as the initial treatment for this patient?
What is the physiologic mechanism of this patients bleeding?
Although the cause of this patients bleeding and endometrial hyperplasia is unopposed estrogen from an
estrogen-secreting tumor, high doses of IV estrogen are effective in quickly stabilizing the endometrium.
Oral contraceptive pills given three to four times a day with a quick taper to one pill a day are also
effective but take longer to work, and with this patient, who is bleeding profusely and is orthostatic with a
dangerously low hemoglobin, the quicker the bleeding stops, the better.
The bleeding in this patient is caused by irregular breakdown and shedding of the hyperplastic
endometrium. Estrogen has its primary effect on the vascular element of the endometrium, supporting the
small vessels and healing the areas of endometrial degeneration. Once the bleeding stops, progestin must
be added to stabilize the endometrium and to allow an orderly sloughing after 3 to 4 weeks. The

hyperplasia is solely the result of the unopposed estrogen and would be reversed either by ongoing,
continuous or intermittent progestin administration (i.e., for 12 days each month) or by removal of the
estrogen source.