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Abnormal Vaginal Bleeding

Menorrhagia (excessive bleeding) is most commonly caused by anovulatory menstrual cycles. Occasionally it is caused by thyroid dysfunction, infections or cancer.

Pathophysiology of normal menstruation

In response to gonadotropin-releasing hormone from the hypothalamus, the pituitary gland synthesizes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which induce the ovaries to produce estrogen and progesterone.
During the follicular phase, estrogen stimulation causes an increase in endometrial thickness. After ovulation, progesterone causes endometrial maturation. Menstruation is caused by estrogen and progesterone withdrawal.
Abnormal bleeding is defined as bleeding that occurs at intervals of less than 21 days, more than 36 days, lasting longer than 7 days, or blood loss
greater than 80 mL.

Clinical evaluation of abnormal vaginal bleeding

A. A menstrual and reproductive history should include last menstrual period, regularity, duration, frequency; the number of pads used per day, and
intermenstrual bleeding.

B. Stress, exercise, weight changes and systemic diseases, particularly thyroid, renal or hepatic diseases or coagulopathies, should be sought. The method of birth control should be determined.

C. Pregnancy complications, such as spontaneous abortion, ectopic pregnancy, placenta previa and abruptio placentae, can cause heavy bleeding. Pregnancy should always be considered as a possible cause of abnormal vaginal bleeding.

Puberty and adolescence--menarche to age 16

A. Irregularity is normal during the first few months of menstruation; however, soaking more than 25 pads or 30 tampons during a menstrual period is abnormal.

B. Absence of premenstrual symptoms (breast tenderness, bloating, cramping) is associated with anovulatory cycles.

C. Fever, particularly in association with pelvic or abdominal pain may, indicate pelvic inflammatory disease. A history of easy bruising suggests a coagulation defect. Headaches and visual changes suggest a pituitary tumor.

D. Physical findings

Pallor not associated with tachycardia or signs of hypovolemia suggests chronic excessive blood loss secondary to anovulatory bleeding, adenomyosis, uterine myomas, or blood dyscrasia.
Fever, leukocytosis, and pelvic tenderness suggests PID.
Signs of impending shock indicate that the blood loss is related to pregnancy (including ectopic), trauma, sepsis, or neoplasia.
Pelvic masses may represent pregnancy, uterine or ovarian neoplasia, or a pelvic abscess or hematoma.
Fine, thinning hair, and hypoactive reflexes suggest hypothyroidism.
Ecchymoses or multiple bruises may indicate trauma, coagulation defects, medication use, or dietary extremes.

E. Laboratory tests

CBC and platelet count and a urine or serum pregnancy test should be obtained.
Screening for sexually transmitted diseases, thyroid function, and coagulation disorders (partial thromboplastin time, INR, bleeding time) should be completed.
Endometrial sampling is rarely necessary for those under age 20.

Treatment of infrequent bleeding

1. Therapy should be directed at the underlying cause when possible. If the CBC and other initial laboratory tests are normal and the history and physical examination are normal, reassurance is usually all that is necessary.

2. Ferrous gluconate, 325 mg bid-tid, should be prescribed.

Treatment of frequent or heavy bleeding

1. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) improves platelet aggregation and increases uterine vasoconstriction. NSAIDs are the first choice in the treatment of menorrhagia because they are well tolerated and do not have the hormonal effects of oral contraceptives.

a. Mefenamic acid (Ponstel) 500 mg tid during the menstrual period.
b. Naproxen (Anaprox, Naprosyn) 500 mg loading dose, then 250 mg tid during the menstrual period.
c. Ibuprofen (Motrin, Nuprin) 400 mg tid during the menstrual period.
d. Gastrointestinal distress is common. NSAIDs are contraindicated in renal failure and peptic ulcer disease.

2. Iron should also be added as ferrous gluconate 325 mg tid.

Patients with hypovolemia or a hemoglobin level below 7 g/dL should be hospitalized for hormonal therapy and iron replacement.

Hormonal therapy consists of estrogen (Premarin) 25 mg IV q6h until bleeding stops. Thereafter, oral contraceptive pills should be administered q6h x 7 days, then taper slowly to one pill qd.
If bleeding continues, IV vasopressin (DDAVP) should be administered. Hysteroscopy may be necessary, and dilation and curettage is a last resort. Transfusion may be indicated in severe hemorrhage.
Iron should also be added as ferrous gluconate 325 mg tid.

Primary childbearing years – ages 16 to early 40s

A. Contraceptive complications and pregnancy are the most common causes of abnormal bleeding in this age group. Anovulation accounts for 20% of cases.

B. Adenomyosis, endometriosis, and fibroids increase in frequency as a woman ages, as do endometrial hyperplasia and endometrial polyps. Pelvic inflammatory disease and endocrine dysfunction may also occur.

C. Laboratory tests

1. CBC and platelet count, Pap smear, and pregnancy test.
2. Screening for sexually transmitted diseases, thyroid-stimulating hormone, and coagulation disorders (partial thromboplastin time, INR, bleeding time).
3. If a non-pregnant woman has a pelvic mass, ultrasonography or hysterosonography (with uterine saline infusion) is required.

D. Endometrial sampling

Long-term unopposed estrogen stimulation in anovulatory patients can result in endometrial hyperplasia, which can progress to adenocarcinoma; therefore, in perimenopausal patients who have been anovulatory for an extended interval, the endometrium should be biopsied.
Biopsy is also recommended before initiation of hormonal therapy for women over age 30 and for those over age 20 who have had prolonged bleeding.
Hysteroscopy and endometrial biopsy with a Pipelle aspirator should be done on the first day of menstruation (to avoid an unexpected pregnancy) or anytime if bleeding is continuous.

E. Treatment

1. Medical protocols for anovulatory bleeding (dysfunctional uterine bleeding) are similar to those described above for adolescents.

2. Hormonal therapy

In women who do not desire immediate fertility, hormonal therapy may be used to treat menorrhagia.
A 21-day package of oral contraceptives is used. The patient should take one pill three times a day for 7 days. During the 7 days of therapy, bleeding should subside, and, following treatment, heavy flow will occur. After 7 days off the hormones, another 21-day package is initiated, taking one pill each day for 21 days, then no pills for 7 days.
Alternatively, medroxyprogesterone (Provera), 10-20 mg per day for days 16 through 25 of each month, will result in a reduction of menstrual blood loss. Pregnancy will not be prevented.
Patients with severe bleeding may have hypotension and tachycardia. These patients require hospitalization, and estrogen (Premarin) should be administered IV as 25 mg q4-6h until bleeding slows (up to a maximum of four doses). Oral contraceptives should be initiated concurrently as described above.

3. Iron should also be added as ferrous gluconate 325 mg tid.

4. Surgical treatment can be considered if childbearing is completed and medical management fails to provide relief.

Premenopausal, perimenopausal, and postmenopausal years--age 40 and over

A. Anovulatory bleeding accounts for about 90% of abnormal vaginal bleeding in this age group. However, bleeding should be considered to be from cancer until proven otherwise.

B. History, physical examination and laboratory testing are indicated as described above. Menopausal symptoms, personal or family history of malignancy and use of estrogen should be sought. A pelvic mass requires an evaluation with ultrasonography.

C. Endometrial carcinoma

In a perimenopausal or postmenopausal woman, amenorrhea preceding abnormal bleeding suggests endometrial cancer. Endometrial evaluation is necessary before treatment of abnormal vaginal bleeding.
Before endometrial sampling, determination of endometrial thickness by transvaginal ultrasonography is useful because biopsy is often not required when the endometrium is less than 5 mm thick.

D. Treatment

1. Cystic hyperplasia or endometrial hyperplasia without cytologic atypia is treated with depomedroxyprogesterone, 200 mg IM, then 100 to 200 mg IM every 3 to 4 weeks for 6 to 12 months. Endometrial hyperplasia requires repeat endometrial biopsy every 3 to 6 months.

2. Atypical hyperplasia requires fractional dilation and curettage, followed by progestin therapy or hysterectomy.

3. If the patient's endometrium is normal (or atrophic) and contraception is a concern, a low-dose oral contraceptive may be used. If contraception is not needed, estrogen and progesterone therapy should be prescribed.

4. Surgical management

Vaginal or abdominal hysterectomy is the most absolute curative treatment.
Dilatation and curettage can be used as a temporizing measure to stop bleeding.
Endometrial ablation and resection by laser, electrodiathermy “rollerball,” or excisional resection are alternatives to hysterectomy.

2011-07-29