Abnormal uterine bleeding is a departure from the normal and what do we consider normal? A total volume of 30 to 60 cc. This has been evaluated by doing tests on menstrual pads from a number of women to get a total volume. Once you get above 80 cc of blood – these are the patients who have menorrhagia, menometrorrhagia – and will get into anemia situations over time. A good way of estimating blood loss is with a chart that a woman can use, to circle number of pads she uses, how much bleeding there has been on the pads and so forth. You can add them up and pretty well quantify, on a visual basis, the menstrual bleeding so that you can estimate whether or not this patient really has a bleeding problem or is it something that she’s just misinterpreting. The other thing about normal is the pattern. We normally expect the menses to start anywhere from 21 to 35 days. We count menstrual periods from the start to the start. Many patients do not do this. Many patients will count from the end of their period to the start of their next period. So I ask them to either bring in a menstrual calendar or question them very thoroughly about start to start. If they say, “Oh, yeah, it’s the same day every month”, then it’s right in this 28 to 30 day cycle. The duration is generally 4 to 6 days. I’ve seen some patients that go seven to eight days. Some patients that were shorter than four to six days. But these are what we generally consider as the normal ranges for those characteristics.
Abnormal Uterine Bleeding
Abnormal patterns; we can term them into hypomenorrhea, which is a diminished total flow, oligomenorrhea which are menses occurring less than every 35 days, menorrhagia which is a profuse flow on regular intervals. So anywhere in that 21 to 35 day interval, if she’s having a profuse flow then she’s got menorrhagia. Menometrorrhagia is an excess of flow occurring on an irregular basis. So that’s excessive and irregular. Intermenstrual spotting or bleeding is light, regular, usually about mid-cycle. This is what we generally see with ovulatory spotting, as we call it, or ovulatory bleeding. Where at the time of ovulation estrogen drops a little bit, there’s no progesterone production yet and the patient has a few spots of blood. Premenstrual occurs usually the week or a few days prior to the menses as light, and postmenstrual is when they continue to spot after their normal, regular flow. In doing evaluations and things like that, I count the day that the patient begins their regular flow as being day one of their cycle. Not if they are having this light spotting prior to the menses. A lot of patients will count that as being the day that they start, but I count the day that they actually begin their flow as the first day of their menses.
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We can divide abnormal bleeding into two causes, really, or two general categories. Those that are caused by anatomic problems and those that are dysfunctional or generally hormonal in etiology. Anatomical etiologies – and I think someone probably does the presentation for you on pregnancy and complications, such as placenta previa, abruptio and so forth – cervical polyps can cause it. Leiomyomas, infection, trauma, adenomyosis and of course carcinoma. And these are anywhere in the GI tract. We can see a carcinoma of the vagina, which is fairly rare, carcinoma of the cervix. We see endocervical polyps, cervical polyps, carcinomas of the endocervix, sarcomas and carcinomas of the endometrium and myometrium. Myometrial polyps, submucous leiomyoma will cause menstrual problems and bleeding, and then ovarian dysfunction’s. So those are pretty much the anatomic sites.
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Premenopausal, perimenopausal, and postmenopausal years–age 40 and over
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.
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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.
If a woman has a pelvic mass, an evaluation with ultrasonography, CT, and/or MRI is necessary.
In a perimenopausal or postmenopausal woman, amenorrhea preceding abnormal bleeding suggests endometrial cancer.
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Endometrial evaluation is necessary before treatment of abnormal vaginal bleeding.
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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.
Treatment
Cystic hyperplasia or endometrial hyperplasia without cytologic atypia is treated with depo-medroxyprogesterone, 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.
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Atypical hyperplasia requires fractional dilation and curettage, followed by progestin therapy or hysterectomy.
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 replacement therapy should be prescribed.
Surgical management
Vaginal or abdominal hysterectomy is the most absolute curative treatment.
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Dilatation and curettage can be used only as a temporizing measure to stop bleeding.
Endometrial ablation and resection by laser, electrodiathermy “rollerball,” or excisional resection are alternatives to hysterectomy.
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 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. Hysterosonography with uterine saline infusion may also be used.
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Treatment
Medical protocols for anovulatory bleeding (dysfunctional uterine bleeding) are similar to those above.
Hormonal therapy Human growth hormone
In women who do not desire immediate fertility, hormonal therapy may be used to treat menorrhagia.
A 21-day package of oral contraceptives, containing 35 mcg of estrogen ( Ortho-Novum 1/30), 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 a day for 21 days, then no pills for 7 days.
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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 intravenously as 25 mg every 4-6 hours until bleeding slows (up to a maximum of four doses). Oral contraceptives should be initiated concurrently as described above.
Iron should also be added as ferrous gluconate 325 mg tid.
Surgical treatment can be considered if childbearing is completed and medical management fails to provide relief.
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Mefenamic acid ( Ponstel) 500 mg tid daily for 3 days during the menstrual period.
Naproxen ( Anaprox, Naprosyn) 500-mg loading dose, then 250 mg three times daily for 3 days during the menstrual period.
Ibuprofen (Order cheap Motrin, Nuprin) 400-600 mg tid during the menstrual period.
These agents are equally effective. Gastrointestinal distress is common, and NSAIDs are contraindicated in renal failure and peptic ulcer disease.
Iron should also be added as ferrous gluconate 325 mg tid.
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Patients with hypovolemia or a hemoglobin level below 7 g/dL should be hospitalized for hormonal therapy, iron replacement, and possibly transfusion.
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.
Iron should also be added as ferrous gluconate 325 mg tid.
Primary childbearing years–ages 16 to early 40’s
Contraceptive complications and pregnancy are the most common causes of abnormal bleeding in this age group. Anovulation accounts for 20% of cases.
Adenomyosis, endometriosis, and fibroids increase in frequency as a woman ages, as do endometrial hyperplasia and endometrial polyps. PID and endocrine dysfunction may also occur.
Laboratory tests
CBC and platelet count, Pap smear, and a pregnancy test.
Screening for sexually transmitted diseases, thyroid dysfunction, and coagulation disorders (partial thromboplastin time, INR, bleeding time) is completed.
If a non-pregnant woman has a pelvic mass, evaluation is required with ultrasonography or hysterosonography (with uterine saline infusion), and, if necessary, CT or laparoscopy.
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Physical findings
Pallor not associated with tachycardia or signs of hypovolemia suggests chronic excessive blood loss, such as that occurring with anovulatory bleeding, adenomyosis, uterine myomas, or blood dyscrasia.
Signs of impending shock indicate that the blood loss is likely related to pregnancy (including ectopic), trauma, sepsis, or neoplasia.
Pelvic masses may represent pregnancy, uterine or ovarian neoplasia, or a pelvic abscess or hematoma.
Fever, leukocytosis, and pelvic tenderness suggests PID.
Fine, thinning hair, and hypoactive reflexes suggest hypothyroidism.
Ecchymoses or multiple bruises may indicate trauma, coagulation defects, medication use, or dietary extremes
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Laboratory tests
CBC and platelet count and a urine or serum pregnancy test should be completed.
Screening for sexually transmitted diseases, thyroid function, and coagulation disorders (partial thromboplastin time, INR, and bleeding time) is necessary.
Endometrial sampling is rarely necessary for those under age 20.
Treatment of infrequent bleeding
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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.
Ferrous gluconate, 325 mg bid-tid, should be prescribed.
Treatment of frequent or heavy bleeding
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) improve platelet aggregation and increase uterine vasoconstriction.
NSAIDs are the first choice in the treatment of menorrhagia because they are well tolerated and they do not have the hormonal effects of oral contraceptives. Additionally, women with menorrhagia frequently also have dysmenorrhea, and NSAIDs are effective for this problem.
Menorrhagia (excessive bleeding) is most commonly caused by anovulatory menstrual cycles. Occasionally it is caused by thyroid dysfunction, infections or cancer. Menorrhagia caused by anovulation is referred to as dysfunctional uterine bleeding.
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 and secretory changes. 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 menstrual and reproductive history is obtained, including last menstrual period, regularity, duration, and frequency; the number of pads used per day and the presence of intermenstrual bleeding should be assessed.
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.
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Pregnancy complications, such as spontaneous abortion, ectopic pregnancy, placenta previa and abruptio placentae, can cause non-cyclical, heavy bleeding. Pregnancy should always be considered as a possible cause of abnormal vaginal bleeding.
Determine whether the patient is having ovulatory or anovulatory cycles
Ovulatory cycles are characterized by menstrual flows occurring at regular intervals, preceded by premenstrual symptoms (breast tenderness or fullness, pelvic cramping, and edema).
If cycles are anovulatory, the patient has dysfunctional uterine bleeding.
Puberty and adolescence–menarche to age 16
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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.
Absence of premenstrual symptoms (breast tenderness, bloating, cramping) is associated with anovulatory cycles.
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.
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