Abnormal uterine bleeding not associated with tumor, inflammation, or pregnancy.

Dysfunctional uterine bleeding, the most common cause of abnormal uterine bleeding, is a diagnosis of exclusion. It occurs most commonly at the extremes of reproductive life; > 50% of cases occur in women > 45 yr, and 20% occur in adolescents. It may occur with anovulatory (> 70% of episodes) or ovulatory cycles. The bleeding in anovulatory women generally results from stimulation of the endometrium with unopposed estrogen (eg, in women taking exogenous estrogen or with normogonadotropic anovulation), which may result in endometrial hyperplasia. The endometrium, thickened by the estrogen, sloughs incompletely and irregularly, and bleeding becomes irregular, prolonged, and sometimes profuse. In ovulatory cycles, abnormal bleeding is generally due to luteal phase abnormalities. Dysfunctional uterine bleeding is common in women with polycystic ovary syndrome. About 20% of women with endometriosis have dysfunctional uterine bleeding due to unknown mechanisms.

History and physical examination cannot determine if endometrial hyperplasia is present. Measuring endometrial thickness during transvaginal ultrasonography can help assess hyperplasia. In anovulatory women, a thickness of <= 4 mm is rarely associated with hyperplasia; a thickness of > 4 mm may be normal or indicate hyperplasia or cancer. Women >= 35 yr, those with polycystic ovary syndrome and/or a prolonged history of anovulatory bleeding, and obese women should have an endometrial biopsy before medical therapy is initiated, because they are at increased risk for endometrial carcinoma. Hct and Hb should be measured to evaluate the chronicity and severity of the bleeding.

Treatment
Treatment varies with the age of the patient, the extent of the bleeding, pathologic assessment of the endometrium, and the patient’s wishes. Even acute episodes of profuse bleeding in anovulatory women can generally be treated with a combination oral contraceptive q 6 h for 5 to 7 days. Bleeding should stop in 12 to 24 h, but it usually resumes, often with cramping, 2 to 4 days after stopping therapy. Recurrence is prevented by giving combination oral contraceptives cyclically for at least 3 mo. If spontaneous cyclic menses do not resume and pregnancy is not desired or if oral contraceptives are contraindicated, the patient can be treated with a progestin (medroxyprogesterone acetate 5 to 10 mg/day po for 10 to 14 days each month).

An acute episode of anovulatory bleeding can also be treated with conjugated estrogens 25 mg IV q 4 h until bleeding abates. A progestin (medroxyprogesterone acetate 5 to 10 mg/day po for 10 days) should be started simultaneously or within 2 or 3 days of starting estrogen. After cessation of therapy, withdrawal bleeding results. The patient is then treated with oral contraceptives for at least 3 cycles.

Uterine curettage is indicated if a patient does not respond to hormonal therapy (as indicated in a subsequent biopsy) or if irregular bleeding persists.

For women with anovulatory bleeding that is not profuse, treatment with cyclic oral contraceptives or a progestin can be offered if pregnancy is not desired.

If pregnancy is desired, ovulation induction with clomiphene citrate can be offered. Clomiphene citrate can be used to treat luteal dysfunction, as can human chorionic gonadotropin 1500 to 2500 IU IM q 2nd or 3rd day, beginning on postovulatory day 2, and progesterone 50 mg/day IM in oil or 50 mg bid as vaginal suppositories.

Because women with atypical adenomatous hyperplasia (seen on biopsy) are at risk of developing adenocarcinoma of the endometrium, a fractional dilation and curettage and hysteroscopy should be performed to rule out coexisting carcinoma before any therapy is started. Medroxyprogesterone acetate 20 to 40 mg/day po for 3 to 6 mo is recommended. If a repeat endometrial biopsy indicates resolution of the hyperplasia, the woman may be treated with cyclic medroxyprogesterone acetate (5 to 10 mg/day po for 10 to 14 days each month) or, if pregnancy is desired, with clomiphene citrate to induce ovulation. Hysterectomy is performed only if drug therapy is ineffective. Women with more benign cystic hyperplasia or adenomatous hyperplasia can generally be treated cyclically with medroxyprogesterone acetate, but a biopsy should be repeated after about 3 mo.