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Disorders of the Menstrual Cycle

Abnormal Uterine Bleeding

Between menarche and the menopause, almost every woman experiences one or more episodes of abnormal uterine bleeding, here defined as any bleeding pattern that differs in frequency, duration, or amount from the pattern observed during a normal menstrual cycle. In normal women, the average menstrual cycle is 28 ± 3 days, the mean duration of menstrual flow is 4 ± 2 days, and the average blood loss is 35 to 80 mL. A variety of descriptive terms (such as menorrhagia, metrorrhagia, and menometrorrhagia) have been used to characterize patterns of abnormal uterine bleeding. A more logical approach is to divide abnormal uterine bleeding into those patterns associated with ovulatory cycles and those associated with anovulatory cycles.

Ovulatory Cycles

Normal menstrual bleeding with ovulatory cycles is spontaneous, regular, cyclic, and predictable and is frequently associated with discomfort (dysmenorrhea). Deviations from this pattern associated with cycles that are still regular and predictable are most often due to organic disease of the outflow tract. For example, regular but prolonged and excessive bleeding episodes unassociated with bleeding dyscrasias (hypermenorrhea or menorrhagia) can result from abnormalities of the uterus such as submucous leiomyomas, adenomyosis, or endometrial polyps. Regular, cyclic, predictable menstruation characterized by spotting or light bleeding is termed hypomenorrhea and is due to obstruction of the outflow tract as from intrauterine synechiae or scarring of the cervix. Intermenstrual bleeding between episodes of regular, ovulatory menstruation is also often due to cervical or endometrial lesions. An exception to the association between organic disease and abnormal uterine bleeding is the occurrence of regular menstruation more frequently than 21 days apart (polymenorrhea). Such cycles may be a normal variant.

Anovulatory Cycles

Dysfunctional uterine bleeding refers to bleeding that is unpredictable with respect to amount, onset, and duration and is usually painless. This disorder is not due to abnormalities of the uterus but rather to chronic anovulation and occurs when there is interruption of the normal sequence of follicular and luteal phases under the influence of a dominant follicle and its resulting corpus luteum. As discussed above, uterine bleeding in ovulatory cycles occurs because of progesterone withdrawal and requires that the endometrium first be primed with estrogen. (When castrates or postmenopausal women are given progesterone, withdrawal bleeding usually does not occur.)

Dysfunctional uterine bleeding can occur in women who have a transient disruption of the synchronous hypothalamic-pituitary-ovarian patterns necessary for ovulatory cycles, most often at the extremes of the reproductive life - in the early menarche and in the perimenopausal period - but also after temporary stress or intercurrent illness.

Primary dysfunctional uterine bleeding can result from three disorders.

1. Estrogen withdrawal bleeding occurs when estrogen is given to a castrated or postmenopausal woman and then withdrawn. As in other types of dysfunctional uterine bleeding, this form of menstrual bleeding is usually painless.

2. Estrogen breakthrough bleeding occurs when there is continuous estrogen stimulation of the endometrium not interrupted by cyclic progesterone secretion and withdrawal. This is the most common type of dysfunctional uterine bleeding and is usually due to anovulation associated with chronic acyclic estrogen production, as in women with PCOS. Such women may have histories of irregular, unpredictable menses; oligomenorrhea; or amenorrhea (see below). Alternatively, estrogen breakthrough bleeding can occur in hypogonadal women given estrogens chronically rather than intermittently and in women with estrogen-secreting tumors of the ovary. Estrogen breakthrough bleeding may be profuse and is unpredictable with respect to duration, amount of flow, and time of occurrence. The endometrium is typically thin because its repair between episodes of bleeding is incomplete.

3. Progesterone breakthrough bleeding occurs in the presence of abnormally high ratios of progesterone to estrogen, i.e., in women using continuous low-dose oral contraceptives.

The approach to a patient with dysfunctional uterine bleeding begins with a careful history of menstrual patterns and prior hormonal therapy. Since not all urogenital tract bleeding is from the uterus, rectal, bladder, and vaginal or cervical sources must be excluded by physical examination. If the bleeding is from the uterus, a pregnancy-related disorder such as abortion or ectopic pregnancy must be ruled out.

Treatment

Once the diagnosis of dysfunctional uterine bleeding is established, a rational approach to management is as follows: During a first episode of dysfunctional bleeding, it is reasonable to observe the patient without intervention, provided the bleeding is not copious and no evidence of bleeding dyscrasia is present. If bleeding is moderately severe, control can be achieved with relatively high dose estrogen oral contraceptives for 3 weeks. Alternatively, a regimen of three or four low-dose oral contraceptive pills per day for 1 week followed by tapering to the usual dosage for up to 3 weeks is also effective.

If uterine bleeding is more severe, hospitalization, bed rest, and intramuscular injections of estradiol valerate (10 mg) and hydroxyprogesterone caproate (500 mg) or intravenous or intramuscular conjugated estrogens (25 mg) usually control the bleeding. After initial treatment, iron replacement should be instituted, and recurrence can be prevented by cyclic oral contraceptives for 2 to 3 months (or more if pregnancy is not desired). Alternatively, menses can be induced every 2 to 3 months with medroxyprogesterone acetate, 10 mg taken orally once or twice a day for 10 days. If hormone therapy fails to control uterine bleeding, an endometrial biopsy, hysteroscopy, or dilatation and curettage may be required for diagnosis and therapy. Indeed, uterine sampling should be performed prior to hormone therapy in women at risk for endometrial cancer (e.g., in women who are approaching the age of menopause or who are massively obese); endometrial cancer is rare in ovulatory women of reproductive age.

Provided by ArmMed Media
Revision date: June 11, 2011
Last revised: by Sebastian Scheller, MD, ScD

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