Abnormal (Dysfunctional) Uterine Bleeding in Emergency Medicine

The normal menstrual cycle is 28 days and starts on the first day of menses. During the first 14 days (follicular phase) of the menstrual cycle, the endometrium thickens under the influence of estrogen. In response to rising estrogen levels, the pituitary gland secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the release of an ovum at the midpoint of the cycle. The residual follicular capsule forms the corpus luteum.

After ovulation, the luteal phase begins and is characterized by production of progesterone from the corpus luteum. Progesterone matures the lining of the uterus and makes it more receptive to implantation. If implantation does not occur, in the absence of human chorionic gonadotropin (hCG), the corpus luteum dies, accompanied by sharp drops in progesterone and estrogen levels. Hormone withdrawal causes vasoconstriction in the spiral arterioles of the endometrium. This leads to menses, which occurs approximately 14 days after ovulation when the ischemic endometrial lining becomes necrotic and sloughs. ^[4]

Terms frequently used to describe abnormal uterine bleeding:

• Menorrhagia - Prolonged (>7 d) or excessive (>80 mL daily) uterine bleeding occurring at regular intervals

• Metrorrhagia - Uterine bleeding occurring at irregular and more frequent than normal intervals

• Menometrorrhagia - Prolonged or excessive uterine bleeding occurring at irregular and more frequent than normal intervals

• Intermenstrual bleeding - Uterine bleeding of variable amounts occurring between regular menstrual periods

• Midcycle spotting - Spotting occurring just before ovulation, typically from declining estrogen levels

• Postmenopausal bleeding - Recurrence of bleeding in a menopausal woman at least 6 months to 1 year after cessation of cycles

• Amenorrhea - No uterine bleeding for 6 months or longer

Abnormal uterine bleeding is a diagnosis of exclusion. It is ovulatory or anovulatory bleeding, diagnosed after pregnancy, medications, iatrogenic causes, genital tract pathology, malignancy, and systemic disease have been ruled out by appropriate investigations. Approximately 90% of dysfunctional uterine bleeding cases result from anovulation, and 10% of cases occur with ovulatory cycles. ^[5]

Anovulatory dysfunctional uterine bleeding results from a disturbance of the normal hypothalamic-pituitary-ovarian axis and is particularly common at the extremes of the reproductive years. When ovulation does not occur, no progesterone is produced to stabilize the endometrium; thus, proliferative endometrium persists. Bleeding episodes become irregular, and amenorrhea, metrorrhagia, and menometrorrhagia are common. Bleeding from anovulatory dysfunctional uterine bleeding is thought to result from changes in prostaglandin concentration, increased endometrial responsiveness to vasodilating prostaglandins, and changes in endometrial vascular structure.

In ovulatory dysfunctional uterine bleeding, bleeding occurs cyclically, and menorrhagia is thought to originate from defects in the control mechanisms of menstruation. It is thought that, in women with ovulatory dysfunctional uterine bleeding, there is an increased rate of blood loss resulting from vasodilatation of the vessels supplying the endometrium due to decreased vascular tone, and prostaglandins have been strongly implicated. Therefore, these women lose blood at rates about 3 times faster than women with normal menses. ^[6]

Systemic disease, including thrombocytopenia, hypothyroidism, hyperthyroidism, Cushing disease, liver disease, diabetes mellitus, and adrenal and other endocrine disorders, can present as abnormal uterine bleeding.

Pregnancy and pregnancy-related conditions may be associated with vaginal bleeding.

Trauma to the cervix, vulva, or vagina may cause abnormal bleeding.

Carcinomas of the vagina, cervix, uterus, and ovaries must always be considered in patients with the appropriate history and physical examination findings. Endometrial cancer is associated with obesity, diabetes mellitus, anovulatory cycles, nulliparity, and age older than 35 years.

Other causes of abnormal uterine bleeding include structural disorders, such as functional ovarian cysts, cervicitis, endometritis, salpingitis, leiomyomas, and adenomyosis. Cervical dysplasia or other genital tract pathology may present as postcoital or irregular bleeding.

Polycystic ovary disease results in excess estrogen production and commonly presents as abnormal uterine bleeding. 

A retrospective study by Maslyanskaya et al identified 125 female patients, 8-20 years of age, who were admitted for treatment of abnormal uterine bleeding and reported that PCOS accounted for 33% of admissions and was the most common underlying etiology. Other underlying causes were hypothalamic pituitary ovarian axis immaturity (31%); endometritis (13%); and bleeding disorders (10%). ^[7]

Primary coagulation disorders, such as von Willebrand disease, myeloproliferative disorders, and immune thrombocytopenia, can present with menorrhagia. ^[8]

Excessive exercise, stress, and weight loss cause hypothalamic suppression leading to abnormal uterine bleeding due to disruption along the hypothalamus-pituitary-ovarian pathway.

Bleeding disturbances are common with combination oral contraceptive pills as well as progestin-only methods of birth control. However, the incidence of bleeding decreases significantly with time. Therefore, only counseling and reassurance are required during the early months of use.

Contraceptive intrauterine devices (IUDs) can cause variable vaginal bleeding for the first few cycles after placement and intermittent spotting subsequently. The progesterone impregnated IUD (Mirena) is associated with less menometrorrhagia and usually results in secondary amenorrhea. ^[4]

Cesarean scar defects may also cause abnormal uterine bleeding, possibly via a a pouch or "isthmocele" in the lower uterine segment that causes delayed menstrual bleeding. ^[9] Potential risk factors for these defects may be the number of previous cesarean sections, uterine position, labor before cesarean section, and surgical technique for uterine incision closure. ^[9]

Niches in cesarean scars are also potential causes of abnormal uterine bleeding. ^[10] In a prospective study from The Netherlands, investigators found a 64.5% prevalence of niche via gel instillation sonohysterography (GIS) in women 6-12 weeks postcesarean section. They noted that postmenstrual spotting was more prevalent in women with a niche and in those with a residual myometrial thickness of less than 50% of the adjacent myometrium. ^[10]

United States statistics

Abnormal uterine bleeding is one of the most often encountered gynecologic problems. An estimated 5% of women aged 30-49 years will consult a physician each year for the treatment of menorrhagia. About 30% of all women report having had menorrhagia. ^[6]

International statistics

No cultural predilection is present with this disease state.

Race- and age-related demographics

Abnormal uterine bleeding has no predilection for race; however, Black women have a higher incidence of leiomyomas and, as a result, they are prone to experiencing more episodes of abnormal vaginal bleeding.

Abnormal uterine bleeding is most common at the extreme ages of a woman's reproductive years, either at the beginning or near the end, but it may occur at any time during her reproductive life. Note the following:

• Most cases of dysfunctional uterine bleeding in adolescent girls occur during the first 2 years after the onset of menstruation, when their immature hypothalamic-pituitary axis may fail to respond to estrogen and progesterone, resulting in anovulation. ^[11]

• Abnormal uterine bleeding affects up to 50% of perimenopausal women. In the perimenopausal period, dysfunctional uterine bleeding may be an early manifestation of ovarian failure causing decreased hormone levels or responsiveness to hormones, thus also leading to anovulatory cycles. In patients who are 40 years or older, the number and quality of ovarian follicles diminishes. Follicles continue to develop but do not produce enough estrogen in response to FSH to trigger ovulation. The estrogen that is produced usually results in late-cycle estrogen breakthrough bleeding. ^{[4, 12]}

Hormonal contraceptives reduce blood loss by 40-70% when used long term.

Although medical therapy is generally used first, over half of women with menorrhagia undergo hysterectomy within 5 years of referral to a gynecologist. ^[4]

Morbidity/mortality

Morbidity is related to the amount of blood loss at the time of menstruation, which occasionally is severe enough to cause hemorrhagic shock. Excessive menstrual bleeding accounts for two thirds of all hysterectomies and most endoscopic endometrial destructive surgery. Menorrhagia has several adverse effects, including anemia and iron deficiency, reduced quality of life, and increased healthcare costs. ^[2]

Complications

Complications include the following:

• Anemia (may become severe)

• Adenocarcinoma of the uterus (if prolonged, unopposed estrogen stimulation)

Instruct patients to continue prescribed medications, although bleeding may still be occurring during the early part of the cycle. Also, patients should be told to expect menses after cessation of the regimen.

Young patients with small amounts of irregular bleeding need reassurance and observation only prior to instituting a drug regimen. Express to patients that pharmacologic intervention will not be necessary once menstrual cycles become regular.

Discuss ways the patient can avoid prolonged emotional stress and maintain a normal body mass index.

For  patient education resources, see Women's Health Center, as well as Vaginal Bleeding and Painful Ovulation (Mittelschmerz).