Dysfunctional Uterine Bleeding in Pediatrics 

Dysfunctional uterine bleeding (DUB) is classically defined as excessively heavy, prolonged, or frequent bleeding of uterine origin that is not caused by pregnancy or recognizable pelvic or systemic disease.^{[1, 2]}

DUB usually results from disordered functioning of the hypothalamic-pituitary-ovarian (HPO) axis and is often associated with anovulatory cycles. The classic definition has proved less useful because of the current understanding of the pathophysiology of DUB. However, it does highlight that anovulatory uterine bleeding is a diagnosis of exclusion. DUB occurs most often in women at the extreme ends of their reproductive lifetime. Because premenarchal females have several anovulatory cycles per year, DUB is a common problem in adolescent females.^{[3, 4, 5]}

The normal menstrual cycle, characterized by sequential growth, maturation, and eventual sloughing of the endometrial mucosa, is produced by the cyclic release of estrogen and progesterone from the ovary. This occurs (orchestrated by the HPO axis) with amazing regularity throughout most of a woman's reproductive lifetime. An understanding of the normal cyclic fluctuations of the 2 gonadotropins (ie, luteinizing hormone [LH], follicle-stimulating hormone [FSH]) and the primary female reproductive hormones (ie, estrogen, progesterone) helps clarify the derangements associated with anovulation.^[6]

The first 14 days of a typical 28-day menstrual cycle (day 1 is defined as the first day of menstrual flow) are characterized by rising FSH levels, which stimulate ovarian follicle development and the subsequent production of estrogens (primarily estradiol). Serum progesterone levels are extremely low during this stage. LH levels climb more slowly but abruptly peak on day 12 or 13 in positive response to rising estrogen levels. See the image below.

During that first 14 days, the endometrium, under the influence of estrogen, undergoes proliferation. The LH surge stimulates ovulation (on or about day 14) and conversion of the ovulatory follicle to a corpus luteum, which is responsible for estrogen and progesterone production. Under the influence of this progesterone, the endometrium is converted to a secretory state in preparation for implantation if fertilization of the ovum should occur. Progesterone is produced only if ovulation occurs. As LH levels drop (assuming fertilization and production of human chorionic gonadotropin [HCG] by the developing conceptus did not occur), the corpus luteum regresses, estrogen and progesterone levels plummet, and the endometrium deteriorates and is sloughed.

The average menstrual cycle is 28-29 days (range 21-35 d). Initially, some teenagers can have cycles as long as 45 days. Over time, the menstrual cycle becomes fairly consistent from month to month in any given woman. Normal menstrual flow lasts 7 or fewer days and produces an average total blood loss of 25-69 mL. Bleeding more frequently than every 21 days or less frequently than 45 days, menstrual flow longer than 7 days, and blood loss exceeding 80 mL are considered abnormal.

With anovulation, estrogen levels rise as usual in the early phase of the cycle. In the absence of ovulation, a corpus luteum never forms and progesterone is not produced. The endometrium moves into a hyperproliferative state, ultimately outgrowing its estrogen supply. This leads to irregular sloughing of the endometrium and excessive bleeding from spiral arteries that have not undergone physiological senescence.

Frequency

United States

The exact incidence of DUB is unknown. The understanding of the epidemiology comes from case series reports from tertiary institutions with patients who are unlikely to reflect the general population. Nearly one half of all women have irregular periods in the first year after menarche, and over one half of the cycles are anovulatory. Irregular periods can persist for up to 5 years after menarche in 20% of women.

International

International rates should reflect those of the United States.

Mortality/Morbidity

The main complication of DUB is anemia.

• Acute blood loss can occasionally lead to a profound anemia. Blood product transfusion (with the attendant risks and complications) is occasionally required.
• Chronic or recurrent DUB can result in an iron-deficient state.
• Blood loss in the healthy female adolescent is rarely of a fatal magnitude.

Race

Race does not seem to contribute significantly to the incidence of DUB.

Age

The average age of menarche in the United States is 12.3 years.^[7] Irregular and anovulatory cycles may persist for as long as 1-5 years after the onset of menstrual periods.