Amenorrhea, defined as the absence of menses, is common during adolescence. Determining the underlying cause of amenorrhea necessitates an understanding of the normal menstrual cycle. Although the broad differential diagnosis includes genetic, endocrine, structural, environmental, and psychological disorders, pregnancy should always be considered. Evaluation should begin soon after amenorrhea is noted because underlying pathological conditions can cause tremendous physical and emotional sequelae.

Menarche, a pivotal event of puberty, requires intact and functioning interactions between the hypothalamus, pituitary, ovaries, and uterine endometrial lining. Successful menstrual cycles also require the presence of an unobstructed uterus, cervix, and vagina. The body must have an adequate amount of fat and not be under any extremes of stress (e.g., excessive exercise, emotional stress). Normal (regular) cycles indicate the presence of ovulation. Menarche is one of the latest signs of puberty in females, occurring at Tanner stage (or sexual maturity rating) IV in the majority of adolescents. Menarche generally occurs ˜3 years after the growth spurt, 2 to 2.5 years after thelarche, and 1 year after peak height velocity. In the United States, 12.5 years is the average age of menarche (the average age is lower for black females, intermediate for Mexican American females, and later for white females). Race, nutritional status, body fat, and maternal age at menarche all influence an individual’s age of menarche. The majority of cycles are anovulatory for the first year and remain so for an average of ≥2 years. Normal menstrual cycles are 21 to 45 days, have flow lasting 2 to 7 days, and have an average blood loss of between 30 and 40 mL.

The menstrual cycle begins with pulsatile release of gonadotropin-releasing hormone from the hypothalamus, causing secretion of follicle-stimulating hormone (FSH) and luteinizing hormone from the pituitary. Ovarian follicles grow and develop under the influence of FSH. Theca cells produce androgens that are
converted to estrogen by granulosa cells. This increased estrogen not only inhibits the pituitary release of FSH, causing follicles to involute, but also stimulates uterine development and endometrial growth. In the first part of the cycle, increased estrogen leads to decreased FSH release. Midcycle, FSH results in a luteinizing hormone surge and ovulation. In early adolescence, although estrogen levels are high, the feedback patterns are not mature, and menses may be anovulatory, representing sloughing of a proliferative endometrium rather than shedding secondary to the luteal phase of an ovulatory cycle. Clinically, this may be characterized by irregular or heavy bleeding (dysfunctional uterine bleeding) and lack of dysmenorrhea.

Primary amenorrhea is the absence of menarche by 16 years of age (with normal pubertal development), 13 years of age (without normal pubertal development), or within 2 years after completion of sexual maturation. Secondary amenorrhea is the absence of menstruation for at least three consecutive cycles (if regular cycles), or for 6 months (if irregular cycles). Although primary and secondary amenorrhea are helpful in describing menstrual cycle interruption in terms of timing, the terms do not indicate an underlying cause or offer information about treatment or prognosis. In addition, because several of the processes that cause amenorrhea can present as primary or secondary, a more informative evaluation and diagnostic strategy is to distinguish whether normal pubertal and sexual development have occurred or not.