Menstrual dysfunction is a component of the Female Athlete Triad and is more commonly observed with certain kinds of athletic activities. This chapter will review normal menstrual function, causes and consequences of abnormal menstrual function in athletes, and management strategies for menstrual dysfunction.

Pubertal onset and the hypothalamic–pituitary–gonadal axis: The hypothalamus secretes gonadotropin-releasing hormone (GnRH) is a pulsatile fashion, which then stimulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary gland, and FSH and LH in turn stimulate secretion of estrogen and progesterone by the ovaries in girls. Puberty begins when the hypothalamic–pituitary–gonadal (HPG) axis awakens from its quiescent prepubertal state and is characterized by very specific changes in patterns of gonadotropin pulsatility. Early in puberty, GnRH pulsatility (reflected by LH pulsatility) changes from a prepubertal pattern of very low amplitude pulses to a pattern of nighttime increases in pulse amplitude, followed eventually by an increase in daytime pulsatility to approximate adult patterns. Factors that trigger pubertal onset are still under investigation; however, a withdrawal of inhibitory signals (such as GABA and neuropeptide YY) and an increase in excitatory signals (such as kisspeptin, glutamate, norepinephrine, and certain growth factors) have been implicated in this process. Nutritional signals are also key to pubertal onset. Although there is no threshold body weight or fat mass above which pubertal onset occurs, it is likely that a genetically determined threshold exists for any single individual for puberty to begin and progress. Proposed endocrine, metabolic, and nutritional signals for pubertal onset and progression include leptin, ghrelin, insulin, insulin-like growth factor-1 (IGF-1), galanin-like peptide, glucose, and free fatty acids.

Pubertal changes and their timing: During puberty, increasing estradiol secretion from ovarian follicles causes the development of secondary sexual characteristics, namely enlargement of breasts and the uterus. Breast development in girls heralds the onset of puberty (Tanner stage 2), and typically begins between 8 and 13 years of age. Rising levels of estradiol are followed by increases in growth hormone (GH) and IGF-1, which cause the pubertal growth spurt. In girls, growth velocity peaks at Tanner stage 3 of puberty. With further maturation of gonadotropin pulsatility and increasing secretion of gonadal steroids, menses begin, usually toward the end of Tanner stage 4 of puberty. In healthy girls, menarche, or the onset of menses, occurs 2–3 years after the onset of breast development and between 10 and 15 years of age. The average age for menarche is 12.7 years (SD 1.3 years) for girls in the United States, and minor racial and ethnic differences are reported. Cycles are often anovulatory, and hence, irregular for a variable period following menarche as the positive feedback effect of estradiol on the HPG axis is yet to be established. Over time, a larger proportion of cycles become ovulatory, leading to a more regular pattern of menstrual cyclicity.

Puberty is considered to have occurred early if breast and pubic hair development begin before 8 years, and delayed if these begin after 13 years. Menarche is considered delayed if menses does not occur within 2–3 years of starting breast development or by 15 years of age. Lack of any menses at 16 years despite otherwise normal pubertal development is referred to as primary amenorrhea. In contrast, amenorrhea that occurs after a period of normal or near normal menses is referred to as secondary amenorrhea. The duration of absent menses to qualify for secondary amenorrhea remains a matter of debate and ranges from 3 to 6 months.

Normal menstrual cycle: In the early follicular phase, increasing secretion of FSH causes enlargement and maturation of secondary ovarian follicles into antral follicles, proliferation of granulosa cells, induction of aromatase activity, and increased expression of FSH receptors on granulosa cells. Theca cells are evident as a layer of cells around the granulosa cells in the preantral stage, and secrete androgens in response to LH. Cross-talk between the theca and granulosa cells and aromatization of androgens (produced in theca cells) to estrogens within the granulosa cells lead to high levels of estrogen within the follicle. Rising estradiol levels cause thickening of the endometrial lining of the uterus with proliferation of stroma and uterine glands, and elongation of spiral arterioles. This is the proliferative phase of the uterine endometrium, corresponding with the follicular phase of the cycle.

Increasing estradiol secretion in the follicular phase then causes inhibition of FSH secretion by negative feedback. This allows selection of a dominant follicle, as smaller follicles that are still FSH dependent for growth become atretic. Increasing estradiol secretion from the dominant follicle around mid-cycle triggers the mid-cycle LH surge, followed by ovulation.

In the second half of the menstrual cycle, granulosa cells become luteinized and secrete progesterone. This is the luteal phase, and progesterone levels typically peak around day 21 of the cycle. Rising progesterone levels stabilize the endometrium and prepare it for implantation by a fertilized embryo. The granulosa cells of the corpus luteum also secrete inhibin, which inhibits FSH secretion and prevents growth of other follicles. If fertilization of the oocyte does not occur, there is eventual regression of the corpus luteum, a decrease in levels of estrogen and progesterone and constriction of the spiral arterioles, followed by shedding of the uterine lining as menses. The period between ovulation and menses is the luteal phase of the menstrual cycle, which corresponds to the secretory phase of the uterine lining. A gradual increase in FSH then heralds the onset of the next menstrual cycle.

Cycle length and menstrual flow: During the adolescent years, cycle length ranges between 20 and 45 days, and decreases to 24–38 days with increasing maturity. Cycle length longer than 45 days indicates oligomenorrhea and requires evaluation. In adolescents, 60–80% of cycles are between 21 and 35 days long by the third postmenarchal (gynecologic) year. While anovulatory cycles are more likely to be associated with short- or long-cycle length, there is a significant overlap with ovulatory cycles. The absence of premenstrual symptoms and dysmenorrhea suggests anovulatory cycles. Earlier menarche has been associated with earlier establishment of regular ovulatory cycles. Some women have ovulatory cycles with a short luteal phase, referred to as luteal phase dysfunction. The latter may be a cause of infertility or frequent miscarriages.

While a complete description of the causes and work-up of menstrual dysfunction is beyond the scope of this chapter, these include (i) heavy bleeding (menorrhagia), (ii) irregular bleeding, and (iii) amenorrhea. Heavy bleeding may occur in the years following menarche and often resolves spontaneously over time. Other causes include (a) bleeding, coagulation, and platelet disorders (including von Willebrand disease and idiopathic thrombocytopenic purpura), (b) thyroid dysfunction, (c) hyperprolactinemia and PCOS (associated with anovulatory cycles), (d) fibromyomas and adenomyosis, or (e) dysfunctional uterine bleeding. Evaluation should focus on these possible causes of menorrhagia and should include an assessment of hematocrit and iron studies to determine the need for iron supplementation.

Irregular bleeding includes oligomenorrhea (infrequent irregular cycles) and frequent episodes of irregular bleeding. Oligomenorrhea and amenorrhea are often collectively termed oligoamenorrhea, which can have hypogonadotropic or hypergonadotropic causes. Primary amenorrhea also needs to be worked up for eugonadotropic