This chapter reviews normal menstrual physiology, and the next several chapters discuss common menstrual abnormalities in adolescents and young adults (AYAs).

The development of the menstrual cycle depends on the maturation of the hypothalamic-pituitary-ovarian (HPO) axis that occurs during puberty. A coordinated sequence of events is required for cyclic menses to occur, beginning with the hypothalamic secretion of gonadotropin-releasing hormone (GnRH). In response to GnRH, the pituitary secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and the ovaries secrete estrogen, progesterone, activin, and inhibins.¹ The endometrium of the uterus responds to estrogen and progesterone with endometrial growth and differentiation. In the absence of fertilization, this process culminates in menses.²

Growth acceleration can be the first sign of puberty, followed by thelarche (breast budding), then pubarche (presence of pubic hair), and finally menarche (the onset of menses).³ Menarche occurs on average 2.6 years after the onset of puberty and after the peak of growth has passed.³ In the US, the median age of menarche is 12.34 years, and in approximately two-thirds of girls, it occurs at a sexual maturity rating (SMR) of 4. The timing of menarche occurs approximately 2.3 years after thelarche. In the first 2 years after menarche, 55% to 82% of cycles are anovulatory.⁴ Menarche is followed by approximately 5 to 7 years of increasing regularity as the cycles shorten to reach the usual reproductive pattern.³

The exact trigger of menarche is unknown. We know that both inhibitory and excitatory neurotransmitters, as well as peptides, modulate the activity of the HPO axis. The axis is inactive from late infancy continuing through childhood secondary to central inhibitory mechanisms suppressing GnRH secretion, and to a lesser extent the high sensitivity to low levels of gonadal steroid feedback. At gonadarche, the HPO axis is reactivated in response to metabolic signals from the periphery. FSH and LH levels rise followed by a gradual increase in estradiol concentrations, which stimulates breast development. The increase in pulsatile LH secretion occurs first at night, during sleep, but gradually extends throughout the day. At midpuberty, estrogen production increases sufficiently to stimulate endometrial proliferation, ultimately resulting in menarche.³ Evidence suggests that menarche may be associated with achieving a critical body weight of 46 to 47 kg and a minimum fatness level of 17%, although this point has generated controversy. The maintenance or restoration of menstruation is thought to require a minimum of 22% body fat.⁵