Amenorrhea: Primary and Secondary

Amenorrhea is classified as primary (absence of menarche by age 15 with normal secondary sexual characteristics, or by age 13 without secondary sexual characteristics) or secondary (absence of menstruation for >= 3 months in previously cycling women or >= 6 months in women with irregular cycles). Secondary amenorrhea is far more common and the diagnostic workup proceeds systematically. Pregnancy is the most common cause and must always be excluded first with beta-hCG. After excluding pregnancy, the clinician evaluates TSH (hypothyroidism increases TRH, which stimulates prolactin and suppresses GnRH), prolactin (hyperprolactinemia suppresses GnRH pulsatility), and FSH (elevated FSH > 40 IU/L indicates primary ovarian insufficiency; low/normal FSH suggests hypothalamic or pituitary cause). Functional hypothalamic amenorrhea results from suppression of GnRH pulsatility due to energy deficit, excessive exercise, or psychological stress. PCOS is the most common cause of anovulatory amenorrhea in reproductive-age women, characterized by hyperandrogenism and insulin resistance disrupting normal follicular development.