Secondary amenorrhea is defined as the cessation of previously established menstrual cycles for at least 3 months in individuals who previously had regular cycles, or for 6 months in those with previously irregular cycles. In contrast to primary amenorrhea, which often arises from congenital or developmental issues, secondary amenorrhea occurs after normal menarche. It commonly results from disruptions within the hypothalamic-pituitary-ovarian (HPO) axis or structural or functional abnormalities involving the uterus, cervix, vagina, or endometrium. Additionally, endocrine conditions beyond the HPO axis such as thyroid disorders or hyperprolactinemia may influence menstrual regularity. It is important to differentiate physiologic causes of secondary amenorrhea like pregnancy, lactation, and menopause from any pathologic absence of menses in a reproductive-age individual.

Secondary amenorrhea typically affects women of reproductive age, with a prevalence of approximately 3%-4% in the general population, excluding cases related to pregnancy, lactation, or menopause. Patients present with absent menstrual cycles and may also experience additional symptoms such as weight gain, weight loss, headaches, vision changes, milky nipple discharge, fatigue, cold intolerance, acne, hirsutism, or pelvic pain. Those approaching menopause often report a history of hot flashes and vaginal dryness. Patients with functional hypothalamic amenorrhea (FHA) frequently have concerns related to weight loss, excessive exercise, or high levels of stress.

Secondary amenorrhea can be caused by a variety of etiologies, each disrupting different points of menstruation. It is important to first differentiate pathologic explanations from physiologic. Physiologic reasons for amenorrhea can include hormone use, such as a levonorgestrel intrauterine device (IUD), or continuous oral contraceptives, Depo-Provera injections, pregnancy, suppression due to breastfeeding, and being postmenopausal. The most frequent pathologic etiologies include disruptions to the hormonal HPO axis or structural abnormalities. The HPO axis is involved in menstrual regulation via hormones such as gonadotropin-releasing hormone (GnRH), which occur in a pulsatile fashion; this is important for adequate follicle stimulating hormone (FSH) release and luteinizing hormone (LH) surge, which regulates estrogen and progesterone levels. Of endocrine abnormalities, the most common include FHA, polycystic ovarian syndrome (PCOS), hyperprolactinemia, thyroid dysfunction, pituitary tumors (prolactinomas), primary ovarian insufficiency (POI), stress, and eating disorders.

Of structural abnormalities, the most common findings include intrauterine adhesions (Asherman syndrome) resultant from uterine trauma and cervical stenosis, whether iatrogenic or secondary to other cervical interventions.

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