Description

• Primary amenorrhea
  • No menses by age 13 years with absence of secondary sexual characteristics OR
  • No menses by age 15 years with normal secondary characteristics
• Secondary amenorrhea: cessation of menses for 3 months if previously normal menstrual cycles or 6 months if a history of irregular cycles
• System(s) affected: endocrine/metabolic; reproductive

Pregnancy Considerations
Pregnancy is by far the most common cause of secondary amenorrhea.

Epidemiology

Prevalence

• Primary amenorrhea: <1% of female population
• Secondary amenorrhea: 3–4% of female population
• No evidence for race and ethnicity affecting prevalence

Etiology and Pathophysiology

Absence of menses that can be temporary, intermittent, or permanent due to dysfunction of the hypothalamus, pituitary, uterus, ovaries, or vagina

• Primary amenorrhea
  • Gonadal dysgenesis (e.g., Turner syndrome [45,X]) or failure (e.g., autoimmune, idiopathic)
  • Anatomic abnormalities (e.g., müllerian agenesis, imperforate hymen, transverse vaginal septum)
  • Hypothalamic-pituitary abnormalities
    • Functional hypothalamic amenorrhea (reduced GnRH secretion, e.g., weight loss/anorexia nervosa)
    • Physiologic delay of puberty
    • Central lesions (tumors, hypophysitis, granulomas)
    • Pituitary dysfunction (hyperprolactinemia, abnormal follicle-stimulating hormone [FSH], luteinizing hormone [LH], or GnRH)
    • Thyroid dysfunction
  • Polycystic ovarian syndrome (PCOS)
  • Androgen insensitivity syndrome
• Secondary amenorrhea
  • Pregnancy
  • Hypothalamic dysfunction (reduced GnRH secretion)
    • Functional hypothalamic amenorrhea (stress, anorexia nervosa, and/or excessive exercise)
    • Hypothalamic tumors
    • Severe systemic illness (e.g., diabetes mellitus type 1 or celiac disease)
  • Pituitary disease (e.g., hyperprolactinemia, Sheehan syndrome, Cushing syndrome)
  • Thyroid disease
  • PCOS
  • Ovarian disorders (e.g., primary ovarian insufficiency [due to chemotherapy, radiation, fragile X syndrome] or ovarian tumors)
  • Anatomic abnormalities (e.g., intrauterine adhesions [Asherman syndrome], obstructive fibroids, polyps, iatrogenic cervical stenosis)
• Pathophysiology varies, depending on etiology.

Genetics
May occur with Turner syndrome or testicular feminization

Risk Factors

• Obesity
• Excessive exercise (commonly associated “female athlete triad”)
• Eating disorders
• Malnutrition
• Stress (emotional or illness-induced [e.g., myocardial infarct, severe burns])
• Family history of amenorrhea or early menopause
• Treatment with antipsychotic medications

General Prevention

Maintenance of proper body mass index (BMI) and healthy lifestyle with respect to food and exercise

Commonly Associated Conditions

• Primary ovarian insufficiency may be associated with autoimmune abnormalities (autoimmune thyroiditis, type 1 diabetes).
• PCOS is associated with insulin resistance and obesity.
• Decreased exposure to estrogen may increase risk for osteopenia or osteoporosis.