What are the potential causes and treatments for secondary amenorrhea (absence of menstruation) in a female?

Evaluation and Management of Secondary Amenorrhea (No Periods for 2 Months)

Two months of absent menstruation requires immediate pregnancy testing, but formal evaluation for secondary amenorrhea should begin at 3 months for previously regular cycles or 6 months for irregular cycles. 1, 2, 3

Initial Assessment at 2 Months

At this early stage, the priority is to:

• Rule out pregnancy immediately with a urine or serum pregnancy test 1, 2, 4
• Document menstrual history including age of menarche, previous cycle regularity, and duration of current irregularity 1
• Assess for recent weight changes (gain or loss), eating patterns, exercise intensity, and psychological stressors 1, 2
• Review all medications, particularly hormonal contraceptives, antipsychotics, and antiepileptics 1, 4
• Calculate BMI, as obesity is associated with PCOS and low BMI with hypothalamic amenorrhea 1

When to Proceed with Full Workup

Do not wait the full 3 months if any red flags are present: 2, 4

• Galactorrhea (suggests hyperprolactinemia requiring pituitary evaluation) 2, 4
• Severe headaches or visual changes (suggests pituitary pathology) 2, 4
• Signs of eating disorder or significant weight loss 2, 4
• Symptoms of hyperandrogenism (severe acne, hirsutism) 4
• History of cancer treatment with alkylating agents or pelvic radiation 4

Laboratory Evaluation (When Indicated)

Initial mandatory tests include: 1, 2

• FSH and LH: Elevated FSH >40 mIU/mL indicates primary ovarian insufficiency; LH/FSH ratio >2 suggests PCOS 1, 2
• Prolactin: Levels >20 μg/L indicate hyperprolactinemia, potentially from pituitary adenoma or medication effect 1
• TSH: Identifies thyroid dysfunction as a reversible cause 1, 2
• Estradiol: Low levels suggest hypoestrogenism from functional hypothalamic amenorrhea 1, 2

Draw FSH, LH, and testosterone between cycle days 3-6, or at any time if amenorrheic 1

Imaging Studies

• Pelvic ultrasound to assess endometrial thickness and ovarian morphology 1, 2
  • Thin endometrium (<5 mm) suggests estrogen deficiency
  • Thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen
  • Polycystic ovarian morphology supports PCOS diagnosis 2

Common Causes by Age and Context

In adolescents and young women: 5, 2

• Functional hypothalamic amenorrhea (FHA) accounts for 20-35% of cases, caused by stress, excessive exercise, or inadequate nutrition 2
• Polycystic ovary syndrome (PCOS) is the most common cause overall 2
• Female Athlete Triad in athletic patients: energy deficiency, menstrual dysfunction, and low bone density 5, 2

In all reproductive-age women: 2, 3

• Hyperprolactinemia (20% of cases) 2
• Primary ovarian insufficiency 2
• Thyroid dysfunction 2

Critical Management Considerations

For patients with FHA or prolonged amenorrhea >6 months: 5, 2

• Screen for eating disorders and disordered eating behaviors 5, 2
• Order DXA scan for bone mineral density assessment, as low estrogen increases fracture risk 5, 2
• Address underlying stressors: inadequate nutrition, excessive exercise, psychological stress 2, 4
• Consider estrogen replacement with cyclic progesterone if non-pharmacological interventions fail and bone density is compromised 5

For athletes specifically: 5

• Evaluate for Relative Energy Deficiency in Sport (RED-S) 2
• Counsel on increasing energy availability and optimizing nutrition 5
• Ensure calcium intake 1000-1300 mg/day and vitamin D levels 32-50 ng/mL 5

Common Pitfalls to Avoid

• Do not assume amenorrhea in athletes or stressed individuals is benign—other pathology must be excluded 2, 4
• Do not overlook eating disorders—adolescents often minimize or deny disordered eating 2, 4
• Do not delay bone density assessment if amenorrhea extends beyond 6 months despite addressing stressors 5, 2
• Do not presume infertility in patients with primary ovarian insufficiency, as unpredictable ovarian function can persist 2, 3

Special Population: Premenopausal Women

In menstruating women, menstrual loss and pregnancy are common causes of amenorrhea 5. Women over age 45 require full investigation regardless of menstrual history, while those under 45 should have antiendomysial antibody testing to exclude celiac disease if upper GI symptoms are absent 5.