What is the initial treatment for a patient with secondary amenorrhea (absence of menstruation)?

Initial Treatment for Secondary Amenorrhea

The initial treatment for secondary amenorrhea should be progesterone therapy, specifically progesterone capsules 400 mg daily at bedtime for 10 days to induce withdrawal bleeding. 1

Diagnostic Approach Before Treatment

Before initiating treatment, it's essential to determine the underlying cause of secondary amenorrhea:

1. Rule out pregnancy with a pregnancy test (most common cause)
2. Laboratory assessment:
   • Luteinizing hormone (LH)
   • Follicle-stimulating hormone (FSH)
   • Prolactin
   • Thyroid-stimulating hormone (TSH)
3. Progesterone challenge test to assess estrogen status and endometrial responsiveness

Common Causes of Secondary Amenorrhea

Secondary amenorrhea (absence of menses for >3 months in previously regular cycles or >6 months in previously irregular cycles) is typically caused by:

• Functional hypothalamic amenorrhea (FHA) - due to stress, weight loss, or excessive exercise 2
• Polycystic ovary syndrome (PCOS)
• Hyperprolactinemia
• Primary ovarian insufficiency

Treatment Algorithm Based on Cause

1. Functional Hypothalamic Amenorrhea (FHA)

• First-line: Optimize energy availability through nutritional counseling 2
• Medication: Progesterone 400 mg daily at bedtime for 10 days 1
  • Clinical studies show 80% of women experience withdrawal bleeding within 7 days of the last dose
  • In multicenter studies, 73.8-76.8% of women with secondary amenorrhea experienced withdrawal bleeding after progesterone treatment

2. PCOS-Related Amenorrhea

• First-line: Progesterone therapy to induce withdrawal bleeding
• Second-line: Combined hormonal contraceptives for those needing contraception or with hyperandrogenism

3. Hyperprolactinemia

• First-line: Treat underlying cause (medication adjustment, prolactin-lowering drugs)
• Second-line: Progesterone therapy for cycle regulation

4. Primary Ovarian Insufficiency

• Treatment: Hormone replacement therapy to prevent hypoestrogenic state

Progesterone Therapy Details

• Dosage: 400 mg orally daily at bedtime for 10 days 1
• Administration: Take at bedtime due to potential drowsiness and dizziness
• Caution: Contains peanut oil - contraindicated in patients with peanut allergies
• Expected response: Withdrawal bleeding typically occurs within 7 days after completing the 10-day course

Important Considerations

• Timing: If no withdrawal bleeding occurs after progesterone challenge, this suggests hypoestrogenism requiring further evaluation
• Safety: Progesterone is generally well-tolerated but may cause drowsiness, dizziness, and in rare cases blurred vision or difficulty speaking 1
• Follow-up: If no withdrawal bleeding occurs after progesterone therapy, further evaluation with imaging and additional hormone testing is warranted

When to Consider Alternative Treatments

• For contraception needs: Consider combined hormonal contraceptives (failure rate 5-9%) 3
• For persistent amenorrhea: Consider underlying causes requiring specific treatments
• For women desiring pregnancy: Different treatment approach focused on ovulation induction may be needed

Progesterone therapy not only helps diagnose the underlying cause of amenorrhea but also provides treatment by inducing withdrawal bleeding in women with adequate estrogen levels, making it the appropriate initial treatment for secondary amenorrhea.