What is the best treatment for amenorrhea (absence of menstruation)?

Treatment of Amenorrhea

The best treatment for amenorrhea depends on identifying and addressing the underlying cause, with hormone replacement therapy (transdermal estradiol with cyclic oral progestin) being the preferred first-line treatment for functional hypothalamic amenorrhea to protect bone health. 1

Diagnostic Approach to Guide Treatment

1. Rule out pregnancy first in all women of reproductive age

2. Categorize the amenorrhea:

   • Primary amenorrhea: absence of menarche by age 16
   • Secondary amenorrhea: cessation of menses for ≥3 months in previously regular cycles or ≥6 months in previously irregular cycles

3. Initial laboratory workup:

   • Pregnancy test
   • Luteinizing hormone (LH)
   • Follicle-stimulating hormone (FSH)
   • Prolactin
   • Thyroid-stimulating hormone (TSH)

Treatment Based on Specific Causes

1. Functional Hypothalamic Amenorrhea (FHA)

• First-line treatment: Transdermal estradiol (100 μg patch applied twice weekly) with cyclic oral progestin (200 mg for 12 days each month) 1
• Avoid oral contraceptives as they inhibit IGF-1 production via first-pass hepatic metabolism, potentially decreasing osteoblastic activity 1
• Address underlying causes:
  • Optimize energy availability through nutritional counseling
  • Reduce excessive exercise if present
  • Manage psychological stressors

2. Polycystic Ovary Syndrome (PCOS)

• For menstrual regulation: Cyclic progestogen or sequential estrogen plus progestogen 2
• For contraception and hyperandrogenism: Combined oral contraceptives, especially for patients with acne and hirsutism 2
• For fertility: Clomiphene citrate (starting on day 5 of cycle) 3
• Metabolic management: Screen for glucose intolerance and dyslipidemia 4

3. Hyperprolactinemia

• First-line treatment: Dopamine agonists (e.g., bromocriptine) to normalize prolactin levels 2, 5
• For menstrual regulation: Cyclical progestogen or hormone replacement therapy 2
• For contraception: Combined oral contraceptives 2

4. Primary Ovarian Insufficiency

• First-line treatment: Hormone replacement therapy to prevent hypoestrogenic complications (cardiovascular disease and osteoporosis) 2
• Important note: These patients can maintain unpredictable ovarian function and should not be presumed infertile 6, 4

5. Post-Oral Contraceptive Amenorrhea

• For those with normal prolactin: Consider clomiphene citrate challenge test 5
• For those with elevated prolactin and galactorrhea: Bromocriptine therapy (5 mg daily) 5

Special Considerations

Bone Health

• Amenorrhea, particularly FHA, increases risk of osteoporosis and fractures
• Monitor bone mineral density in patients with prolonged amenorrhea
• Calcium and vitamin D supplementation is recommended 1
• Avoid exercise-related LEA (Low Energy Availability) which can impair bone health when energy availability drops below 30 kcal/kg FFM/day in women 1

Contraception

• Despite amenorrhea, contraception may still be needed as ovulation can occur unpredictably
• Important: Contraception is mandatory before starting any potentially teratogenic treatments 1

Common Pitfalls to Avoid

1. Treating with combined oral contraceptives for FHA: This masks the return of spontaneous menstruation and may not protect bone health 1

2. Assuming infertility in all cases: Particularly in primary ovarian insufficiency, unpredictable ovarian function may occur 6, 4

3. Focusing only on menstrual regulation: Treatment should address underlying causes and prevent long-term complications like osteoporosis and cardiovascular disease 2

4. Overlooking eating disorders: In FHA, disordered eating should be evaluated and addressed 1, 4

5. Missing pregnancy as a cause: Always rule out pregnancy before initiating any treatment 6, 4

By identifying the specific cause of amenorrhea and implementing appropriate treatment, clinicians can effectively manage this condition while preventing associated complications and preserving fertility when possible.