Amenorrhoea, secondary (Amenorrhea)

Secondary Amenorrhea – Treatment Overview

Introduction
Secondary amenorrhea is the absence of menstruation for ≥3 months in women with previously regular cycles or ≥6 months in those with irregular cycles. It is more common than primary amenorrhea and may result from physiological states (pregnancy, lactation, menopause) or pathological conditions involving the hypothalamus, pituitary, ovaries, uterus, or systemic illness. Management requires identifying and treating the underlying cause, while also protecting long-term health (bone density, fertility, metabolic balance).

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General Diagnostic Workup

1. Exclude pregnancy (always first step).

2. History: weight changes, stress, exercise, medications, chronic disease.

3. Examination: BMI, secondary sexual characteristics, galactorrhea, hirsutism, thyroid signs.

4. Investigations:

   • Labs: FSH, LH, prolactin, TSH, estradiol, androgens.

   • Pelvic ultrasound to assess uterus and ovaries.

   • MRI pituitary if prolactin elevated or other pituitary signs.

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Treatment Options (Cause-Specific)

1. Hypothalamic Causes (stress, weight loss, excessive exercise, eating disorders)

• Nutritional rehabilitation and weight gain if underweight.

• Reduce excessive exercise.

• Stress management, psychotherapy if needed.

• If persistent hypoestrogenism:

  • Combined oral contraceptives (COCs) or cyclic estrogen + progestin to protect bone and endometrial health.

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2. Pituitary Disorders

• Hyperprolactinemia (prolactinoma):

  • Cabergoline 0.25–1 mg twice weekly or Bromocriptine 2.5 mg orally 2–3 times daily.

• Sheehan’s syndrome or hypopituitarism: Replace deficient hormones (thyroxine, hydrocortisone, estrogen/progestin).

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3. Ovarian Causes

• Polycystic Ovary Syndrome (PCOS):

  • Lifestyle modification (weight loss, exercise).

  • COCs for cycle regulation and endometrial protection.

  • Metformin 500–850 mg orally 2–3 times daily for insulin resistance.

  • Letrozole or Clomiphene citrate for ovulation induction if fertility desired.

• Premature Ovarian Insufficiency (POI):

  • Hormone replacement therapy (HRT): Estrogen + progestin until average age of menopause (~50 years).

  • Fertility: Egg donation may be required.

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4. Uterine/Outflow Tract Causes

• Asherman’s syndrome (intrauterine adhesions):

  • Hysteroscopic adhesiolysis.

  • Post-surgery estrogen therapy (e.g., estradiol valerate 2–4 mg daily for 4–6 weeks) to encourage endometrial regeneration.

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5. Thyroid and Other Systemic Disorders

• Hypothyroidism: Levothyroxine replacement (starting ~1.6 mcg/kg/day, adjust to TSH).

• Hyperthyroidism: Antithyroid drugs (e.g., methimazole 10–30 mg/day).

• Chronic illnesses (e.g., diabetes, celiac disease, renal/hepatic failure): Optimize control of the primary disease.

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Supportive Measures

• Bone health protection: Calcium, Vitamin D, and weight-bearing exercise; bisphosphonates may be considered in persistent hypoestrogenic states.

• Psychological support: Counseling for stress-related amenorrhea or infertility.

• Fertility counseling: Early referral to reproductive endocrinology if pregnancy is desired.