What are the next steps for a 29-year-old female with secondary amenorrhea, normal thyroid function, and no current use of contraceptives (birth control), who has not had a period for 4 months?

Evaluation and Management of Secondary Amenorrhea in a 29-Year-Old Woman with Normal Thyroid Function

For a 29-year-old woman with secondary amenorrhea (no period for 4 months), normal thyroid function, and not using contraceptives, the next step should be to rule out pregnancy and then measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels to determine the underlying cause. 1, 2

Initial Diagnostic Approach

• Confirm absence of pregnancy with a pregnancy test (most common cause of secondary amenorrhea in reproductive-age women) 1, 2
• Measure serum hormone levels including:
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin
  • Thyroid-stimulating hormone (TSH) - already reported as normal 1, 2

Diagnostic Algorithm Based on Laboratory Results

If elevated prolactin:

• Consider hyperprolactinemia as the cause of amenorrhea 3
• Evaluate for medications that can increase prolactin levels 3
• Consider pituitary imaging to rule out prolactinoma 4

If elevated FSH/LH:

• Suggests primary ovarian insufficiency 1, 2
• Consider karyotyping if patient is younger than 30 years 2
• Patients may still have unpredictable ovarian function and should not be presumed infertile 1

If low/normal FSH and LH:

• Suggests hypothalamic amenorrhea or polycystic ovary syndrome (PCOS) 1, 2
• Evaluate for:
  • Stress, excessive exercise, or disordered eating (hypothalamic cause) 3, 2
  • Signs of hyperandrogenism such as hirsutism or acne (PCOS) 4, 3

If normal prolactin, normal TSH, and normal/low gonadotropins:

• Consider measuring androgens (testosterone, androstenedione) to evaluate for PCOS 4, 2
• Consider pelvic ultrasonography to assess for polycystic ovaries or structural abnormalities 4, 2

Management Based on Diagnosis

For PCOS:

• Screen for metabolic abnormalities (glucose intolerance, dyslipidemia) 1, 2
• Consider cyclic progestogen or combined hormonal contraceptives to regulate cycles 3
• For women desiring pregnancy, clomiphene citrate may be indicated 5

For Hypothalamic Amenorrhea:

• Address underlying causes (stress reduction, weight gain if underweight) 3, 2
• Consider hormone replacement therapy to prevent bone loss 3
• Evaluate for low bone density if amenorrhea persists 1, 2

For Hyperprolactinemia:

• Treat with dopamine agonists if prolactinoma is present 3
• Address any medications that may be causing elevated prolactin 3

For Primary Ovarian Insufficiency:

• Hormone replacement therapy until the average age of menopause 1, 2
• Referral for fertility options if pregnancy is desired 3

Special Considerations

• If amenorrhea persists without clear etiology after initial testing, consider rare causes such as Asherman's syndrome or outflow tract abnormalities 2, 6
• Clomiphene citrate is indicated for ovulatory dysfunction in women desiring pregnancy, particularly those with PCOS, post-oral-contraceptive amenorrhea, or certain cases of secondary amenorrhea of undetermined etiology 5
• The recommended starting dose of clomiphene is 50 mg daily for 5 days, beginning on day 5 of the cycle (spontaneous or progestin-induced) 5
• Patients with hypothalamic amenorrhea may have normal responses to GnRH stimulation tests but fail to respond to clomiphene citrate, indicating a higher-level dysfunction 7

Pitfalls to Avoid

• Don't assume infertility in women with primary ovarian insufficiency, as they may maintain unpredictable ovarian function 1, 2
• Don't overlook the possibility of pregnancy, which is the most common cause of secondary amenorrhea 1, 3
• Don't neglect evaluation for metabolic abnormalities in women with PCOS 1, 2
• Don't attribute amenorrhea solely to thyroid dysfunction when it's normal; further investigation is needed 7
• Don't delay treatment in women with prolonged amenorrhea due to risk of bone density loss 1, 2