In a reproductive‑age woman with hypothyroidism presenting with irregular cycles, oligomenorrhea, menorrhagia, or amenorrhea, what is the first‑line management to normalize menses?

Hypothyroidism and Menstruation: First-Line Management

Initiate levothyroxine replacement therapy immediately to normalize thyroid function, as this is the definitive first-line treatment that directly resolves menstrual irregularities in hypothyroid women, with menstrual cycles typically normalizing within 2-5 days of achieving adequate thyroid hormone replacement. 1

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis with:

• TSH and free T4 measurement to establish the diagnosis and severity of hypothyroidism, targeting a TSH within the normal reference range (0.4-4.5 mIU/L) 1
• Pregnancy test in all reproductive-age women to rule out pregnancy as a cause of menstrual irregularities 1
• Prolactin level since hypothyroidism can cause hyperprolactinemia through TRH-mediated prolactin release 1
• LH, FSH (day 3-6 of cycle), and mid-luteal progesterone to assess ovulatory status, with progesterone <6 nmol/L indicating anovulation 1

Levothyroxine Dosing Strategy

Start levothyroxine at 1.6 mcg/kg/day for patients without cardiac risk factors (age <70, no cardiac disease, not frail) 1, 2. This weight-based approach ensures adequate initial replacement.

• Monitor TSH levels 6-8 weeks after initiation or any dose change 2, 3
• Titrate dosage every 2 weeks as needed based on serum TSH or free-T4 until the patient is euthyroid 2
• Once stable, monitor TSH every 6-12 months 1

Management of Persistent Heavy Bleeding

If menorrhagia persists despite initiating thyroid replacement:

1. First-line: NSAIDs such as mefenamic acid 500 mg three times daily for 5 days during bleeding episodes 1

   • Avoid aspirin, as it may increase blood loss in women with baseline menstrual blood loss <60 mL 1

2. Second-line: Tranexamic acid significantly reduces menstrual blood loss compared to placebo 1

   • Contraindicated in women with active thromboembolic disease or history/risk of thrombosis 1

3. Third-line: Short-term hormonal therapy such as low-dose combined oral contraceptives 1

   • Caution: Increases venous thromboembolism risk 3-4 fold 1

4. Long-term option: Levonorgestrel-releasing IUD reduces menstrual blood loss by 71-95% 1

Expected Timeline for Resolution

Complete resolution of heavy bleeding typically occurs within one week of achieving adequate thyroid hormone replacement 1. The rapid response (2-5 days for cycle normalization) underscores that thyroid replacement is the definitive treatment, not symptomatic management 1.

Critical Pitfalls to Avoid

• Do not assume menstrual irregularities are unrelated to hypothyroidism: Hypothyroidism causes menstrual irregularities in approximately 23% of patients, including oligomenorrhea and menorrhagia 3, 4
• Review all medications: Certain antiepileptic drugs (valproate, carbamazepine, phenytoin) can worsen menstrual irregularities and affect SHBG levels 1
• Reassess if bleeding persists despite euthyroid state: Evaluate for structural pathology (polyps, fibroids, adenomyosis, endometrial hyperplasia) and consider PCOS (affects 4-6% of women) 1
• Refer to gynecology if bleeding persists despite two treatment attempts 1

Mechanism of Menstrual Dysfunction

Hypothyroidism disrupts menstruation through multiple mechanisms:

• Shifts the hemostatic system toward a hypocoagulable and hyperfibrinolytic state, increasing bleeding risk 5
• Disrupts the hypothalamic-pituitary-ovarian axis, causing anovulation 6, 4
• Severe hypothyroidism is commonly associated with failure of ovulation, though mild hypothyroidism may still permit ovulation and conception (albeit with increased risk of abortion, stillbirth, or prematurity) 4

Special Considerations

Pelvic ultrasound (transvaginal preferred) should be considered if hormonal tests suggest ovarian pathology or to exclude structural causes 1. However, this is adjunctive—thyroid replacement remains the primary intervention 1.