Decreased Levothyroxine Requirement in Women with Hypothyroidism during Androgen Therapy for Breast Cancer

Abstract

OBJECTIVE: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer. DESIGN: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment. INTERVENTIONS: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth. PATIENTS: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism. MEASUREMENTS: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated. RESULTS: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values. In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism. CONCLUSIONS: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.