Evaluation of danazol therapy for patients with PiZZ alpha-1-antitrypsin deficiency

M. D. Wewers, J. E. Gadek, B. A. Keogh, G. A. Fells, R. G. Crystal

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An inherited deficiency of α1-antitrypsin with blood concentrations less than 80 mg/dl is associated with the accelerated development of emphysema. Current concepts of the pathogenesis of emphysema suggest that an imbalance between neutrophil elastase and α1-antitrypsin in the lung allows neutrophil elastase to work unimpeded to destroy the alveolar structures. Because the common form of the inherited deficiency (homozygous Z) results from impaired hepatic release of α1-antitrypsin, one therapeutic approach to increase plasma and hence lung α1-antitrypsin concentrations is to enhance hepatic release or production of α1-antitrypsin. In a preliminary trial with 6 α1-antitrypsin-deficient subjects, we have previously shown that in 1 month, the impeded androgen danazol can augment serum α1-antitrypsin concentrations by 37%. To evaluate the use of impeded androgens in α1-antitrypsin deficiency on a broader scale, we have treated: (1) 43 homozygous Z patients with danazol 200 mg given orally 3 times a day for 30 days; (2) 6 homozygous Z patients with a similar danazol dose but given for 6 to 18 months; and (3) 7 homozygous Z patients with stanazolol, another synthetic androgen, 2 mg given orally 3 times a day for 30 days. Of the 43 patients treated with danazol for 1 month, (23) 53% responded with a serum α1-antitrypsin concentration ≥ 20% higher than baseline, an average increase of 52% over the pretreatment concentration. Side effects were minimal and reversible but included muscle cramps and hepatic enzyme elevations in 20% of those with ≥ 20% increase in α1-antitrypsin concentrations. Of the 6 patients treated chronically, all maintained their increased α1-antitrypsin concentrations, and none had significant complications. In contrast to danazol, stanazolol therapy for 1 month produced minimal increases in serum α1-antitrypsin concentrations above baseline. These findings suggest that danazol therapy can increase α1-antitrypsin concentrations in a significant proportion of Z homozygous, α1-antitrypsin-deficient patients without major side effects.

Original languageEnglish
Pages (from-to)476-480
Number of pages5
JournalAmerican Review of Respiratory Disease
Issue number3
Publication statusPublished - 19 Nov 1986


ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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