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

An inherited deficiency of alpha 1-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 alpha 1-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 alpha 1-antitrypsin, one therapeutic approach to increase plasma and hence lung alpha 1-antitrypsin concentrations is to enhance hepatic release or production of alpha 1-antitrypsin. In a preliminary trial with 6 alpha 1-antitrypsin-deficient subjects, we have previously shown that in 1 month, the impeded androgen danazol can augment serum alpha 1-antitrypsin concentrations by 37%. To evaluate the use of impeded androgens in alpha 1-antitrypsin deficiency on a broader scale, we have treated: 43 homozygous Z patients with danazol 200 mg given orally 3 times a day for 30 days; 6 homozygous Z patients with a similar danazol dose but given for 6 to 18 months; and 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 alpha 1-antitrypsin concentration greater than or equal to 20% higher than baseline, an average increase of 52% over the pretreatment concentration.(ABSTRACT TRUNCATED AT 250 WORDS)