Danazol-induced augmentation of serum alpha 1-antitrypsin levels in individuals with marked deficiency of this antiprotease.

Gadek JE; Fulmer JD; Gelfand JA; Frank MM; Petty TL; Crystal RG

doi:10.1172/jci109838

Danazol-induced augmentation of serum alpha 1-antitrypsin levels in individuals with marked deficiency of this antiprotease.

Gadek JE, Fulmer JD, Gelfand JA, Frank MM, Petty TL, Crystal RG

The Journal of clinical investigation · 1980 · doi:10.1172/jci109838 · PMID:6967489 · PMC371508

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Danazol significantly increased serum alpha1-antitrypsin levels and trypsin inhibition in patients with severe deficiency, though the study does not relate to endometriosis or adenomyosis.

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This study investigated whether danazol could elevate serum alpha 1-antitrypsin levels in individuals with severe deficiency of this antiprotease, a condition linked to accelerated emphysema. Seven patients with alpha 1-antitrypsin deficiency received 600 mg of danazol daily for thirty days, resulting in significant increases in serum alpha 1-antitrypsin antigen and trypsin inhibition capacity among most participants. The researchers noted that while the increases were statistically significant, the clinical relevance regarding lung disease progression remained speculative at the time of publication. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Individuals with serum alpha1-antitrypsin levels below 80 mg/dl are clearly at risk for the development of accelerated panacinar emphysema. One possible approach to the therapy of this disorder would be to raise serum levels of this major antiprotease to establish protease-antiprotease homeostasis within the lung parenchyma. Because danazol, an impeded androgen, elevates levels of C1 inhibitor in patients deficient of that serum antiprotease, we hypothesized that this agent might also increase alpha1-antitrypsin levels in patients with alpha1-antitrypsin deficiency. To evaluate this concept, seven patients with severe emphysema associated with alpha1-antitrypsin deficiency (six PiZ and 1 M(Duarte)Z) and one asymptomatic individual (PiSZ) received 600 mg of danazol daily for 30 d. Five of the six PiZ patients responded to danazol therapy with significant increases in serum alpha1-antitrypsin levels (mean increase of 37%; P < 0.03). The two individuals who were heterozygous for the Z protein increased their serum levels by 85% (PiM(Duarte)Z) and 87% (PiSZ), respectively. These increases in serum alpha1-antitrypsin antigen were accompanied by commensurate increases in serum trypsin inhibition. Crossed immunoelectrophoresis showed no alterations of the microheterogeneity of the alpha1-antitrypsin or the presence of protease-antiprotease complexes in serum during danazol therapy. These data demonstrate that serum alpha1-antitrypsin levels can be augmented by danazol therapy in PiZ individuals as well as those heterozygotes with severe deficiency of alpha1-antitrypsin. The clinical relevance of these increases in serum alpha1-antitrypsin remains speculative, but these findings suggest that danazol may provide a means of improving the protease-antiprotease balance in these individuals and thus impede the progression of their lung disease.

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Advertisement Research Article Free access | 10.1172/JCI109838 Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Gadek, J. in: PubMed | Google Scholar Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Fulmer, J. in: PubMed | Google Scholar Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Gelfand, J. in: PubMed | Google Scholar Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Frank, M. in: PubMed | Google Scholar Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Petty, T. in: PubMed | Google Scholar Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20205 Find articles by Crystal, R. in: PubMed | Google Scholar Published July 1, 1980 - More info Published in Volume 66, Issue 1 on July 1, 1980 J Clin Invest. 1980;66(1):82–87. https://doi.org/10.1172/JCI109838. © 1980 The American Society for Clinical Investigation J Clin Invest. 1980;66(1):82–87. https://doi.org/10.1172/JCI109838. © 1980 The American Society for Clinical Investigation Published July 1, 1980 - Version history - Abstract Individuals with serum α1-antitrypsin levels below 80 mg/dl are clearly at risk for the development of accelerated panacinar emphysema. One possible approach to the therapy of this disorder would be to raise serum levels of this major antiprotease to establish protease-antiprotease homeostasis within the lung parenchyma. Because danazol, an impeded androgen, elevates levels of C1 inhibitor in patients deficient of that serum antiprotease, we hypothesized that this agent might also increase α1-antitrypsin levels in patients with α1-antitrypsin deficiency. To evaluate this concept, seven patients with severe emphysema associated with α1-antitrypsin deficiency (six PiZ and 1 MDuarteZ) and one asymptomatic individual (PiSZ) received 600 mg of danazol daily for 30 d. Five of the six PiZ patients responded to danazol therapy with significant increases in serum α1-antitrypsin levels (mean increase of 37%; P < 0.03). The two individuals who were heterozygous for the Z protein increased their serum levels by 85% (PiMDuarteZ) and 87% (PiSZ), respectively. These increases in serum α1-antitrypsin antigen were accompanied by commensurate increases in serum trypsin inhibition. Crossed immunoelectrophoresis showed no alterations of the microheterogeneity of the α1-antitrypsin or the presence of protease-antiprotease complexes in serum during danazol therapy. These data demonstrate that serum α1-antitrypsin levels can be augmented by danazol therapy in PiZ individuals as well as those heterozygotes with severe deficiency of α1-antitrypsin. The clinical relevance of these increases in serum α1-antitrypsin remains speculative, but these findings suggest that danazol may provide a means of improving the protease-antiprotease balance in these individuals and thus impede the progression of their lung disease. Images. - Version history - Version 1 (July 1, 1980): No description Advertisement Advertisement Copyright © 2026 American Society for Clinical Investigation ISSN: 0021-9738 (print), 1558-8238 (online)

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