Shelton and Rajfer (2012) noted that androgen deficiency in aging men is common, and the potential sequelae are numerous. In addition to low libido, erectile dysfunction, decreased bone density, depressed mood, and decline in cognition, studies suggest strong correlations between low testosterone, obesity, and the metabolic syndrome. Because causation and its directionality remain uncertain, the functional and cardiovascular risks associated with androgen deficiency have led to intense investigation of testosterone replacement therapy in older men. Although promising, evidence for definitive benefit or detriment is not conclusive, and treatment of LOH is complicated.
Until more is known, caution is advised in the use of danazol in the presence of known or suspected malignant disease (see also contraindications). Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment. In the event of virilisation, Danazol should be withdrawn. Whilst androgenic reactions will generally prove reversible, continued use of danazol in the face of evident virilisation is likely to cause irreversible androgenic effects.
A 2016 phase 1–2 prospective study orally administered 800 mg per day to 27 patients with telomere diseases. The primary efficacy endpoint was a 20% reduction in the annual rate of telomere attrition measured. Toxic effects formed the primary safety endpoint. The study was halted early, after telomere attrition was reduced in all 12 patients who could be evaluated. 12 of 27 patients achieved the primary efficacy end point, 11 of whom increased telomere length at 24 months. Hematologic responses (secondary efficacy endpoint) occurred in 10 of 12 patients who could be evaluated at 24 months. Elevated liver-enzyme levels and muscle cramps (known adverse effects) of grade 2 or less occurred in 41% and 33% of the patients, respectively.