Lack of endocrine systemic side effects after topical application of spironolactone in man

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Abstract
In six healthy male volunteers, the percutaneous absorption of spironolactone was compared with placebo in a double-blind crossover study. The subjects were randomly given either a cream containing 5% spironolactone or placebo to be applied in a randomized sequential way to a well defined skin area equivalent to 55% of body area. During the 72 h following the application of the ointment, blood levels of canrenone, the major metabolite of spironolactone, have been determined. In order to estimate the systemic antiandrogenic effect of spironolactone, plasma levels of 17-α-Hydroxy progesterone (17α-OH-P), Testosterone (pT) and non-conjugated 3α-Androstanediol (3α-diol, metabolite of the active androgen 5α-Dihydrotestosterone or DHT) as well as salivary Testosterone (sT) which relate to the free and active plasma testosterone fraction have also been measured. Urinary levels of canrenone have been determined 48 hours after cream application. No changes in any levels of these hormones have been detected and plasma canrenone levels were undetectable during the 72 hours of topical treatment. Topically administered, spironolactone appears to have only a local skin impregnation.