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.
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Corvol P., Michaud A., Menard J., Freifeld M., Mahoudeau J. Antiandrogenic effect of spironolactones: mechanism of action. Endocrinology 97: 52, 1975.
Shapiro G., Evron S. A novel use of spironolactone: treatment of hirsutism. J. Clin. Endocrinol. Metab. 51: 429, 1980.
Cumming D.C., Yang J.C., Rebar R.W, Yen S.S.C. Treatment of hirsutism with spironolactone. JAMA 247: 1295, 1982.
Dorrington-Ward P., McCartney A.C.E., Holland S., Scully J., Carter G., Alaghband-Zadeh J., Wise P. The effect of spironolactone on hirsutism and female androgen metabolism. Clin. Endocrinol. (Oxf.) 23: 161, 1985.
Goodfellow A., Alaghband-Zadeh J., Carter G., Cream J.J., Holland S., Scully J., Wise P. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br. J. Dermatol. 111: 209, 1984.
Caminos-Torres R., Ma L., Snyder P.J. Gynecomastia and semen abnormalities induced by spironolactone in normal men. J. Clin. Endocrinol. Metab. 45: 255, 1977.
Stripp B., Taylor A.A., Bartter F.C., Gillette J.R., Loriaux D.L., Easley R., Menard R.H. Effect of spironolactone on sex hormones in man. J. Clin. Endocrinol. Metab. 41: 777, 1975.
Pentikainen P.J., Pentikainen L.A., Huffman D.H., Azarnoff D.L. The effect of spironolactone on sexual hormones in males. Clin. Res. 21: 472, 1973, (Abstract).
Serafini P.C., Catalino J., Lobo R.A. The effect of spironolactone on genital skin 5α-reductase activity. J. Steroid Biochem. 23: 191, 1985.
Weissmann A., Bowden J., Frank B.L., Horwitz S.N., Frost P. Antiandrogenic effects of topically applied spironolactone on the hamster flank organ. Arch. Dermatol. 121: 57, 1985.
Nielsen P.G. Treatment of moderate idiopathic hirsutism with a cream containing canrenone (an antiandrogen). Dermatologica 165: 636, 1982.
Messina M., Manieri C., Rizzi G., Molinatti G.M. A new therapeutic approach to acne: an antiandrogen percutaneous treatment with spironolactone. Current Ther Res. 34: 319, 1983.
Walton S., Cunliffe W.J., Lookingbill P., Keczkes K. Lack of effect of topical spironolactone on sebum excretion. Br.J. Dermatol 114: 261, 1986.
Krause W., Karras J., Jakobs U. Determination of canrenone, the major metabolite of spironolactone, in plasma and urine by high-performance liquid chromatography. J. Chromatogr. 277: 191, 1983.
Magrini G., Chiodoni G., Rey F., Felber J.P. Further evidence for the usefulness of the salivary testosterone radioimmunoassay in the assessment of androgenicity in man in basal and stimulated conditions. Horm. Res. 23: 65, 1986.
Riad-Fahmy D., Read G.F., Walker R.F., Griffiths K. Steroids in saliva for assessing endocrine function. Endocr. Rev. 3: 367, 1982.
Pugeat M.M., Dunn J.F., Nisula B.C. Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J. Clin. Endocrinol. Metab. 53: 69, 1981.
Dunn J.F., Nisula B.C., Rodbard D. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J. Clin. Endocrinol. Metab. 53: 58, 1981.
Lobo R.A., Shoupe D., Serafini P., Brinton D., Horton R. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. Fertil. Steril. 43: 200, 1985.
Gomez F., Ramelet A.A., Ruedi B., Mühlemann M. Lack of effect of spironolactone-containing cream on hair growth in hirsute women. Dermatologica 174: 102, 1987.
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Rey, F.O., Valterio, C., Locatelli, L. et al. Lack of endocrine systemic side effects after topical application of spironolactone in man. J Endocrinol Invest 11, 273–278 (1988). https://doi.org/10.1007/BF03350151
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DOI: https://doi.org/10.1007/BF03350151