Endocrine Effects of Spironolactone in Man

Abstract

A double blind, controlled study was carried out in order to investigate the effects of administering spironolactone, 200 mg daily, to five healthy male volunteers. The patterns of change in plasma testosterone (T) and luteinizing hormone (LH) after spironolactone were significantly different from placebo and there were significant increases in the urinary excretion of androsterone (A), aetiocholanolone (EC) and total oestrogen. Urinary dehydroepiandrosterone (DHA) excretion, after an initial rise, declined progressively during the treatment period relative to controls. The results are discussed in the light of previous observations. It is concluded that treatment with spironolactone for 2--4 days will lead to a transient rise in plasma T and urinary DHA. Continued treatment (4--10 days) is thought to cause increased LH secretion, with normalization of plasma T and DHA excretion. These changes are accompanied by increased androgen catabolism and a slightly increased conversion of androgens to oestrogens. Healthy men may therefore show alterations in sex steroid metabolism if treated for several days with high doses of spironolactone.

The Influence of Hormones and Pharmaceutical Agents on DHEA and DHEA‐S Concentrations: A Review of Clinical Studies

“…Spironolactone has been reported to ameliorate hirsutism and decrease serum DHEA-S concentrations in women. 92 In healthy men 93 and in men with prostatic carcinoma, 94 it decreased concentrations of DHEA as well as testosterone and androstenedione. Other studies have not shown changes in DHEA and/or DHEA-S concentrations, potentially because of small sample size, 95,96 or the previous administration of dexamethasone to decrease steroid concentrations.…”

In‐vivo Metabolites of Spironolactone and Potassium Canrenoate: Determination of Potential Anti‐androgenic Activity by a Mouse Kidney Cytosol Receptor Assay

“…Since over 80% of administered spironolactone is irreversibly converted to canrenone/canrenoic acid, its much higher anti-androgen activity on radioreceptor assay and bioassay may point to the generation of unidentified, minor metabolites with very high affinity for androgen receptors and/or a very long plasma half-life.Spironolactone is widely used as a potassium-sparing diuretic, although chronic highdose therapy can lead to side effects such as gynaecomastia and menstrual disorders (Stripp et al. 1975;Huffman et al, 1978;Tidd et al, 1978). The pathogenesis of these sideeffects is not completely understood.…”

“…Spironolactone is widely used as a potassium-sparing diuretic, although chronic highdose therapy can lead to side effects such as gynaecomastia and menstrual disorders (Stripp et al. 1975;Huffman et al, 1978;Tidd et al, 1978). The pathogenesis of these sideeffects is not completely understood.…”

“…Spironolactone acts as an androgen antagonist in target tissues (Corvol et id., 1975); it also affects the synthesis (Menard et al, 1974;Abshagen et al, 1977;Baba et al, 1978;Tuck et al, 1981). metabolism (Tidd et al, 1978) and the metabolic clearance of endogenous androgens and/or oestrogens (Rose P t a/., 1977). The anti-androgenic properties of the drug have been used in the treatment of (Address for offprints) Australia.…”

Female Hirsutism: Pathophysiological Considerations and Therapeutic Implications*

“…It retains *a weak progestational activity (183), and, as recent re-"ports suggest, an antiestrogenic effect (184). The administration of S-Fin man results in a number of hormonal changes such as transient rise of plasma total T and urinary DHA, followed by an increase of LH secretion (185). A significant increase in urinary excretion of estrone (Ei) and estriol (E 3 ) and a significant rise in plasma fevels of progesterone and 17-hydroxyprogesterone have 'also been reported (186,187).…”