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[30] [70] [71] [72] Although spironolactone is said to be a relatively weak inhibitor of 17α-hydroxylase and 17,20-lyase, [73] [30] at least compared to more potent steroidogenesis inhibitors like ketoconazole and abiraterone acetate (which can reduce testosterone concentrations to castrate levels), this action may contribute to a significant ...
At very high doses (400 mg/day), spironolactone has also been associated with testicular atrophy and reversibly reduced fertility, including semen abnormalities such as decreased sperm count and motility in cis men. [110] [111] However, such doses of spironolactone are rarely used clinically. [111]
Due to its progestogenic (and by extension antigonadotropic) activity, CPA is able to suppress circulating testosterone levels by 70 to 80% in men at high dosages. [ 25 ] [ 94 ] In contrast, NSAAs increase testosterone levels by up to 2-fold via blockade of the AR , a difference that is due to their lack of concomitant antigonadotropic action ...
Eplerenone may have a lower incidence than spironolactone of sexual side effects such as feminization, gynecomastia, impotence, low sex drive and reduction of size of male genitalia. [18] This is because other antimineralocorticoids have structural elements of the progesterone molecule, causing progestogenic and antiandrogenic outcomes. [ 4 ]
The trial was stopped early because the beneficial effect of spironolactone on all-cause death exceeded the prespecified discontinuation requirements. Spironolactone reduced the risk of death by 30% compared to placebo. Additionally, there was a 35% reduction in the risk of hospitalization for worsening heart failure in the spironolactone group.
Canrenone is an active metabolite of spironolactone, canrenoic acid, and potassium canrenoate, and is considered to be partially responsible for their effects. [9] It has been found to have approximately 10 to 25% of the potassium-sparing diuretic effect of spironolactone, [ 16 ] whereas another metabolite, 7α-thiomethylspironolactone (7α-TMS ...
Spironolactone is a prodrug with a short terminal half-life of 1.4 hours. [5] [6] [7] The active metabolites of spironolactone have extended terminal half-lives of 13.8 hours for 7α-TMS, 15.0 hours for 6β-OH-7α-TMS, and 16.5 hours for canrenone, and accordingly, these metabolites are responsible for the therapeutic effects of the drug. [5] [6]
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