The medication reportedly has no birth control effect.It has been suggested that the weak progestogenic activity of spironolactone is responsible for these effects, although this has not been established and spironolactone has been shown to possess insignificant progestogenic and antiprogestogenic activity even at high dosages in women. An alternative proposed cause is inhibition of 17α-hydroxylase and hence sex steroid metabolism by spironolactone and consequent changes in sex hormone levels. Indeed, CYP17A1 genotype is associated with polymenorrhea. Regardless of their mechanism, the menstrual disturbances associated with spironolactone can usually be controlled well by concomitant treatment with a birth control pill, due to the progestin component. Mood changes
Research is mixed on whether antimineralocorticoids like spironolactone have positive or negative effects on mood. In any case, it is possible that spironolactone might have the capacity to increase the risk of depressive symptoms. However, a 2017 hybrid systematic review found that the incidence of depression in women treated with spironolactone for acne was less than 1%. Likewise, a 10-year observational study found that the incidence of depression in 196 transgender women taking high-dose spironolactone in combination with an estrogen was less than 1%. Rare reactions
Aside from hyperkalemia, spironolactone may rarely cause adverse reactions such as anaphylaxis, kidney failure, hepatitis (two reported cases, neither serious), agranulocytosis, DRESS syndrome, Stevens–Johnson syndrome or toxic epidermal necrolysis. Five cases of breast cancer in patients who took spironolactone for prolonged periods of time have been reported. Spironolactone bodies
Long-term administration of spironolactone gives the histologic characteristic of "spironolactone bodies" in the adrenal cortex.
Current recommendations from the American Heart Association are to use spironolactone in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%.In a randomized evaluation which studied people with severe congestive heart failure, people treated with spironolactone were found to have a relative risk of death of 0.70 or an overall 30% relative risk reduction compared to the placebo group, indicating a significant death and morbidity benefit of the medication. People in the studys intervention arm also had fewer symptoms of heart failure and were hospitalized less frequently. Likewise, it has shown benefit for and is recommended in patients who recently had a heart attack and have an ejection fraction less than 40%, who develop symptoms consistent with heart failure, or have a history of diabetes mellitus. Spironolactone should be considered a good add-on agent, particularly in those patients "not" yet optimized on ACE inhibitors and beta-blockers. Of note, a recent randomized, double-blinded study of spironolactone in patients with symptomatic heart failure with "preserved" ejection fraction (i.e. >45%) found no reduction in death from cardiovascular events, aborted cardiac arrest, or hospitalizations when spironolactone was compared to placebo.It is recommended that alternatives to spironolactone be considered if serum creatinine is greater than 2.5 mg/dL (221 μmol/L) in males or greater than 2 mg/dL (176.8 μmol/L) in females, if glomerular filtration rate is below 30 mL/min or with a serum potassium of greater than 5.0 mEq/L given the potential for adverse events detailed elsewhere in this article.