Does Spironolactone Increase Cancer Risk?

Emma asked

I have been taking 75mgs of Spironolactone daily for acne treatment. However, recently I stumbled upon an online article that associated the usage of Spironolactone with growth of tumor in rodents. Needless to say, this worried me. I am wondering if my concern is reasonable or should I disregard it? Also, are there any major risks/side effects associated with Spironolactone that I should be on the look out for? Thank you.

Answer

Aldactone (spironolactone) is a potassium-sparing diuretic and is used for a variety of indications including:

• Heart failure
• Edema
• Acne (off label)
• Excess hair growth (off label)
• Ascites
• Low potassium (i.e. hypokalemia)

Spironolactone has a complex mechanism of action, with effects in many areas of the body. It works mainly by inhibiting the effects of aldosterone on the renal tubules which has the following effects:

• Enhances sodium, chloride, and water excretion
• Reduces the excretion of potassium, ammonium, and phosphate

Spironolactone also acts as an androgen receptor blocker, blocking the effects of the hormones aldosterone and testosterone. Spironolactone can interfere with steroid synthesis.

Due to the effect of spironolactone on steroid hormones in the body, there has been long standing concern that it may affect cancer rates in individuals taking the medication.  There have been anecdotal reports of breast cancer as well. Adding to the concern is the fact that spironolactone is a known tumorigen (i.e. causing tumors) based on toxicity studies in rats.

Spironolactone And Tumor Risk In Humans

Studies in rats have shown that spironolactone is associated with an increased risk of tumor growth, especially on endocrine organs (such as the thyroid) and the liver. However, human studies have continually reported results that spironolactone does not increase cancer risk in humans.

One study concluded the following:

"With respect to breast, uterus, ovarian and cervical cancer, there is no evidence of increased risk with spironolactone or furosemide use"

Another study, investigating prostate cancer risk, found similar results:

"In this study, spironolactone use was associated with a lower incidence of prostate cancer, the most common cancer in men in the UK."

Yet another, study looking into breast cancer rates, reported the following:

"These data suggest that the long term management of cardiovascular conditions with spironolactone does not increase the risk of breast cancer in women older than 55 years with no history of the disease.

"After a mean follow-up of 4 years, both the exposed and unexposed cohorts had unadjusted breast cancer annual incidence rates of 0.4%. Both adjustment for risk factors and subgroup analyses confirmed no excess risk for breast cancer."

So, while rat studies have shown an increased tumor risk, human studies have not. Nevertheless, it would be difficult to make a conclusive statement regarding cancer risk with spironolactone as more studies certainly need to be done that take into account as many factors as possible.

Spironolactone Side Effects

As spironolactone has a wide range of effects on the body, it also has a long list of potential side effects, although serious ones are rare. The most common side effects include:

• Increased urination frequency
• Sedation
• Dizziness
• Nausea
• Diarrea
• Muscle cramps

Serious, but rare side effects include:

• Male gynecomastia (due to effects on testosterone)
• Hyperkalemia (high potassium), which could cause fatigue and cardiac problems
• Menstrual cycle changes (e.g. breakthrough bleeding)
• Loss of libido

Summary

• Spironolactone is associated with increased tumor risk in rat studies.

• Human studies however, have failed to show increased cancer rates with spironolactone.