Spironolactone for Hormonal Acne: Is It Right For Me?
Those of you battling hormonal acne have probably heard of spironolactone. Either it has been recommended to you by a doctor, or you've heard about someone who was on it for their hormonal imbalance.
Although it is not generally considered a primary option in the management of acne in females, a spotlight has recently been placed on the use of this agent for acne treatment.
First developed in 1957, spironolactone is an aldosterone antagonist that was used initially as a potassium-sparing diuretic in the treatment of hypertension and congestive heart failure. The antiandrogenic effects of spironolactone were first discovered when it was being used to treat hypertension in women with concurrent polycystic ovary syndrome (PCOS) and hirsutism.
It has now been used for women with hormonal-pattern acne, defined as primarily inflammatory papules, usually deep-seated and tender, that are located predominantly on the lower half of the face and anterior-lateral neck region. Currently, dermatologists prescribe spironolactone for off-label use, with acne being a non-United States Food and Drug Administration (FDA)-approved indication.
The rationale for using spironolactone in the treatment of acne is that is has been shown to inhibit sebaceous gland activity, as inhibition of sebaceous gland functions leads to reduced formation of acne lesions. Even though the majority of women with late-onset acne do not exhibit an increase in sebum androgen levels, they may still benefit substantially from spironolactone. This is because spironolactone also decreases 5-alpha reductase activity via increased clearance of testosterone, and increases the level of steroid hormone binding globulin (SHBG), reducing circulating free testosterone as more is bound by the increased quantity of SHBG. Spironolactone also acts locally by competing with dihydrotestosterone (DHT) for cutaneous androgen receptors, thereby inhibiting testosterone and DHT binding.
Spironolactone is typically used in doses of 25 to 200mg/day for treatment of acne in women; however, it is important to start with a lower dose and escalate only if needed, depending on the clinical situation.
Although it is not often used initially, spironolactone can be initiated as monotherapy.
It has been shown to be both efficacious and safe in treating acne. At a lower dosage range of 50 to 100mg/day, spironolactone has been shown to reduce sebum excretion rate by 30-50% and improve adverse events. The efficacy of spironolactone has been established by several studies showing improvement, with lesion reductions ranging from 50 -100%.
There is also some promising data to suggest that spironolactone not only improves facial acne, but is efficacious in improving body acne as well. One study of adult women on 75 to 150mg of spironolactone daily, over a mean treatment duration of 17 months, reported at least a 50% improvement of facial acne and body acne in 37.5% of the cases. In a 12-week, randomized, placebo-controlled study of spironolactone 50mg daily, 24 of 34 patients were clear of acne lesions as compared to improvement in 2 of 31 patients in the placebo group.
All of this is great. But what about safety?
Is spironolactone safe for long-term use?
There are sufficient data to suggest that long-term use of spironolactone appears to be safe overall. This was revealed in one long-term study with patients who received spironolactone for up to eight years for the treatment of acne. Although 60% of patients experienced some side effects (lightheadedness, polyuria, gastrointestinal upset), only 15% discontinued medications with no serious adverse events reported. The most common side effects were diuretic effects (29%), menstrual irregularities (22%), and breast tenderness (17%). Although some side effects were relatively common, they were usually not troublesome or severe enough to result in cessation of the drug.
There were no cases of breast carcinoma in this long-term study; however, four patients underwent breast biopsies with benign outcomes. It was unknown if these benign breast lesions were linked to spironolactone, or other factors such as diet, genetics or a pre-existing health condition. Regardless, it is recommended that spironolactone be avoided in women with an increased risk for breast cancer or estrogen-related tumors (either through personal or family history). The concerns stemmed from a report of breast tumors in rodents, with no proven association noted in humans. The potential for spironolactone-related breast cancer was also raised in 1975 after a case report of breast carcinoma that occurred in five women who were concurrently using several medications, including spironolactone. Another study of 1,475 individuals prescribed spironolactone and followed for 3 to 7 years reported nine cases of breast cancer compared with an age-specific rate of 8.3 cases. So the effects, if any, seem negligible. The data suggests that there is no definitive documented association between breast carcinoma and spironolactone ingestion after more than 30 years of spironolactone availability in the marketplace.
Overall, spironolactone as a monotherapy or in combination with other agents is well tolerated if properly dosed and adjusted and has been shown to be beneficial for women with acne, especially in those exhibiting the hormonal pattern clinically.
In conclusion, data from medical literature, clinical experience over many years support that, overall, spironolactone is a safe and efficacious therapy for adult women with acne in many clinical circumstances.