Spironolactone and Topical Retinoids in Adult Female Cyclical Acne

February 2014 | Volume 13 | Issue 2 | Original Article | 126 | Copyright © February 2014

Erin Lessner MD,a Samantha Fisher MD,b Katherina Kobraei MD,b Michael Osleber MD,b Rebecca Lessner BS,c Lauren Elliott MD,d and Stanton Wesson MDb

aDepartment of Ophthalmology, University of South Carolina, Columbia, SC
bDepartment of Dermatology, University of Florida, Gainesville, FL
cLincoln Memorial University, DeBusk School of Medicine, Harrogate, TN
dDepartment of Emergency Medicine, University of California San Diego, San Diego, CA

tumors.26 No cases of breast cancer linked to the use of spironolactone have been reported.27 However, caution should be used when prescribing the medication to women with a personal or family history of breast cancer.21,26

Drug Interactions

Drug interactions with spironolactone center around its actions on its P-glycoprotein inhibition properties and its actions on the kidney as a potassium sparing/sodium wasting diuretic. As a P-glycoprotein modulator, it alters serum concentrations of medications that rely on these proteins for bioavailability such as digoxin.28 Any drug that has a tendency to increase serum potassium such as heparin or trimethoprim, potassium containing medications such as penicillin G, or repeated transfusions with blood products containing potassium salts have been cautioned for use when on spironolactone.29 In addition, medications that are dosed based on serum electrolytes can reach toxic levels, such as lithium, due to increased excretion of sodium. Medications that depend on the serum concentration of potassium, such as warfarin, may be altered when co-administered with spironolactone. When taken with other anti-hypertensives, spironolactone may cause hypotension. Caution must be taken when prescribing spironolactone to patients with renal insufficiency.


Initially, recommendations for spironolactone dosing for acne were similar to the higher doses recommended for hair loss and hirsutism at 150- 200 mg/day.30 Current data suggests that doses of 50mg-100mg/day result in significant improvement comparable to results seen in higher doses; in a recent study, 66% of patients dosed at 50-100mg/day of spironolactone showed marked improvement to complete resolution of acne lesions when compared to the previous studies of higher doses.16 Anti-androgen activity may be augmented without increasing the dose of spironolactone by adding Ethinyl estradiol/ drospirenone (EE/DRSP). Drospirenone is a derivative of 17 alpha spironolactone, which acts as an antagonist at androgen and aldosterone sites. The equivalent to approximately 20- 25mg of spironolactone is 3mg of drospirenone.20,31

Drug Monitoring

Spironolactone does not appear to cause clinically significant elevations in serum potassium levels in healthy patients at acne doses (50-100mg). A study of 35 patients dosed at 100mg/day were monitored for 3 months, serum potassium levels showed no significant deviation from normal range during treatment.32 A recent study evaluating low dose spironolactone (50-100mg) monitored potassium levels in 73 patients, and 13.7% showed mild hyperkalemia ranging from 4.8-5.3; however, these mild elevations were not considered to be clinically significant.16 A study evaluating serum potassium levels in patients on spironolactone and EE/DRSP showed post therapy levels to be on average 4.35 with a range of 3.5-5.3.20


We conducted a retrospective chart review on 41 female adult patients with cyclical acne. Data was collected on 58 patients, however 17 were lost to follow up. The 41 female patients in this study were age 19-57. They were examined over the course of 2 to 102 months while taking 50 to 200mg of spironolactone and topical tretinoin 0.025% cream or adapalene 0.1% cream. The majority of patients had been on their topical retinoid prior to initiation of spironolactone treatment. All patients were prescribed 50-100mg of spironolactone with one patient with acne and alopecia on 200mg daily. All were diagnosed with acne rated mild to severe, prior to treatment, and were started on an initial dose of 50mg po daily. If significant improvement was not seen within the first 3-6 months, the dose was either held or increased in 25mg increments every 3 months. Eleven patients were increased to 75mg, and four patients were increased from 75mg to 100mg. The majority of patients were concurrently treated with tretinoin 0.025% or adapalene 0.1% cream and instructed to apply a thin layer to the face at bedtime. Patients on oral and topical antibiotics, as well as patients on photodynamic therapy were excluded from our study. The response to treatment was rated on a 0-4 scale with 0 being no response and 4 corresponding to clear skin. As shown in graph 1, only one patient (2.4%) had no response to treatment. This patient was only on 50mg po daily and only treated for 2 months. Only 5 (12.2%) patients had minimal response to treatment and 9 (22.0%), 12 (29.3%), and 14 (34.1%) had a good, excellent or clear response respectively. The study showed that 26 (63.4%) of women on treatment with spironolactone and topical retinoids had an excellent or clear outcome, and 35 (85.4%) were considered to have a good, excellent, or clear response. As the majority of patients in our study had been on retinoids prior to the initiation of spironolactone with minimal response, the addition of spironolactone to topical retinoid treatment suggests a superior response to retinoids alone in clearance of female adult cyclical acne.
In our review, there were minimal side effects noted as a result of spironolactone therapy. There was no change in tolerance to topical retinoids in any of the patients as a result of spironolactone treatment. Lightheadedness was reported in one patient (2.4%) on a 50 mg dose that subsided with continuation of treatment. Irregular periods were reported in two patients (4.9%), which occurred with dosages of 200 mg and 50 mg. Orthostatic hypotension was recorded in one patient (2.4%) taking a 50 mg dose. Only one flare (2.4%) was reported in a patient taking 50 mg. There were no severe adverse events in the women on treatment. None of our patients were elderly or had cardiac or renal abnormalities warranting electively following laboratory studies. There were no reports of malignancy in the patients taking spironolactone. This coincides with the lack of reported human malignancy cases to the FDA in the over 50 years spironolactone has been approved for medical use.