Spironolactone: An increasingly recognized hero in acne therapy

By David A. Wetter, MD
July 1, 2020
Vol. 2, No. 26

In 1983, Bonnie Tyler released the catchy and powerful anthem, “Holding Out for a Hero.” Emotion exudes from the lyrics:

I need a hero
I’m holding out for a hero ‘til the morning light
He’s gotta be sure
And it’s gotta be soon
And he’s gotta be larger than life (1)

These lyrics recently reminded me of a “hero” in dermatology: spironolactone for the treatment of acne in adult women. Anecdotally within the dermatologic community, spironolactone has been a wonderfully effective (and indispensable) acne treatment. Indeed, in my experience spironolactone is a “sure” thing that has become “larger than life” in my acne armamentarium. Yet, for many years evidence-based literature regarding the efficacy of spironolactone has lagged behind our day-to-day experience with spironolactone in the dermatology clinic. Fortunately, there has been a resurgence within the dermatologic literature regarding the beneficial effects of spironolactone in the treatment of adult acne in women. (2-6)

During the COVID-19 pandemic, like many institutions, Mayo Clinic has been performing an increasing amount of teledermatology consultations. Last week, I had a teledermatology consultation of a 22-year-old woman with a recalcitrant dermatitic facial eruption. During our video interaction, I noted that the patient had an unrelated eruption of the lower face and chin compatible with hormonally related acne. When I inquired about this, she confirmed that her acne worsened around the time of her menses and often was painful and bothersome. She was currently taking an oral contraceptive pill (OCP) but was not on any other acne treatment; upon further questioning she expressed interest in other treatment options for her acne. She was thankful that I asked about her acne, even though this was not the reason for her consultation. I informed her about spironolactone and she was excited to learn more, particularly after I mentioned that we had recently published a paper demonstrating excellent results in the treatment of adult acne with spironolactone. (7) Using the data from our publication, I was able to provide her with clinically-relevant information about the drug. She agreed to taking spironolactone (100 mg daily) and planned a return visit in 3 months. Even though her facial dermatitis was the impetus for the video consultation, spironolactone became the anticipated “hero” of the visit!

Over the last decade, experiences like these prompted me to spearhead a retrospective review of our Mayo Clinic experience regarding spironolactone for the treatment of adult female acne. I was fortunate to collaborate with my superb colleagues, notably Erin Roberts, MD (one of our graduating senior dermatology residents) and Somaira Nowsheen (soon to be receiving her MD and PhD degrees). This study analyzed data of 395 adult women (age ≥21years; median age, 32) with acne that was treated with spironolactone at Mayo Clinic in Rochester, Minnesota, from 2007 through 2017. Inclusion criteria for the study were (1) diagnosis of acne by a dermatologist, (2) treatment with spironolactone for at least 3 months, and (3) dermatologic follow-up for at least 3 months after initiation of spironolactone. The 4-grade European classification system was used to assess the severity of acne. (8) Approximately 75% of patients had acne unresponsive to other oral treatments prior to spironolactone administration.

Several “clinical pearls” emerged from this article which can be used with patients to decide whether spironolactone may be helpful for their acne:

• Two-thirds of patients (66.1%) experienced a complete response (CR) .

• About 6 out of every 7 patients (85.1%) experienced either a CR or a partial response greater than 50% (PR>50) .

• Acne of all severity responded to spironolactone; for those with grade 4 acne, nearly two-thirds (64.6%) experienced CR and an additional 18.3% had PR>50 .

• Median effective dosage was 100 mg daily (maximum dose, 200 mg daily) .

• Median time to initial response was 3 months .

• Median time to maximal response was 5 months. (Thus, in order to avoid premature discontinuation of spironolactone, it is important to counsel patients about how long it usually takes to see an initial and maximal response.)

• Spironolactone appeared to be effective as “monotherapy,” as 327 of the 395 patients (82.8%) were classified as receiving spironolactone monotherapy. (For the study, “monotherapy” was defined as no concomitant oral acne treatments; for patients taking a concomitant OCP, they were considered to be on spironolactone “monotherapy” if the OCP was started greater than 6 months before spironolactone.)

• Median treatment duration was 13 months (range, 3-132 months) — allows us to counsel patients that it is safe to stay on spironolactone for a long duration, if needed.

• Spironolactone was well tolerated. About 9 out of every 10 patients (89.6%) had no side effects from spironolactone; only 1 out of every 16 patients (6.3%) discontinued spironolactone because of adverse effects (dizziness, menstrual irregularity, fatigue, headaches, lightheadedness, or increase in urinary frequency) .

Despite its retrospective design, Roberts et al (7) strongly suggest that spironolactone is an effective and safe treatment for adult female acne in real-world clinical practice. Spironolactone has become established as an important long-term treatment option for adult women with acne, especially as dermatologists are looking for safe ways to mitigate the chronic use of oral antibiotics in acne. (9) For the sake of our patients who are struggling with acne, hopefully the findings of Roberts et al spur prospective studies to corroborate these conclusions.

Point to Remember: In the unsettling times of the COVID-19 pandemic, we need commonplace dermatologic “heroes” to inspire us. Given its efficacy and tolerability in the treatment of adult female acne, spironolactone is well-positioned to be a “hero” the entire dermatologic community can rally behind!

Our expert's viewpoint

John S. Barbieri, MD, MBA
Research Fellow, Department of Dermatology
University of Pennsylvania Perelman School of Medicine

Shining a spotlight on spironolactone

Dr. Wetter highlights many key aspects about the potential benefits of spironolactone as an effective treatment for women with acne and the cited study by Roberts and colleagues adds to the growing list of case series describing its effectiveness. Two recent studies have also supported that for young, healthy women taking spironolactone for acne, potassium monitoring is of low value. (10, 11) Although it is always important to individualize treatment regimens to the specific needs of the patient, spironolactone is a great medication to have in our armamentarium to help our patients achieve clear skin. (12)

Notably, in a 2019 survey of acne patients and their parents, nearly 75% responded that they would prefer an effective, antibiotic-free prescription rather than an oral antibiotic for acne. However, only 32% of antibiotic users in the survey responded that they were aware of non-antibiotic treatments, such as spironolactone. (13) In addition, while use of spironolactone has been increasing, oral antibiotics are still prescribed 3 to 5 times more often than spironolactone for women with acne. (14) As a result, it is likely that spironolactone may be underutilized, particularly among non-dermatologists. Although the study by Roberts et al. provides helpful evidence to support the use of spironolactone for women with acne, there is a need for prospective, randomized trials to evaluate both the effectiveness of spironolactone as well as how spironolactone compares to other treatment options such as oral antibiotics.

In the setting of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there has been recent discussion about the safety of spironolactone. Since angiotensin-converting enzyme 2 (ACE2) has been shown to be a co-receptor for SARS-CoV-2 entry into cells, there have been concerns that medications which influence the renin–angiotensin–aldosterone system, such as angiotensin-converting enzyme inhibitors and spironolactone, could result in increased ACE2 expression and thus increased susceptibility to SARS-CoV-2. However, for spironolactone, empirically it may be the case that it instead decreases ACE2 expression. (15) In addition, there is no clinical evidence to suggest that antihypertensive medications or spironolactone have a meaningful negative effect with respect to SARS-CoV-2 and guidance from the American Academy of Dermatology recommends continuing spironolactone for patients who are currently on treatment or indications in which spironolactone is known to be beneficial (16, 17, 18).

1. http:/www.google.com. Source: LyricFind. Accessed April 16, 2020.

2. Park JH, Bienenfeld A, Orlow SJ, Nagler AR. The use of hormonal antiandrogen therapy in female patients with acne: a 10-year retrospective study. Am J Clin Dermatol 2018;17:632-638.

3. Barbieri JS, Choi JK, Mitra N, Margolis DJ. Frequency of treatment switching for spironolactone compared to oral tetracycline-class antibiotics for women with acne: a retrospective cohort study 2010-2016. J Drugs Dermatol 2018;17:632-638.

4. Isvy-Joubert A, Nguyen JM, Gaultier et al. Adult female acne treated with spironolactone: a retrospective data review of 70 cases. Eur J Dermatol 2017;27:393-398.

5. Grandhi R, Alikhan A. Spironolactone for the treatment of acne: a 4-year retrospective study. Dermatology 2017;233:141-144.

6. Charny JW, Choi JK, James WD. Spironolactone for the treatment of acne in women, a retrospective study of 110 patients. Int J Womens Dermatol 2017;3:111-115.

7. Roberts EE, Nowsheen S, Davis MDP et al. Treatment of acne with spironolactone: a retrospective review of 395 adult patients at Mayo Clinic, 2007-2017. J Eur Acad Dermatol Venereol 2020 Feb 20. [Epub ahead of print]

8. Nast A, Dreno B, Bettoli V et al. European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version. J Eur Acad Dermatol Venereol 2016;30:1261-1268.

9. Zaenglein AL, Pathy AL, Schlosser BJ et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-973.e33.

10. Plovanich M, Weng QY, Mostaghimi A. Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne. JAMA Dermatol. 2015;151(9):941-944.

11. Thiede RM, Rastogi S, Nardone B, et al. Hyperkalemia in women with acne exposed to oral spironolactone: A retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program. Int J Womens Dermatol. 2019;5(3):155-157.

12. Barbieri JS, Spaccarelli N, Margolis DJ, James WD. Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments. J Am Acad Dermatol. October 2018.

13. Del Rosso JQ, Rosen T, Palceski D, Rueda MJ. Patient Awareness of Antimicrobial Resistance and Antibiotic Use in Acne Vulgaris. J Clin Aesthetic Dermatol. 2019;12(6):30-41.

14. Barbieri JS, James WD, Margolis DJ. Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004-2013. J Am Acad Dermatol. 2017;77(3):456-463.e4.

15. Stoll D, Yokota R, Sanches Aragão D, Casarini DE. Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1-7)/MAS receptor axes in human mesangial cells. Physiol Rep. 2019;7(11):e14105. doi:10.14814/phy2.14105.

16. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19 [published online ahead of print, 2020 May 1]. N Engl J Med. 2020;10.1056/NEJMoa2008975. doi:10.1056/NEJMoa2008975.

17. Guidance on the use of immunosuppressive agents. https://www.aad.org/member/practice/coronavirus/clinical-guidance/biologics.

18. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19 [published online ahead of print, 2020 May 1]. N Engl J Med. 2020;NEJMoa2006923. doi:10.1056/NEJMoa2006923

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