740 Research Letters
SEPTEMBER 2021
Correspondence to: Matan Rothschild, MD,
Department of Internal Medicine, Froedtert
Hospital and Medical College of Wisconsin,
87701 W Watertown Plank Rd, Milwaukee, WI
53226
E-mail: rothschildmatan@hotmail.com
REFERENCES
1. Montagna W, Carlisle K. Structural changes in aging human
skin. J Invest Dermatol. 1979;73:47-53.
2. Rittie L, Fisher GJ. Natural and sun-induced aging of human
skin. Cold Spring Harb Perspect Med. 2015;5:a015370.
3. Lovell CR, Smolenski KA, Duance VC, Light ND, Young S,
Dyson M. Type I and III collagen content and fibre distribution
in normal human skin during ageing. Br J Dermatol. 1987;117:
419-428.
https://doi.org/10.1016/j.jaad.2019.07.101
High-dose spironolactone for acne
in patients with polycystic ovarian
syndrome: A single-institution
retrospective study
Polycystic ovary syndrome (PCOS) affects up to 10%
of women of reproductive age and often presents
with cutaneous manifestations of hyperandrogen-
ism, including acne, hirsutism, and androgenic
alopecia.1 Barbieri et al2 showed superior
long-term drug use survival with spironolactone
versus oral antibiotics in patients with acne. We
present our experience using spironolactone to treat
acne in a multidisciplinary PCOS clinic at an
academic tertiary care center.
Our analysis included patients who had at least
2 visits with a dermatologist between 2010 and
2019 for acne and were prescribed spironolactone.
Baseline visit was defined as the first visit at
which a patient had active acne lesions.
Physician-assessed acne severity was characterized
as mild if comedonal, moderate if papular or
pustular, and severe if nodular or cystic. The
Global Acne Grading Scale (GAGS), implemented
in April 2018, was also used to monitor overall
change. All data were analyzed via independent
t test and chi-square test in Stata 15 (StataCorp,
College Station, Tx).
Overall, 59 patients taking spironolactone for
acne were analyzed; baseline characteristics are
summarized in Table I. Of these, 52 (88.1%) were
taking spironolactone without oral antibiotics, and
7 (11.9%) were receiving combination therapy
(Table II). More than 85% of all patients were using
oral contraceptives and topical treatments (benzoyl
J AM ACAD DERMATOL
Table I. Baseline characteristics of the study
population (N ¼ 59)
Characteristics Value
Acne onset age in years, mean (SD) 20.2 (2.9)
Body mass index in kg/m2, mean (SD) 34.0 (1.0)
Current metformin use, n (%) 5 (8.5%)
PCOS diagnosis age in years, mean (SD) 24.4 (1.2)
Rotterdam criteria met,* n (%) 55 (93.2)
Acne severity at baseline, n (%)
Mild 13 (22.0)
Moderate 42 (71.2)
Severe 4 (6.8)
Follow-up time in days, mean (SD) 557.4 (643.8)
Total visits for acne, mean (SD) 3.5 (2.9)
SD, Standard deviation.
*Two of the following 3 Rotterdam criteria are required for a
diagnosis of PCOS along with exclusion of other etiologies
(congenital adrenal hyperplasia, androgen secreting tumors,
Cushing syndrome, thyroid dysfunction, and hyperprolactinemia).1
 Oligoovulation/anovulation
 Clinical or biochemical hyperandrogenism
 Polycystic ovaries on ultrasonography
peroxide, retinoids, clindamycin). There were 46
(78%) patients with moderate or severe acne
at baseline. Patients taking combination oral
antibiotics and spironolactone had more severe
acne at baseline (P ¼ .026) and at the last recorded
visit (P ¼ .009) than those taking spironolactone
alone. Mean treatment duration with spironolactone
was 408.9 days.
Overall, 24 (41%) patients taking spironolactone
experienced physician-assessed acne improve-
ment (Table II). The mean spironolactone
dose was 143.0 mg/d. Patients who had
physician-assessed acne improvement took a
significantly higher mean dose than those who
did not (166.1 mg vs 130.7 mg, P \.0001). Of the 9
(15.3%) patients for whom 2 or more GAGS scores
were collected, those whose GAGS scores
improved took a significantly higher mean dose
than those whose scores did not (122.2 mg
vs 50.0 mg, P ¼ .001). Of the 9 (15.3%)
patients who discontinued spironolactone therapy
during follow-up, 2 experienced adverse effects,
including lightheadedness and gastrointestinal
disturbances. Two patients (28.6%) taking
combination therapy reported adverse effects
with oral tetracyclines, including gastrointestinal
disturbances and vaginal infection.
Overall, our patients with PCOS with acne taking
spironolactone were younger on average than the
general population of patients with acne taking
J AM ACAD DERMATOL Research Letters 741
VOLUME 85, NUMBER 3

Table II. Combination therapy with oral antibiotics versus spironolactone only for acne treatment in the
study population
Spironolactone with Spironolactone
Characteristic oral antibiotics* (n = 7) only (n = 52) P value
Acne onset age in years, mean (SD) 23.5 (13.9) 18.7 (6.5) .26
Acne severity at baseline, n (%) .026
Mild 0 (0) 13 (25)
Moderate 5 (71) 37 (71)
Severe 2 (29) 2 (4)
Acne severity at last visit, n (%)y .009
Mild 1 (14) 17 (33)
Moderate 4 (57) 21 (40)
Severe 2 (29) 1 (0.02)
Severity improved from baseline to last visit, n (%)y 2 (29) 22 (42) .487
Concurrent topical treatment, n (%)y 7 (100) 47 (90) .35
Concurrent OCP use, n (%)y 6 (86) 44 (85) .82
Follow-up time in days, mean (SD) 399.0 (473.1) 453.1 (622.4) .67

OCP, Oral contraceptive; SD, standard deviation.

*Five patients taking doxycycline, 1 patient taking minocycline, and 1 patient who switched from minocycline to doxycycline.
y
Thirteen patients in the spironolactone-only group had only postinflammatory hyperpigmentation or scarring at last recorded visit.

spironolactone described by Barbieri et al2 (20 vs
27 years). Additionally, combination oral antibiotic
therapy with spironolactone is more often used for
patients with PCOS with acne of higher severity.
Although no studies have compared hormonal
agents with oral antibiotics in patients with PCOS,
guidelines support oral antibiotics as second-line
therapy for short-term adjunctive treatment when
hormonal therapies alone are insufficient.3 Our
preliminary data suggest that spironolactone is well
tolerated and that doses higher than those typically
used in general dermatology practice (#100 mg/d)
are required to observe acne improvement in the
population with PCOS.4,5 Limitations of our study
include its small size, single-center design, and
potential selection bias toward a population with
more severe PCOS due to multidisciplinary
involvement.
Pallavi Basu, MPH,a,b,c Scott A. Elman, MD,c Boya
Abudu, MD,d Ashley Beckles, BS,c Prerna Salian,
BS,c Daniel A. Yanes, MD,c Martina L. Porter,
MD,c and Rachel V. Reynolds, MDc
Reprints not available from the authors.
Correspondence to: Rachel V. Reynolds, MD, 330
Brookline Ave, Boston, MA 02215
E-mail: rreynold@bidmc.harvard.edu
REFERENCES
1. Schmidt TH, Khanijow K, Cedars MI, et al. Cutaneous findings
and systemic associations in women with polycystic ovary
syndrome. JAMA Dermatol. 2016;152:391-398.
2. Barbieri JS, Choi JK, James WD, Margolis DJ. Real-world drug
usage survival of spironolactone versus oral antibiotics for the
management of female patients with acne. J Am Acad
Dermatol. 2019;81(3):848-851.
3. Buzney E, Sheu J, Buzney C, Reynolds RV. Polycystic ovary
syndrome: a review for dermatologists: part II. Treatment. J Am
Acad Dermatol. 2014;71:859.e1-859.e15.
4. Layton AM, Eady EA, Whitehouse H, Del Rosso JQ,
Fedorowicz Z, van Zuuren EJ. Oral spironolactone for acne
vulgaris in adult females: a hybrid systematic review. Am J Clin
Dermatol. 2017;18:169-191.
5. Yemisci A, Gorgulu A, Piskin S. Effects and side-effects of
spironolactone therapy in women with acne. J Eur Acad
Dermatol Venereol. 2005;19:163-166.
https://doi.org/10.1016/j.jaad.2019.07.102

From the Department of Biostatistics, Harvard

School of Public Health, Boston, Massachusettsa;
School of Medicine, University of California San
Diegob; Department of Dermatology, Beth Israel
Deaconess Medical Center, Boston, Massachu-
settsc; Department of Medicine, Kaiser Perma-
nente Oakland Medical Center, California.d
Funding sources: None.
Conflicts of interest: None disclosed.
Incidence of nonmelanoma skin
cancer in the United States
population aged 65 years and older,
2014
To the Editor: Nonmelanoma skin cancer (NMSC) is
the most common malignancy in the United States
(US), with substantial associated morbidity, cost, and
small but significant mortality1; yet, its incidence is