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Spironolactone for the treatment of acne in women, a retrospective study of 110 patients

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Spironolactone for the treatment of acne in women, a retrospective study of 110 patients

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Background: There is limited evidence on the safety and efficacy of spironolactone in the treatment of women with acne. Thus, for many dermatologists spironolactone remains an alternative rather than a mainstay treatment for female patients with acne. Methods: An electronic medical records search tool was used to select data from a group of women who received spironolactone to treat acne and were evaluated with the comprehensive acne severity scale (CASS) before treatment and at all follow-up visits. Data points were collected for CASS scores at each follow-up visit, concurrent and previous treatments, and side effects. These data points were used to draw conclusions about the safety and efficacy of spironolactone in this patient population. Results: There were 110 patients that met all eligibility requirements. Of these, 94 patients saw an improvement in their CASS score and 61 patients completely cleared their score to 0. There were 16 patients who did not improve and six who relapsed after initial improvement. The women saw an average improvement in their acne by 73.1% for the face, 75.9% for the chest, and 77.6% for the back. Fifty-one women experienced side effects, but only six found them bothersome enough to stop taking spironolactone. Conclusion: A majority of women in this study saw a dramatic improvement in their acne while treated with spironolactone. There were low rates of relapse or discontinuation of the medication. To further promote the use of spironolactone as a first-line systemic treatment for women with acne, there must be more prospective controlled trials.
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Original Research
Spironolactone for the treatment of acne in women, a retrospective
study of 110 patients
,
☆☆
,
J.W. Charny, BS, J.K. Choi, MD, PhD, W.D. James, MD
Department of Dermatology, University of Pennsylvania, Philadelphia, PA
abstractarticle info
Article history:
Received 10 October 2016
Received in revised form 15 December 2016
Accepted 16 December 2016
Available online xxxx
Keywords:
acne
spironolactone
comprehe nsive acne s everity s cale
CASS
Background: There is limited evidence on the safety and efcacy of spironolactone in the treatment of
women with acne. Thus, for many dermatologists spironolactone remains an alternative rather than a
mainstay treatment for female patients with acne.
Methods: An electronic medical records search tool wasused to select data from a group of women who re-
ceived spironolactoneto treat acne and were evaluated with the comprehensive acne severity scale (CASS)
before treatment and at all follow-up visits. Data points were collected for CASS scores at each follow-up
visit, concurrent and previous treatments, and side effects. These datapoints were used to draw conclusions
about the safety and efcacy of spironolactone in this patient population.
Results: There were 110patients that met all eligibilityrequirements. Of these, 94 patients saw an improve-
ment in their CASS score and 61 patients completely cleared their score to 0. There were 16 patients who
did not improve and six whorelapsed after initial improvement. The women saw an average improvement
in their acne by 73.1% for the face, 75.9%for the chest, and 77.6% for the back. Fifty-onewomen experienced
side effects, but only six found them bothersome enough to stop taking spironolactone.
Conclusion: A majorityof women in this study saw a dramaticimprovement in their acnewhile treated with
spironolactone. There were low rates of relapse or discontinuation of the medication. To further promote
the use of spironolactone as a rst-line systemic treatment for women with acne, there must be more
prospective controlled tri als.
© 2016 The Authors. Published by Elsevier Inc. on behalf of Women's Dermatologic Society. This is an open
access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Introduction
Acne vulgaris is a common, treatable dermatologic disease that can
cause scarring, disgurement, and socio-psychological distress.
Current treatment guidelines generally recommend topical treat-
ments for mild acne or a combination of topical and systemic treat-
ments for moderate-to-severe acne (Zaenglein et al., 2016). Systemic
treatments fall into three groups and each targets a mechanism of
acne pathophysiology: antibiotic medications, hormonal therapy,
and isotretinoin. For women whose acne failed to improve with
topical treatments, hormonal therapies in the form of spironolactone
and/or combined oral contraceptive pills have become an important
treatment strategy.
Spironolactone is a mineralocorticoid receptor antagonist that is
currently indicated for the treatment of primary hyperaldosteronism,
congestive heart failure, cirrhosis, nephrotic syndrome, essential
hypertension, hypokalemia, and edema of pregnancy (FDA, 2014).
The safety of long-term spironolactone use is well established given
that it has been approved by the U.S. Food and Drug Administration
(FDA) since 1960. Furthermore, the groundbreaking Randomized
Aldactone Evaluation Study has shown that spironolactone deni-
tively reduces morbidity and mortality in patients with heart failure
(Pitt et al., 1999). It is also an androgen receptor antagonist and has
been shown to reduce sebum production in vivo (Goodfellow et al.,
1984), leading to an increase in off-label usage for the treatment of
hyperandrogenism. Because androgens mediate increased sebum
production, they have been implicated in the pathophysiology of
acne (Zouboulis et al., 1994), which led to the current acceptance of
spironolactone as a non-antibiotic alternative to traditional systemic
treatments for women with acne.
International Journal of Women's Dermatology xxx (2016) xxxxxx
Conicts of interest: None.
☆☆ Funding sources: This research did not receive any specic grant from funding
agencies in the public, commercial, or not-for-prot sectors.
Submission declaration: Thiswork has not beenpublished previously, is notunder
consideration for publication elsewhere, and is approved by all authors. If accepted, it
will not bepublished elsewhereincluding electronicallyin the same form, in Englishor
in any other language, without the written consent of the copyright-holder.
Corresponding Author.
E-mail address: william.james@uphs.upenn.edu (W.D. James).
http://dx.doi.org/10.1016/j.ijwd.2016.12.002
2352-6475/© 20 16 The Authors. Published by Elsevier Inc. on behalf of Women's Dermatologic Society. Thi s is an open access article under th e CC BY license (http://
creativecommons.org/licenses/by/4.0/).
Contents lists available at ScienceDirect
International Journal of Women's Dermatology
Please cite this article as: Charny JW, et al, Spironolactone for the treatment of acne in women, a retrospective study of 110 patients, Inter-
national Journal of Women's Dermatology (2016), http://dx.doi.org/10.1016/j.ijwd.2016.12.002
Spironolactone is generally well tolerated in women and its poten-
tially most worrisome side effects, hyperkalemia and increased risk of
cancer, are not sufciently supported by evidence. Common side
effects of long-term use of spironolactone during treatment for acne
include irregular menstruation, urinary frequency, dizziness, head-
aches, nausea, vomiting, breast tenderness, and breast enlargement
(Shaw and White, 2002). Male patients who take spironolactone
often experience gynecomastia, loss of libido, and general feminiza-
tion that results in the termination of treatment (Hughes and Cunliffe,
1988). Therefore, men are generally not prescribed spironolactone for
the treatment of acne.
Because of its anti-androgenic effects, spironolactone has been
hypothesized to be associated with an increased risk of estrogen-
sensitive cancers but there is currently no evidence to support
this in human subjects (Biggar et al., 2013; Mackenzie et al., 2012).
Additionally, a recent study investigated hyperkalemia as a potential
complication of this potassium-sparing diuretic in healthy young
women with acne who are the typical demographic for off-label
spironolactone use (Plovanich et al., 2015). With the exclusion
of women with heart failure or kidney disease, this study showed
that serum potassium levels were not found to be elevated above
those of the controls and it was concluded that routine potassium
monitoring is unnecessary for this relatively young and healthy
cohort. Spironolactone is classied as a Pregnancy Category C drug
due to its association with feminization of male fetuses in animal
studies (FDA, 2014). Without the need for regular blood testing or
the risk of severe teratogenicity, spironolactone is an attractive alter-
native to treatment with isotretinoin.
The safety prole of spironolactone is better established than its
efcacy in the treatment of acne. Since the characterization of its
anti-androgenic effects, there have been two important randomized
placebo-controlled, double blind studies of spironolactone for the
treatment of patients with acne. The studies had only 36 and 21 sub-
jects, respectively, but showed a statistically signicant improvement
in acne (Goodfellow et al., 1984; Muhlemann et al., 1986). A larger
retrospective study showed that 93.4% of 85 patients had some amount
of improvement in their acne when treated with spironolactone
(Shaw, 2000). In an effort to reduce systemic effects, physicians have
also begun testing the efcacy of topical spironolactone gels. One
early study showed that there was no reduction in sebum excretion
(Walton et al., 1986). Recent randomized controlled trials have
shown mixed results in the improvement of acne, which indicates
that topical spironolactone gel is not an effective alternative for sys-
temic spironolactone (Afzali et al., 2012; Kelidari et al., 2016).
Although current evidence demonstrates the effectiveness of oral
spironolactone for the treatment of acne, the studies are too few and
small to prompt FDA approval or a recommendation for use by the
Cochrane Database of Systemic Reviews (Brown et al., 2009). Thus,
for many dermatologists spironolactone remains an alternative rather
than a mainstay treatment for female patients with acne. There is a
need for further research for spironolactone to gain legitimacy as a sys-
temic acne medication. The addition of this larger retrospective study
to the literature will contribute further to the ever-clearer picture of
spironolactone as a safe and effective treatment for patients withacne.
Methods
In recent years, providers at the University of Pennsylvania have
evaluated patients with acne using the comprehensive acne severity
scale (CASS) as an acne grading system. A CASS score of 0 (no or barely
visible acne lesions) to 5 (highly inammatory lesions with nodules
and cysts) is assigned separately for the face, chest, and back on the
basis of the severity of the acne in that area. All patient records at
the University of Pennsylvania Health System were accessed with
PennSeek, an electronic medical record search tool, to select data
from those patients with the terms acne, CASS, and spironolactone
in their medical records. From this group, patients who were over
the age of 12 years, treated with spironolactone for acne after January
1, 2007, and evaluated with CASS scores at both the initial and follow-
up appointments by one of two specic dermatology providers were
selected as eligible for the study.
These patientsmedical records were thoroughly reviewed with
data points inputted into a data collection sheet. The data points
included age, race, height, weight, body mass index (BMI), previous
topical and systemic treatments, CASS scores at the initial and
follow-up visits for the face, chest, and back, spironolactone dose,
side effects, and discontinuation and relapse reasons. Data tables
were constructed to show the percentage of women who discontinued
or relapsed and their reasons, the prevalence of side effects, the fre-
quencies of all prior and concurrent treatments, and the percentage
of women with improvement in both total and body-site specic
CASS. No advanced statistical analysis was performed on the data;
therefore, the collection sheet and tables served as the primary sources
to draw conclusions.
Results
There were 4,621,497 patients in the PennSeek database of
which 464 patients had the terms acne, CASS, and spironolactone in
their medical records. Of these patients, 127 were over the age of
12 years, treated with spironolactone for acne after January 1, 2007,
and evaluated with CASS scores at both the initial and follow-up
appointments by one of two specic dermatology providers. An addi-
tional 17 patients were excluded from the study due to medication
non-compliance (12 patients), running out of medication (4 patients),
or lack of timely follow-up (1 patient). Of the 110 remaining patients,
there were 70 patients (63.6%) who were Caucasian, 7 patients (6.4%)
were African American, 13 patients (11.8%) were Asian, and 10 pa-
tients (9.1%) were of other and 10 (9.1%) of unknown race. The
median age was 27 years and the average BMI was 23.03.
Previous treatments, which were tried both separately and in
combination, included benzoyl peroxide, topical clindamycin, topical
retinoids, intralesional kenalog, systemic antibiotic medications, oral
contraceptive pills, and isotretinoin. Many patients who were already
using topical acne medications or oral contraceptive pills continued
their use while treated with spironolactone. There were 104 patients
who used some form of concurrent therapy while taking
spironolactone, 92 of which were topical medications that were
already used prior to the initiation of spironolactone therapy. Of
these 104 patients, 15 patients were prescribed systemic antibiotic
medications concurrently either as a tapering of existent antibiotic
use or as an adjunct therapy due to a lack of response to treatment
with spironolactone. Thirty-ve patients were taking oral contracep-
tive pills concurrently with spironolactone therapy, 19 of whom were
already taking these although not specically for the treatment of
acne and 16 of whom began taking these as a form of birth control
while treated with spironolactone. The type of oral contraceptive
pill was unknown in 15 patients. Of the remaining 20 patients, 19 pa-
tients took combination estrogen/progesterone pills and 1 patient
took progesterone-only pills.
Of the 110 patients, 94 patients experienced some reduction in
CASS score while treated with spironolactone and 61 patients became
completely clear (i.e., CASS score of 0 on the face, chest, and back). The
time from initial visit to each follow-up visit varied but was on average
4 months to the rst follow-up, 7 months to the second follow-up,
13 months to the third follow-up, and 17 months to the fourth
follow-up visit.
Before treatment, 108 patients had CASS scores that were greater
than 0 on the face. Of these, 86 patients saw a reduction in their CASS
score by the time of their rst follow-up visit, an additional 7 patients
2JW. Charny et al. / International Journal of Women's Dermatology xxx (2016) xxxxxx
Please cite this article as: Charny JW, et al, Spironolactone for the treatment of acne in women, a retrospective study of 110 patients, Inter-
national Journal of Women's Dermatology (2016), http://dx.doi.org/10.1016/j.ijwd.2016.12.002
by the second follow-up visit, and an additional 1 patient by the
fourth follow-up visit (Table 1). Before treatment, 42 patients had a
CASS score that was greater than 0 on the chest. Of these, 31 patients
saw a reduction in their CASS score by the time of their rst follow-up
visit, an additional 2 patients by the second follow-up visit, and an
additional 1 patient by the fourth follow-up visit (Table 2). Before
treatment, 45 patients had a CASS score that was greater than 0 on
the back. Of these, 34 patients saw a reduction in their CASS score
bythetimeoftheirrst follow-up visit, an additional 5 patients
saw a reduction by the second follow-up visit, and anadditional 1 pa-
tient by the fourth follow-up visit (Table 3). There was a 73.1%, 75.9%,
and 77.6% reduction in CASS scores of the face, chest, and back, re-
spectively (Table 4).
Of the 101 patients (92%) who initiated a 100-mg/day dose of
spironolactone, 85 patients showed an initial improvement in their
acne and 40 patients became completely clear when treated with this
dose. Of the remaining patients, an additional 20 patients improved
and 12 patients cleared their acne when treated with 150-mg/day
doses, and 10 patients improved and 3 patients cleared with
200-mg/day doses. Sixteen patients did not experience improvement
when treated with spironolactone and four of these patients
discontinued the medication for this reason. Six patients improved
but later relapsed while treated with spironolactone. Three patients re-
lapsed while tapering their dose of spironolactone due to good initial
improvement, two patients relapsed after completing a treatment
course with good results, and one patient relapsed after receiving a
medroxyprogesterone acetate (Depo-Provera) injection. Concurrent
treatments were similarly represented in both those patients who
experienced improvement and those who did not.
There were 14 patients (12.7%) who discontinued treatment with
spironolactone after a consultation with their provider: six patients
due to the side effects, four patients due to lack of effectiveness,
three patients due to completed course of treatment, and one patients
due to pregnancy. The reported side effects that led to the treatment
discontinuation were excessive sleepiness, breakthrough vaginal
bleeding, urinary frequency and tachycardia, irregular periods, diffuse
pruritus, and anxiety. These six women represent 11.7% of the 51
women who experienced side effects during treatment with
spironolactone. In total, 34 patients experienced menstrual and 26 pa-
tients experienced non-menstrual side effects (Table 5).
Discussion
The results of this study showed that acne improved in the vast
majority of the women and completely cleared in a large percentage
during treatment with spironolactone, which further strengthens the
evidence that spironolactone is an effective treatment for women
with acne. Patients showed 73.1%, 75.9%, and 77.6% improvements
on the face, chest, and back, respectively, which supports that
spironolactone is equally effective in treating acne in multiple areas
of the body. Improvements in acne regardless of the body site
occurred in 85% of patients with 55% of patients who were completely
clear (CASS score of 0 in all body sites) and 26% of patients who were
almost clear (maximum CASS score of 1 in one or more body sites)
during treatment.
Current guidelines by the American Academy of Dermatology
recommend a 3-month course of oral antibiotic medications and spe-
cically of the tetracycline class as the initial systemic treatment for
moderate-to-severe acne (Zaenglein et al., 2016). No particular tetra-
cycline has been found to be more or less effective than any other
(Garner et al., 2012). Minocycline, for example, has been studied
with various methods of outcome measurement and has been found
to show improvement in 51% of cases (Ozolins et al., 2004) and
completely or mostly clear acne in 23.6% of cases (Stewart et al.,
2006). These rates suggest that a treatment regimen of 3 months
with oral antibiotic medication is often not sufcient to result in
marked improvement or clearance of acne. In fact, one study found
that 29% of 79,565 patients were treated with oral tetracycline-class
antibiotic medications for longer than 6 months (Barbieri et al., 2016).
Comparatively, a study of patients who took oral contraceptive
pills to treat acne demonstrated an improvement in 81.7% of patients
with clearance or almost clearance in 48.4% of patients (Leyden et al.,
Table 1
Face CASS score changes at each follow-up visit
Face CASS Score First
Follow-up
Visit
Second
Follow-up
Visit
Third
Follow-up
Visit
Fourth
Follow-up
Visit
Total
Improvement No. 86 7 0 1 94
% 79.6 6.5 0.0 0.9 87.0
Cleared No. 37 20 4 4 65
% 34.3 18.5 3.7 3.7 60.2
No Improvement No. 22 15 15 14 14
% 20.4 13.9 13.9 13.0 13.0
CASS, comprehensive acne severity scale.
Note: Percentages are calculated from a tot al of 108 patients with initial face CASS
scores greater than 0. Of the 108 patients, 94 patientsacne improved (65 of which
were completely clear) and 14 patientsdid not.
Table 2
Chest CASS score changes at each follow-up visit
CASS Chest First
Follow-up
Visit
Second
Follow-up
Visit
Third
Follow-up
Visit
Fourth
Follow-up
Visit
Total
Improvement No. 31 2 0 1 34
% 73.8 4.8 0.0 2.4 81.0
Cleared No. 27 4 0 2 33
% 64.3 9.5 0.0 4.8 78.6
No Improvement No. 11 9 9 8 8
% 26.2 21.4 21.4 19.0 19.0
CASS, comprehensive acne severity scale.
Note: Percentages are calculated from a tot al of 42 patients with initial ches t CASS
scores greater than 0. Of the 42 patients, 34 patientsacne improved (3 3 of which
were completely clear) and 8 patientsdid not.
Table 3
Back CASS score changes at each follow-up visit.
CASS Back First
Follow-up
Visit
Second
Follow-up
Visit
Third
Follow-up
Visit
Fourth
Follow-up
Visit
Total
Improvement No. 34 5 0 1 40
% 75.6 11.1 0.0 2.2 88.9
Cleared No. 28 7 0 2 37
% 62.2 15.6 0.0 4.4 82.2
No improvement No. 11 6 6 5 5
% 24.4 13.3 13.3 11.1 11.1
CASS, comprehensive acne severity scale.
Note: Percentages are cal culated from a total of 45 patients with initial back CASS
scores greater than 0. Of the 45 patients, 40 patientsacne improved (37 of which
were completely clear) and 5 patientsdid not.
Table 4
Average before and afterCASS scores and percentage of improvement forwomen who
initiated treatment with CASS score greater than 0 for the face, chest, and back
Average CASS Scores
(At Treatment Initiation N0)
Before After Improvement (%)
Face 2.19 0.59 73.06
Chest 1.41 0.34 75.89
Back 1.65 0.37 77.58
CASS, comprehensive acne severity scale.
3JW. Charny et al. / International Journal of Women's Dermatology xxx (2016) xxxxxx
Please cite this article as: Charny JW, et al, Spironolactone for the treatment of acne in women, a retrospective study of 110 patients, Inter-
national Journal of Women's Dermatology (2016), http://dx.doi.org/10.1016/j.ijwd.2016.12.002
2002). Other similar studies used total lesion count rather than an
established severity index such as CASS scores as the primary outcome
with an investigators global assessment, which is a subjective mea-
sure, as a secondary outcome (Lucky et al., 1997; Rosen et al., 2003;
van Vloten et al., 2002). On the other hand, isotretinoin caused a
complete clearance of acne in nearly all patients with one or more
treatment course. Approximately 40% of patients remained clear
of acne, with 40% of patients presenting with a mild relapse and
20% with a relapse that required an additional course of therapy
(James, 2005). Treatment with isotretinoin, however, is not as safe
as spironolactone because it has multiple, potentially serious side
effects such as teratogenicity and depression. Spironolactone, which
has higher percentage improvement rates compared with minocycline,
percentage improvement rates that are similar to oral contraceptive
pills, and a better safety prole than isotretinoin, gives women an
excellent opportunity to achieve and maintain acne clearance with
daily use.
In contrast with the two major clinical trials of spironolactone for
the treatment of acne, this study explores the maintenance of the
observed efcacy (Goodfellow et al., 1984; Muhlemann et al., 1986).
Most signicantly, there were no women in this study who relapsed
when treated with spironolactone unless they were weaned to
lower doses (ve patients) or their concurrent treatments were
altered (one patient relapsed after receiving a medroxyprogesterone
acetate injection). On the basis of this nding, a patient should main-
tain a dose that is effective for at least 2 months. Once this period has
passed without active disease, the risk of relapse should be addressed
in patients who plan to wean or discontinue treatment.
Side effects were frequent and experienced by 51 patients (46%)
but only 6 patients (5%) discontinued the medication secondary to
these side effects. This indicates that those women who continued
the medication despite experiencing side effects either found the side
effects to be generally mild or they were outweighed by the
benets of the acne improvement. The most common side effects
were breakthrough bleeding or spotting, followed by amenorrhea
and lightheadedness. In clinical trials of doxycycline, esophageal
erosion and photosensitivity were the most common side effects.
Minocycline, on the other hand, has been associated most-commonly
with side effects of lightheadedness and non-specic gastrointestinal
disturbances; however, reports of lupus-like syndromes and hepatitis
have also been associated with treatment (Smith and Leyden, 2005).
The chronic use of oral tetracycline antibiotic medications, which is
common in the treatment of acne, has been associated with an
increased risk of antibiotic resistance (Levy et al., 2003), upper respira-
tory tract infections (Margolis et al., 2005), and inammatory bowel
disease (Margolis et al., 2010). Spironolactone, with a similar side
effect prole regardless of the duration of treatment, may be a safer
treatment option than oral antibiotic medications for chronic acne
treatment. Isotretinoin has more signicant side effects including
teratogenicity, depression, xerosis, arthralgia, hypertriglyceridemia,
and elevated liver enzymes (Peck et al., 1982; Strauss et al., 1984).
Without the need for registration in a mandatory national distribution
program (iPledge; FDA, 2012), laboratory monitoring, and pregnancy
testing, spironolactone is a safer and more convenient treatment
choice than isotretinoin.
Limitations
The study was limited in its retrospective nature and lack of a
control group. Factors such as concurrent treatment, time to follow-
up, dose, and duration of treatment were observed and recorded
but not controlled for. Concurrent treatments may confound the ob-
served efcacy of spironolactone. Of those patients who took oral
contraceptive pills while treated with spironolactone, 52% had
already been taking them and 44% initiated them to prevent preg-
nancy, help regulate irregular menses due to spironolactone, or as
an adjunct treatment to spironolactone. Of the 15 patients who
were prescribed systemic antibiotic medications while treated with
spironolactone, 4 patients were tapered off of the preexisting anti-
bio tic regimens, 10 patients initiated antibiotic medications after a trial
of spironolactone alone was not effective, and 1 patients was both
tapered off of a preexisting antibiotic regimen and initiated a new
regimen. These patients did not take trimethoprim-sulfamethoxazole
as an adjunctive treatment to spironolactone because this antibiotic
medication can potentially cause hyperkalemia. No uniform blood
pressure or potassium testing was conducted because this generally
young, healthy patient population was screened by history to have
no hypertension, cardiac, or renal disease.
A major strength of this study is its relatively large sample size of
110 patients. This sample size is comparable to that of the retrospec-
tive study conducted by Shaw (2000) that included 85 patients. By
using CASS scores and only patients who were treated by two derma-
tologists who are trained in the use of CASS, objective measures of
acne severity could be obtained and compared across time with
minimal variation in the assessment between patients. The large
sample size and encouraging results in terms of efcacy, relapse
rate, and safety make this an important studyto promote more wide-
spread use of spironolactone in the treatment of women with acne.
Conclusions
Spironolactone is effective to treat women with acne on the face,
chest, and back and it retains its utility over the course of long-term
therapy. This study reafrms the results of previous studies in terms
of effectiveness and safety but adds to the literature by showing the
low rate of relapse. Future spironolactone studies should focus on
evaluating both the duration and dosage of treatment because these
factors are vital to the development of reliable prescribing guidelines.
To further promote the use of spironolactone as a rst-line systemic
treatment for women with acne, more prospective controlled trials
must be conducted. Studies such as these will increase our knowledge
base, help determine exactly how effective spironolactone is as mono-
therapy, and pave the way for more widespread usage.
Table 5
Side effects reported among women who were treated with spironolactone
No. of Patients
(N = 110)
Menstrual Side Effects
Breakthrough bleeding/spotting 25
Amenorrhea (cessation of menses) 7
Irregular menses (varied duration between periods) 4
Oligomenorrhea (periods greater than 35 days apart) 2
Non-menstrual Side Effects
Lightheadedness/dizziness 7
Breast tenderness 4
Increased Urinary Frequency 4
Weight gain 2
Worsening of restless legs 2
Sleepiness/drowsiness 2
Breast enlargement 2
Dehydration 1
Weight loss 1
Hair loss 1
Generalized pruritus 1
Fatigue 1
Decreased libido 1
Photosensitivity 1
Anxiety 1
Tachycardia 1
Metallic taste 1
Abdominal pain 1
4JW. Charny et al. / International Journal of Women's Dermatology xxx (2016) xxxxxx
Please cite this article as: Charny JW, et al, Spironolactone for the treatment of acne in women, a retrospective study of 110 patients, Inter-
national Journal of Women's Dermatology (2016), http://dx.doi.org/10.1016/j.ijwd.2016.12.002
Acknowledgements
PennSeek software training was provided by Yevgeny Jesse
Zlatsin of the Data Analytics Center, Corporate Information Services,
University of Pennsylvania in Philadelphia, PA.
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national Journal of Women's Dermatology (2016), http://dx.doi.org/10.1016/j.ijwd.2016.12.002
... 8 Dating back to the 1980s, prospective studies on oral spironolactone have shown statistically significant efficacy against acne vulgaris in women. [8][9][10][11] Although studies have shown efficacy in spironolactone for acne, they have been small in sample size. A recent retrospective study of 110 patients concluded that spironolactone therapy provided patients with improvement in their acne. ...
... A recent retrospective study of 110 patients concluded that spironolactone therapy provided patients with improvement in their acne. 11 Similar to COCs, the systemic exposure of oral anti-androgens poses risks for potential side effects. Common side effects are menstrual irregularities, dizziness, breast enlargement, and nausea. ...
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Carol Sanchez,1 Jonette Keri1,2 1University of Miami Department of Cutaneous Surgery and Dermatology, Miami, FL, USA; 2Miami Veterans Affairs Medical Center, Miami, FL, USACorrespondence: Carol Sanchez, University of Miami Department of Cutaneous Surgery and Dermatology, 7815 NW 104 AVE, Doral, Miami, FL, 33178, USA, Email csanc159@fiu.eduAbstract: The purpose of this narrative review is to provide a summary of the clinical trials on the efficacy and safety of clascoterone 1% cream (Winlevi) to grant providers an understanding of which patients will benefit most from this novel topical antiandrogen medication. Clascoterone 1% cream (Winlevi) offers a new and exciting treatment approach for a difficult and common skin condition such as acne vulgaris. This topical androgen antagonist is the first of its kind but will hopefully provoke investigations into other androgen receptor antagonists with similar or better efficacy.Keywords: hormonal acne, anti-androgens, CB-03-01, Winlevi
... Conventional therapy in form of oral/topical antibiotics and retinoids are the pillars of therapeutics in AV. However, few 17 In another 4 year retrospective study, 86% patients had improvement. 27 A study in adolescent females (n=80) reported improvement in acne in 80% patients on spironolactone. ...
... Spironolactone is one of the oldest androgen receptor blockers, indicated for the management of primary hyperaldosteronism, congestive heart failure, cirrhosis, nephrotic syndrome, essential hypertension due to its mineralocorticoid action (aldosterone antagonist). 17 It is used in treatment of hormone mediated acne with/without alopecia/hirsutism. Different mechanisms contribute to its anti-androgenic action. ...
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Acne vulgaris is a multifactorial chronic disorder of the pilosebaceous unit. Established treatments include topical retinoids, antibiotics in mild cases, and oral antibiotics and isotretinoin in moderate to severe cases. Anti-androgens and other hormonal therapies constitute another group of drugs in the armamentarium of acne management. These can be used in patients who do not respond to the aforementioned treatments or when other systemic drugs cannot be tolerated. Recent approval of topical androgen receptor blocker is an additional armamentarium for the management of acne. Considering limited systemic exposure and good efficacy, it has potential for wide usage in patients with acne. In this article, we critically review currently available hormonal treatment options based on published literature search of an electronic database (MEDLINE/PubMed) performed through June 2021. J Drugs Dermatol. 2022;21(6):618-623. doi:10.36849/JDD.6494.
... The drug that acts as an aldosterone antagonist has been used initially as a potassium-sparing diuretic to treat high blood pressure and congestive heart failure. Recently, spironolactone was repositioned to treat acne and alopecia by observing its effect on reducing the activity of 5α-reductase, decreasing the DHT levels with a consequent reduction in androgenic effects on sebaceous glands and hair bulb [6][7][8]. ...
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To investigate whether exposure to spironolactone treatment affects the risk of incident breast cancer in women over 55 years of age. Retrospective, matched cohort study. General Practice Research Database, a primary care anonymised database representative of the general population in the United Kingdom. 1,290,625 female patients, older than 55 years and with no history of breast cancer, from 557 general practices with a total follow-up time of 8.4 million patient years. We excluded patients with poor quality data and those with no contacts with their general practitioner after their current registration date. Exposed cohort included women who received at least two prescriptions of spironolactone after age 55 years, who were followed up from the first prescription (index date). We randomly selected two unexposed female controls for every exposed patient, matched by practice, year of birth, and socioeconomic scores (if information was available), and followed up from the same date. New cases of breast cancer, using Read codes to confirm diagnoses. Index dates for study patients ranged from 1987 to 2010, and 29,491 new cases of breast cancer were recorded in the study population (incidence rate 0.35% per year). The exposed cohort of 28,032 patients and control cohort of 55,961 patients had unadjusted incidence rates of 0.39% and 0.38% per year, respectively, over a mean follow-up time of 4.1 years. Time-to-event analysis, adjusting for potential risk factors, provided no evidence of an increased incidence of breast cancer in patients exposed to spironolactone (hazard ratio 0.99, 95% confidence interval 0.87 to 1.12). 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.
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Background Spironolactone has been used for over 20 years as an antiandrogen in the treatment of acne and hirsutism. No long-term studies of the safety of spironolactone used in this manner have been published. We present a study of the long-term safety and tolerance of spironolactone in 91 women with acne who were followed for up to 8 years. Methods A survey questionnaire was sent to 210 patients, and a comparison chart review of all patients to whom the survey was sent was made. Results Ninety-one completed surveys were analyzed, comprising 506 person-years of followup and 200 person-years of spironolactone exposure. Mean treatment length was 28.5 months (range = 0.5–122 months). During the 8-year followup period, there were no cases of serious illness attributable to spironolactone use. Side effects were present in 59% and resulted in cessation of the drug in 15%. Diuretic effect and menstrual irregularities were the most common adverse effects. Conclusions After 200 person-years of exposure to spironolactone and 506 person-years of followup over 8 years, no serious illnesses thought to be attributed to spironolactone were reported. The long-term use of spironolactone in the treatment of acne in women appears to be safe. Side effects, however, are common, although not usually a cause for stopping the drug.
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Background: Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. Objective: We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. Methods: We conducted a retrospective cohort study using the Health Improvement Network database. Results: The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. Limitations: The Health Improvement Network does not include information on acne severity and clinical outcomes. Conclusions: Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne.
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Spironolactone, an aldosterone-antagonist, is associated with gynecomastia. Digoxin, which can also cause gynecomastia, has been associated with increased incidence of breast and uterus cancers. We therefore postulated that spironolactone use might also increase these cancer risks. Using a nationwide prescription drug registry between 1995 and 2010, we identified use of spironolactone in a cohort of Danish women (≥20 years old). In users and non-users, incidence rate ratios adjusted by age group and calendar-year examined risk of breast and uterus cancers, both estrogen-sensitive, and ovary and cervix cancers, both relatively estrogen-insensitive. As an added control exposure, risk ratios in women who used another diuretic, furosemide, were examined by the same approach. Among 2.3 million women (28.5 million person-years), risks of breast, uterus, ovary, and cervix cancers were generally increased about 10-30% in both spironolactone and furosemide users. In the first year of drug exposure, incidences were increased, especially for ovary cancers. However, incidence increases in the first year of use were not specific for estrogen-sensitive cancers, occurred with both spironolactone and furosemide, and were driven by exposures immediately prior to diagnosis. For drug exposure ≥1 years before cancer diagnosis, incidences of these cancers were not significantly increased. We conclude that associations observed with first use in the year immediately before cancer diagnosis were driven by reverse causality, i.e., because of treatment for symptoms related to the incipient cancer. With respect to breast, uterus, ovarian and cervical cancer, there is no evidence of increased risk with spironolactone or furosemide use.
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Minocycline is an oral antibiotic used for acne vulgaris. Its use has lessened due to safety concerns (including potentially irreversible pigmentation), a relatively high cost, and no evidence of any greater benefit than other acne treatments. A modified-release version of minocycline is being promoted as having fewer side-effects. To assess new evidence on the effects of minocycline for acne vulgaris. Searches were updated in the following databases to November 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials registers and checked reference lists for further references to relevant randomised controlled trials (RCTs).The Cochrane Skin Group's Trials Search Co-ordinator undertook searches exploring minocycline's adverse effects in EMBASE and MEDLINE in February 2012. We selected randomised controlled trials (RCTs) comparing minocycline, at any dose, to an active or a placebo control, in participants with inflammatory acne vulgaris. For adverse effects, we selected additional studies that reported the number of adverse effects and the number of participants treated. Outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and participants' global assessments, adverse effects, and dropout rates. Two authors independently assessed the quality of each study. Effect sizes were calculated, and meta-analyses were undertaken where possible.Sixteen studies met the inclusion criteria for the review of adverse effects. We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline.The identified RCTs were generally small and poor quality. Meta-analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately-severe acne vulgaris, there was no evidence that it is better than any of the other commonly-used acne treatments. One company-sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used.The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person-years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended-release preparation is safer than standard minocycline preparations. Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.