|Year : 2019 | Volume
| Issue : 2 | Page : 89-94
Efficacy and safety of topical spironolactone 5% gel versus placebo in the treatment of acne vulgaris
Enayat M Attwa1, Al Shimaa M Ibrahim1, Marwa F Abd El-Halim2, Hanan M Mahmoud3
1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Dermatology, Zagazig General Hospital, Zagazig University, Zagazig, Egypt
3 Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
|Date of Submission||17-Oct-2018|
|Date of Acceptance||14-Mar-2019|
|Date of Web Publication||03-Jul-2019|
Al Shimaa M Ibrahim
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig, 44511
Source of Support: None, Conflict of Interest: None
Background Acne is an inflammatory disorder of the pilosebaceous unit that imposes negative effects on the psychological state of patients. Indeed, even mild acne can adversely affect the patients’ quality of life. Therefore, successful management is needed. Spironolactone is one of the effective systemic treatments for acne, but its adverse effects limit its use.
Objectives To assess the effectiveness and safety of 5% spironolactone gel in the treatment of acne.
Patients and methods This study was a split-face study in which 22 adult patients with mild and moderate acne vulgaris were instructed to apply topical 5% spironolactone gel to their right hemifaces and topical placebo gel to their left hemifaces twice daily for 8 weeks.
Results This study reported a statistically significant reduction in the total lesion count and acne severity index from the baseline. The improvement was significantly higher in the spironolactone side than the placebo side. Spironolactone mainly improves comedones and inflammatory papules. Minimal tolerable adverse effects were recorded in the form of stinging and mild erythema.
Conclusion The data provided by this study support the use of topical spironolactone in the treatment of mild to moderate acne vulgaris.
Keywords: acne vulgaris, placebo, spironolactone gel
|How to cite this article:|
Attwa EM, Ibrahim AM, Abd El-Halim MF, Mahmoud HM. Efficacy and safety of topical spironolactone 5% gel versus placebo in the treatment of acne vulgaris. Egypt J Dermatol Venerol 2019;39:89-94
|How to cite this URL:|
Attwa EM, Ibrahim AM, Abd El-Halim MF, Mahmoud HM. Efficacy and safety of topical spironolactone 5% gel versus placebo in the treatment of acne vulgaris. Egypt J Dermatol Venerol [serial online] 2019 [cited 2019 Sep 23];39:89-94. Available from: http://www.ejdv.eg.net/text.asp?2019/39/2/89/262039
| Introduction|| |
Acne vulgaris is a common inflammatory skin disease affecting millions of people worldwide . Not only does acne affect youth but also it persists into middle age. If it is left without an appropriate treatment, it can be a source of significant physical sequelae and psychological problems .
Acne is a disease of the pilosebaceous unit that is mainly under hormonal control. Multifactorial etiopathogenesis have been suggested involving follicular hyperkeratinization, obstruction of the sebaceous duct, marked sebum production which is guided by androgen, increased colonization of Propionibacterium acnes (P. acnes), and inflammation .
Microcomedones, the primary lesions of acne, are the results of disturbed desquamation of the epithelium that ends into obstruction of the sebaceous duct . This obstruction along with the presence of increased sebum production induced by the high level of androgen at puberty leads to the formation of black and white heads ,. The production of excess amounts of sebum in the presence of follicular obstruction makes the good milieu for the proliferation of P. acnes with a subsequent release of different inflammatory mediators that lead to peculiar inflammation . Accordingly, the main targets in the treatment of acne are control of sebum production, normalization of follicular epithelization, inhibition of proliferation of P. acnes, and decrease of inflammation. Proper evaluation of the type and severity of acne is essential for a successful management, where mild acne can be treated by topical treatment only, whereas moderate and severe acne need systemic treatment in addition to topical treatment .
Spironolactone is a synthetic steroid with a structural resemblance to aldosterone. In addition to the blockage of aldosterone receptors, spironolactone also has antiandrogenic effect by altering steroidogenesis and by affecting the target organ response to circulating androgens. It has been used for more than 20 years as an anti-androgen in the systemic treatment of acne and hirsutism with an average daily dose of 50–200 mg/day. However, its adverse effects limit its use. Previous studies revealed that topical spironolactone affects follicular duct cornification and comedones formation and decreases sebum production, so it can be one of the effective and safe treatments of acne . This study was designed to assess the effectiveness and safety of 5% spironolactone gel in the treatment of mild and moderate acne, as severe acne is mainly controlled by systemic treatment.
| Patients and methods|| |
Sixty-six patients with acne vulgaris were recruited from the outpatient clinic of dermatology at Z.U.H. We evaluated the characteristics of the acne lesions including types (comedones, papules, and pustules), the number, and the severity, which was assessed by the global acne grading system. According to global acne grading system, cases were classified into mild if the score was between 1 and 18, moderate with a score of 19–30, severe if the score was 31–38, or very severe if it was more than 39 . After baseline evaluation of acne severity, mild and moderate cases were selected for the study. The study included 22 adult patients with mild and moderate acne vulgaris. Patients with severe acne, with a background of systemic disease and pregnant or lactating women, were excluded from participation. Other patients were excluded owing to other criteria such as using anti-acne antibiotics, hormonal medications for the past 3 months, or isotretinoin for the past 6 months. A written consent was obtained from each patient before their participation in the study. This study was approved by the Z.U.H Institutional Review Board.
Lesion photographs were taken before starting the treatment and at each follow-up visit every 2 weeks. This study was a split-face trial. All patients were instructed to use topical 5% spironolactone gel on the right hemiface and topical placebo gel on the left hemiface twice daily for 8-week duration. Blood pressure measurements were performed at each follow-up visit. Immediate and late adverse effects of the treatment were evaluated at each visit.
Preparation of spironolactone 5% gel
For each 100 g, a formula containing spironolactone 5%, ethanol 20%, glycerin 10%, propylene glycol 10%, lactic acid 5%, methyl cellulose 3%, Na benzoate 0.03%, with the amount of water sufficient to prepare 100 g, was used. Placebo gel contained the same ingredients without spironolactone. Spironolactone and placebo gel were prepared at Department of Pharmaceutics, Faculty of Pharmacy, Z University.
Site of preparation
The study was conducted at Department of Pharmaceutics, Faculty of Pharmacy, Z University.
Assessment of the clinical response
The final assessment to determine the efficacy of the treatment was done by comparing the number of comedones, papules, and pustules and the result of the following two formulations before and after treatment:
- Total lesion count (TLC)=comedones+papules+pustules
- Acne severity index (ASI)=papules + (2 x pustules)+(comedones/4) (Afzali, et al. 2012).
Data were checked, entered, and analyzed using SPSS (Microsoft Excel software. Inc., Chicago, Illinois, USA), version 23 for data processing. Qualitative variables were expressed as number and percentage, whereas quantitative data were expressed as mean±SD. The comparison was done using Wilcoxon signed-rank test to compare paired data before and after a time and χ2 test to find the association between row and column variables.
| Results|| |
Characteristics of the patients
All 22 patients (seven males and 15 females) completed the study. The clinical characteristics of all participants are shown in [Table 1].
Response to treatment with spironolactone 5% gel
After 8 weeks of treatment, there was a statistically significant reduction in the number of comedones and papules, with significant reduction of the TLC and ASI from the baseline in both treatment and control side; however, the improvement was significantly higher in the spironolactone side than the control side. There was no statistically significant reduction in the number of pustules from the baseline in both sides ([Table 2], [Table 3] and [Figure 1],[Figure 2],[Figure 3]).
|Table 2 The number of acne lesions before and after treatment in spironolactone side (eight hemiface)|
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|Table 3 The number of acne lesions before and after the study in the control side|
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|Figure 1 Twenty-four-year old patient with acne shows good improvement with spironolactone (a) right hemiface before treatment with spironolactone 5% gel and (b) right hemiface after treatment with spironolactone 5% gel.|
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|Figure 2 Thirty-year old patient with moderate inflammatory acne (a) right hemiface before treatment with spironolactone 5% gel and (b) right hemiface after treatment with spironolactone 5% gel.|
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|Figure 3 Fifteen-year old patient with comedonal acne shows excellent improvement to topical spironolactone (a) forehead before treatment and (b) forehead after treatment.|
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The percent of improvement in the number of acne lesions in both sides
The therapeutic response to spironolactone was significantly higher than the placebo. The highest improvement was in comedones by 50% in spironolactone side versus 15% in the control side. It is followed by papules that improved by 48% in the treatment side versus 12% in the control side. The least improvement was in pustules, which improved by 35% in the treatment side versus 5% in the control side. TLC reduction reached 60% in the treatment side versus 18% in the control side, whereas ASI reduction represented 77% in the treatment side versus 17% in the control side ([Table 4]).
|Table 4 The percent of improvement in the number of acne lesions in both sides|
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Minimal tolerable adverse effects were reported during the treatment course in the form of scaling, stinging, and mild erythema, with no statistically significant difference between spironolactone and placebo side ([Table 5]).
| Discussion|| |
Pilosebaceous unit is the main affected target in acne that mainly affects face, chest, and back owing to the presence of large numbers of these sebaceous units . Acne is neither a life-threatening nor systemic disease, yet its psychological effects are multiple like disappointments with appearance, lack of self-possession, and shame. Indeed, even mild acne can adversely affect the patients’ quality of life. Therefore, successful management is needed .
Spironolactone, a synthetic 17-lactone steroid, is a nonselective antagonist of the mineralocorticoid receptor that also has a moderate affinity for androgen and progesterone receptors. Spironolactone has been used mainly for its diuretic effect, but since the 1980s, it has been used also as an effective systemic treatment for acne. It inhibits the binding of dihydrotestosterone to its receptor within sebocytes leading to inhibition of the sebocytes proliferation with a subsequent decrease in the sebum production. Moreover, the premenstrual flare of acne that is accompanied by fluid retention can be improved by spironolactone owing to its diuretic effect ,. Although oral spironolactone significantly decreases acne lesions, it is not a common alternative acne treatment for females, probably owing to its common adverse effects like menstrual irregularities, disturbed menstrual flow, headache, diuretic effect, drowsiness, and hypotension. In addition, spironolactone is not tolerated by men owing to its annoying adverse effects like gynecomastia and decreased libido ,. Therefore, topical spironolactone can provide an effective alternative acne treatment for both male and female patients, which overcome its systemic undesirable adverse effects. Kelidari et al.  reported that the usage of spironolactone as a topical treatment allows high penetration of the drug to the active site with the advantage of minimizing unwanted adverse effects of oral spironolactone.
This study was carried out to assess the efficacy of topical spironolactone 5% gel in the treatment of acne vulgaris of mild and moderate severity. Topical spironolactone 5% gel prepared in this study contained ethanol and lactic acid 5%, which act as a penetration enhancer that increases the penetration of the drug through horny cell layer of the skin, and also ethanol enhances the solubility of the drug to increase its ability to penetrate the skin.
At the end of the treatment, the spironolactone side showed a statistically higher significant improvement than the control side, as comedones reduced by 50 versus 15% in the control side, papules reduced by 48 versus 12%, TLC improved by 60 versus 18%, and ASI improved by 77 versus 17%, respectively. These results came in accordance with Califano et al. , Afzali et al.  and Bagherani .
The reduction in acne lesions in the placebo side can be attributed to the lactic acid used in placebo preparation. In addition, we also suggest that the effect of spironolactone is not limited to the treatment side, but it extends to involve the other side as well. However, this analysis needs to be confirmed. The psychic support to patients may play an important role.In this study, the percent of improvement in noninflammatory lesions (comedones) was much better than inflammatory lesions (papules and pustules). These results correspond with the results provided by previous studies ,. Theoretically, these findings may be attributed to the reduced penetration of spironolactone in inflammatory acne lesions, as suggested by Afzali and colleagues ; or might have resulted from the deactivation of spironolactone by P. acnes and their products, as the microenvironmental state in the inflammatory acne lesions may deactivate spironolactone by the destruction of androgenic receptors at the pilosebaceous unit. Moreover, inflammatory lesions might need a longer treatment duration than 12 weeks, which was the duration of this study, to show better improvement.
On discussing adverse effects, 59% of cases showed minimal tolerable adverse effects during treatment like stinging, which lasted only for 10 min after gel application, erythema, and scaling. These adverse effects were regressed by the use of emollients. It is worth mentioning that we had no recorded cases about either blood pressure changes, which were confirmed by measuring blood pressure at each visit, menstrual disturbance, or gynecomastia.
| Conclusion|| |
The data provided by the current study support the use of topical spironolactone in the treatment of mild and moderate acne vulgaris in both male and female patients. Further controlled studies on a larger number of patients and for a longer treatment duration evaluating topical spironolactone efficacy and tolerability compared with other topical medications can be useful.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]