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Oral spironolactone has been used for over two decades in the dermatological setting. Although it is not generally considered a primary option in the management of female patients with acne vulgaris, the increase in office visits by post-teenage women with acne vulgaris has recently placed a spotlight on the use of this agent in this subgroup of pa...
Citations
... Spironolactone, an antiandrogenic diuretic, has proven effective against acne, particularly in female patients, by blocking androgen receptors to reduce sebum production [202,207,211]. Comparable in effectiveness to oral antibiotics, spironolactone is frequently prescribed for long-term management, often alongside oral contraceptives to enhance its antiandrogenic effects and to prevent pregnancy [212,213]. Recent studies suggest that the risk of hyperkalemia in healthy young women taking spironolactone is similar to the baseline risk in this demographic, indicating that routine monitoring of serum potassium may be unnecessary [214]. Common side effects include menstrual irregularities in women not on combined oral contraceptives and potential gynecomastia, though it is not linked to an increased risk of breast or gynecological cancers [213]. ...
Acne vulgaris is a common dermatological condition that can present across different ages but predominantly affects adolescents and young adults. Characterized by various lesion types, the pathogenesis of acne is complex, involving genetic, hormonal, microbial, and inflammatory factors. This review comprehensively addresses current and emerging acne management strategies, emphasizing both topical and systemic treatments, procedural therapies, and dietary modifications. Key topical agents include retinoids, benzoyl peroxide, antibiotics, and other specialized compounds. Systemic options like antibiotics, hormonal therapies, and retinoids offer significant therapeutic benefits, particularly for moderate to severe cases. Procedural treatments such as laser devices, photodynamic therapy, chemical peels, and intralesional injections present viable alternatives for reducing acne symptoms and scarring. Emerging therapies focus on novel biologics, bacteriophages, probiotics, and peptides, providing promising future options. This review underscores the importance of personalized approaches to treatment due to the multifaceted nature of acne, highlighting the potential of innovative therapies for improving patient outcomes.
... 3 Clinical studies have demonstrated the anti-acne effects of Spironolactone (SPN), and the outcomes of the treatment have been consistently positive. 4 Research has shown that daily oral administration of SPN at a dosage of 200mg has proven to be an effective alternative treatment for women with acne vulgaris. 5 The main limitation in utilizing SPN has been its low solubility in aqueous solutions at physiological pH, which hampers its oral administration. ...
Purpose: Spironolactone (SPN), which is classified as an anti-androgen, has demonstrated efficacy in treating acne. This study aimed to utilize ultrasonication to create a chitosan-coated nano lipid carrier (NLC) for enhancing the delivery of SPN to the skin and treating acne. Methods: Various Hydrophilic-Lipophilic Balance (HLB) values were investigated to optimize the SPN-NLCs. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of SPN in nanoparticle form. Additionally, the optimized formulation was used in a double-blind, randomized clinical trial. Results: Reducing the HLB of the surfactant mixtures resulted in a reduction in the size of SPN-NLCs. The formula with the smallest particle diameter (238.4±0.74 nm) and the lowest HLB value (9.65) exhibited the highest encapsulation efficiency of 79.88 ± 1.807%. Coating the optimized SPN-NLC with chitosan increased the diameter, PDI, zeta potential, and encapsulation efficiency. In vitro skin absorption studies demonstrated sustained release profiles for chitosan-coated SPN-NLC. In the double-blind trial, a gel containing chitosan-coated SPN-NLC effectively treated mild to moderate acne vulgaris, leading to improved healing and reduced lesion count after 8 weeks of therapy compared to the placebo. It successfully addressed both non-inflammatory and inflammatory lesions without adverse effects on the skin. Conclusion: The findings indicate that chitosan-coated SPN-NLCs have the potential as nanoparticles for targeted SPN delivery to the skin, offering novel options for the treatment of acne vulgaris.
... Meskipun spironolakton masih sebagai terapi off-label untuk indikasi akne, obat ini telah banyak digunakan sebagai terapi alternatif untuk pasien wanita dengan jerawat yang tidak membaik dengan pemberian terapi konvensional. [4][5] ...
... Selain itu juga dapat diberikan sebagai monoterapi atau dikombinasi dengan agen lain dan terbukti dapat ditoleransi dengan baik terutama untuk wanita dewasa dengan akne vulgaris yang menunjukkan pola hormonal secara klinis. 5 Pada penelitian retrospektif Grandhi et al., didapati rejimen rejimen pengobatan yang paling umum digunakan adalah terapi kombinasi (terapi topikal, oral, dan spironolakton) dan didapati sebesar 88% pasien mengalami perbaikan, sedangkan dengan monoterapi spironolakton mendapat perbaikan sebesar 85%. 6 Hal ini sesuai dengan American Academy of Dermatology (AAD) yang memang menyarankan penggunaan beberapa agen dengan mekanisme kerja yang berbeda untuk pengobatan akne. ...
... Efek samping yang dapat ditimbulkan, yaitu menstruasi yang tidak teratur, nyeri payudara, sakit kepala, badan terasa lemas, dan hiperkalemia. 5 ...
Acne vulgaris is a skin disease that attacks pilosebaceous follicles which can be either inflammatory or non-inflammatory lesion. One of the important factors causing acne vulgaris is androgen hormone. One of the hormonal therapies that can be given for acne vulgaris is spironolactone which has a function as an antiandrogen. The purpose of writing this literature review is to determine the effectiveness, mode of action, indications, contraindications, and side effects of spironolactone in the treatment of acne vulgaris. The method in making this final project is Literature Review. Literature searches were obtained using electronic databases such as Google Scholar, PubMed, Proquest, International Journal of Women's Dermatology, and NCBI. The keywords used were spironolactone, hormonal therapy, acne vulgaris, effectiveness of spironolactone for acne vulgaris. There are 10 supporting journals based on the suitability of topics in the last 10 years. The results showed that the administration of spironolactone for acne vulgaris proved to be effective with an average dose of 50-100 mg/day which resulted in 70-90% clinical improvement and caused minimal side effects. Spironolactone has good effectiveness and tolerability for alternative therapy of acne vulgaris in adult women and for patients who do not respond well to conventional therapy.
... None of these are suitable for male or pregnant patients due to systemic anti-androgenic effects. 1 Acne therapies targeting this pathway may take time to result in improvement. Spironolactone efficacy has generally been evaluated only after 12 weeks, 28 and improvements in acne with oral contraceptives also take time, with significant effects usually observed after at least 3 cycles (28-day cycle, in a 24/4-day regimen). 1,[29][30][31] ...
Acne vulgaris is the most common skin condition in the US, affecting up to 50 million Americans. The American Academy of Dermatology (AAD) guidelines on acne treatment were developed to provide recommendations for the diagnosis, grading, and treatment of acne in adolescents and adults to support clinicians in their therapeutic decision-making process. The most recent acne guidelines were published in 2016, and the approach to care and the therapeutic landscape of acne have evolved since that time. The Acne Management Consensus Roundtable was convened in 2022 to discuss unmet needs in the management of acne. The main focus of the meeting was the role of androgens in acne pathology; the evaluation of clascoterone, the first topical anti-androgen that specifically addresses sebum production in acne; and the identification of the place of clascoterone in therapy. Clascoterone was approved by the US Food and Drug Administration for the treatment of acne in patients 12 years and older in 2020. This report aims to highlight important limitations of the 2016 AAD treatment guidelines and to familiarize practitioners with clascoterone and its indication, efficacy and safety profile, and potential use across diverse patient populations. With its new mechanism of action, clascoterone may be able to fulfill important unmet needs in acne treatment. Baldwin H, Farberg AS, Frey C, et al. Unmet needs in the management of acne vulgaris: a consensus statement. J Drugs Dermatol. 2023;22(6):582-587. doi:10.36849/JDD.7587.
... Previous studies showed that long-term use of hormonal contraceptives might develop some adverse side effects like Venous thromboembolism or the formation of blood clots inside deep veins [20], Migraine and cerebrovascular diseases [21], Obesity [22], Hypertension [23], and decreased libido [24]. Some most studied steroidal anti-androgens, e.g., Spironolactone, Cyproterone acetate, etc., also cause menstrual irregularities and fatigue [25]. ...
... [16,17] Spironolactone is also found to produce reproductive side effects, [18] due to its anti-androgenic effects. [19] Eplerenone, discovered in 2002, was the first selective mineralocorticoid receptor (MR) blocker due to its lesser side effects than spironolactone. [20] is development did not resolve the risk of developing hyperkalemia. ...
Diabetes is the major cause of chronic and end-stage renal disease worldwide. Despite recent breakthroughs in diabetic kidney disease (DKD) therapy, there is still a significant need for more choices to enhance renal and cardiovascular outcomes. Mineralocorticoid overactivity adds to inflammation and fibrosis, which leads to the advancement of DKD. The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone slow the course of DKD as well as the risk of hospitalizations and death in patients with heart failure (HF) with reduced ejection fraction but their potential of causing hyperkalemia, particularly in individuals with renal dysfunction, restricts their usage. Finerenone, a new non-steroidal MRA, has showed potential cardiac and renoprotective advantages in DKD as well as has a better affinity for the mineralocorticoid receptor (MR) than eplerenone and higher selectivity for the MR than spironolactone. Studies have shown that the selective non-steroidal MRA finerenone reduces the risk of cardiovascular events and chronic kidney disease (CKD) progression in individuals with CKD and type 2 diabetes mellitus. Finerenone selectivity and higher binding affinity to the MR may lower the risk of hyperkalemia and renal dysfunction, overcoming the reluctance to initiate MRAs in patients with HF and DKD.
... subsets of patients such as those having clinical features of hyperandrogenism like polycystic ovarian syndrome (PCOS), SAHA syndrome (menstrual irregularities, oligomenorrhea, hirsutism, hair-loss, seborrhoea), virilization (clitoromegaly, deepening of voice, and increased muscle mass), hyperinsulinemia (obesity, skin tags, and acanthosis nigricans), premenstrual flares, acne presenting in the third decade, and acne localized to the lower third of the face (adult acne) which may not respond to conventional treatment. 5 These patients may need hormonal work-up, 15 including free and total testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone and luteinizing hormone/ follicle stimulating hormone (LH/FSH) ratio. [3][4][5] Obese patients, especially those with acanthosis nigricans, can be screened for serum insulin and glucose levels (fasting and postprandial) as hyperinsulinemia is associated with PCOS. ...
... 13 Although androgens play an important role in AV development, most women with classical hormonal acne may have normal testosterone levels. In such cases, increased endorgan sensitivity of the androgen receptors to androgens may be the cause for the development of AV. 14,15 Other processes involve proliferation of Cutibacterium Acne (P. acne) that causes release of enzymes such lipase and protease that damage the follicular wall followed by the release of proinflammatory mediators leading to inflammation of the follicle and surrounding dermis. ...
... It also increases the level of SHBG that results in a decrease of free testosterone levels. 15,18 Thus sebum production is reduced. ...
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.
... It acts on acne through an anti-androgenic action, mainly targeting the blocking of androgen receptors; it decreases the amount of sebum production induced by androgens by competing with testosterone and DHT. It also raises the level of SHBG, inhibits testosterone synthesis by lowering liver 17β-hydroxylase activity, reducing the conversion of androstenedione to testosterone, influences the LH/FSH ratio by lowering the response of LH to GnRH, and lowers 5α-reductase activity [27]. ...
... SP's mechanism of action includes blocking 5αreductase activity through increasing testosterone clearance as a result of enhanced liver hydroxylase activity. 5 Reported side effects include breast tenderness, urinary frequency, menstrual irregularities, hyperkalemia, fatigue, headache, dizziness, lethargy, hypotension, and birth defects. 6,7 However, the use of a topical form of spironolactone could have similar efficacy with lower possible side effects. ...
Background
Spironolactone is an effective treatment for female patients with acne vulgaris. However, topical spironolactone could be a valuable treatment option in both male and female acne patients due to the less possibility of systemic side effects with its topical formulation.
Objective
To evaluate the efficacy and safety of 5% spironolactone cream in the treatment of mild to moderate acne vulgaris.
Methods
In this pilot clinical trial, topical spironolactone 5% was evaluated to treat patients with mild to moderate acne twice a day for 8 weeks. The rate of improvement as any alterations in the number of open and closed comedones, facial inflammatory papules, and acne global grading scores were assessed. Moreover, skin biometric characteristics including skin hydration, erythema, transepidermal water loss (TEWL), pH, sebum, and Propionibacterium acnes bacteria activity were also assessed following the treatment.
Results
Fifteen patients participated in our study with a mean age of 25 ± 4.87 years old. A total of 66.6% (n = 10) were female and 33.4% (n = 5) were male. The number of acne papules, open and closed comedones, and acne global grading score decreased significantly 4 and 8 weeks after the beginning of treatment (P < .05). No considerable side effect was reported. Moreover, there was no significant difference between the skin hydration, melanin, erythema, TEWL, pH index, sebum, and P acnes bacteria activity before, 4, and 8 weeks after the treatment with topical spironolactone cream (P > .05).
Conclusion
The topical 5% spironolactone cream seems to be an effective and safe treatment of acne vulgaris in both male and female patients.
... Initiation of anti-androgenic treatment at an earlier stage (i.e. during adolescence rather than later in life) suggests early awareness of PCOS, which, in turn, may affect reproductive choices and family planning. However, we consider anti-androgenic treatment at an earlier age as an unlikely marker of a deliberate attempt at achieving pregnancy since anti-androgenic drugs either are contraceptives or are teratogenic (Eibs et al., 1982;Kim and Del Rosso, 2012). One could therefore wonder whether the higher FR among early users observed in our study could be attributed to a long-lasting pharmacological effect of the anti-androgens, extending even after the period of use. ...
STUDY QUESTION
Is anti-androgen treatment during adolescence associated with an improved probability of spontaneous conception leading to childbirth in women with polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Early initiation of anti-androgen treatment is associated with an increased probability of childbirth after spontaneous conception among women with PCOS.
WHAT IS KNOWN ALREADY
PCOS is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism and menstrual irregularities associated with PCOS typically emerge in early adolescence. Previous work indicates that diagnosis at an earlier age (<25 years) is associated with higher fecundity compared to a later diagnosis.
STUDY DESIGN, SIZE, DURATION
This population-based study utilized five linked Swedish national registries. A total of 15 106 women with PCOS and 73 786 control women were included. Women were followed from when they turned 18 years of age until the end of 2015, leading to a maximum follow-up of 10 years. First childbirth after spontaneous conception was the main outcome, as identified from the Medical Birth Registry.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants included all women born between 1987 and 1996 with a diagnosis of PCOS in the Swedish Patient Registry and randomly selected non-PCOS controls (ratio 1:5). Information on anti-androgenic treatment was retrieved from the Swedish Prescribed Drug Registry with the use of Anatomic Therapeutic Chemical (ATC) codes. Women with PCOS who were not treated with any anti-androgenic medication were regarded as normo-androgenic, while those treated were regarded as hyperandrogenic. Women were further classified as being mildly hyperandrogenic if they received anti-androgenic combined oral contraceptive (aaCOC) monotherapy, or severely hyperandrogenic if they received other anti-androgens with or without aaCOCs. Early and late users comprised women with PCOS who started anti-androgenic treatment initiated either during adolescence (≤ 18 years of age) or after adolescence (>18 years), respectively. The probability of first childbirth after spontaneous conception was analyzed with the use of Kaplan–Meier hazard curve. The fecundity rate (FR) and 95% confidence interval for the time to first childbirth that were conceived spontaneously were calculated using Cox proportional hazards regression models, with adjustment for obesity, birth year, country of birth and education level.
MAIN RESULTS AND THE ROLE OF CHANCE
The probability of childbirth after spontaneous conception in the PCOS group compared to non-PCOS controls was 11% lower among normo-androgenic (adjusted FR 0.68 (95% CI 0.64–0.72)), and 40% lower among hyperandrogenic women with PCOS (adjusted FR 0.53 (95% CI 0.50–0.57)). FR was lowest among severely hyperandrogenic women with PCOS compared to normo-androgenic women with PCOS (adjusted FR 0.60 (95% CI 0.52–0.69)), followed by mildly hyperandrogenic women with PCOS (adjusted FR 0.84 (95% CI 0.77–0.93)). Compared to early anti-androgenic treatment users, late users exhibited a lower probability of childbirth after spontaneous conception (adjusted FR 0.79 (95% CI 0.68–0.92)).
LIMITATIONS, REASONS FOR CAUTION
We lacked direct information on the intention to conceive and the androgenic biochemical status of the PCOS participants, applying instead the use of anti-androgenic medications as a proxy of hyperandrogenism. The duration of anti-androgenic treatment utilized is not known, only the age at prescription. Results are not adjusted for BMI, but for obesity diagnosis. The period of follow-up (10 years) was restricted by the need to include only those women for whom data were available on the dispensing of medications during adolescence (born between 1987 and 1996). Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes.
WIDER IMPLICATIONS OF THE FINDINGS
Early initiation of anti-androgen treatment is associated with better spontaneous fertility rate. These findings support the need for future interventional randomized prospective studies investigating critical windows of anti-androgen treatment.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the Health Research Council of New Zealand (18-671), the Swedish Society of Medicine and the Uppsala University Hospital. Evangelia Elenis has, over the past year, received lecture fee from Gedeon Richter outside the submitted work. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.
TRIAL REGISTRATION NUMBER
N/A
