The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Spironolactone hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism: in silico studies, statistical optimization, ex vivo, and in vivo studies.

Spironolactone (SP) is a potassium sparing diuretic with antiandrogenic properties. This study aimed at formulating SP into hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism. HAECs were prepared by ethanol injection method, according to D-optimal design, after a proper in silico study. HAECs were evaluated by measuring their entrapment efficiency (EE%), particle size (PS), and polydispersity index (PDI). Optimal hyaluronic acid enriched cerosomes (OHAECs) were subjected to further in vitro and ex-vivo and in-vivo studies. The in silico study concluded better interactions between SP and phosphatidyl choline in presence of hyaluronic acid (HA) and high stability of their binding in water. The prepared HAECs had acceptable EE%, PS, and PDI values. The statistical optimization process suggested OHAEC containing 10.5 mg ceramide III and 15 mg HA, utilizing Kolliphor® RH40. OHAEC had EE% and PS of 89.3 ± 0.3% and 261.8 ± 7.0 nm, respectively. OHAEC was stable for up to 3 months. It also showed a mixed tubular and vesicular appearance under transmission electron microscope. The ex vivo and in vivo studies concluded better skin deposition and accumulation of SP from OHAEC. The histopathological study demonstrated the safety of OHAEC for topical application. Therefore, OHAEC could be considered as effective system for topical application of SP to manage hirsutism, with prolonged action, coupled with minimized side effects.

Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy.

Diabetic retinopathy remains a major cause of vision loss worldwide. Mineralocorticoid receptor (MR) pathway activation contributes to diabetic nephropathy, but its role in retinopathy is unknown. In this study, we show that MR is overexpressed in the retina of type 2 diabetic Goto-Kakizaki (GK) rats and humans and that cortisol is the MR ligand in human eyes. Lipocalin 2 and galectin 3, two biomarkers of diabetes complications regulated by MR, are increased in GK and human retina. The sustained intraocular delivery of spironolactone, a steroidal mineralocorticoid antagonist, decreased the early and late pathogenic features of retinopathy in GK rats, such as retinal inflammation, vascular leakage, and retinal edema, through the upregulation of genes encoding proteins known to intervene in vascular permeability such as Hey1, Vldlr, Pten, Slc7a1, Tjp1, Dlg1, and Sesn2 but did not decrease VEGF. Spironolactone also normalized the distribution of ion and water channels in macroglial cells. These results indicate that MR is activated in GK and human diabetic retina and that local MR antagonism could be a novel therapeutic option for diabetic retinopathy.

Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats.

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.

OPALS: A New Osimertinib Adjunctive Treatment of Lung Adenocarcinoma or Glioblastoma Using Five Repurposed Drugs.

BACKGROUND: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib's growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility. DATA SOURCES: All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth.

Multiple retrospective analysis of survival and evaluation of cardiac death predictors in a population of dogs affected by degenerative mitral valve disease in ACVIM class C treated with different therapeutic protocols.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

Effect of preload reducing therapy on right ventricular size and function in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. To date, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model. OBJECTIVE: The purpose of this study was to describe our experience with preload reducing therapy in patients with ARVC and symptomatic right ventricular (RV) dysfunction. METHODS: We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC who had serial echocardiographic measurements and an implantable cardioverter-defibrillator. Six of the 20 patients with RV end-diastolic area (RVEDA) above median (>25 cm2) and New York Heart Association functional class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg tid (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, RV fractional area change (FAC), and RV outflow tract measurements. Generalized estimating equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression. RESULTS: Patients who received preload reducing agents (n = 6) were older and had larger RVs with lower FAC at baseline. However, treatment with preload reducing agents was associated with less RVEDA enlargement during mean 3.3 (range 1-6.7) years of treatment in multivariate analysis (% change in RVEDA associated with treatment -7.71; 95% confidence interval -13.29 to -2.13; P = .007). CONCLUSION: Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC and show possible disease-modifying potential.

A retrospective study on the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure.

ABSTRACT: To explore the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40 mg/d spironolactone) and High-dose group (taking 80 mg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (P < .05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (P < .05), LVEF and 6-MWT were significantly increased (P < .05). Compared with the Low-dose group, the high-dose group BNP (117.49 ±â€Š50.32 vs 195.76 ±â€Š64.62, P < .05), NT-pro BNP (312.47 ±â€Š86.28 vs 578.47 ±â€Š76.73, P < .05), LVEDD (45.57 ±â€Š5.69 vs 51.96 ±â€Š5.41, P <.05), LVEDV (141.63 ±â€Š51.14 vs 189.85 ±â€Š62.49, P < .05) and NYHA grading (1.29 ±â€Š0.41 vs 1.57 ±â€Š0.49, P < .05) were significantly reduced, but, 6-MWT (386.57 ±â€Š69.72 vs 341.73 ±â€Š78.62, P < .05), LVEF (41.62 ±â€Š2.76 vs 36.02 ±â€Š2.18, P < .05) and total effective rate (92.68% vs 81.39%, P < .05) increased significantly.Compared with 40 mg spironolactone, 80 mg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy.

Temporal Trends and Clinician Variability in Potassium Monitoring of Healthy Young Women Treated for Acne With Spironolactone.

Importance: Although recent studies and guideline recommendations indicate that potassium level monitoring is of low usefulness for healthy young women being treated for acne with spironolactone, little is known about whether these recommendations have been implemented in clinical practice. Objective: To evaluate trends in rates of potassium level monitoring among young women treated for acne with spironolactone and clinician variability in monitoring practices. Design, Setting, and Participants: This retrospective cohort study was conducted between January 1, 2008, and June 30, 2019, using data from the Optum deidentified Clinformatics Data Mart database. Participants comprised 108 547 healthy female patients aged 12 to 45 years who were treated for acne with spironolactone. Main Outcome and Measures: The primary outcome was the proportion of women who received a test for baseline potassium level and the proportion of women whose potassium levels were monitored in the first 180 days of being treated for acne with spironolactone. For clinicians who had prescribed at least 5 courses of spironolactone, the percentage of clinicians who ordered baseline potassium testing or monitoring and the percentage of clinicians who always monitored potassium were compared between 2008 and 2015 vs between 2016 and 2018. Results: For 108 547 women included in this cohort study, the mean (SD) age at the start of treatment was 30.7 (8.6) years, and the mean (SD) course duration was 159 (218) days. Between 2008 and 2018, the percentage of women whose potassium levels were monitored within 180 days of starting spironolactone by all clinicians decreased from 41.4% to 38.5%, with a decrease from 48.9% to 41.0% among dermatologists and from 39.7% to 37.7% among internists but with an increase from 71.4% to 75.4% among advanced practice clinicians (ie, nurse practitioners and physician assistants). The proportion of dermatologists who always monitored potassium decreased from 10.6% between 2008 and 2015 to 4.2% between 2016 and 2018. There was no significant difference in the proportion of internists who always monitored potassium from 2008 to 2015 (15.8%) vs from 2016 to 2018 (17.7%). Conclusions and Relevance: Despite increasing evidence and guidelines supporting the elimination of potassium monitoring among healthy young women treated for acne with spironolactone, the present study findings suggest that potassium monitoring remains common, with substantial variability in clinician practices. There is a need for future implementation and dissemination research to understand underlying factors for this variation and to develop strategies to address this practice gap.

Factors affecting the urinary aldosterone-to-creatinine ratio in healthy dogs and dogs with naturally occurring myxomatous mitral valve disease.

BACKGROUND: Chronic renin-angiotensin-aldosterone system (RAAS) activation in course of heart diseases contributes to cardiac remodeling and heart failure. Myxomatous mitral valve disease (MMVD) is characterized by different stages of severity and trend of RAAS activity during the course of the disease is still uncertain. The urinary aldosterone-to-creatinine ratio (UAldo:C) has been proven to reflect RAAS activation in dogs and might be a useful marker in monitoring therapy and disease progression, but data about this parameter need to be expanded. The objective of this study was to evaluate the UAldo:C in healthy dogs and dogs with naturally occurring MMVD, and to investigate the relationships between this parameter and clinical, echocardiographic and laboratory variables. RESULTS: The study population consisted of 149 dogs: 49 healthy and 100 MMVD dogs (45 stage B1, 13 stage B2 and 42 stage C). Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of any stages. Breed, sex and age showed a significant impact on UAldo:C. In particular, Chihuahua and Cavalier King Charles spaniel showed significantly higher UAldo:C than other breeds, as well as intact females than other genders. In stage C dogs, UAldo:C appeared to be increased by spironolactone and was positively associated with furosemide dose (P = 0.024). Aldosterone breakthrough (ABT) appeared to occur in 36% (8/22) of stage C dogs not receiving spironolactone. A significant positive association between UAldo:C and left atrium-to-aortic root ratio (LA/Ao) was found. CONCLUSIONS: Individual factors such as breed, sex and age appeared to influence UAldo:C, and therapy seemed to add further variability. In the light of these results, comparing the UAldo:C of a single patient with a population-based reference value might lead to wrong interpretations and an individual monitoring should be considered. The prevalence of ABT in the present study (36%) was in line with those previously reported. However, due to the high individual variability of UAldo:C found in the study, even this result should be re-evaluated in the setting of an individual longitudinal approach. The positive association between UAldo:C and LA/Ao supports the mutual relationship between RAAS and cardiac remodeling.

Emulsions with alkyl polyglucosides as carriers for off-label topical spironolactone - safety and stability evaluation.

Androgens play an important role in the pathogenesis of acne. Being an anti-androgen drug with many side effects, spironolactone has recently been used in dermatology as a topical therapy for acne. Off-label drug use in dermatology is common, although those drugs are basically available as compounded formulations; the choice of a proper vehicle is often neglected in that case. Alkyl polyglucosides (APGs) are a FDA certified class of polyethylene glycol (PEG)-free surfactants produced from the renewable resources. Following the preformulation tests, two different APG emulsifiers were used in this study to stabilize emulsions as carriers for topical spironolactone. Assessment of the physical stability of emulsions per se and after incorporation of 5% of spironolactone was performed using polarization microscopy, electrical conductivity and pH measurements. The skin irritation profile and moisturizing potential was assessed in vivo on human volunteers. APG-based emulsions per se and with 5% of spironolactone showed acceptable skin irritation profiles and significant potential for skin hydration, which is important in acne treatment. Good physical stability and satisfying preliminary safety profile of all investigated samples were also obtained showing that moisturizing APG-based emulsions could be promoted as vehicles for off-label topical spironolactone.

Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease.

BACKGROUND: Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 and potassium < 5.0 mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD). METHODS: This single-center, retrospective cohort study evaluated patients ≥ 18 years with HF and CKD stages 3-5 who received ≥ 48 h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5 mEq/L). RESULTS: Overall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia-all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22 mL/min/1.73 m2; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05). CONCLUSION: Spironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.

Long-term use of spironolactone for acne in women: A case series of 403 patients.

BACKGROUND: There are limited data regarding the long-term outcomes of spironolactone use for women with acne and its effect on truncal acne. OBJECTIVE: To comprehensively describe outcomes of patients treated with spironolactone in routine clinical practice, including long-term outcomes. METHODS: We performed a retrospective case series of 403 adult women treated for acne with spironolactone at an academic medical center between 2008 and 2019. Rates of objective, as assessed by Comprehensive Acne Severity Scale scores, and subjective acne clearance were evaluated, as well as rates of treatment discontinuation, dosage changes, and drug survival. Logistic regression was used to assess for association between incidence of menstrual adverse effects and combined oral contraceptive use. RESULTS: As evaluated by Comprehensive Acne Severity Scale scores, at the first follow-up, 75.5%, 84.0%, and 80.2% of patients with available data had reduction or complete clearance of acne on the face, chest, and back, respectively. The mean drug survival was 470.7 days. Menstrual adverse effects were less common among those using combined oral contraception (odds ratio, 0.23; 95% confidence interval, 0.11-0.50). LIMITATIONS: This study was conducted at a single academic medical center. CONCLUSIONS: Spironolactone improves clinical outcomes and is well tolerated for many adult women with acne using it for an extended duration.

Profiling gene expression dynamics underpinning conventional testing approaches to better inform pre-clinical evaluation of an age appropriate spironolactone formulation.

There is a need to accelerate paediatric formulation evaluation and enhance quality of early stage data in drug development to alleviate the information pinch point present between formulation development and clinical evaluation. This present work reports application of DNA microarrays as a high throughput screening tool identifying markers for prediction of bioavailability and formulation driven physiological responses. With a focus on enhancing paediatric medicine provision, an oral liquid spironolactone suspension was formulated addressing a paediatric target product profile. Caco-2 cells cultured on transwell inserts were implemented in transport assays in vitro and DNA microarrays were used to examine gene expression modulation. Wistar rats were used to derive in vivo bioavailability data. In vitro, genomic, and in vivo data sets were concurrently evaluated linking drug transport and the genomic fingerprint generated by spironolactone formulation exposure. Significant changes in gene expression are reported as a result of formulation exposure. These include genes coding for ATP-binding cassette (ABC) transporters, solute carrier (SLC) transporters, cytochrome P450 (CYP) enzymes, and carboxylesterase enzymes. Genomic findings better inform pre-clinical understanding of pharmacokinetic and pharmacodynamic responses to spironolactone and its active metabolites than current in vitro drug transport assays alone.

Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS.

Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.

Optimizing the Trial Design for a Comparative Effectiveness Study of Spironolactone versus Oral Antibiotics for Women With Acne: A Delphi Consensus Panel.

For women with acne, their acne often persists into adulthood, with over 50% of women reporting acne between 20–29 years of age and over 35% of women reporting acne between 30–39 years of age.1 While mild acne can usually be managed with topical medications, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, spironolactone, and isotretinoin.2 Although oral antibiotics are the most common systemic medication prescribed for women with moderate to severe acne, spironolactone may represent a safe and effective therapeutic alternative that can decrease our reliance on oral antibiotics for the treatment of acne.3–5 However, while spironolactone use is increasing, oral antibiotics are still prescribed 3 to 5 times more often than spironolactone.3.