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Dermatologic Therapy Jan 2020Androgenetic alopecia (AGA) is common and associated with significant psychosocial distress. Treatment options are needed for patients that do not adequately respond to...
Androgenetic alopecia (AGA) is common and associated with significant psychosocial distress. Treatment options are needed for patients that do not adequately respond to first line treatments of finasteride or minoxidil. Topical ketoconazole has been proposed as a promising treatment. The goal of this systematic review was to evaluate the efficacy of topical ketoconazole in the treatment of AGA. A systematic literature search was conducted within the MEDLINE database using the key terms "ketoconazole" and "alopecia." Forty-seven papers were screened for inclusion, of which nine were assessed for eligibility. Seven articles were included in the qualitative synthesis, including two animal studies (total of 40 participants) and five human studies (total of 318 participants). Murine studies demonstrated a significant increase in mean ratio of hair regrowth to denuded area in the ketoconazole treatment groups compared to controls. Human studies reported increased hair shaft diameter following ketoconazole use. One study reported a significant increase in pilary index (percent anagen phase × diameter) following treatment. Studies also demonstrated clinical improvement of AGA based on photographic assessment and subjective evaluation. Topical ketoconazole is a promising adjunctive or alternative therapy in the treatment of AGA. Randomized controlled trials are needed.
Topics: Administration, Topical; Alopecia; Animals; Hair; Humans; Ketoconazole; Mice; Treatment Outcome
PubMed: 31858672
DOI: 10.1111/dth.13202 -
Advances in Nutrition (Bethesda, Md.) Jun 2021Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk...
Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.
Topics: Humans; Male; Plant Extracts; Spices; Testosterone
PubMed: 33150931
DOI: 10.1093/advances/nmaa134 -
Skin Appendage Disorders Mar 2022In this systematic review, we summarize the efficacy and safety of intradermal and intramuscular botulinum toxin injections for androgenic alopecia (AGA). Using PubMed,...
In this systematic review, we summarize the efficacy and safety of intradermal and intramuscular botulinum toxin injections for androgenic alopecia (AGA). Using PubMed, we conducted a literature search up to February 2021 using the following keyword combinations: "botulinum toxin" or "botox" and "androgenetic alopecia," "hair loss," or "alopecia." Five clinical studies met our inclusion criteria: 4 prospective cohorts and 1 randomized clinical trial (RCT). Study durations ranged from 24 to 60 weeks. No studies included control groups or compared botulinum toxin injections against approved treatments. A total of 165 participants were identified - all of whom were males with AGA. Of the 4 studies measuring response rates (i.e., subjects with >0% hair changes), response rates ranged from 75 to 79.1%. Within studies measuring hair count changes from intramuscular injections, changes ranged from 18 to 20.9%. No serious adverse events were reported. Studies on botulinum toxin injections have produced favorable outcomes for AGA subjects. However, results should be interpreted with caution due to the absence of control groups, small numbers of participants, and relatively low Jadad quality scores. Large RCTs are recommended to confirm efficacy and safety, explore the effects of botulinum toxin on females with pattern hair loss, and establish best practices for intradermal and intramuscular injection methodologies.
PubMed: 35415183
DOI: 10.1159/000518574 -
The Lancet. Diabetes & Endocrinology Oct 2019The benefits and risks of testosterone treatment for women with diminished sexual wellbeing remain controversial. We did a systematic review and meta-analysis to assess... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The benefits and risks of testosterone treatment for women with diminished sexual wellbeing remain controversial. We did a systematic review and meta-analysis to assess potential benefits and risks of testosterone for women.
METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for blinded, randomised controlled trials of testosterone treatment of at least 12 weeks' duration completed between Jan 1, 1990, and Dec 10, 2018. We also searched drug registration applications to the European Medicine Agency and the US Food and Drug Administration to identify any unpublished data. Primary outcomes were the effects of testosterone on sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42018104073.
FINDINGS
Our search strategy retrieved 46 reports of 36 randomised controlled trials comprising 8480 participants. Our meta-analysis showed that, compared with placebo or a comparator (eg, oestrogen, with or without progestogen), testosterone significantly increased sexual function, including satisfactory sexual event frequency (mean difference 0·85, 95% CI 0·52 to 1·18), sexual desire (standardised mean difference 0·36, 95% CI 0·22 to 0·50), pleasure (mean difference 6·86, 95% CI 5·19 to 8·52), arousal (standardised mean difference 0·28, 95% CI 0·21 to 0·35), orgasm (standardised mean difference 0·25, 95% CI 0·18 to 0·32), responsiveness (standardised mean difference 0·28, 95% CI 0·21 to 0·35), and self-image (mean difference 5·64, 95% CI 4·03 to 7·26), and reduced sexual concerns (mean difference 8·99, 95% CI 6·90 to 11·08) and distress (standardised mean difference -0·27, 95% CI -0·36 to -0·17) in postmenopausal women. A significant rise in the amount of LDL-cholesterol, and reductions in the amounts of total cholesterol, HDL-cholesterol, and triglycerides, were seen with testosterone administered orally, but not when administered non-orally (eg, by transdermal patch or cream). An overall increase in weight was recorded with testosterone treatment. No effects of testosterone were reported for body composition, musculoskeletal variables, or cognitive measures, although the number of women who contributed data for these outcomes was small. Testosterone was associated with a significantly greater likelihood of reporting acne and hair growth, but no serious adverse events were recorded.
INTERPRETATION
Testosterone is effective for postmenopausal women with low sexual desire causing distress, with administration via non-oral routes (eg, transdermal application) preferred because of a neutral lipid profile. The effects of testosterone on individual wellbeing and musculoskeletal and cognitive health, as well as long-term safety, warrant further investigation.
FUNDING
Australian National Health and Medical Research Council.
Topics: Androgens; Female; Hormone Replacement Therapy; Humans; Libido; Sexual Dysfunction, Physiological; Testosterone; Treatment Outcome; Women's Health
PubMed: 31353194
DOI: 10.1016/S2213-8587(19)30189-5 -
Medicina (Kaunas, Lithuania) Nov 2020Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused...
Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers' bodies. A systematic review of the scientific literature was performed using the PubMed database and the keywords "nandrolone decanoate". The inclusion criteria for articles or abstracts were English language and the presence of the following words: "abuse" or "adverse effects". After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study. The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%). Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.
Topics: Adolescent; Anabolic Agents; Androgens; Exercise; Humans; Male; Nandrolone; Nandrolone Decanoate
PubMed: 33187340
DOI: 10.3390/medicina56110606 -
Current Neuropharmacology Jan 2015The use of anabolic-androgenic steroids (AASs) by professional and recreational athletes is increasing worldwide. The underlying motivations are mainly performance... (Meta-Analysis)
Meta-Analysis Review
The use of anabolic-androgenic steroids (AASs) by professional and recreational athletes is increasing worldwide. The underlying motivations are mainly performance enhancement and body image improvement. AAS abuse and dependence, which are specifically classified and coded by the DSM-5, are not uncommon. AAS-using athletes are frequently present with psychiatric symptoms and disorders, mainly somatoform and eating, but also mood, and schizophrenia-related disorders. Some psychiatric disorders are typical of athletes, like muscle dysmorphia. This raises the issue of whether AAS use causes these disorders in athletes, by determining neuroadaptive changes in the reward neural circuit or by exacerbating stress vulnerability, or rather these are athletes with premorbid abnormal personalities or a history of psychiatric disorders who are attracted to AAS use, prompted by the desire to improve their appearance and control their weights. This may predispose to eating disorders, but AASs also show mood destabilizing effects, with longterm use inducing depression and short-term hypomania; withdrawal/discontinuation may be accompanied by depression. The effects of AASs on anxiety behavior are unclear and studies are inconsistent. AASs are also linked to psychotic behavior. The psychological characteristics that could prompt athletes to use AASs have not been elucidated.
Topics: Anabolic Agents; Antisocial Personality Disorder; Athletes; Athletic Performance; Humans; Mental Disorders; Psychopathology; Steroids; Substance-Related Disorders; Testosterone Congeners
PubMed: 26074746
DOI: 10.2174/1570159X13666141210222725 -
The Journal of Steroid Biochemistry and... Jun 2021Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in dietary patterns, and men's testosterone levels have declined in western countries. Cross-sectional studies show inconsistent associations between fat intake and testosterone in men.
METHODS
Studies eligible for inclusion were intervention studies, with minimal confounding variables, comparing the effect of low-fat vs high-fat diets on men's sex hormones. 9 databases were searched from their inception to October 2020, yielding 6 eligible studies, with a total of 206 participants. Random effects meta-analyses were performed using Cochrane's Review Manager software. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
There were significant decreases in sex hormones on low-fat vs high-fat diets. Standardised mean differences with 95 % confidence intervals (CI) for outcomes were: total testosterone [-0.38 (95 % CI -0.75 to -0.01) P = 0.04]; free testosterone [-0.37 (95 % CI -0.63 to -0.11) P = 0.005]; urinary testosterone [-0.38 (CI 95 % -0.66 to -0.09) P = 0.009]; and dihydrotestosterone [-0.3 (CI 95 % -0.56 to -0.03) P = 0.03]. There were no significant differences for luteinising hormone or sex hormone binding globulin. Subgroup analysis for total testosterone, European and North American men, showed a stronger effect [-0.52 (95 % CI -0.75 to -0.3) P < 0.001].
CONCLUSIONS
Low-fat diets appear to decrease testosterone levels in men, but further randomised controlled trials are needed to confirm this effect. Men with European ancestry may experience a greater decrease in testosterone, in response to a low-fat diet.
Topics: Diet, Fat-Restricted; Diet, High-Fat; Dihydrotestosterone; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33741447
DOI: 10.1016/j.jsbmb.2021.105878 -
Human Reproduction Update Nov 2023Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.
SEARCH METHODS
Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.
OUTCOMES
The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity.
WIDER IMPLICATIONS
Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.
Topics: Humans; Female; Middle Aged; Androgens; Polycystic Ovary Syndrome; Hyperandrogenism; Cross-Sectional Studies; Prospective Studies; Obesity; Menopause; Cholesterol
PubMed: 37353908
DOI: 10.1093/humupd/dmad015 -
Sports Medicine (Auckland, N.Z.) Sep 2017Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system.
OBJECTIVE
This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users.
METHODS
An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation.
RESULTS
Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) -3.37 IU/L, 95% confidence interval (CI) -5.05 to -1.70, p < 0.001], follicle-stimulating hormone (WMD -1.73 IU/L, 95% CI -2.67 to -0.79, p < 0.001), and endogenous testosterone levels (WMD -10.75 nmol/L, 95% CI -15.01 to -6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13-24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD -9.40 nmol/L, 95% CI -14.38 to -4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility.
CONCLUSION
The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.
Topics: Anabolic Agents; Androgens; Athletes; Female; Genitalia; Gonadotropins; Humans; Hypogonadism; Male; Steroids; Testosterone; Testosterone Congeners
PubMed: 28258581
DOI: 10.1007/s40279-017-0709-z -
American Journal of Clinical Dermatology Apr 2017The management of acne in adult females is problematic, with many having a history of treatment failure and some having a predisposition to androgen excess. Alternatives... (Review)
Review
BACKGROUND
The management of acne in adult females is problematic, with many having a history of treatment failure and some having a predisposition to androgen excess. Alternatives to oral antibiotics and combined oral contraceptives (COCs) are required.
OBJECTIVE
Our aim was to conduct a hybrid systematic review of the evidence for benefits and potential harms of oral spironolactone in the management of acne in adult females.
METHODS
The review was conducted according to a previously published protocol. Three reviewers independently selected relevant studies from the search results, extracted data, assessed the risk of bias, and rated the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Ten randomized controlled trials (RCTs) and 21 case series were retrieved. All trials were assessed as being at a 'high risk' of bias, and the quality of evidence was rated as low or very low for all outcomes. Apart from one crossover trial that demonstrated statistical superiority of a 200 mg daily dose versus inflamed lesions compared with placebo, data from the remaining trials were unhelpful in establishing the degree of efficacy of lower doses versus active comparators or placebo. Menstrual side effects were significantly more common with the 200 mg dose; frequency could be significantly reduced by concomitant use of a COC. Pooling of results for serum potassium supported the recent recommendation that routine monitoring is not required in this patient population.
CONCLUSION
This systematic review of RCTs and case series identified evidence of limited quality to underpin the expert endorsement of spironolactone at the doses typically used (≤100 mg/day) in everyday clinical practice.
Topics: Acne Vulgaris; Administration, Oral; Adult; Androgens; Anti-Bacterial Agents; Contraceptives, Oral, Combined; Female; Humans; Hyperandrogenism; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Sebaceous Glands; Spironolactone; Treatment Failure
PubMed: 28155090
DOI: 10.1007/s40257-016-0245-x