-
The Journal of Dermatological Treatment Nov 2022Androgenetic alopecia (AGA) is the most common cause of hair loss, often challenging to treat. While oral finasteride (1 mg/d) is an FDA-approved treatment for male... (Review)
Review
BACKGROUND
Androgenetic alopecia (AGA) is the most common cause of hair loss, often challenging to treat. While oral finasteride (1 mg/d) is an FDA-approved treatment for male AGA, oral minoxidil and oral dutasteride are not approved yet. However, clinicians have been increasingly using these two drugs off-label for hair loss. Recently, Japan and South Korea have approved oral dutasteride (0.5 mg/d) for male AGA.
EFFICACY AND SAFETY
A probable efficacy ranking, in decreasing order, is - dutasteride 0.5 mg/d, finasteride 5 mg/d, minoxidil 5 mg/d, finasteride 1 mg/d, followed by minoxidil 0.25 mg/d. Oral minoxidil predominantly causes hypertrichosis and cardiovascular system (CVS) symptoms/signs in a dose-dependent manner, whereas oral finasteride and dutasteride are associated with sexual dysfunction and neuropsychiatric side effects.
PHARMACOKINETICS AND PHARMACODYNAMICS
The average plasma half-lives of minoxidil, finasteride, and dutasteride are ∼4 h, ∼4.5 h, and ∼5 weeks, respectively. Minoxidil acts through multiple pathways to promote hair growth. It has been shown as a vasodilator, an anti-inflammatory agent, a Wnt/β-catenin signaling inducer, and an antiandrogen. Finasteride inhibits 5α-reductase (5AR) type II isoenzyme, while dutasteride inhibits both type I and type II. Thus, dutasteride suppresses DHT levels more than finasteride in the serum and scalp.
Topics: Male; Humans; Minoxidil; Finasteride; Dutasteride; Hair; Alopecia; 5-alpha Reductase Inhibitors
PubMed: 35920739
DOI: 10.1080/09546634.2022.2109567 -
Fertility and Sterility Jan 2020Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or... (Review)
Review
Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Clinical Trials as Topic; Finasteride; Humans; Male; Observational Studies as Topic; Prostatic Hyperplasia; Sexual Dysfunction, Physiological; Syndrome; Withholding Treatment
PubMed: 32033719
DOI: 10.1016/j.fertnstert.2019.11.030 -
Faculty Reviews 2022Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate... (Review)
Review
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate to severe physical, affective, or behavioral symptoms that impair daily activities and quality of life. PMS and PMDD have recently raised great interest in the research community for their considerable global prevalence. The etiology of PMS/PMDD is complex. Ovarian reproductive steroids (estradiol and progesterone) are considered pathogenetic effectors, but the key feature seems to be an altered sensitivity of the GABAergic central inhibitory system to allopregnanolone, a neurosteroid derived from progesterone produced after ovulation. Also, a reduced availability of serotonin seems to be involved. New insights point to a role for genetic and epigenetic modifications of hormonal and neurotransmitter pathways, and inflammation is the potential link between peripheral and neurological integrated responses to stressors. Thus, new therapeutic approaches to PMS/PMDD include inhibition of progesterone receptors in the brain (i.e., with ulipristal acetate), reduced conversion of progesterone to its metabolite allopregnanolone with dutasteride, and possible modulation of the action of allopregnanolone on the brain GABAergic system with sepranolone. Further research is needed to better understand the interaction between peripheral inflammatory molecules (cytokines, interleukins, C-reactive protein, and reactive oxygen species) and the brain neurotransmitter systems in women with PMS/PMDD. If confirmed, neuroinflammation could lead both to develop targeted anti-inflammatory therapies and to define prevention strategies for the associated chronic inflammatory risk in PMS/PMDD. Finally, the observed association between premenstrual disorders and psychological diseases may guide prompt and adequate interventions to achieve a better quality of life.
PubMed: 35574174
DOI: 10.12703/r/11-11 -
JAMA Dermatology Mar 2022There are knowledge gaps regarding the relative efficacy of 3 commonly used drugs for androgenetic alopecia (AGA), namely, minoxidil and the two 5-α reductase... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
There are knowledge gaps regarding the relative efficacy of 3 commonly used drugs for androgenetic alopecia (AGA), namely, minoxidil and the two 5-α reductase inhibitors dutasteride and finasteride.
OBJECTIVE
To examine the relative efficacy of any dose and administration route of minoxidil, dutasteride, and finasteride for the treatment of male AGA.
DATA SOURCES
Systematic searches were performed in PubMed on March 5, 2021, without date restrictions.
STUDY SELECTION
Eligible studies included those that investigated monotherapy with any dose and administration route of minoxidil, dutasteride, and finasteride.
DATA EXTRACTION AND SYNTHESIS
Data on the mean (SD) difference and sample size were used for the bayesian network meta-analyses. League tables and surface under the cumulative ranking curve values were used to examine the relative efficacy of the interventions.
MAIN OUTCOMES AND MEASURES
Study end points were change in total and terminal hair count after 24 and 48 weeks of therapy. The 4 end points were quantified in hairs per square centimeters.
RESULTS
The PubMed search yielded 848 records; after the 2 stages of screening, 23 studies were eligible for quantitative analyses. Mean (SD) age of patients ranged from 22.8 (3.3) years to 41.8 (12.3) years. The greatest increase in total hair count at 24 weeks (ie, first end point) was with 0.5 mg/d of dutasteride, which was significantly more efficacious than 1 mg/d of finasteride (mean difference, 7.1 hairs/cm2; 95% CI, 5.1-9.3 hairs/cm2) and minoxidil (0.25 mg/d [mean difference, 23.7 hairs/cm2; 95% CI, 9.5-38.0 hairs/cm2], 5 mg/d [mean difference, 15.0 hairs/cm2; 95% CI, 3.9-26.1 hairs/cm2], and 2% solution [mean difference, 8.5 hairs/cm2; 95% CI, 4.8-12.3 hairs/cm2]). The greatest increase in terminal hair count at 24 weeks (ie, second end point) was with 5 mg/d of minoxidil, which was significantly more efficacious than the 0.25-mg/d dose (mean difference, 43.6 hairs/cm2; 95% CI, 29.7-57.7 hairs/cm2) and its topical forms (in 2% [mean difference, 29.3 hairs/cm2; 95% CI, 21.1-37.5 hairs/cm2] and 5% [mean difference, 29.8 hairs/cm2; 95% CI, 19.7-39.8 hairs/cm2]); 5 mg/d of minoxidil was significantly more efficacious than 1 mg/d of finasteride (mean difference, 10.4 hairs/cm2; 95% CI, 2.2-18.6 hairs/cm2). The greatest increase in total hair count at 48 weeks (ie, third end point) was with 5 mg/d of finasteride, which was significantly more efficacious than 2% topical minoxidil (mean difference, 20.7 hairs/cm2; 95% CI, 9.5-31.9 hairs/cm2). The greatest increase in terminal hair count at 48 weeks (ie, fourth end point) was with 1 mg/d of finasteride, which was significantly more effective than topical minoxidil (in 2% [mean difference, 32.1 hairs/cm2; 95% CI, 23.9-40.3 hairs/cm2] and 5% [mean difference, 26.2 hairs/cm2; 95% CI, 16.2-36.2 hairs/cm2]).
CONCLUSIONS AND RELEVANCE
As efficacy data from head-to-head trials accumulate, there could be a better sense of the relative efficacy of the different doses of the 5-α reductase inhibitors and minoxidil. The findings of this meta-analysis contribute to the comparative effectiveness literature for AGA therapies with regard to the compared interventions.
Topics: 5-alpha Reductase Inhibitors; Adult; Alopecia; Bayes Theorem; Dutasteride; Finasteride; Humans; Male; Minoxidil; Network Meta-Analysis; Treatment Outcome; Young Adult
PubMed: 35107565
DOI: 10.1001/jamadermatol.2021.5743 -
The World Journal of Men's Health Jul 20205α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate,... (Review)
Review
5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5α-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5α-DHT in the physiological function of liver, pancreatic β-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5α-reductases with finasteride or dutasteride to reduce 5α-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (AGA) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5α-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5α-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with AGA. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.
PubMed: 32202088
DOI: 10.5534/wjmh.200012 -
American Journal of Clinical Dermatology Jan 2023Male androgenetic alopecia is a common condition and represents a major concern for patients who experience this condition. While there are different treatments to stop...
Male androgenetic alopecia is a common condition and represents a major concern for patients who experience this condition. While there are different treatments to stop hair loss and improve hair density, the 5-alpha reductase inhibitors have demonstrated to be effective in improving androgenetic alopecia in men and can maintain a positive response for many years. Oral finasteride 1 mg is a US FDA-approved option, but dutasteride 0.5 mg has been proven to induce better responses, especially in the frontal area. Both have been shown to be safe in clinical trials but there is widespread concern about sexual adverse effects among patients. The use of topical finasteride has increased during the last few years as a useful option to avoid systemic therapy. The efficacy of topical finasteride 0.25% daily has been demonstrated in clinical trials, with a less marked decrease in serum dihydrotestosterone levels than with oral intake. Mesotherapy with dutasteride has also become more widespread recently, although evidence of its effectiveness is limited to retrospective studies in real clinical practice. The use of oral minoxidil in androgenetic alopecia has not been approved by the FDA, however several clinical studies have shown that it is an effective treatment option. The initial dose recommended to treat male hair loss is 2.5 mg daily, although the dose is frequently increased to 5 mg daily. The main adverse effect of oral minoxidil is hypertrichosis, followed by dizziness or lower limb edema, which are much less common. Platelet-rich plasma is a non-pharmacological option to treat male androgenetic alopecia, with some clinical trials demonstrating an improvement in hair count after several months. Among the published studies, the main limitation to compare its efficacy is the heterogeneity of the procedure. The most frequent regimens propose treatment every 4 weeks for 3 months initially to assess the individual response. Another treatment alternative is the use of light devices with wavelengths of between 630 and 660 nm, known as low-level laser therapy. These devices can be used at home every day for 15-30 min. Their efficacy has been shown in a limited number of clinical trials; however, there is a lack of evidence about the efficacy of these devices compared with other medical options or as a complementary therapy in hair loss. The pipeline of potential new treatments for male androgenetic alopecia is strong. Pyrilutamide and GT20029 are being studied as topical antagonists of the androgen receptor, while cetirizine is another topical option with some initial promising results. Furthermore, according to isolated studies with heterogeneous treatment schemes, the use of botulinum toxin in the scalp might improve androgenetic alopecia, and lastly, scalp threading might increase the total hair count as growth factors are released during implantation.
Topics: Humans; Male; Alopecia; Dutasteride; Finasteride; Minoxidil; Retrospective Studies; Treatment Outcome
PubMed: 36169916
DOI: 10.1007/s40257-022-00730-y -
Journal of Drugs in Dermatology : JDD Jul 20225-alpha inhibitors are an effective treatment for androgenetic alopecia. Mesotherapy with dutasteride has been proposed as an effective method to improve hair loss and...
BACKGROUND
5-alpha inhibitors are an effective treatment for androgenetic alopecia. Mesotherapy with dutasteride has been proposed as an effective method to improve hair loss and reducing systemic absorption.
OBJECTIVE
The main objective was to describe the safety profile of mesotherapy with dutasteride in real clinical practice in a large cohort of patients with androgenetic alopecia. A secondary aim was to describe the effectiveness of this treatment.
METHODS AND MATERIALS
A multicentric retrospective study was designed. Patients treated with at least 6 months of follow-up were included in the study. Side effects and response to the treatment were analyzed.
RESULTS
A total of 541 patients were included. The commonest approach during the first year was to perform the treatment every 3 months. Response to the mesotherapy in monotherapy could be assessed in 86 patients (15.9%) after one year. Most of them presented clinical improvement, being a marked improvement in 33 patients (38.4%). Pain was the most frequent side effect of the treatment (246 patients, 45.5%). No serious or sexual adverse events were detected.
CONCLUSION
Mesotherapy with dutasteride was effective in male and female hair loss in real clinical practice. Side effects related to the treatment were mild and self-limited. This therapy may be an effective option for select patients wishing to avoid oral treatment. J Drugs Dermatol. 2022;21(7):742-747. doi:10.36849/JDD.6610.
Topics: Alopecia; Dutasteride; Female; Hair; Humans; Male; Mesotherapy; Retrospective Studies; Treatment Outcome
PubMed: 35816059
DOI: 10.36849/JDD.6610 -
The Journal of Dermatological Treatment Dec 2023Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through... (Review)
Review
Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through intradermal injections, mesotherapy can increase the residence time of therapeutic agents in the affected area, thus allowing for the use of lower doses and longer intervals between sessions which may in turn improve the treatment outcome and patient compliance. This systematic review aims to summarize the current literature that evaluates the efficacy of this technique for the treatment of hair loss and provides an overview of the results observed. Of the 416 records identified, 27 articles met the inclusion criteria. To date, mesotherapy using 6 classes of agents and their combinations have been studied; this includes dutasteride, minoxidil, growth factors or autologous suspension, botulinum toxin A, stem cells, and mesh solutions/multivitamins. While several studies report statistically significant improvements in hair growth after treatment, there is currently a lack of standardized regimens. The emergence of adverse effects after mesotherapy has been reported. Further large-scale and controlled clinical trials are warranted to evaluate the utility of mesotherapy for hair loss disorders.
Topics: Humans; Mesotherapy; Alopecia; Minoxidil; Treatment Outcome; Injections, Intradermal
PubMed: 37558233
DOI: 10.1080/09546634.2023.2245084