Male pattern hair loss (MPHL), also known as androgenetic alopecia (AGA), is a common condition characterized by progressive hair loss due to changes in the hair cycle, follicular miniaturization, and inflammation. AGA is influenced by genetics and an excessive response to androgens. Finasteride, a 5-α-reductase inhibitor (5-ARI), is used to treat AGA by preventing the conversion of testosterone to dihydrotestosterone (DHT).
Androgenetic alopecia (AGA) is the most prevalent cause of hair loss in men, typically starting between adolescence and 30 years of age. A younger onset often predicts a more severe form of the condition. AGA is characterized by an excessive response to androgens, leading to changes in the hair cycle.
During normal hair growth, the activation of the androgen receptor shortens the anagen (growth) phase. Excessive activation of the androgen receptor by DHT leads to progressively shorter anagen phases and follicular miniaturization. This results in shorter and thinner hair follicles that are unable to reach the surface of the scalp, creating the appearance of hair loss seen in patients with AGA.
Finasteride is a competitive inhibitor of the type II and III isoenzymes of 5-alpha reductase, inhibiting testosterone conversion to dihydrotestosterone (DHT). Finasteride is a type II 5-ARI used to limit the conversion of testosterone to DHT. By reducing the amount of circulating DHT, finasteride reduces its potential impact on androgen receptors, thereby improving hair growth in men with AGA.
Oral finasteride, 1 mg daily, is the only 5-ARI that has received Food and Drug Administration (FDA) approval for AGA treatment. It works by inhibiting the enzyme, 5-alpha reductase, which regulates the production of dihydrotestosterone (DHT). By lowering DHT levels in the scalp, it reduces DHT's harmful effect on hair follicles.
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Clinical trials have demonstrated the effectiveness of finasteride in treating AGA.
In two 1-year trials, 1553 men with AGA were treated with oral finasteride, 1 mg, or placebo daily, and 1215 men continued in blinded extension studies for a second year. These trials showed that finasteride led to improvement in hair counts, patient/investigator assessments of hair growth, and panel review of photographs. In a systematic review that included 12 studies, 3927 men with AGA were randomized to receive either oral finasteride or placebo.
In a multicenter, open-label, prospective outpatient study, 110 Japanese men with AGA completed 52 weeks of treatment with dutasteride, 0.5 mg, daily. Hair growth, hair restoration, and global appearance of hair at 52 weeks improved from baseline in this study. In a randomized, placebo-controlled study, researchers compared the efficacy of dutasteride to finasteride. This study had a large sample size of 917 men with AGA and participants were randomized to receive dutasteride (0.02, 0.1, or 0.5 mg/d), finasteride (1 mg/d), or placebo. Dutasteride, 0.5 mg, significantly increased hair count and improved hair growth at week 24 compared with finasteride (P = .003, P = .004, and P = .002, respectively) and placebo (all P < .001). Two different meta-analyses demonstrated that oral dutasteride was more effective than oral finasteride for the treatment of male AGA. In the first meta-analysis, 23 studies were included, with 2 studies being single-group observational studies and the remaining 21 studies being randomized trials. This meta-analysis showed that taking oral dutasteride, 0.5 mg, daily led to a greater increase in total hair count after 24 weeks. The other meta-analysis found that dutasteride provided better efficacy than finasteride in treating men with AGA during a 24-week treatment period. Three articles with 576 participants were included in the meta-analysis.
In recent years, topical administration of finasteride has been studied. In a randomized, double-blind, double-dummy, parallel-group study conducted in men with AGA over a 24-week period, patients were randomized to either receive topical finasteride, oral finasteride, or placebo. Compared with placebo, topical finasteride significantly increased hair count from baseline to week 24 (adjusted mean change, 20.2 vs.
Research published on topical dutasteride in treating AGA is limited to a few studies where topical dutasteride has been used as an agent in mesotherapy. In a blinded, placebo-controlled study, participants were randomized to receive 7 intradermal mesotherapy injections of either 0.05% dutasteride containing solution or 0.9% saline over 12 weeks or receive placebo. The study found that those receiving dutasteride had a statistically significant increase in mean hair count when compared with placebo (Mean Density, 7.90 hairs [95% CI, 7.14-8.66]; P ≤ .001). There was a statistically significant improvement with dutasteride in independent observer assessment (P = .001) and participants’ self-assessment (P < .001). A recent randomized, double-blind, placebo-controlled trial evaluated the use of microneedling with topical 0.01% solution dutasteride compared with saline solution over a 20-week period in men with AGA. We found only 1 study comparing topical and oral dutasteride in the treatment of AGA. A systematic review compared the findings of 5 studies with oral dutasteride and 3 studies with intralesional dutasteride. None of the included studies directly compared oral vs intralesional dutasteride. Researchers compared the mean change in hair count between oral or intralesional dutasteride and placebo, although only 1 study reported hair count for intralesional dutasteride.
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The most common category of complications reported with finasteride use is sexual adverse effects. A recent systematic review evaluated sexual dysfunction in men taking systemic dermatologic medication. This review found that most studies with patients taking high-dose finasteride described relatively common sexual adverse effects of decreased libido, impotence, and ejaculation disorders. However, high-dose finasteride at 5 mg daily is typically used to treat BPH and is rarely used in dermatology. It is also important to note that prostate disease itself is a risk factor for erectile dysfunction, which may contribute to the development of sexual dysfunction. Among studies with men taking low-dose finasteride at 1 mg daily for AGA, there was less conclusive evidence of sexual adverse effects. Five studies included in the systematic review did not support increased risk of sexual dysfunction, while 10 studies provided evidence of increased rates of sexual adverse effects. The researchers acknowledged that this review included studies limited by sample size and methodology, with some studies not including any formal evaluation of male sexual function. A meta-analysis examined the risk of adverse sexual effects in men treated with 5-ARIs for AGA. A subgroup analysis of 11 studies found that among men with AGA, there was a statistically significant increase in sexual dysfunction in those treated with finasteride, 1 mg, daily compared with placebo. Finasteride, 1 mg, daily had a 1.66-fold risk of adverse sexual effects overall compared with placebo (95% CI, 1.20-2.30). When sexual adverse events occur in patients taking finasteride, some studies have indicated that symptoms often resolve either while continuing treatment or with discontinuation of the medication. However, in recent years, there have been reports of persistent sexual (low libido, erectile dysfunction, and orgasmic dysfunction) and psychological (depression, anxiety, and suicidal ideation) symptoms that persist despite discontinuation of finasteride. This led to the coining of the term postfinasteride syndrome. In a retrospective study examining this topic, 71 men with a history of finasteride treatment and persistent sexual adverse symptoms underwent standardized interviews. The participants reported new-onset sexual dysfunction (low libido, erectile dysfunction, and problems with orgasm) associated with finasteride use and these symptoms remained for at least 3 months despite discontinuation of the medication. This contrasts with the results of the Proscar Long-term Efficacy and Safety Study (PLESS), a 4-year, randomized, double-blind, placebo-controlled trial evaluating the incidence and resolution of sexual adverse effects in 3040 men, aged 45 to 78 years, treated with finasteride, 5 mg daily, for benign prostatic hyperplasia. Researchers found that in the first year, 15% of finasteride-treated patients reported sexual adverse effects compared with 7% in the placebo group (P < .001). In the subsequent 3 years of the study, there was no difference between the finasteride and placebo groups in the incidence of new sexual adverse effects. The reported sexual adverse effects resolved while continuing therapy for 12% of the finasteride-treated patients and 19% of the placebo patients. Only 4% of the finasteride-treated patients and 2% of the placebo patients discontinued the study due to sexual adverse effects. In those who discontinued treatment, 50% in the finasteride group and 41% in the placebo group experienced resolution of their sexual adverse effects after stopping treatment. Researchers concluded that there was a higher incidence of sexual adverse effects associated with finasteride use, but only during the first year of treatment. Furthermore, a systematic review found that most patients treated with finasteride had resolution of symptoms after discontinuation or while continuing finasteride therapy. However, there were some studies that described a subset of patients with persistent adverse effects after discontinuation of finasteride. Similar to users of finasteride, there have been reports of sexual dysfunction among those using dutasteride. A meta-analysis of 3 randomized clinical trials found that the most common adverse effect reported with dutasteride compared with placebo for BPH was sexual dysfunction (odds ratio, 0.41 [95% CI, 0.31-0.54]; P < .001). In the first year of treatment, dutasteride was found to cause a higher incidence of sexual dysfunction events compared with placebo (odds ratio, 2.68 [95% CI, 2.19-3.28]; P < .001). The sexual adverse events reported included impotence, decreased libido, gynecomastia, and ejaculation disorder. The sexual adverse events were 2-fold higher in the dutasteride group (16%) than in the placebo group (8%) during the double-blind period. Although those taking dutasteride had a larger incidence of reported sexual dysfunction, the adverse events were reversible and resolved either during treatment or within 6 weeks after treatment discontinuation. The half-life of dutasteride is 5 weeks compared with 6 to 8 hours for finasteride. For this reason, it has been thought that the potential adverse effects of sexual dysfunction with dutasteride could be longer lasting and more challenging to reverse. Despite this hesitancy about dutasteride use, sexual adverse effects in patients treated with dutasteride have been observed to be comparable with those treated with finasteride. A meta-analysis evaluating the risk of sexual dysfunction in men treated with finasteride, 1 mg, daily or dutasteride, 0.5 mg, daily for AGA included 15 randomized, double-blind, placebo-controlled trials with 4495 participants. The relative risk for sexual dysfunction was 1.66 (95% CI, 1.20-2.30) for finasteride and 1.37 (95% CI, 0.81-2.32) for dutasteride. The sexual adverse effects that develop in some patients treated with oral finasteride are thought to be related to the amount of circulating drug in plasma that is needed to attain an effective concentration at the scalp. A randomized, double-blind trial of men with AGA over 24 weeks compared the efficacy of topical finasteride, oral finasteride, and placebo. It found no significant differences between topical finasteride and placebo in mean scores on the Sexual Dysfunction Questionnaire at week 12 or 24. This study also measured finasteride concentrations in plasma and DHT concentrations in serum. The maximum plasma concentration of finasteride was lower in men treated with topical finasteride compared with oral finasteride. For patients who are concerned about systemic adverse effects of oral dutasteride, the possibility of using dutasteride locally could potentially minimize systemic adverse effects on reproduction. In a meta-analysis comparing sexual adverse effects with oral dutasteride and intralesional dutasteride vs placebo in AGA, there were no studies that reported sexual adverse effects with intralesional dutasteride treatment.
There have been studies evaluating the effects of DHT suppression mediated by finasteride on spermatogenesis. The effect of finasteride on spermatogenesis at a higher dose of 5 mg daily has also been examined. In a multicenter, randomized, double-blinded study, 21 healthy men completed treatment with finasteride, 5 mg, daily for 52 weeks and a 24-week follow-up phase. There was a significant decrease in semen volume, sperm count, sperm concentration, and sperm motility. The use of a higher finasteride dose at 5 mg daily compared with 1 mg daily could explain the differences seen in spermatogenesis in healthy men between these 2 studies. At 1 mg daily, there was no significant effect on spermatogenesis (concentration, sperm count, motility), while at 5 mg there was a significant reduction in volume, count, concentration, and motility. This suggests that the effect of finasteride on spermatogenesis is increased with dose administered. In contrast to the studies discussed in healthy individuals, there has been research assessing the impact of finasteride on individuals with a predisposition to infertility. In a multicenter database study investigating the characteristics and referral patterns of men presenting for male infertility assessments, 4287 men were given a standardized male infertility questionnaire to identify potentially reversible causes of infertility. Furthermore, in a retrospective study, 27 (0.6%) of 4400 men who presented for evaluation of infertility were found to be taking low-dose finasteride. After discontinuation of the drug, there was a statistically significant increase in sperm counts (average 11.6-fold increase), with the most significant increase in men with severe oligospermia initially. This study showed that finasteride, even at low doses, may have caused a decrease in sperm count in some men and ce…
Finasteride is not indicated for use in women with hair loss (female pattern hair loss) but is occasionally used (off-label) postmenopause. Finasteride is contraindicated in women who are or may potentially be pregnant. It is not recommended in men that are subfertile. In men planning to have children, some doctors check sperm counts prior to starting finasteride and repeat it after 6 months of treatment.
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