INTRODUCTION — Male androgenetic alopecia (also known as male pattern hair loss and male balding) is a common, progressive form of hair loss distinguished by the reduction of terminal hairs on the scalp in a characteristic distribution (picture 1A-D). The anterior scalp, mid scalp, temporal scalp, and vertex of the scalp are the typical sites of involvement. Hair loss occurs over the course of years.
Although androgenetic alopecia is a benign and asymptomatic disorder, cosmetic concerns lead some patients to seek treatment. The primary pharmacologic therapies for men with androgenetic alopecia are topical minoxidil and oral finasteride. Hair restoration surgery can also result in cosmetic improvement.
The treatment of androgenetic alopecia in men will be reviewed here. The pathogenesis, clinical features, and diagnosis of male androgenetic alopecia are reviewed in greater detail separately. (See "Androgenetic alopecia in males: Pathogenesis, clinical features, and diagnosis".)
FIRST-LINE THERAPIES — Topical minoxidil and oral finasteride are the therapeutic agents that have been most extensively studied for the treatment of androgenetic alopecia in men. Both drugs have demonstrated efficacy and high tolerability in placebo-controlled randomized trials, supporting their status as first-line agents [1]. The response to treatment with finasteride or minoxidil varies. While some men achieve cosmetically significant regrowth, others benefit most from the slowing of additional hair loss. Continuation of these drugs is required to maintain the results of therapy.
Finasteride — Finasteride is an oral inhibitor of dihydrotestosterone (DHT) production that is efficacious for male androgenetic alopecia.
Mechanism of action — Finasteride competitively inhibits the 5-alpha-reductase type 2 enzyme, and thereby inhibits conversion of testosterone to DHT [2]. At a dose of 1 mg/day, finasteride lowers serum and scalp DHT levels by more than 60 percent [3]. The drug has no affinity for the androgen receptor and does not interfere with testosterone action [2]. (See "Androgenetic alopecia in males: Pathogenesis, clinical features, and diagnosis", section on 'Pathogenesis'.)
Efficacy — A meta-analysis of placebo-controlled randomized trials identified moderate quality evidence in support of the use of finasteride for treatment of androgenetic alopecia in men [4]. After 6 or 12 months of treatment, the mean percentage change in hair count was 9 percent higher among patients treated with finasteride compared with patients who were given placebo (95% CI 8-11 percent). This difference increased over time. After 48 months of therapy, the mean percentage change in hair count was 24 percent (95% CI 18-31 percent) higher in patients treated with finasteride.
The proportion of men who achieve clinically significant responses to finasteride was assessed in two one-year randomized trials that were included in the meta-analysis [5]. A total of 1553 men aged 18 to 41 years with predominantly vertex hair loss were randomly assigned to oral finasteride (1 mg/day) or placebo for one year, with blinded extension studies for a second year in 1215 of the men. Finasteride treatment resulted in clinically significant increases in hair count, while treatment with placebo was associated with progressive hair loss. After two years, scalp coverage as assessed by the study investigators was improved in approximately two-thirds of men taking finasteride, versus only 7 percent of men who received placebo. One-third of the men treated with finasteride had the same amount of hair as they did at the start of the study, and only about 1 percent of patients on finasteride lost hair (versus one-third of patients who received placebo). In addition, more men in the finasteride group reported increased satisfaction with their hair after treatment (51 versus 25 percent).
Although most published studies documenting the efficacy of finasteride have focused on the vertex of the scalp, the efficacy of finasteride is not limited to this area. A randomized trial of 326 men found that the drug was efficacious for frontal scalp hair thinning [6]. In addition, a subsequent randomized trial found statistically significant hair growth in the vertex, anterior/mid, frontal, and temporal scalp, with the best results observed in the vertex and anterior/mid scalp. Age appeared to be relevant in the response to treatment; treatment was more effective in younger men (ages 18 to 41) than older men (ages 41 to 60).
In addition to improved hair counts, other factors, such as increases in hair thickness, pigmentation, and length may contribute to the perception of improved scalp coverage during therapy [3]. This concept is supported by a randomized trial that followed men treated with finasteride for up to 192 weeks and found that net improvements in hair weight were greater than improvements in hair count [7,8].
Administration — For the treatment of male androgenetic alopecia, the recommended dose of finasteride is 1 mg per day. The medication may be taken with or without food.
Treatment with finasteride should continue for at least 12 months to assess the drug's full effects, and the drug must be continued to maintain efficacy. Hair regrowth will be lost over six to nine months if finasteride is discontinued.
Adverse effects — Occasionally, finasteride has deleterious effects on sexual function. These include erectile dysfunction, decreased libido, and ejaculatory dysfunction. A systematic review of nine trials with a total of 3570 patients found an overall absolute increase in sexual dysfunction of 1.5 percent [4]. The risk for sexual side effects increases with age [9].
Sexual side effects related to finasteride usually resolve after discontinuation of the medication [10]. However, persistent sexual dysfunction after the discontinuation of finasteride was reported in a survey-based study of 71 men who associated their symptoms of sexual dysfunction with the use of finasteride for hair loss. The mean age of the study participants was 26 years and the mean duration of finasteride use was 28 months. Twenty percent of these men reported continued symptoms for greater than six years after cessation of the medication [11]. Moreover, a follow-up study of 54 of the interviewed men found that 9 to 16 months after the initial survey, 96 percent continued to report sexual side effects [12]. Additional studies are needed to validate these findings and evaluate the frequency with which persistent sexual dysfunction might occur.
Reductions in sperm count also may occur during treatment with finasteride [13,14]. This effect reverses after drug discontinuation.
Other rare side effects of finasteride include gynecomastia and testicular pain. Side effects are more likely to occur with the typical 5 mg dose used to treat benign prostatic hypertrophy. Although finasteride is teratogenic, the finasteride concentration in semen does not pose a risk to women trying to conceive.
Whether finasteride therapy is a risk factor for suicidality and other adverse psychologic events (eg, depression, anxiety) in patients treated for androgenetic alopecia is unclear [15,16]. Studies exploring this association are limited. A pharmacovigilance study designed to identify disproportional signals of adverse reactions in a global database of drug safety reports suggests either an association between finasteride therapy and risk for suicidality and psychologic adverse events in younger adults treated with finasteride or disproportional signal detection related to stimulated reporting of adverse events [16]. The study identified 356 reports of suicidality (ideation, attempt, or completed suicide) and 2926 reports of psychologic adverse events (depression or anxiety) in users of finasteride; 99 percent of all reports occurred in males, and 71 percent occurred in individuals between the ages of 18 and 44 years. There were significant disproportionality signals for both suicidality (reporting odds ratio [ROR] 1.63, 95% CI 1.47-1.81 with the disproportionality signal driven by suicidal ideation reports) and psychologic adverse events (ROR 4.33, 95% CI 4.17-4.49) for finasteride when compared with reports for other drugs. In addition, when stratified by age and indication, younger patients (ROR 3.47, 95% CI 2.90-4.15) and patients with alopecia (ROR 2.06, 95% CI 1.81-2.34) had significant disproportionality signals for suicidality that were not present in older patients or patients with benign prostatic hyperplasia. The absence of a disproportionality signal for suicidality before 2012, prior to widespread publicization of a potential link between finasteride and psychologic morbidity, suggests a potential contribution of stimulated reporting.
Pending additional data to confirm or negate an association, we discuss a potential risk for psychologic adverse events with patients considering treatment with finasteride.
Precautions — Finasteride may impact measurement of serum prostate-specific antigen (PSA). The PSA can decline significantly in men taking finasteride, resulting in the need to interpret test results accordingly [17]. (See "Measurement of prostate-specific antigen", section on 'Medications'.)
Although randomized trials have found that finasteride therapy decreases risk for prostate cancer, the drug also may increase the risk for high-grade prostate cancer lesions. The relationship between finasteride treatment and prostate cancer is discussed in detail separately. (See "Chemoprevention strategies in prostate cancer", section on 'Finasteride: PCPT'.)
Finasteride is metabolized by the liver. Thus, caution is prudent for use in patients with liver dysfunction. Data are insufficient to conclude whether finasteride influences the risk for male breast cancer [18]. (See "Breast cancer in men".)
Topical minoxidil — In the United States, topical minoxidil is available without a prescription as 2% solution, 5% solution, and 5% foam. Due to evidence in support of greater efficacy of minoxidil 5% solution compared with minoxidil 2% solution in men, use of the 5% concentration is recommended [19].
The subsequent development of minoxidil 5% foam offered an alternative vehicle for drug delivery that is preferred by some patients. In addition, unlike minoxidil solution, the foam formulation is free of propylene glycol, a feature that correlates with a lower risk for skin irritation [20].
Mechanism of action — Minoxidil promotes hair growth by increasing the duration of anagen, shortening telogen, and enlarging miniaturized follicles [21]. The pathophysiologic mechanism through which minoxidil influences follicular structure and follicular cycling is unclear, and the interpretation of the available literature is complicated by studies with conflicting results [3,21]. Minoxidil is a vasodilator, and the induction of vascular endothelial growth factor (VEGF) may be a mechanism by which minoxidil helps to maintain the vascularity and size of dermal papillae (collections of mesenchymal tissue beneath follicles that contribute to follicular development) [22,23]. Since the volume of a dermal papilla correlates with the size of the emerging hair follicle, minoxidil-induced support of the dermal papilla may be relevant. In addition, minoxidil is a regulator of potassium ion channels. This function may also contribute to the drug's beneficial effects [21,24].
Efficacy — Both 2% and 5% minoxidil solution are more efficacious than placebo in male androgenetic alopecia [19,20,25]. However, the 5% solution is more effective than the 2% formulation [19].
In the largest randomized trial that compared the 5% and 2% solutions, 393 men with androgenetic alopecia were randomly assigned to treatment with 5% or 2% topical minoxidil solution or placebo [19]. After 48 weeks of therapy, 5% minoxidil was significantly better than the 2% solution or placebo in terms of change from baseline in nonvellus hair count (increase in count of 18.6, 12.7, and 3.9 per cm2, respectively), patient ratings of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Treatment with 5% minoxidil was also associated with an earlier therapeutic response and an improvement in the patients' psychologic perceptions of hair loss. However, patients treated with 5% compared with 2% minoxidil reported more pruritus and local irritation.
No randomized trials have directly compared the efficacy of minoxidil 5% foam to minoxidil 5% solution. The use of the 5% foam is supported by a 16-week placebo-controlled randomized trial of 352 men [20]. Minoxidil 5% foam was associated with significantly greater improvements in target area terminal hair counts (mean change in terminal hair counts of 20.9 versus 4.7), as well as in scores from patient self-assessments and an investigator global photographic review.
As with finasteride, the response to treatment with minoxidil is variable. In an early study of 56 patients treated with minoxidil 2% or 3% solution, cosmetically significant improvement occurred in approximately 30 percent of patients. Patients with shorter durations of baldness, smaller areas of baldness, and larger numbers of nonvellus miniaturized hairs appeared to respond best to minoxidil therapy [26].
Administration — Men utilizing minoxidil for androgenetic alopecia should be advised of the following:
●Minoxidil solution is to be used for an indefinite time. Once stopped, any hair regrowth eventually will be lost, often over the course of several months.
●Minoxidil is a scalp treatment, not a hair treatment, and must be used exactly as prescribed for maximum benefit.
●Men should apply 1 mL of minoxidil 5% solution or one half of a capful of the 5% foam twice daily to involved areas on a dry scalp. The solution can be spread lightly with a finger; massage is not needed.
●Hair shedding may occur at the initiation of treatment and is thought to occur as a result of the stimulation of telogen follicles to reenter the anagen phase [27]. The increased hair loss usually resolves within two months. Patients should be warned of this side effect to prevent the premature discontinuation of treatment.
●Minoxidil must be used twice a day for at least four months prior to evaluating the initial response to therapy [28]. Hair shedding may occur at the initiation of treatment and usually decreases within two months. Hair growth may be seen within four to eight months and stabilizes at 12 to 18 months. Thus, a full year of treatment is recommended before assessing treatment efficacy.
In the United States, minoxidil usually is not covered by medical insurance.
Adverse effects — Side effects from minoxidil are infrequent. The most common side effects are contact dermatitis and irritant dermatitis [29]. When given systemically, minoxidil has antihypertensive properties, but neither 5% nor 2% minoxidil solution alters systolic or diastolic blood pressure, pulse rate, or body weight when applied topically [30]. Nevertheless, due to the potential for systemic absorption when the scalp skin barrier is not intact, caution should be used in patients with cardiovascular disease. Hypertrichosis of the face may occur [31], but generally is not a problem for men.
Comparative studies — Few studies have directly compared the efficacy of topical minoxidil with finasteride [32-34]. Although high quality studies are needed, the available data from small, incompletely blinded randomized trials suggest that finasteride may be more effective than minoxidil for the induction of hair growth:
●Only one randomized trial has compared finasteride (1 mg/day) with the 5% concentration of minoxidil that is recommended for male androgenetic alopecia. In the 12-month open randomized trial in 65 men with androgenetic alopecia, a higher proportion of patients treated with finasteride exhibited minimal to dense hair growth than patients treated with minoxidil solution (80 versus 52 percent) [33].
●Data from an evaluator-blinded randomized trial of 99 men with midfrontal and/or vertex androgenetic alopecia that compared finasteride 1 mg/day with the 2% formulation of minoxidil are less straightforward. Although patients and evaluating clinicians were more likely to perceive increased hair growth at three months with minoxidil, at 12 months, finasteride was associated with significantly greater increases in hair counts, and the differences in patient and evaluator global assessments of clinical response were not statistically significant (62 versus 56 percent improved on blinded evaluator assessment) [34].
●A randomized, open trial of 100 men with androgenetic alopecia evaluated the efficacies of finasteride (1 mg/day) alone, minoxidil 2% solution alone, finasteride and minoxidil in combination, and finasteride plus ketoconazole 2% shampoo [32]. Increased hair growth was detected in all groups. Patients who received finasteride alone or in combination with minoxidil or ketoconazole had significantly greater improvement than patients who received only minoxidil. The best results were attained by the group treated with both finasteride and minoxidil.
Although the last trial found evidence to suggest that combination therapy with finasteride and topical minoxidil may be superior to monotherapy with either agent [32], further study is needed to determine whether combination therapy should be routinely recommended.
SURGERY — Permanent improvement in androgenetic alopecia can be attained through surgical therapy. Hair transplantation using follicular units has become the mainstay of surgical treatment [35]. More invasive and complex procedures that aim to reorient large areas of hair-bearing skin, such as scalp reduction and flaps, are now less commonly performed. The ideal candidates for hair transplantation are patients with stable or medically controlled androgenetic alopecia who desire permanent improvements in hair loss and have an adequate reservoir of hair for transplantation.
The basic principle governing hair transplantation is that of "donor dominance." Hair follicles removed from non-balding occipital scalp and transplanted into areas affected by androgenetic alopecia will maintain the characteristics of the occipital scalp donor site. Because occipital hair is relatively resistant to androgenetic alopecia, transplanted hairs will remain large caliber hairs.
Modern hair transplant techniques rely on the use of "follicular units," which are the natural groupings of one to four hair follicles that occur in the scalp. There are two fundamental ways that a hair transplant can be performed using follicular units: follicular unit transplantation (FUT) and follicular unit extraction (FUE).
●Follicular unit transplantation – With FUT, a strip of tissue 8 to 15 mm wide and 20 to 30 cm long is surgically excised from the occipital scalp under local anesthesia. Follicular units are carefully dissected from the tissue strip with the aid of microscopes and then transplanted into areas of androgenetic alopecia. The procedure leaves a thin linear scar in the occipital scalp.
●Follicular unit extraction – FUE involves the removal of individual follicular units, one by one, from a wide area of the occipital scalp. Although not truly a "scarless" technique, FUE does not leave a linear scar and has advantages for men who want to wear their hair very short.
It takes five to eight hours to perform a standard hair transplant session, with FUE taking longer to perform than FUT. A small hair transplant session may involve the transplantation of 800 to 1000 follicular units. A large session (megasession) would involve 3000 to 6000 grafts of follicular units.
Patients can continue to lose nontransplanted hairs within susceptible areas following hair transplantation, resulting in diminishing satisfaction with the results. The continuation of medical treatment with minoxidil or finasteride following a hair transplant procedure may help to limit further loss of preexisting scalp hair. In a randomized trial of 79 men who underwent hair transplantation for androgenetic alopecia, those treated with finasteride 1 mg for four weeks prior to the transplant and for 48 weeks after the transplant achieved better results [36].
OTHER THERAPIES — Multiple other therapies have been utilized for androgenetic alopecia. Data on the efficacy of these treatments are more limited than for minoxidil and finasteride.
Dutasteride — Dutasteride, an inhibitor of both type 1 and type 2 5-alpha-reductase, is utilized for the treatment of benign prostatic hyperplasia at a dose of 0.5 mg/day (see "Medical treatment of benign prostatic hyperplasia"). It is prescribed by some clinicians as an off-label treatment for androgenetic alopecia.
Compared with finasteride, dutasteride is three times more potent of an inhibitor of 5-alpha-reductase type 2 and 100 times more potent of an inhibitor of 5-alpha-reductase type 1. Serum DHT concentrations are reduced by 93 to 94 percent with 0.5 mg/day of dutasteride compared with around 70 percent with 5 mg/day of finasteride [13].
In comparison to finasteride, fewer studies have evaluated the efficacy and safety of dutasteride in male androgenetic alopecia. Trials in support of the efficacy of dutasteride include:
●A randomized, placebo-controlled trial in 416 men compared a range of doses of dutasteride with finasteride 5 mg daily [37]. Hair growth showed a dose-response effect with dutasteride, and after 12 and 24 weeks of therapy, dutasteride 2.5 mg daily was more effective than finasteride. This dose of dutasteride is much higher than the standard 0.5 mg dose used for benign prostatic hyperplasia. In this study, 13 percent of men treated with dutasteride 2.5 mg daily reported decreased libido.
●The results of another randomized trial (n = 153) support the efficacy of the lower dose of dutasteride for males with androgenetic alopecia [38]. The trial found that dutasteride (0.5 mg/day) was superior to placebo for the treatment of hair loss; the mean increase in hair counts in men treated with dutasteride was 12.2/cm2, compared with 4.7/cm2 in men treated with placebo. There was no significant difference in the number of adverse effects reported in both groups. The most common drug-related adverse effect was sexual dysfunction, which was noted in 4 percent of study participants in the dutasteride group and 3 percent of those in the control group.
Light therapy — Low level laser light therapy (LLLT) may benefit men with androgenetic alopecia [39-41]. Randomized trials evaluating the efficacy of LLLT combs for androgenetic alopecia have found significantly greater increases in terminal hair density in patients treated with LLLT combs for 26 weeks than in patients given sham treatments [39,40]. Additional studies are necessary to determine the optimal treatment regimen and the durability of response to this treatment. LLLT also has been used for the treatment of androgenetic alopecia in females. (See "Female pattern hair loss (androgenetic alopecia in females): Management".)
The mechanism through which LLLT improves androgenetic alopecia is unclear. Proposed mechanisms include acceleration of cellular mitosis, stimulation of hair follicle stem cells or follicular keratinocytes, effects on cell metabolism leading to increased adenosine triphosphate production and cellular activity, and anti-inflammatory effects [40].
Platelet-rich plasma — There is uncertainty regarding the efficacy of platelet-rich plasma (PRP) for androgenetic alopecia [42-44]. Various protocols have been used for treatment. A placebo-controlled randomized half-head trial in 12 men and 13 women with androgenetic alopecia that evaluated the efficacy of three PRP treatments separated by one month found a greater increase in hair density in sites treated with PRP (mean increase of 12.8±32.6 hairs/cm2) compared with the change in control areas (mean decrease of 2.1±31.3 hairs/cm2) six months after the first treatment [43]. However, differences in percentage of anagen hairs, percentage of telogen hairs, anagen/telogen hair ratio, terminal hair density, and hair count between the treated and control areas were not statistically significant. A separate single-blind trial in which two scalp sites in each of the 19 men with androgenetic alopecia were randomly assigned to receive either PRP injections (two treatments separated by one month) or saline injections as a control did not find PRP beneficial for improving the number of terminal or vellus hairs six months after the first treatment [42]. Larger, high-quality trials are necessary to clarify the efficacy of PRP treatment.
Camouflaging agents — A variety of topical camouflaging products can be used to reduce the appearance of hair loss. These include keratin fibers, which are sprinkled onto the hair and a variety of scalp colorants (sprays, lotions, powder cakes). By minimizing the contrast between the color of the scalp and hair, these products reduce the appearance of hair loss. Wigs, toupees, and hairpieces are also effective camouflaging agents.
Other — Several other treatments for androgenetic alopecia have been studied. A 24-week placebo-controlled randomized trial with 16 male patients showed improvement in hair density using the topical prostaglandin analogue latanoprost 0.1% [45]. Topical ketoconazole 2% shampoo may also have some efficacy in treatment of androgenetic alopecia; a small trial of 39 men with androgenetic alopecia showed an increase in hair density after six months of treatment [46].
The role of other treatments such as carpronium chloride, t-flavone, adenosine, pentadecane, and cepharanthine remains to be fully studied. Data are insufficient to recommend the use of topical finasteride and topical fluridil, both of which are topical antiandrogens [27].
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients (see "Patient education: Androgenetic alopecia in men and women (Beyond the Basics)"). We encourage you to print or e-mail this topic review, or to refer patients to our public website, www.uptodate.com/patients, which includes this and other topics.
SUMMARY AND RECOMMENDATIONS
●Disease overview – Male androgenetic alopecia is a common form of hair loss in men that presents with the loss of terminal hairs in characteristic areas of the scalp (picture 1A-D). Although the condition is benign and asymptomatic, some men seek treatment due to cosmetic concerns. (See 'Introduction' above.)
●Pharmacologic treatment – For male patients with androgenetic alopecia who desire treatment, we suggest treatment with oral finasteride (1 mg/day) over topical minoxidil (Grade 2B). Treatment with minoxidil 5% solution or foam is an alternative first-line therapy that may be preferred by patients who prefer to avoid systemic therapy. The response to treatment with both agents is variable. No high quality randomized trials have directly compared their efficacies. (See 'First-line therapies' above.)
Patients treated with finasteride or minoxidil must continue treatment to maintain efficacy. If treatment is discontinued, hair loss will occur within several months after the cessation of therapy. (See 'First-line therapies' above.)
●Surgery – Hair transplantation can result in permanent improvements in hair growth in areas of the scalp affected by androgenetic alopecia. Continuing treatment with minoxidil or finasteride after hair transplantation may help to minimize additional loss of preexisting terminal hairs. (See 'Surgery' above.)
