Androgenetic alopecia (also known as male or female pattern hair loss and androgenic alopecia) is a common, progressive form of hair loss distinguished by the reduction of terminal hairs on the scalp in a characteristic patterns. The top of the head is the most common problem area, but it can be anywhere. Hair loss usually occurs gradually over the course of years, but can begin rapidly.

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 (hair transplants) can also result in cosmetic improvement.

Androgenic hormones, also referred to as androgens or testoids, are a family of sex hormones that promote male attributes, they are believed to be the most significant underlying factor behind androgenetic alopecia. Dihydrotestosterone, or DHT, is an androgen that can bind to receptors in the hair, causing androgen-sensitive hair follicles to shorten the hair growth phase, shrink and eventually fall out permanently. Dht it is believed to the be the androgenic hormone which has the the strongest necrotic effects on hair follicles.

The treatment of androgenetic alopecia, mostly for 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 men: Pathogenesis, clinical features, and diagnosis".)

Androgenetic alopecia is by far the most common form of hair loss, it can affect both men and women (even dough it is more common in men), and it accounts for more than 95% of hair loss in men. It usually follows one or more of this patterns:

Most common patterns associated with androgenetic alopecia:

Classic male pattern baldness (Norwood scale) More aggressive hair loss and thinning in the temples and/or crown areas, but eventually affects the whole scalp, the severity of recession and balding with this specific pattern is measured by dermatologists using the Norwood scale. (some females suffering from androgenetic alopecia may also have this pattern)

Classic female pattern baldness (Ludwig scale, Savin scale, Sinclair scale) Hair thinning and hair loss become apparent along the middle of the scalp, as the parting width becomes progressively wider. More advanced stages may demonstrate diffuse hair thinning over the apex of the scalp. The severity of recession and balding with this specific pattern is measured by dermatologists using the Ludwig scale or the Savin scale. (Some males suffering from androgenetic alopecia may also have this pattern)

Diffuse Patterned baldness (or diffuse thinning) Hair shedding and thinning occurs throughout the whole scalp, therefore reduced hair density and volume may be noted, often it happens without a marked temple and/or crown recession and without a specific pattern)

Retrograde alopecia (or vertical alopecia) Also known as vertical alopecia, it usually involves thinning and shedding of hair in the sides of the head, (usually above the ear and in the sideburns area) it can also come in a vertical fashion, moving up from the nape of the neck into the lower occipital zone (traditional donor area) of the scalp.

Please take note that these specific patterns can co-exist and they often blend, therefore one or more of this patterns can be present in the same individuals. (Usually male pattern baldness + Retrograde alopecia) or (male pattern baldness+ diffuse thinning).

OTHER NON HORMONAL CAUSES OF HAIR LOSS: (Rare) Being that the cause of the following conditions is not hormonal, often medications indicated for treating male pattern baldness (androgenetic alopecia) may be ineffective and/or unnecessary in the case of one of these conditions:

Telogen effluvium The cause is not hormonal, it is usually triggered strong physical or psychological stress and other possible factors. There Is not a specific pattern, and There Is often no thinning involved, Just less density overall (unlike male pattern baldness, female pattern baldness or diffuse thinning, it does not only effects the crown).

Alopecia areata The cause is autoimmune and not hormonal like in the case of androgenetic alopecia, alopecia areata usually results in patchy hair loss with often bald spots which usually are developed without a specific pattern.

Alopecia totalis It is a rare autoimmune skin condition which involves the loss of all skull and facial hair, including the eyebrows, the cause of this condition is again not hormonal.

Food deficiency induced hair loss This type of hair loss is usually triggered by the lack of vitamins or micronutrients in the body. Usually no sign of hair thinning is noted and it does not have a specific pattern. It's noteworthy to mention that vitamin or micronutrient deficiency also leads to skin, vision, mobility and cognitive problems.

Other rare causes of hair loss may include: bacteria, fungal infections or chemotherapy

FIRST-LINE THERAPIES (FDA, MHRA and EMA approved treatments)

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. 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. Between these two compounds, the first choice for a stand alone treatment especially in the long term should be always finasteride over minoxidil, because of its mechanism of action which indirectly targets the androgens and therefore addresses androgenetic alopecia at its root cause, slowing down/stopping/reversing the androgen induced hair miniaturization process. The combination of this two treatments (topical minoxidil and oral finasteride) is proven to be very effective and superior to using treatments alone.

Finasteride

Finasteride is an oral inhibitor of dihydrotestosterone (DHT) production that is efficacious for male androgenetic alopecia.

Mechanism of action — Finasteride inhibits the 5-alpha-reductase type 2 enzyme, and thereby inhibits conversion of testosterone to DHT [1]. At a dose of 1 mg/day, finasteride lowers serum and scalp DHT levels by more than 60 percent [2]. The drug has no affinity for the androgen receptor and does not interfere with testosterone action [1]. (See "Androgenetic alopecia in men: 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 [3]. 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 [4]. 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 [5]. 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 [2]. 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 [6,7].

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. See here for Finasteride dosing guide by itsasickaz Treatment with finasteride should continue for at least 12 months to assess the full effects, and the drug must be continued to maintain efficacy. Hair regrowth will be lost 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 [3]. The risk for sexual side effects increases with age [8].

Sexual side effects related to finasteride usually resolve after discontinuation of the medication [9]. 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 [10]. 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 [11]. 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 [12,13]. This effect reverses after drug discontinuation.

Other rare side effects of finasteride include gynecomastia, testicular pain, and depression [14]. 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.

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 [15]. (See "Measurement of prostate specific antigen", section on 'Medications'.)

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 [16]. (See "Breast cancer in men".)

Topical minoxidil

In the United States, Europe and the UK, 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 [17]. 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 [18].

Mechanism of action — Minoxidil promotes hair growth by increasing the duration of anagen, shortening telogen, and enlarging miniaturized follicles [19]. 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 [2,19]. 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) [20,21]. 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 [19,22].

Efficacy — Both 2% and 5% minoxidil solution are more efficacious than placebo in male androgenetic alopecia [17,18,23]. However, the 5% solution is more effective than the 2% formulation [17].

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 [17]. 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' psychological 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 [18]. 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.

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 [24].

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 will be lost. ● 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 [25]. 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 [26]. 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 topical 5% minoxidil are infrequent. The most common side effects are contact dermatitis and irritant dermatitis [27]. 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 [28]. 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 [29], but generally is not a problem for men.

Comparative studies — Few studies have directly compared the efficacy of topical minoxidil with finasteride [30-32]. 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) [31]. ● 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) [32]. ● 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 [30]. 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 [30], further study is needed to determine whether combination therapy should be routinely recommended.

# Topical Minoxidil enhancers: summary of the best combination treatments to enhance minoxidil effects. (Microneedling and tretinoin 0.01%) In case 5% topical Minoxidil is not working for you (pretty common, it happens to around 40% of users ), or if you just want to maximize your results, you can consider adding one of these two treatments to your stack in order to improve minoxidil absorption and its convertion to the active form minoxidil sulfate by the skin. These treatments are: Microneedling and Tretinoin 0.01%.

Microneedling + topical 5% minoxidil

Microneedling is a minimally invasive procedure involving the induction of percutaneous wounds with medical-grade needles (12b), and can be done at home using either a motorized device (dermapen, derminator and others) or a manual device (dermaroller, dermastamp), this treatment combined with topical 5% minoxidil is shown in a good number of clinical studies to have a synergistic effect and therefore it can be used as a very effective growth stimulant. Implementing microneedling when using topical minoxidil 5% induces collagen production and improves the absorption of the drug. On average in the largest studies published the group that received this combination treatment saw an improvement which was twice as great as the one seen in the minoxidil 5% only group.

We don’t have data on safety or efficacy of long term microneedling but, however, at the Same time, There is no clue of possible long term side effects of microneedling the scalp, in fact, in all clinical studies conducted on short term (more than 22 studies involving more than 1000 total patients) no patient in the microneedling group reported any adverse and/or permanent side effects(11b). Further research is needed to assess the ideal protocol (depth, frequency, duration, procedure endpoint), however What we currently know based on available research is:

• The best protocol (based on the data we have) is using a manual dermaroller at 1.5 mm once a week, and the endpoint of the procedure should be erythema. (2)
• Another good protocol (based on the data we have) is using a motorized microneedling device (dermapen,derminator and others) at 0.6mm depth once every 14 days and the endpoint of the procedure should be pinpoint bleeding (not excessive).(1)
• According to a study, when using motorized microneedling devices such as a dermapen or a derminator the needle penetration often closely matches depth settings, while when using a manual dermaroller actual penetration depth can only reach 50-75% of the actual needle length, depending on how much pressure is applied. This should be taken into consideration in the case you want to follow a specific protocol designed for a manual dermaroller using a dermapen and vice versa.(12)
• Overall safety and efficacy of at least 12 total microneedling sessions is assessed (with up to a 1.5mm manual dermaroller).(2)
• Needling depths of 0.50–2.50 mm are proven to be safe and effective at least for the short term and when using a manual dermaroller (longer needle lengths will require a lower frequency of treatments, and a lower total number of treatments)(11)
• Overall safety and efficacy with 1.2 mm depth motorized dermapen used once every 14 days until pinpoint bleeding is noted Is assessed, (however 0.6mm should be a better option. according to one study).(2)
• Overall Safety and efficacy of a treatment time that goes from 12 to 24 weeks Is assessed (Please take note that when we talk about treatment time we do not refer to it as number of total Microneedling sessions, but rather the time each therapy lasted).
• Frequency on the microneedling sessions Is found safe and effective in a range that goes from once a week to once a month. Published studies often used different frequencies: once a week frequency, once every two weeks, once every three weeks, and up to once a month when combined the treatments were combined with other treatments like PRP.
• Superiority of 0.6 mm depth vs 1.2 mm depth seems to be assessed, at least with a motorized microneedling device and when the protocol involves a frequency of the session of once every 14 days, and when pinpoint bleeding is set as the endpoint of the treatment.(2)
• The procedure should be performed until erythema (redness) is noted which is recommended. It could also be performed untill pinpoint bleeding is noted, at least when using a 0.6mm up to 1.2mm motorized microneedling device. (1)(2)
• You should not use topicals such as Minoxidil 5% for at least 24 hours after the procedure.
• You should disinfect both the dermaroller and your entire scalp before and after the treatment, ideally you should also avoid wearing a cap/hat/hoodie and avoid showering for at least 12-24 hours after the treatment, also make sure to disinfect your hands before the treatment and in the following hours everytime that you need to touch your scalp.
• The best study we have seems to suggest that majority of the gains made with this combination treatment could be easily maintained with only 5% minoxidil after interrupting the microneedling treatment or after lowering significantly the frequency of the microneedling sessions, at least in the short term. (2) All this parameters were assessed (conclusions were taken) after reviewing the following clinical studies, however before starting any treatment, we recommend everyone to do their own research. for this purpose we linked all the studies we referenced to create this summary on microneedling for androgenetic alopecia.

Summary of 11 studies involving microneedling + topical 5% minoxidil and the different protocols used for microneedling the scalp:

60 patients microneedling biweekly at 1.2mm or 0.6mm with a dermapen for 12 weeks + minoxidil

(6 Total sessions) (most effective depth found in This study =0.6mm, also used: 1.2 mm) (Duration: 12 weeks) (Frequency: once every 2 weeks) (Device: motorized microneedling/ dermapen) (60 total patients all groups included)

“Microneedling in androgenetic alopecia; comparing two different depths of microneedles” Gita Faghihi et al. J Cosmet Dermatol. 2021 Apr. Link: https://pubmed.ncbi.nlm.nih.gov/32897622/

100 patients microneedling weekly 1.5 mm with a dermaroller for 12 weeks + minoxidil (12 Total sessions ) (Duration: 12 weeks) (Frequency: once a week (Device: manual dermaroller) (Depth 1.5mm) (100 Total patients all groups included) “A Randomized Evaluator Blinded Study of Effect of Microneedling in Androgenetic Alopecia: A Pilot Study” Rachita Dhurat, MS Sukesh, and Poonam Pund 2013 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/23960389/

68 patients microneedling weekly for 4 weeks and fornightly for 8 weeks, for a Total duration of 12 weeks + minoxidil (8 Total sessions) (Frequency: 4 sessions weekly, 8 sessions once every 15 days) (Duration: 12 weeks) (68 total patients all groups included) “A Randomized Controlled, Single-Observer Blinded Study to Determine the Efficacy of Topical Minoxidil plus Microneedling versus Topical Minoxidil Alone in the Treatment of Androgenetic Alopecia” Muriki K Kumar et al. J Cutan Aesthet Surg. Oct-Dec 2018. Link:

https://pubmed.ncbi.nlm.nih.gov/30886475/

60 patients microneedling once every Two weeks for six months + minoxidil (6 months) (12 Total sessions) (Duration: 24 weeks ) (Frequency: once every Two weeks) (60 total patients all groups included)

“Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia” Linlin Bao et al. J Cosmet Laser Ther. 2020. Link: https://pubmed.ncbi.nlm.nih.gov/29028377/

71 patients microneedling Every 3 weeks for 6 months + minoxidil (not a dermaroller, but a motorized device was used) (8 Total sessions) (Duration: 24 weeks) (Frequency: once every 3 weeks) (Device: Motorized microneedling device) (71 Total patients all groups included)

“Randomized trial of electrodynamic microneedling combined with 5% minoxidil topical solution for treating androgenetic alopecia in Chinese males and molecular mechanistic study of the involvement of the Wnt/β-catenin signaling pathway”

Linlin Bao et al. J Dermatolog Treat. 2020. Link:

https://pubmed.ncbi.nlm.nih.gov/32412314/

*4 patients microneedling for 6 months, weekly for 4 sessions, then fortnightly for 11 sessions, the duration was 24 weeks + minoxidil * (15 Total sessions) (Duration: 24 weeks) (Frequency: 4 sessions weekly, 11 sessions Fortnightly) (4 Total petients, no placeboo or control group)

“Response to Microneedling Treatment in Men with Androgenetic Alopecia Who Failed to Respond to Conventional Therapy” Rachita Dhurat and Sukesh Mathapati 2015. Link: https://pubmed.ncbi.nlm.nih.gov/26120151/

93 patients minoxidil + prp + microneedling + minoxidil “Platelet-rich plasma and microneedling improves hair growth in patients of androgenetic alopecia when used as an adjuvant to minoxidil’ (93 Total patients all groups included)

Abhijeet Kumar Jha et al. J Cosmet Dermatol. 2019. Link: https://pubmed.ncbi.nlm.nih.gov/30693667/

50 patients microneedling with a dermaroller every month for 6 months +prp + minoxidil (6 Total sessions) (Duration: 24 months) (Frequency: once a month) (Depth: 1.5 mm) (device: manual dermaroller) (50 Total patients all groups included) “A Comparative Study of Microneedling with Platelet-rich Plasma Plus Topical Minoxidil (5%) and Topical Minoxidil (5%) Alone in Androgenetic Alopecia” Kaksha B Shah et al. Int J Trichology. Jan-Mar 2017. Link: https://pubmed.ncbi.nlm.nih.gov/28761259/

19 male patients microneedling once every month for 5 months + minoxidil (5 Total sessions) (Duration: 5 months) (Frequency: once a month) (Device: radiofrequency microneedling device) (19 Total patients all groups included) “A pilot split-scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss” A-J Yu et al. Clin Exp Dermatol. 2018 Oct. Link: https://pubmed.ncbi.nlm.nih.gov/29952106/

11 women microneedling once every two weeks at 0.8/1.0 mm for 12 weeks + minoxidil (6 Total sessions) (Duration: 12 weeks) (Frequency: once every Two weeks) (11 Total patients all groups included) (Depth 0.8/1.0mm) (Device: follica prototype unreleased microneedling device) “A pilot evaluation of scalp skin wounding to promote hair growth in female pattern hair loss”

Laura J.Burns BS Dina Hagigeorges Kelly E.Flanagan James Pathoulas Maryanne M.Senna 2020 aug. Link: https://www.sciencedirect.com/science/article/pii/S2352647520301672

Meta study (review article): (1127 total patients) “Microneedling and Its Use in Hair Loss Disorders: A Systematic Review” Robert S. English Jr., Sophia Ruiz & Pedro DoAmaral 2021 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/34854067/

“Combating photoaging with percutaneous collagen induction” Desmond Fernandes, Massimo Signorini. Clinics in dermatology, Volume 26,Issue 2, March-april 2008, pages 192-199. Link: https://www.sciencedirect.com/science/article/abs/pii/S0738081X07001903

Dermapen or Dermaroller? • From an acne study. https://dermapen.com/dermapen-vs-dermaroller/ " Patients treated with the Dermapen unanimously felt that the procedure was much less painful than the Dermaroller and the downtime was significantly shorter with the Dermapen. Subjectively, patients treated with the Dermapen felt that their atrophic acne scarring had improved to a greater extent than patients with the Dermaroller. Visioscan data showed significantly greater reduction of depth of scars using the Dermapen compared to the Dermaroller. " This is because the dermapen puncture vertically and very quickly so there is smaller chance of tearing the skin and therefore usually less bleeding occurs. Dermapen seems overall safer and more configurable. They have replaceable needles which come factory sterilized, also you can choose whichever length you want (0.25 - 3mm) and the amount of needles (3,12,36 etc), however the best studies we have involve the use of a manual dermaroller, we still have good data about the efficacy of dermapens in the treatment for hair loss so it could make sense to follow a specific protocol designed for a dermaroller using a dermapen, but in this case one should take in consideration that dermapens can penetrate 50-25% more than manual dermarollers.

How to use: First of all make sure your needles are sterilized, if using a dermaroller there are many ways to sterilize here's a link: https://www.wikihow.com/Clean-a-Derma-Roller If you're using a dermapen your needles should be in a closed package and already factory sterilized, but I like to put a little alcohol(70%) on the needle before using just to be safe I suggest you wash your hair beforehand, leaving it wet. This makes moving your hair around easy and reduces the chance of your dermapen/roller getting stuck in your hair and plucking it. If you're using a dermaroller simply roll it around the thinning areas of your scalp, do not apply too much pressure. If you're using a dermapen it takes slightly longer but is also more precise, move the pen in vertical and horizontal lines slowly, again do not apply too much pressure simply move it like a sharpie around the thinning parts of your scalp, make sure the pen is making contact with the scalp and not hovering. All in all the session shouldn't take more than 10 minutes, your scalp will be red afterwards. Side effects: Most side effects are minor, redness, itching, flaking etc. However, when applying minoxidil (or any other serum) you are increasing the absorption into your scalp significantly which in turn goes systematic so be prepared for increased sides or shedding since it's basically making whatever you put on your head 3x times stronger. There is also some theories floating around that microneedling can cause your scalp to be unsuitable for a hair transplant in the future, however there is no proof or studies backing those claims.

Minoxidil 5% + Tretinoin 0.01%

Tretinoin is a prescription drug, before consider using it off label we encourage you to consult you primary care provider, or a dermatologist. Topical tretinoin can be used as a method to increase minoxidil response. Minoxidil sulfate is the active metabolite required to exert the hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra-subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. (13b) In a recent study, researchers demonstrated that topical tretinoin application influences the expression of follicular sulfotransferase. 43% of subjects initially predicted to be non responders to minoxidil were converted to responders following only 5 days of topical tretinoin application. (13b) In another study, retinoids have been reported to increase minoxidil response. A solution of 0.01% tretinoin was Compounded with 5% minoxidil and the group that received this combination treatment only applied the solution once a day, while another group who received minoxidil 5% applied the solution twice a day, at the end of the study, both group saw a similar increase in hair count and hair thickness.(14b)

“Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes” Aseem Sharma et al. Dermatol Ther. 2019 May. Link: https://pubmed.ncbi.nlm.nih.gov/30974011/

Efficacy of 5% minoxidil versus combined 5% minoxidil and 0.01% tretinoin for male pattern hair loss: a randomized, double-blind, comparative clinical trial Hyo Seung Shin et al. Am J Clin Dermatol. 2007. Link: https://pubmed.ncbi.nlm.nih.gov/17902730/

SURGERY

Permanent improvement in androgenetic alopecia can be attained through surgical therapy. Hair transplantation using follicular units has become the mainstay of surgical treatment [33]. 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 non transplanted 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 [34].

OTHER THERAPIES:

Disclaimer: please be aware that data on the efficacy and safety of these treatments are more limited than for minoxidil and finasteride, and some of the treatments discussed here may cause unwanted side effects, some of the compounds discussed in this section are research chemicals and off label prescription treatments (Not all of them, some of them are over the counter medications and are safe to use at any time) consult you primary care provider before starting any off label prescription drug or research chemical. This list is not and endorsement of any of the drugs listed, before using any of this products we encourage you to do your own research, for this reason we included and linked a number of clinical studies for each compound, so that you can look into it and make your own conclusions.

Oral Finasteride and topical Minoxidil to this day remain and should be the best first options in treating androgenetic alopecia, however they are not the only treatments proven to be effective. Regardless of this, they remain the best treatments avialable on the market for safety and efficacy.

This section of the Tressless Wiki aims to help people on reddit find an effective alternative to FDA approved treatments, but this should options be considered only if one finds himself in one of these situations: 1) If regular FDA, MHRA or EMA approved drugs for MPB give you side effects. 2) If FDA, MHR or EMA approved drugs are not working for you (non-responder) if they are not working enough, or are not longer working. (Topical Minoxidil for example has an average success rate or 60%, while for oral finasteride it is around 90%) 3) If you are looking for an adjunction to FDA, MHRA or EMA approved treatments to maximize results.

To be included in this list every compound/treatment must be already available in the market and must have at least a good quality human study which includes a control group who received a placebo treatment. (This was always the case except for ru58841, which was worth mentioning because of its common use off-label, and positive anecdotal reports), and obviously every treatment must be found to be effective by the researchers. And the studies must be conducted on male patients with androgenetic alopecia.

At least 19 different treatments that are not FDA, MHRA and EMA approved proven to be effective and have good quality data to support their efficacy are: Oral Minoxidil - Oral Dutasteride - Topical Finasteride - Ru 58841- latanoprost 0.1% - Fluridil 2% - Alfatradiol 0.025% - Cb-03-01 (Clascoterone 7.5%) - Redensyl 3% - Adenosine - Topical Dutasteride - Low Level Laser Therapy (LLLT) - Platelet Rich Plasma (PRP) - Stemoxydine 5% - Topical Procyanidin B-2 1%- Topical spironalactone 1% - Oral procyanidin B-2 - ketoconazole 2%.

Which one of these numerous treatments is going to be the best adjunction/substitute for FDA, MHRA or EMA approved drugs for you will depend on a number of factors which can differ from an individual to another. To give the tools to find a good treatment for everybody we provided a list of PROS and CONS for every treatment that has been reviewed in this list. Some factors that should be taken into account before choosing a right treatment are:

• Is the product available in my country?
• How much am I willing to spend?
• Am I prone to specific side effects? (For example: If experienced side effects while on Finasteride you may not consider Dutasteride as a viable substitute, the same can be applied to other compounds like oral Minoxidil: If you previously have had issues with topical Minoxidil or if you have had blood pressure/lungs/cardiovascular problems you may not consider it as a viable option; If I have light colored eyes, or a very lean face, you might not consider using Latanoprost because of its possible eyes darkening and localized fat depleting side effects).
• Will It fit in my schedule? (Some treatments require more time and effort than others, choose the one that can fit in your schedule).
• Does It make sense to add this treatment to my stack? ( For example If you are already on finasteride and you look for an adjunction treatment, you may not consider any other 5 alpha reductase inhibitors like topical finasteride, topical dutasteride or oral dutasteride to your stack, the same can be applied to androgen receptor blockers).
• What will be the individual response? (It Is something you cannot predict because it comes down to your genetics; every person is different, therefore everyone is going to respond differently to every drug, some compounds do wonders for some people (hyper responders), and nothing for others (non-responders). FDA has approved only two drugs for hair loss, chances are that you could be a non-responder to one If not both of these drugs ( Which is unlikely but not impossible, Minoxidil for example has a success rate of only about 60%), If you are a non-responder to conventional treatments chances are that you are probably at least a hyper responder to one or more of these 15 treatments, and being that every treatment reviewed has at least one good quality study conducted on human subjects to be included in this meta-analysis, as an human you will probably be a good/decent responder to the majority of these treatments.

Review and summary of all 18 effective treatments: (pros, cons, mechanism of action, trade names, and studies links) Disclaimer: All this conclusions were taken after reviewing the available clinical literature, however before starting any treatment, we recommend everyone to do their own research and make their own conclusions. For this purpose we linked all the studies we referenced in order to create this summary of these various treatments.

ORAL DUTASTERIDE:

Mechanism of action: Indirect anti androgen. Dutasteride is a drug with an inhibiting action of 5-alpha-reductase in the two isoforms I and II.

Pros: More efficacious than finasteride and good as stand-alone treatment.

Cons: Prescription drug. Not approved for androgenetic alopecia so it must be prescribed off label. Some studies have found a higher risk of side effects compared to finasteride, while others have found the same incidence of sides between the two drugs. It has a slower recovery process (going back to baseline levels) when ceasing use compared to Finasteride, higher risk on neurological side effects (anxiety, depression) because of the inhibition of the type 1 5ar enzyme and its effect on neurosteroids.

Trade names: Avodar - Duprost – Deetor - Dutamax, and other brands.

Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study Sujit J S Shanshanwal et al. Indian J Dermatol Venereol Leprol. Jan-Feb 2017. Link: https://pubmed.ncbi.nlm.nih.gov/27549867/

"A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia" Walter Gubelin Harcha et al. J Am Acad Dermatol. 2014 Mar. Link: https://pubmed.ncbi.nlm.nih.gov/24411083/

"5-Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety" Rachita Dhurat et al. Dermatol Ther. 2020 May. Link: https://pubmed.ncbi.nlm.nih.gov/32279398/

Efficacy of Intralesional and Oral Dutasteride in the Treatment of Androgenetic Alopecia: A Systematic Review Maira Elizabeth Herz-Ruelas et al. Skin Appendage Disord. 2020 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/33313048/

"Dutasteride in Androgenetic Alopecia: An Update" Tasleem Arif et al. Curr Clin Pharmacol. 2017. Link: https://pubmed.ncbi.nlm.nih.gov/28294070/

"Mesotherapy with Dutasteride in the Treatment of Androgenetic Alopecia" David Saceda-Corralo et al. Int J Trichology. Jul-Sep 2017. Link: https://pubmed.ncbi.nlm.nih.gov/28932074/

The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis Zhongbao Zhou et al. Clin Interv Aging. 2019. Link: https://pubmed.ncbi.nlm.nih.gov/30863034/

"Androgens and hair loss" Adel Alsantali et al. Curr Opin Endocrinol Diabetes Obes. 2009 Jun.Link: https://pubmed.ncbi.nlm.nih.gov/19396986/

CLASCOTERONE: (cb03-01/Breezula)

Mechanism of action: Topical anti androgen, it acts as an androgen receptor antagonist, it inhibits the ability of DHT to bind with androgen receptors in the scalp.

Pros: efficacy seems to be decent, side effects profile seems to be better than finasteride (less or no sides) at least according to studies published so far, good human studies already conducted, good safety profile assessed. It has been FDA approved for acne but with a smaller concentration, optimal dosages and frequency of use Is assessed (7.5 % twice a day is deemed as most effective, even more effective that higher concentrations applied once per day).

Cons: currently only available as a research chemical, method of application (topical) and frequency of use make it less handy than other oral 5ar inhibitors.

Trade names: BREEZULA (not available yet, waiting for FDA approval) - WINLEVI (already FDA approved for acne but with a low concentration). This compound Is currently only sold in research chemicals websites under the Name: Cb-03-01 or Clascoterone.

Active ingredient: Clascoterone aka Cortexolone 17-alpha propionate aka CB-03-01

"Cassiopea Announces Very Positive Interim Analysis Phase 2 Results for Breezula® (Clascoterone) in Treating Androgenetic alopecia" Jul 2018. Link: https://www.cassiopea.com/2018/07/16/cassiopea-announces-very-positive-interim-analysis-phase-2-results-for-breezula-clascoterone-in-treating-androgenetic-alopecia/

Approval for acne: "Clascoterone: First Approval" Sohita Dhillon. Drugs. 2020 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/33030710/

Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials Adelaide Hebert et al. JAMA Dermatol. 2020. Link: https://pubmed.ncbi.nlm.nih.gov/32320027/

"Pharmacokinetic Profile, Safety, and Tolerability of Clascoterone (Cortexolone 17-alpha propionate, CB-03-01) Topical Cream, 1% in Subjects With Acne Vulgaris: An Open-Label Phase 2a Study" Alessandro Mazzetti et al. J Drugs Dermatol. 2019. Link: https://pubmed.ncbi.nlm.nih.gov/31251549/

"Cortexolone 17α-Propionate (Clascoterone) is an Androgen Receptor Antagonist in Dermal Papilla Cells In Vitro Caridad Rosette et al. J Drugs Dermatol. 2019." Link: https://pubmed.ncbi.nlm.nih.gov/30811143/

RU58841

Mechanism of action: Topical androgen receptor inhibitor capable of blocking DHT from reaching scalp hair receptors.

Pros: It blocks both DHT and testosterone on the scalp. It seems like it could be potentially more effective than finasteride as a treatment for hair loss (at least according to one animal study when they compared the efficacy of the two drugs), currently commonly used off label by many people, many good anecdotal reports can be found online.

Cons: Side effects and safety profile are not clearly assessed. No human study has ever been published, we only have access to animal studies and in vitro, it Is only sold as a research chemical and theoretically it Is only legal to use for research purposes, often its molecular instability makes It inactive especially if stored in a pre-mixed liquid solution, the research and approval for this compound have been abandoned for unknown reasons.

Trade names: This compound Is only sold in research chemical websites under the Name Ru 58841.

"RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism" T Battmann et al. J Steroid Biochem Mol Biol. 1994 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/8136306/

"A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice" B De Brouwer et al. Br J Dermatol. 1997 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/9415227/

"Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques" H J Pan et al. Endocrine. 1998 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/9798729/

"RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia" U Münster et al. Pharmazie. 2005 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/15700772/

LATANOPROST 0.1%

Mechanism of action: Topical growth stimulant, prostaglandin analog. Latanoprost is a direct analogue of Prostaglandin F2α (PGF2α). Appropriate concentrations allow the balance between the anagen (growth), catalogenous (regression) and telogen (fall) phases.

Pros: Good convection of vellus hairs to terminal hairs (something in which Minoxidil often struggles to do), decent potency.

Cons: Difficult to get, very expensive, it needs to be compounded by a pharmacy because it is not industrially produced for the treatment of hair loss. Often available only under prescription. It needs to be stored in the fridge and/or cold shipped. Probably not good as a stand-alone treatment because it does not address the root cause of male pattern baldness (hormonal), it can have localized fat depletion and eyes darkening as a side effects, at least when applied directly in the eyes or in the skin around the eyes.

Trade names: Minoxidilmax: Latoderma - Latanoprost Fagron, but more usually it not industrially produced so it's often compounded by a pharmacy under the prescription of a dermatologist.

"A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia" Ulrike Blume-Peytavi et al. J Am Acad Dermatol. 2012 May. Link: https://pubmed.ncbi.nlm.nih.gov/21875758/

"Latanoprost and minoxidil: comparative double-blind, placebo-controlled study for the treatment of hair loss" Leila Bloch, Cassano Carlos Escudeiro January 2018. Link: https://www.researchgate.net/publication/324736207_Latanoprost_and_minoxidil_comparative_double-blind_placebo-controlled_study_for_the_treatment_of_hair_loss

"Effect of latanoprost on hair growth in the bald scalp of the stump-tailed macacque: a pilot study" Hideo Uno et al. Acta Derm Venereol. 2002. Link: https://pubmed.ncbi.nlm.nih.gov/12013211/

ALFATRADIOL 0.025%

Mechanism of action: Topical estrogen/indirect anti androgen. Alfatradiol acts as an inhibitor of the enzyme 5α-reductase, due to Alfratradiol being a derivative of estrogen it may also act as an indirect anti-androgen against testosterone. Reducing the synthesis of testosterone into DHT.

Pros: Can be used as a weak stand-alone treatment because it address the root cause of male pattern baldness (hormonal), Over the counter, Available online and shipped often worldwide. Can probably be a safe and weak alternative to Finasteride for teenagers and people prone to side effects with 5 alpha reductase inhibitors like finasteride.

Cons: Weak, hair regrowth is very unlikely as it often only slows down/stabilize further loss.

Trade names: Pantostin - El cranell alpha.

_Active Ingredient:_17 alpha estradiol 0.025%

Alfatradiol (0.025 %) - an Effective and Safe Therapy for the Treatment of Androgenetic Alopecia in Women and Men" G. Wozel1 , S. Narayanan2 , A. Jäckel2 , 2005 Link: https://www.thieme-connect.com/products/ejournals/html/10.1055/s-2005-870188

"Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study" C E Orfanos et al. Dermatologica. 1980. Link: https://pubmed.ncbi.nlm.nih.gov/7398983/

"Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women" Ulrike Blume-Peytavi et al. J Dtsch Dermatol Ges. 2007 May. Link: https://pubmed.ncbi.nlm.nih.gov/17451383/

"The Efficacy and Safety of 17α-Estradiol (Ell-Cranell® alpha 0.025%) Solution on Female Pattern Hair Loss: Single Center, Open-Label, Non-Comparative, Phase IV Study" Jae-Hong Kim, M.D., Sung Yul Lee, M.D., [...], and Won-Soo Lee, M.D., Ph.D. 2012 aug. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412238/#!po=84.3750

FLURIDIL 2%:

Mechanism of action: Topical androgen receptor blocker, It suppresses the human androgen receptor in the scalp.

Pros: Studies suggest It can’t go systemic due to its hydrophobic nature which is ideal since you only want it's anti androgenic effects localized on the scalp. Can be used as a stand-alone treatment as it address the root cause of mpb (hormonal). Over the counter and shipped worldwide by the official manufacturer (eucapil). Can probably be a safer alternative to Finasteride for teenagers or people who are prone to side effects.

Cons: Quite expensive and often difficult to get. Available in shops and pharmacies only in few European countries. Mild effect, but still decent.

Trade names EUCAPIL.

Active ingredient: Topilutamide 2%.

Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience Milos Sovak et al. Dermatol Surg. 2002 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/12174057/

TOPICAL FINASTERIDE:

Mechanism of action: Indirect anti androgen. It is a single receptor 5-alpha reductase inhibitor (5-ARI). It acts by blocking the conversion of testosterone to dihydrotestosterone (DHT). This drug inhibits only the 5α-reductase type 2.

Pros: Especially when micro dosed, it looks like often It can reduce a decent amount of scalp DHT when reducing less serum DHT in proportion. Some studies even suggest that it could have a lower risk of side effects compared to oral finasteride.

Cons: method of application (topical) makes It less handy, it often can go heavily systemic. In many countries it’s not approved as a treatment for hair loss and therefore might be difficult to obtain.

Trade names: Essegen-F - Caretopic - Finasteride Biorga, and other brands.

"A Systematic Review of Topical Finasteride in the Treatment of Androgenetic Alopecia in Men and Women" Sung Won Lee et al. J Drugs Dermatol. 2018. Link: https://pubmed.ncbi.nlm.nih.gov/29601622/

"Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial" B M Piraccini et al. J Eur Acad Dermatol Venereol. 2022 Feb. Link: https://pubmed.ncbi.nlm.nih.gov/34634163/

"Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia" Maurizio Caserini et al. Int J Clin Pharmacol Ther. 2016 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/26636418/

"A randomized, double-blind controlled study of the efficacy and safety of topical solution of 0.25% finasteride admixed with 3% minoxidil vs. 3% minoxidil solution in the treatment of male androgenetic alopecia" P Suchonwanit et al. J Eur Acad Dermatol Venereol. 2018 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/29972712/

"Topical finasteride for the treatment of male androgenetic alopecia and female pattern hair loss: a review of the current literature" Poonkiat Suchonwanit et al. J Dermatolog Treat. 2020. Link: https://pubmed.ncbi.nlm.nih.gov/32538225/

TOPICAL DUTASTERIDE:

Mechanism of action: Indirect anti androgen. Dutasteride is a drug with an inhibiting action of 5-alpha-reductase in the two isoforms I and II.

Pros: Some studies seem to suggest that it can lower more DHT in the tissue compared to the DHT in the serum, however further research Is needed.

Cons: Often difficult to get. Anecdotal reports suggest that it could easily lower DHT serum levels significantly. No good human studies published.

Trade names: Minoxidilmax: Duderma - Medikemos: Liposomial gel- Care First specialty pharmacy: Dutasteride Topical Gel Compounded.

"Topical dutasteride with microneedling in treatment of male androgenetic alopecia" Essam nada, sohag medical joirnal, January 2018 Link: https://www.researchgate.net/publication/334740272_Topical_dutasteride_with_microneedling_in_treatment_of_male_androgenetic_alopecia

"Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery" Norhayati Mohamed Noor et al. Eur J Pharm Biopharm. 2017 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/28412472/

"Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA" A. W. Rafi and R. M. Katz 2011 apr. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262531/

"Dutasteride in Androgenetic Alopecia: An Update" rif Tasleem Dorjay Konchok Adil Mohammad Sami Marwa, Current Clinical Pharmacology, Volume 12, Number 1 2017 feb. Link: https://www.ingentaconnect.com/content/ben/ccp/2017/00000012/00000001/art00008

"Development and characterization of dutasteride bearing liposomal systems for topical use" Purushottam Sharma et al. Curr Drug Discov Technol. 2011 Jun. Link: https://pubmed.ncbi.nlm.nih.gov/21513483/

ORAL MINOXIDIL:

Mechanism of action: Oral growth stimulant. The exact mechanism that leads to its beneficial effects on hair growth is still UNKNOWN.

Pros: Usually more effective than topical Minoxidil because of the increased convention of Minoxidil into it's active form Minoxidil sulfate by the sult1a1 (sulfotransferase) enzyme in the liver.

Cons: Prescription drug. Higher risk of serious side effects compared to the topical version (only 1% of topical minoxidil Is absorbed systemically). Some of the possible (rare) side effects are potentially life threatening, it is a prescription drug not approved for MPB, so It must be prescribed off label from a doctor for treating androgenetic alopecia. The human studies are low quality.

Trade names: Loniten – Lonitab - Noxidil, and others.

"Efficacy and Safety of Oral Minoxidil 5 mg Once Daily in the Treatment of Male Patients with Androgenetic Alopecia: An Open-Label and Global Photographic Assessment" Ratchathorn Panchaprateep et al. Dermatol Ther (Heidelb). 2020 Dec Link: https://pubmed.ncbi.nlm.nih.gov/32970299/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649170/

Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia" Juan Jimenez-Cauhe et al. J Am Acad Dermatol. 2019 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/31054970/

“Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients” Sergio Vañó-Galván et al. J Am Acad Dermatol. 2021 Jun. Link: https://pubmed.ncbi.nlm.nih.gov/33639244/ https://www.jaad.org/article/S0190-9622(21)00418-7/fulltext

"Low-dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series" Renée A Beach et al. J Am Acad Dermatol. 2021 Mar. https://pubmed.ncbi.nlm.nih.gov/33098962/ https://www.jaad.org/article/S0190-9622(20)32844-9/fulltext

"Effect of Oral Minoxidil for Alopecia: Systematic Review" Israel Junior Borges do Nascimento et al. Int J Trichology. Jul-Aug 2020. Link: https://pubmed.ncbi.nlm.nih.gov/33376283/

“Oral minoxidil treatment for hair loss: A review of efficacy and safety” Michael Randolph et al. J Am Acad Dermatol. 2021 Mar. Link: https://pubmed.ncbi.nlm.nih.gov/32622136/

“Low-dose oral minoxidil as treatment for non-scarring alopecia: a systematic review” Ajay N Sharma et al. Int J Dermatol. 2020 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/32516434/

"Review of oral minoxidil as treatment of hair disorders: in search of the perfect dose" A Villani et al. J Eur Acad Dermatol Venereol. 2021 Jul. Show details Link: https://pubmed.ncbi.nlm.nih.gov/33660357/

Oral Minoxidil: A Possible New Therapy for Androgenetic Alopecia Arieh Gomolin et al. J Cutan Med Surg. Jan/Feb 2020. Link: https://pubmed.ncbi.nlm.nih.gov/31994933/

"Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: A randomized clinical trial" Paulo Müller Ramos et al. J Am Acad Dermatol. 2020 Jan Link: https://pubmed.ncbi.nlm.nih.gov/31473295/ https://www.jaad.org/article/S0190-9622(19)32666-0/fulltext

"Case series of oral minoxidil for androgenetic and traction alopecia: Tolerability & the five C's of oral therapy" Renée A Beach. Dermatol Ther. 2018 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/30246901/ https://onlinelibrary.wiley.com/doi/10.1111/dth.12707

TOPICAL SPIRONOLACTONE 1%:

Mechanism of action: Topical anti androgen. Spironolactone belongs to the drug class of mineralocorticoid receptor antagonists, and it is a nonselective antagonist that can bind to androgen and progesterone receptors.

Pros: It might have similar efficacy compared to topical finasteride or topical minoxidil (at least for the short term according to two small studies). Studies suggest that it can be a good adjunction treatment to topical minoxidil (in a small study the minoxidil+ Spironolactone group had a 100% success rate). Short term studies with limited number of patients seem to suggest that the drug does not have a strong systemic absorption when applied topically (they usually do that by putting progesterone it into an oil base so that it has a slow, timed release that works very well at keeping the active ingredients stationary in the scalp once absorbed, but the expenses involved make it prohibitive.) In the case of women and men transitioning to women, It can be taken orally and be an effective and safe treatment for androgenetic alopecia.

Cons: Further research is needed to assess safety and effectiveness long term. If the drug goes systemic, it can significantly lower androgens such as testosterone and DHT, therefore it can have a negative impact on virility and could promote feminization in men. the compound’s smell is very bad.

Trade names: Maxogen-S (5%), S5 cream (5%), S5 Plus cream (5%), and other brands.

Study on men: "Topical Finasteride versus Topical Spironolactone in the Treatment of Androgenetic Alopecia" AHMED S. ABDELSHAFY, M.D.; MOUSA A.S. ALMABROUK, M.Sc., Article 5, Volume 88, June, June 2020, Page 1017-1022. Link: https://mjcu.journals.ekb.eg/article_110836.html

Study on men: A novel topical combination of minoxidil and spironolactone for androgenetic alopecia: Clinical, histopathological, and physicochemical study Hamza Abdel-Raouf et al. Dermatol Ther. 2021 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/33320406/

Study on women (oral route): "Spironolactone for treatment of female pattern hair loss" Laura J Burns et al. J Am Acad Dermatol. 2020 Jul. Link: https://pubmed.ncbi.nlm.nih.gov/32259535/

Study on women (oral route): "Efficacy and safety profile of oral spironolactone use for androgenic alopecia: A systematic review" JaBreia F James et al. J Am Acad Dermatol. 2022 Feb. Link: https://pubmed.ncbi.nlm.nih.gov/34352345/

TOPICAL KETOCONAZOLE 2% (Shampoo):**

Mechanism of action: Direct anti androgen and anti-fungal .Ketoconazole binds to the human androgen receptor.

Pros: Easy to use and it can simply be a replacement of your regular shampoo.

Cons: Very weak. Often can dry out your hair. Doesn’t remain much time on the scalp and it’s not good as a stand-alone treatment because of its mild effect.

Trade names: Nizoral – Ketonaz – Ketocip - Revita, and other brands.

"Ketoconazole shampoo: effect of long-term use in androgenic alopecia" C Piérard-Franchimont et al. Dermatology. 1998. Link: https://pubmed.ncbi.nlm.nih.gov/9669136/

"Ketoconazole as an adjunct to finasteride in the treatment of androgenetic alopecia in men" B S Hugo Perez. Med Hypotheses. 2004. Link: https://pubmed.ncbi.nlm.nih.gov/14729013/

"Topical ketoconazole for the treatment of androgenetic alopecia: A systematic review" Jaime R Fields et al. Dermatol Ther. 2020 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/31858672/

TOPICAL PROCYANIDIN B-2 1%:

Mechanism of action: Growth stimulant. Promotes hair epithelial cell growth and stimulate anagen induction. Hair-growing activity of procyanidin B-2 could be related to its downregulation or inhibition of translocation of PKC isozymes in hair epithelial cells (theoretical), procyanidin B-2 also upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. Researchers speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-beta(1)- or TGF-beta(2)-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.

Pros: Natural ingredients . No side effects.

Cons: May be difficult to obtain, depending on which part of the word you live. Probably not good as a stand-alone treatment because it does not address the root cause of male pattern baldness (hormonal).

Trade names: Annurmets hair: Lozione - Annurmets hair: Schiuma - Bodyline: mela annurca hair lozione.

"Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent" A Kamimura et al. Phytomedicine. 2000 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/11194183/

"The first clinical trial of topical application of procyanidin B-2 to investigate its potential as a hair growing agent" T Takahashi et al. Phytother Res. 2001 Jun. Link: https://pubmed.ncbi.nlm.nih.gov/11406858/

'Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as a hair-growing agent" Tomoya Takahashi et al. J Cosmet Dermatol. 2005 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/17168871/

"Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms" A Kamimura et al. Skin Pharmacol Physiol. 2006 Link: https://pubmed.ncbi.nlm.nih.gov/16778458/

"Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study" A Kamimura et al. Br J Dermatol. 2002 Jan Link: https://pubmed.ncbi.nlm.nih.gov/11841365/

ORAL PROCYANIDIN B-2:

Mechanism of action:: Procyanidin B-2 Ignite Keratin production in hair follicles by inhibiting the pentose phosphate pathway and amino acid oxidation.

Pros:: side effects free.

Cons: The human study lack a control group, however every patient from the treatment group got a placebo for the first weeks. Extracts may be difficult to purchase depending on which part of the word you live. Not good as a stand-alone treatment because it does not address the root cause of mpb (hormonal) Further research is needed.

Trade names:: Annurkap: ANNUTRICOMPLEX - Annurmets hair: ANNUTRICOMPLEX.

"Annurca Apple Nutraceutical Formulation Enhances Keratin Expression in a Human Model of Skin and Promotes Hair Growth and Tropism in a Randomized Clinical Trial" Gian Carlo Tenore et al. J Med Food. 2018 Jan. Link: https://pubmed.ncbi.nlm.nih.gov/28956697/

"Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation" Nadia Badolati et al. Nutrients. 2018. Link: https://pubmed.ncbi.nlm.nih.gov/30279339/

STEMOXYDINE 5%:

Mechanism of action: Topical growth stimulant. Hair kenogen phase shortener. It works by creating a hypoxia environment in the scalp to help stimulate hair regrowth.

Pros: No adverse side effects. Easily available. Not very expensive.

Cons: Quite weak, the 3 Clinical studies conducted by L’Oréal saw an average increase of 4% in hair density in the subjects treated with Stemoxydine 5% compared to placebo. Probably not good as a stand-alone treatment because it does not address the root cause of mpb (hormonal).

Trade names: Serioxyl - Redken Cerafill Retaliate - Kerastase Densifique - Matrix Biolage Full Density.

011 Stemoxydine, a hair kenogen phase shortener,leading to increased hair density. Pascal Reygagne, centre de santé sabourard, sant Louis hospital, France. 2014 jul-sep. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158624/

PLATELET-RICH PLASMA (PRP):

Mechanism of action: Growth stimulant. It works by improving follicle vascularization, inhibiting apoptosis, and thereby prolonging the anagen phase, and inducing a faster transition from the telogen to the anagen phase in dermal papilla cells.

Pros: None.

Cons: Weak. Very expensive. Very painful. Probably not good as a stand-alone treatment because it does not address the root cause of mpb (hormonal).

"The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial" Pietro Gentile et al. Stem Cells Transl Med. 2015 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/26400925/

"Platelet-rich Plasma for Androgenetic Alopecia Treatment: A Randomized Placebo-controlled Pilot Study" Paul Gressenberger et al. Acta Derm Venereol. 2020. Link: https://pubmed.ncbi.nlm.nih.gov/32735021/

"Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia: A randomized controlled trial" Jerry Shapiro et al. J Am Acad Dermatol. 2020 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/32653577/

"Platelet-rich plasma for androgenic alopecia: A randomized, placebo-controlled, double-blind study and combined mice model experiment" Qian Qu et al. J Cosmet Dermatol. 2021 Oct. Link: https://pubmed.ncbi.nlm.nih.gov/33752252/

"Efficacy of platelet-rich plasma in androgenetic alopecia patients" Ghazala Butt et al. J Cosmet Dermatol. 2019 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/30393988/

"The effect of platelet-rich plasma injection in the treatment of androgenetic alopecia" Mousa Bayat et al. J Cosmet Dermatol. 2019 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/30895745/

TOPICAL ADENOSINE:

Mechanism of action: This anti-inflammatory agent works for hair regrowth through biochemical processes like energy transfer and signal transduction. To treat male pattern baldness, it regulates the expression of growth factors in dermal papilla cells.

Pros: Side effects free.

Cons: Weak. Quite expensive. Not good as a stand-alone treatment because it does not address the root cause of mpb (hormonal).

Trade names: Shiseido: Adenogen Hair Energizing Formula, and others.

“Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial” Hajimu Oura et al. J Dermatol. 2008 Dec. Link: https://pubmed.ncbi.nlm.nih.gov/19239555/

"Topical adenosine increases thick hair ratio in Japanese men with androgenetic alopecia” Y Watanabe et al. Int J Cosmet Sci. 2015 Dec." Link: https://pubmed.ncbi.nlm.nih.gov/25925959/

"Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia" Tokuro Iwabuchi et al. J Dermatol. 2016 May. Link: https://pubmed.ncbi.nlm.nih.gov/26508659/

REDENSYL 3%:

Mechanism of action: Topical growth stimulant. It acts as regenerative medicine and targets the hair follicle stem cells, which are known as outer root sheath cells. The stem cells of the hair follicle play a major role in initiating the anagen phase of the hair cycle.

Pros: Decent potency: studies showed an average increase of 10.000 more hair. Side effects free. Over the counter. Available online and shipped worldwide.

Cons: Not good as a stand-alone treatment because it does not address the root cause of mpb (hormonal). Comes often in a sticky formula. Difficult to establish if a product bought online really contains Redensyl since a lot of different companies claim to include It in their products.

Trade names: Actsyl-3, irestore: hair growth serum - Man matters: hair growth tonic - Redenhair: hair regenerator serum forte, and other brands.

Active ingredient: Redensyl 3% which contains: Dihydroquercetin-Glucoside (DHQG) Epigallocatechin Gallate-Glucoside (EGCG2), Meta-bisulfite, Zinc Chloride, Glycerine, Glycine.

"A randomized, single-blinded, vehicle-controlled study of a topical active blend in the treatment of androgenetic alopecia" Alexander C Katoulis et al. Dermatol Ther. 2020 Jul. Link: https://pubmed.ncbi.nlm.nih.gov/32473084/

LOW LEVEL LASER THERAPY (LLLT):

Mechanism of action: Growth stimulant. It increases the amount of adenosine triphosphate (ATP), the fuel of the living cells within the follicle. It reduces inflammation and stimulate cellular energy to create a healthier environment for hair growth.

Pros: No adverse side effects.

Cons: Very weak and expensive. Time consuming. Not good as a stand-alone treatment because It does not address the root cause of MPB (hormonal).

Brand names: Illumiflow – Kiier – Capillus – Hairmax - Irestore, and others.

"Low-level laser therapy for the treatment of androgenetic alopecia in Thai men and women: a 24-week, randomized, double-blind, sham device-controlled trial" Poonkiat Suchonwanit et al. Lasers Med Sci. 2019 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/30569416/

"Low-level light therapy using a helmet-type device for the treatment of androgenetic alopecia: A 16-week, multicenter, randomized, double-blind, sham device-controlled trial" Jung Soo Yoon et al. Medicine (Baltimore). 2020. Link: https://pubmed.ncbi.nlm.nih.gov/32702878/

"Low-level light therapy for androgenetic alopecia: a 24-week, randomized, double-blind, sham device-controlled multicenter trial" Hyojin Kim et al. Dermatol Surg. 2013 Aug. Link: https://pubmed.ncbi.nlm.nih.gov/23551662/

"Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial" Sabrina Mai-Yi Fan et al. Dermatol Surg. 2018 Nov. Link: https://pubmed.ncbi.nlm.nih.gov/29957664/

"Efficacy and safety of a low-level laser device in the treatment of male and female pattern hair loss: a multicenter, randomized, sham device-controlled, double-blind study" Joaquin J Jimenez et al. Am J Clin Dermatol. 2014 Apr. https://pubmed.ncbi.nlm.nih.gov/24474647/

Camouflaging agents

A variety of 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.

Keratin fibers Hair building fibers are camouflaging products made of keratin protein. Human hair has a high positive electric charge to it. So hair fibers are treated with a negative electric charge, this creates a magnetic effect, binding the Fibers to the human hair and giving the appearance of thicker and denser hair. Hair systems Hair systems are a non-surgical hair replacement system for men, it is a modern hair loss solution that works by offering complete or partial coverage of the hair loss area on your head.

Scalp micropigmentation:(SMP) Scalp Micropigmentation is a non-invasive treatment that uses detailed micro-needles to deposit pigment into the scalp In order recreate the look of the hair follicles, which can help you create the illusion of a full head of hair.

SUMMARY AND RECOMMENDATIONS

●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.)

●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.)

●Men 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.)

●Treatment with finasteride and minoxidil is generally well tolerated. Scalp dermatitis is the most common adverse effect of minoxidil. Occasional patients treated with finasteride experience sexual side effects. (See ‘Adverse effects’ above and ‘Adverse effects’ above.)

●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.)

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