Breanne M. Mefford, PharmD, BCCCP; J. Chris Donaldson, PharmD, BCCCP

Abstract and Introduction

Abstract

Male pattern baldness, or androgenic alopecia, is commonly seen in men aged older than 50 years. Unfortunately, hair loss can be a devastating condition, impacting one's confidence, social interactions, and feelings of attractiveness. Fortunately, there are several medications and emerging therapies to alleviate some of the negative impacts of hair loss. Treatment options available for addressing androgenic alopecia include finasteride and minoxidil. Other emerging therapies include topical antiandrogens, hair transplantation, and platelet-rich plasma.

Introduction

Hair loss can be a highly devastating condition. Throughout a person's life, hair loss might occur, and the need for appropriate diagnosis and treatment is important for the clinician. Additionally, the clinician must also recognize the emotional distress associated with hair loss. Balding men were consistently rated as less physically and socially attractive, older, less reliable, and less virile.^[1] Unfortunately, sometimes hair loss in men can begin as early as the late teens or early twenties. Usually, by age 50 years, more than half of white men have visible signs of male pattern hair loss, called androgenic alopecia.^[2] Patients may notice a receding hairline and a bald spot on the top of the head, which can cause thinning and hair loss over the years. Although, typically, the cause of hair loss can be easily identified, the diagnosis can be challenging and relies heavily on the patient interview and physical examination.

To appropriately diagnosis hair loss, an in-depth patient interview should occur. This should include information on the medical history, medication use, hair products, family history, and description of hair loss. The description of hair loss should include the duration and rate of progression, location and pattern, and extent. Interestingly, hair care practices may also help determine the cause of hair loss. When the hair shaft is damaged, this can lead to hair breakage, and this commonly occurs in patients with tight braids or ponytails, leading to a traction alopecia.^[3]

The physical examination is an important part of diagnosing baldness. Physical examination may include scalp and hair examination, visual inspection, and a hair pull test. If the cause of hair loss has not been identified yet, there are other diagnostic techniques that can be used, including microscopic examination, scalp biopsies, and some laboratory studies. While the patient interview and physical examination should take precedence in the diagnosis of male pattern hair loss, most commonly patients have androgenic alopecia, which is a genetic disorder due to an excessive response to androgens.^[4] While other causes of hair loss may be prevalent, this review aims to discuss the treatment of androgenic alopecia in men and the treatment utilized.

Pathophysiology

In male pattern baldness, the anagen phase (an active growth phase during which hair is produced continuously via division and growth of epidermal cells) shortens.^[5] Additionally, the telogen phase lengthens or may remain the same.^[4] The telogen phase is when the old club hair is shed and a new hair bulb is formed.^[5] Overall, this leads to a hair follicle not reaching the skin surface. Additionally, when the time between the two phases lengthens, the number of hairs decreases.^[5] Male pattern baldness is known to rely on androgens, specifically dihydrotestosterone (DHT). DHT comes from testosterone via the 5-alpha-reductase type 1 and type 2 enzymes.^[4] Type 2 5-alpha-reductase enzymes are found in the outer root sheath of hair follicles.^[4] In androgenic alopecia, excessive activation of the androgen receptor leads to thinner and shorter hair follicles.

FDA-approved Medication Management

Finasteride

As excessive activation of the androgen receptor leads to androgenic alopecia, the use of medications targeting this mechanism could be of benefit. Finasteride is a 5-alpha-reductase type 2 inhibitor that was initially marketed as a benign prostatic hyperplasia medication. Finasteride gained traction when it was shown to decrease serum and scalp DHT levels by 60% to 70%.^[6] Clinical efficacy of finasteride has been well documented in multiple trials. In a doubleblind study, finasteride was found to slow hair loss and increase hair density in 1 year compared with placebo.^[7] Recently, a meta-analysis sought to evaluate the efficacy of any dosage and administration route of minoxidil, dutasteride, and finasteride.^[8] The objective was to determine the clinical change in total and terminal hair count at 24 and 48 weeks of use. Articles that investigated only safety and adverse events, only psychological disorders, alopecia in women, or other conditions of alopecia were excluded. The authors found that while 0.5 mg per day of dutasteride was more effective than 1 mg per day of finasteride, based on change in total hair count at 24 weeks, dutasteride was not different from 5 mg per day of finasteride.^[8] At 24 and 48 weeks, the efficacies of 5 mg and 1 mg per day of finasteride were not different from each other. One percent topical finasteride was similar to 1 mg per day of systemic finasteride; however, it is unknown if the side-effect profile may differ.^[8] Finasteride, overall, is well tolerated with long-term use. Most side effects are related, predictably, to its mechanism of action on DHT. Some patients report sexual adverse effects, such as decreased libido, erectile dysfunction, and ejaculatory disorders.^[9] Pregnant females should be advised not to handle finasteride. Additionally, baldness progresses to baseline as DHT returns to pretreatment levels when finasteride is stopped.^[5] Thus, most patients take finasteride on a long-term daily basis.

Minoxidil

Oral minoxidil is not approved by the FDA for hair loss; however, topical minoxidil is. There are two FDA-approved concentrations of topical minoxidil currently on the market. Minoxidil is a potassium channel blocker that leads to dilation of blood vessels, which leads to more oxygen, blood, and nutrients to the follicles to promote the anagen phase.^[4] Per the aforementioned meta-analysis, the 5% concentration of minoxidil was more effective than the 2% for changes in terminal hair after 48 weeks. But at 24 weeks, the efficacy between the two concentrations was not different.^[8] Potentially longer utilization of the topical minoxidil leads to better outcomes. Minoxidil's peak effect appears to be around 4 months after initiation of therapy.^[5] A benefit of minoxidil might be that there are OTC options available in various strengths. The most common adverse effects include pruritis and flaking due to irritation.

Emerging Therapies

Topical Antiandrogens

Given the aforementioned adverse effects of systemic therapies, topical antiandrogen administration has been explored. Topical finasteride was first studied in 1997 by Mazzarella and colleagues, and it was found to slow the rate of hair loss compared with placebo. Furthermore, it did not impact plasma total testosterone, free testosterone, or DHT levels.^[10] More recently, a systematic review demonstrated that topical finasteride was noninferior to systemic finasteride for hair regrowth. Both scalp and plasma DHT were found to be significantly decreased with topical finasteride, but serum testosterone was not impacted. Based on these findings, the authors suggest that 100- and 200-mcL doses of 0.25% topical finasteride applied daily are efficacious. Notable side effects included scalp irritation, erythema, contact dermatitis, transaminitis, testicular pain, headaches, presyncope, and oropharyngeal pain.^[11] A subsequent trial randomized patients to one of three treatment arms—topical finasteride (50–200 mL of 0.25% solution daily) and oral placebo, topical placebo and oral placebo, or topical placebo and oral finasteride (1 mg daily). The authors found that there was a statistically significant improvement in hair count with both topical and systemic finasteride and that the efficacy of topical finasteride was similar to oral administration. Plasma finasteride levels were found to be 100- fold lower with topical administration versus systemic. Furthermore, they found the incidence of systemic side effects, such as sexual dysfunction, to be lower in the topical arm, leading to fewer discontinuations of therapy.^[12] It is prudent to note that topical finasteride formulations have to be specially compounded, and there are no studies comparing various topical formulations, which include both gels and solutions. Accordingly, no formulation can be recommended over another with the existing literature.^[11,13]

Hair Transplantation

Hair transplantation is a surgical option typically reserved for patients who either have failed medical intervention or have a large, affected surface area.^[13,14] Generally, hair follicles are taken from nonaffected occipital scalp and transplanted to affected areas. This is performed via two methods—follicular unit transplantation (FUT) and follicular unit extraction (FUE). In FUT, a strip of tissue with donor follicles is excised, and the follicles are then removed and transplanted into the affected areas. In FUE, individual follicular units are removed and then transplanted.^[14] FUE is more time-intensive but may be preferred by patients who want to wear their hair shorter, as FUT will leave a scar from the area of donor tissue. Occipital hair tends to be more resistant to the impact of androgenic alopecia, so the transplantation is typically considered permanent; however, patients can continue to lose hair in the affected area, so continuation of medical treatment may be considered.^[14,15]

Platelet-rich Plasma

Platelet-rich plasma (PRP) is an alternative treatment modality for early androgenic alopecia in which patients still have intact hair follicles. Patients have a blood sample drawn, the sample is then centrifuged, and the plasma component is injected subcutaneously into the affected tissue. Mechanistically, PRP contains growth factors that are believed to stimulate restorative effects.^[13] A recent systematic review that included 16 studies and 389 patients found that men treated with PRP generally saw positive results. The authors were unable to conduct statistical analyses given the heterogeneity in the data. Notably, 10 of the 16 studies included used monthly PRP injections for 3 to 4 months. Three of the included studies demonstrated significantly greater hair loss when used in combination with medical treatment.^[16] The most commonly reported adverse effects include scalp pain, headache, and burning sensations that are generally self-limiting.^[13] Absolute contraindications for PRP are critical thrombocytopenia, platelet dysfunction, hemodynamic instability, sepsis, and local infection at administration site, while relative contraindications include nonsteroidal anti-inflammatory drug use within previous 48 hours, glucocorticoid injection at the treatment site within 1 month prior, systemic glucocorticoid use within 3 weeks prior, tobacco use, recent illness or fever, hematolymphoid malignancy, anemia, and mild thrombocytopenia.

Conclusion

Unfortunately, by age 50 years, more than half of white men have visible signs of male pattern hair loss. This can lead to serious deleterious social and interpersonal impact. Frequently, male pattern baldness can be a detriment to one's confidence, social interactions, and feelings of attractiveness. In fact, one study compared individuals' initial impressions to sketches and photos of balding men compared with nonbalding men. Balding men were consistently rated as less physically and socially attractive, older, less reliable, and less virile.

Fortunately, there are several options and emerging therapies to alleviate some of the negative impacts of hair loss. The two FDA-approved medications for androgenic alopecia include finasteride and topical minoxidil. These are excellent options for men looking to increase hair growth. Additionally, other emerging therapies such as topical antiandrogens, hair transplant, and PRP exist. Pharmacists play a key role in the treatment of androgenic alopecia because of their closeness to the community. Pharmacists are able to educate and counsel men on the benefits of medications and the impact of baldness. While androgenic alopecia is not life-threatening, individuals should be counseled about the risks of harm such as sunburn, cold, mechanical injury, and potential for increased risk of cellular damage due to sunburn. Promising future developments in the treatment of androgenic alopecia may continue to enhance one's self-confidence and self-worth.