10 Medical Treatment of Male and Female Pattern Hair Loss
Summary
Keywords: minoxidil finasteride dutasteride laser platelet-rich plasma camouflage
Key Points
•Topical minoxidil is the only U.S. Food and Drug Administration (FDA)-approved medication for hair loss in women.
•Topical minoxidil and oral finasteride are the only U.S. FDA-approved medications for hair loss in men.
•Oral finasteride and dutasteride can be used in women but only if there is no risk of pregnancy.
•The half-life of dutasteride is much longer than that of finasteride, so too are the side effects.
•Although they have FDA-510K clearance, we do not have as much data to confirm the ideal protocols for treatment with low-level light therapy or platelet-rich plasma.
10.1 Introduction
Hair transplantation provides a permanent solution for hair loss sufferers. However, it does not address the ongoing hair loss aspect of male and female pattern hair loss. Many patients can benefit from medical therapy, before, during, or after surgery. Medical therapy can also provide a boost to the results with surgery alone. This chapter will outline the mechanism of action, side effects and expected results for each Food and Drug Administration (FDA)-approved medication. We will also discuss some other commonly used off-label treatments such as dutasteride, low-level light therapy (LLLT), and platelet-rich plasma (PRP). See (Video 10.1).
10.2 Minoxidil
Minoxidil remains the only FDA-approved medication for female pattern hair loss, and it is one of only two medications approved for men. It is available as a 2% solution, a 5% solution, a 5% foam, and more recently as a spray formulation. It was first implemented during the 1970s as an oral medication for refractory hypertension. By 1979, patients treated with the oral formulation were observed to develop hypertrichosis.1 One year later, a case of reversal of baldness was reported in a patient receiving minoxidil for hypertension.2 However, side effects of the oral formulation included an unsafe drop in blood pressure, water retention, and weight gain. To avoid this, a topical version of minoxidil was developed and successfully reported for hair regrowth in 1984.3
10.2.1 Mechanism of Action
Table 10.1 describes a complete list of minoxidil’s various proposed mechanisms of actions. The most prominent theories involve its vasodilatory and angiogenic properties. Its efficacy among different individuals appears to vary based on levels of sulfotransferase enzymes, which exist in the lower outer root sheath of the hair follicle. Minoxidil must first be converted to minoxidil sulfate to stimulate hair follicles. Patients with a better response to topical minoxidil are found to have greater enzyme activity.4
Table 10.1 Minoxidil: proposed mechanisms of action
Vasodilatory properties |
Angiogenic properties |
Enhanced cell proliferation and DNA synthesis |
Potassium channel opener |
Antiandrogen effect |
Suppression of collagen synthesis |
Immunosuppressive effects |
Cultures of human epidermal cells treated with minoxidil can survive longer than control cultures.5 Minoxidil slows down the senescence of keratinocytes, and reduces the rate at which cells are lost from the germinative pool. Research in balding stump-tailed macaques found that treatment with minoxidil increased the proportion of hair follicles in anagen, reduced the number of telogen follicles, and increased the follicle size overall.6 This suggests at least a relative shift chronologically from telogen to anagen. Abell supported the finding of increased anagen/telogen ratios after 12 months of minoxidil treatment in balding men.7 However, the main finding was an increase in mean hair diameter, evident at 4 months. This has been confirmed in other histologic studies at 12 and 24 weeks.
10.2.2 Minoxidil Formulation
Table 10.2 describes the timeline of events as various concentrations and formulations came to the market. Now, the 5% foam and solution have become the mainstay treatment among most dermatologists and hair specialists, for both men and women. In women, the added benefits must be weighed against the increased risk of side effects such as pruritus, irritation, and hypertrichosis. The new 5% foam has no propylene glycol and is often better tolerated.8 Trials have demonstrated the efficacy of 5% foam in men and women compared to placebo. In studies where 5% foam is similar in efficacy to 2% solution, women report significantly less pruritus and dandruff with 5% foam compared to 2% solution, and less interference with grooming practices.9,10
Table 10.2 Timeline for FDA approval of Rogaine solutions and foam
FDA approvals of Rogaine (minoxidil) solution |
1979—Oral formulation FDA approved for severe hypertension (see above) |
1988—FDA approved 2% solution, with prescription, for hair loss in men with AGA |
1992—FDA approved 2% solution for hair loss in women |
1996—FDA approved 2% solution for OTC use in men and women with AGA |
1997—FDA approved 5% for OTC use in men, calling it “extra strength for men” |
2006—FDA approved 5% foam for OTC use in men |
2014—FDA approved 5% foam for OTC use in women |
Abbreviations: AGA, androgenetic alopecia; FDA, Food and Drug Administration; OTC, over the counter. |
10.2.3 Minoxidil Uses and Applications
Each of the conditions listed in Table 10.3 have shown some response to topical minoxidil. Male and female pattern hair loss, or androgenetic alopecia (AGA) has been most responsive overall. Although most studies of minoxidil have focused on the vertex area, there is now published evidence showing that 5% foam may stabilize hair loss in the frontotemporal areas as well. An 80-week extension of a 24-week trial of 5% foam demonstrated that hair count and hair width in both frontotemporal and vertex areas were statistically similar in men at baseline compared to after 104 weeks of daily application of 5% foam.11
Table 10.3 Uses and applications for topical minoxidil
Male and female pattern hair loss (androgenetic alopecia) |
Alopecia areata |
Before/after hair transplantation, to enhance results |
Chemotherapy-induced alopecia |
Traction alopecia |
10.2.4 Minoxidil after Hair Transplantation
Topical minoxidil can be a useful adjunct to hair transplant surgery for AGA. In one study of 16 patients who applied topical 2% minoxidil 4 weeks before surgery, had a 3-week interruption perioperatively and resumed it for 3 months postoperatively, there was less shedding than usually seen by the author.12 A roundtable consensus of 11 international hair transplant surgeons found that most physicians use minoxidil as their primary medical treatment, both in patients who were and were not candidates for hair transplant surgery.13 They cited advantages such as stabilizing hair loss, increasing the number of hairs in anagen phase, increasing hair weight and density by enlarging miniaturized suboptimal follicles (also making transplanting easier), and decreasing the postsurgical telogen effluvium. Most advise their patients to stop minoxidil 2 to 3 days before surgery and wait 1 to 2 weeks after surgery before restarting.
10.2.5 Side Effects
Sufficient systemic absorption of topical minoxidil can translate to hypertrichosis on the sides of the face or tops of the arms in women. Although this effect is completely reversible upon discontinuation, women with hirsutism or an ethnic tendency for hair growth should probably begin with the 2% formulation. There are also many reports of contact dermatitis with minoxidil. These were historically thought to be due to minoxidil itself, but patch testing identified propylene glycol (present in minoxidil solution) as the causative agent in 9/11 patients while only 4/11 reacted to the minoxidil.14 Patients who are allergic to propylene glycol may benefit from the new 5% foam, which does not contain propylene glycol.
According to the package insert, minoxidil may be harmful if used when pregnant or breastfeeding. It is pregnancy category C. Although a 1-year, prospective study showed no increase in cardiovascular events or adverse pregnancy outcomes among patients on topical minoxidil versus controls, there have been scattered reports of fetal malformations. Minoxidil crosses biological barriers and accumulates in lipids, thus, brain and fetal concentrations may be higher than that found in serum. If planning to become pregnant, patients should wait until after they have delivered and finished breastfeeding to start minoxidil therapy.
10.2.6 Minoxidil in Everyday Practice
In our experience, we recommend once-daily application of minoxidil 5% foam, solution, or spray (Fig. 10.1a, b). This increases compliance. For patients with sensitive skin, using the foam may decrease the risk of contact allergy to propylene glycol. In women with evidence of hyperandrogenism or ethnic hirsutism, we might conservatively start with the 2% strength. However some women are so happy with regrowth that we use other methods (laser hair removal, eflornithine cream) remove of unwanted hair. We do recommend it for use in the frontal two-thirds of the scalp and vertex, even though packaging recommends only the vertex. We mention the risk of shedding in the first 3 to 4 weeks but explain that this paradoxically indicates that the medication is working.
Fig. 10.1 Use of topical minoxidil 5% foam (a) before and (b) after 6 months.
Another possible method of administration is oral minoxidil. In one case report it has been used successfully at 1 mg daily to regrow permanent chemotherapy-induced alopecia. Sinclair et al have also used oral minoxidil extensively either alone or in combination with oral spironolactone to treat female pattern hair loss. It has been reported to work in doses as low as 0.1 mg daily with no changes in blood pressure. It has also been used to fortify donor hairs leading up to, and in conjunction with, hair transplant surgery.15 ,16
10.3 Finasteride
The relationship of baldness with testosterone levels was observed by Hippocrates, who noticed that young male eunuchs did not develop hair loss. Male pattern thinning also does not occur in men with a genetic deficiency of the second isoenzyme of 5-alpha-reductase. Both types I and II 5-alpha reductase convert testosterone to dihydrotestosterone (DHT). Type I predominates in the skin, including the scalp, while type II is present in hair follicles and the prostate. The finasteride molecule works by inhibiting type II 5-alpha reductase. This lowers serum and scalp levels of DHT, while increasing scalp levels of testosterone, Table 10.4 summarizes the effect of finasteride on scalp and serum hormone levels.15,16
Table 10.4 Comparison of 5-alpha reductase inhibitors
Finasteride | Dutasteride | |
Scalp DHT | ↓ | ↓ |
Scalp testosterone | ↑ | ↑ |
Serum DHT | ↓ | ↓↓ |
Serum testosterone | No effect /↑ up to 10% (dose dependent) | ↑↑ |
Mechanism of action | Inhibits type I 5-alpha reductase enzyme | Inhibits type I and II 5-alpha reductase enzymes |
Half-life | 6–8 h | 5 wk |
Abbreviation: DHT, dihydrotestosterone. | ||
10.3.1 Efficacy and Safety in Men
Finasteride is an excellent adjunct to hair transplantation surgery. We know from large, extensive, placebo-controlled studies that it can help retain and enhance the growth of existing hair follicles. A randomized trial of 1,553 men given either finasteride 1 mg daily or placebo for 1 year with a blinded extension for a second year showed significantly greater hair counts in the balding vertex after 1 year than in patients receiving placebo.17 Five-year results from this same trial showed that hair growth peaked at 1 to 2 years, but still stayed at or above baseline for 90% of patients.18,19 In comparison, the placebo group continued to lose hair. Although we have no longer-term studies (such as 10 years), the safety and tolerability of the medication do not preclude its extended use.
A randomized, placebo-controlled trial using finasteride 1 mg/day in men showed that it additionally had efficacy in treating frontal hair loss, defined as those areas anterior to the vertex. This study specifically showed increased hair growth in men with a modified Norwood/Hamilton grade II, II vertex, IIa, III, or III vertex throughout the second year of the study.20 Longer term studies are needed to demonstrate long-term efficacy in this region of the scalp. Finasteride is also helpful in the setting of hair transplantation. A randomized, double-blind trial of 79 men with AGA were treated with finasteride 1 mg daily or placebo for 4 weeks prior to and 48 weeks after hair transplantation demonstrated that the treatment group had significant improvement from baseline, in comparison with placebo.21
Finasteride has several effects on hair follicles. Like minoxidil, it has been shown to increase the ratio of anagen to telogen hairs.22 Other long-term, placebo-controlled studies showed a sustained increase in hair weight, even after 3 to 4 years.23,24
10.3.2 Efficacy and Safety in Women
Initial data examining finasteride for women showed that it was not effective at the 1 mg/day dose.25 This finding, combined with the risk of teratogenicity, resulted in this product never being submitted for approval by the FDA for female pattern hair loss. However more recent data have suggested that it may be helpful for women at higher doses of 5 mg daily.26,27
10.3.3 Side Effects
Patients taking finasteride will see their prostate-specific antigen (PSA) score decrease by approximately half.28 The Prostate Cancer Prevention Trial (PCPT) demonstrated that patients taking 5 mg of finasteride daily had a 24.8% relative reduction in the prevalence of prostate cancer compared with those taking placebo.29 However, tumors with higher Gleason scores (7–10) were more frequent in the finasteride-treated group (37% of tumors vs. 22% of tumors, p < 0.01). Since then, mathematical models have refuted the idea that taking finasteride can create a more aggressive prostate cancer.
There have been some reports that finasteride can cause a decrease in sperm count and/or motility but the exact prevalence is less than 1%.30 There is no evidence that it can affect sperm morphology. Stopping finasteride in situations of impaired fertility may improve semen parameters, and help the couple avoid more invasive fertility treatments.
The original clinical trials demonstrated that 1 in 50, or 2% of men, reported one or more sexual side effects during finasteride (decreased libido, erectile dysfunction, and ejaculation disorder) compared with 1% in the placebo group. More recent publications have described a post-finasteride syndrome, wherein patients develop sexual side effects, mood changes, and suicidal ideation even after discontinuation of the drug.31 To date, the condition remains poorly understood, but it is likely related to complex neurotransmitters in the brain. There have also been reports of mood changes and breast enlargement. Two large retrospective studies have found no link between breast cancer and the use of 5-alpha reductase inhibitors in men.32,33
10.3.4 Finasteride Everyday
Finasteride is an excellent option for male patients experiencing AGA, alone or in combination with surgery or other medical therapies. It can be taken any time of the day, with or without food. There are no known drug interactions or allergies that have been reported. We do not routinely perform LFTs unless there is a history of hepatitis or other liver abnormalities. We instruct patients to allow at least 6 to 9 months to see results (Fig. 10.2a, b). We prescribe 90 tablets, with three refills to last an entire year. Patients who are weary of the expense may be given a prescription for the 5-mg pills with instructions to take a quarter pill daily. Patients who are concerned about sexual side effects may start taking it two to three times per week and increase to a daily dose as tolerated.
Fig. 10.2 (a, b) Use of oral finasteride 1 mg daily before and after 6 months.
Related posts:
Over-the-Counter Preparations
Pathogenesis and Classification of Female Pattern Hair Loss
Pathogenesis and Classification of Male Pattern Hair Loss (Androgenic Alopecia)
Methods and Techniques to Study Hair Cell Survival
Hair Transplantation: The Promise of Cell Therapy
OSHA, Laboratory Screening, and Office-Based Surgery
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