Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.42 Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.44 Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.45 One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.44 Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.46
The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.47 Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.48 Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.42 Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.49
Low-Level Laser Light Therapy
Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.50
Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.51 The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.51 Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).52 However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.53
Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.51 With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.52
Platelet-Rich Plasma
Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.
Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.56 One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.57 On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.60 However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.60 Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.64
Microneedling
Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.65 It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.51 Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.65 Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.
Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.66 Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.67 The treated area is then washed and an antibiotic ointment is applied.55 Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.
Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).68 It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.66
Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.69 Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.69 When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.
The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.71