Minoxidil is used as 2% or 5% topical lotion. Minoxidil sulphate is the active form of this medication in the body and is a potassium channel opener that relaxes smooth muscles and initiates vasodilatation. In vitro studies however have shown that its’ effect on hair growth is independent from its vasodilatory effect (27, 28). In fact it works by initiating the transition from telogen to anagen and maintaining anagen in the follicular life cycle (29). Minoxidils effect on hair growth can vary from 16% to a 44% increase(30). The main side effect of minoxidil is contact dermatitis due to irritation by its’ carrier vehicle propylene glycol. This problem can be resolved by switching to its foam preparation (Regaine Foam) that doesn’t have propylene glycol but instead uses glycerine as its’ vehicle (31). Finally, a study by Shine et al showed that mixing minoxidil with tretinoin once a day makes it as effective of twice a day minoxidil only (27). It is worth noting that minoxidil is mostly absorbed within 90 minutes but is retained in the stratum corneum for us to 21 hours.
Beside minoxidil, topical combinations of 0.025% progesterone and 0.03% spironolactone have also been tried successfully in premenopausal women. For postmenopausal women, 0.03% of estradiol valerate has been recommended (30).
Fluridil (Eucapil) is a topical anti-androgenic medication that has been used widely in Europe and found to be effective in treatment of FPHL(32).
Systemic and anti-androgenic treatments:
Finasteride is a testosterone conversion inhibitor that inhibits the 5α reductase type 2 isonenzyme and has been examined in different studies with controversial results in women .Overall it seems a 12 months intake of 2.5 mg/day to 5 mg/day finasteride in norm-androgenic women can improve hair density and hair thickness with no difference between pre and post menopausal women (33-35). Similarly, 12 months of 2.5 mg/day finasteride with oral contraceptives has been reported to improve hair loss in norm-androgenic premenopausal women(36). For women with hyper-androgenism a lower dose of finasteride (1.25 mg/day) was also found to be effective (37). One explanation for why finasteride in higher doses has been more successful in norm-androgenic women is that those women might have had higher activity of 5α reductase enzyme in their scalp(38). Finasteride is a well tolerated medication with infrequent side effects including breast tenderness and increased libido(8). Dutasteride is a combined 5α reductase type 1 and 2 inhibitor and has been tested is small studies with results still not that clear(39), however other small studies have shown significant improvement of hair loss even with 0.25 mg/day of dutasteride (40).
Spironolactone works as an androgen inhibitor by suppression of the testosterone production in adrenal it also competitively inhibits binding of the androgens to the hair follicles and suppresses their action (41). Spironolactone has been used successfully for decades in Australia (100 to 200 mg/day) for the treatment of FPHL. It is recommended to start spironolactone with 50 mg a day and increase by 50 mg monthtly to the maximum dose of 200 mg/day (30). The combination of Spironolactone and Finasteride has been shown to be superior to each of them used alone . Common side effects of spironolactone are hyperkalaemia, orthostatic hypotension, fatigue and urticaria as well as reduced libido and irregular vaginal bleeding. Regular blood pressure and potassium control, especially in the first few months after initiating it, as well as prescribing oral contraceptives are crucial(30).
All anti-androgenic medications potentially carry risks of genital abnormalities in a male foetus therefore a reliable contraceptive is recommended in premenopausal women(15). At the same time, the benefit of the combined oral contraceptives have been known for a while on pilosebaceous unit (PSU) disorders including acne vulgaris and hirsutism, and can benefit FPHL, another form of “PSU disorder”. Ethinyloestradiol reduces circulating androgens by inhibiting FSH and LH and increasing sex hormone binding proteins. Progesterone on the other hand, blocks androgen binding receptors in the PSU(42).
Cyproterone acetate is an anti-androgen that inhibits gonadotropin releasing hormone (GnRH) and blocks androgen receptors. It is readily available in Australia in a very low dose (2 mg) combined with estradiol (Diane-35) however higher dosages have been used for the treatment of FPHL, including continuous 50 mg a day with side effects including loss of libido, hypertension, weight gain (30), depression and menstrual disturbance (43). We couldn’t identify any study to find cypreterone superior to other anti-androgenic medications even though its’ side effects seem to be more serious. Finally with recent outcomes of French study on Diane-35 and risk of death from thrombo-embolic events and the alert by the TGA on Diane-35, the risks using the much higher dose of cyproterone acetate should be examined (44).
Flutamide is a potent anti-androgen, acting via androgenreceptor antagonism. As such, it is commonly used to treat advanced prostate cancer and hirsutism. Previous studies showed its superiority over finasteride and cyproterone acetate on a daily dose of 250 mg/day however its adverse effects including dose related hepatotoxicity made it less attractive (20, 45). A new prospective cohort study however showed its efficacy on FPHL treatment with higher tolerability and no hepatotoxicity when prescribed at 62.5 mg/day (46). It is still recommended during the early months of treatment to regularly follow up the liver enzymes and stop the treatment if transaminase levels exceed the twice level of normal range (45).
Low-Level Light Therapy
Low-level light therapy (LLLT) was initially used to create cancer in mice but it grew hair instead (47).Later on it was used by the National Aeronautics and Space Administration (NASA) to improve wound healing in space and in 2007, was approved by the FDA as a treatment for hair loss(48). LLLT, as is clear from its’ name, uses low power light (as small as 5mW) in a wavelength varying from 600 nm to 1400 nm. Some studies at 1500nm using different sources of light including IPL, diode laser, long-pulsed alexandrite lasers as well as erbium-glass laser have been tried (24, 49).This range of wavelength is very close to the absorption spectrum of haemoglobin, water and cytochrome C a respiratory chain component (24, 50). It is hypothesized that the light absorbed by cytochrome C mayultimately result in increased ATP production, which may alter cell metabolism(50). In a study on 28 Korean patients, a 1550 nm fractional erbium–glass laser was used for five months to treat FPHL and showed an increase in mean hair density from 100 to 158 / cm2 and increased mean hair thickness from 58 to 75 µm (24). Overall this method is new and larger studies are needed, however, it seems to be effective in some patients (49).
This is a surgical treatment with more visible outcomes and can be very successful in women with good occipital donor hair. Some clinicians keep this as a last resort though it should be considered as a possible part of the treatment strategy in more severe cases right from the beginning. Even for women who are on topical and systemic medication, hair transplants can be used to improve the outcome while continuing medical treatment can help to keep the transplanted hair in place longer and also slow down the hair loss in other areas.
Cell Therapy/Follicular Cell Implantation is also potentially a novel treatment that uses stem cells in the hair follicle to grow hairs in culture and reimplant them to the scalp. Currently being researched, if successful, this method is going to be the ultimate treatment of hair loss (32).