Female pattern hair loss: Treatment options
Pharmacological
Pharmacological options can be divided into drugs with androgen-independent and androgen-dependent mechanisms of action.
Androgen-independent medications
Minoxidil
Currently the only androgen-independent medication in widespread use is minoxidil topical solution. This medication’s proposed mechanism of action is by affecting hair cycling, causing premature termination of telogen, and probably prolonging anagen (
Messenger and Rundegren 2004). Understanding exactly how minoxidil exerts these effects is currently the subject of intense research. Although this is available in both 2% and 5% preparations, only the 2% solution is currently FDA-approved for FPHL (
DeVillez et al 1994). A study comparing the efficacy of the two concentrations using target area hair counts at 48 weeks as a primary endpoint showed a mild nonsignificant advantage for the 5% solution (
Olsen et al 2002).
Usually 1 ml of minoxidil is applied twice daily to dry scalp with a dropper. This is left for 1 hour before shampooing or wetting of the hair is allowed to maximize medication absorption. Patients should be warned that in the initial 2–8 weeks, a temporary telogen effluvium may occur, which is self-limiting and subsides when subsequent anagen regrowth begins, and should not be a cause for treatment cessation. Common adverse effects of minoxidil include scalp irritation including dryness, scaling, itching, and/or redness (
Friedman et al 2002). Specific to its use in FPHL, hypertrichosis may occur, primarily on the cheeks and forehead. If this occurs, it generally disappears within 4 months of ceasing the medication. Treatment should be continued for at least 12 months before an accurate appraisal of efficacy can be made.
Recently, it has been found that most cases (82%) of scalp irritation after use of topical minoxidil results from a contact dermatitis to propylene glycol, one of the vehicles of the solution, rather than the minoxidil itself (
Leffek and Herrick 2006). There is emerging data on a new foam vehicle for minoxidil which has significantly reduced levels of propylene glycol indicating at least equivalent efficacy and increased preference by subjects due to the lack of the sticky residue associated with current formulations (
Lucky et al 2004).
Androgen-dependent medications
The use of all androgen-dependent medications to treat FPHL carries a risk of causing abnormalities in the genitalia of the male fetus. Thus, these medications are contraindicated in women who are pregnant, which leads many physicians to recommend that women start and remain on an oral contraceptive pill throughout their course of treatment with these medications. As with minoxidil, all androgen-dependent medications need to be continued for at least 1 year before an accurate appraisal of efficacy can be made.
Finasteride
Finasteride works by inhibiting 5α-reductase II enzyme, which is responsible for catalyzing the conversion of testosterone to the much more active chemical 5 DHT. Thus, finasteride suppresses overall androgen activity by restricting total circulating androgen activity. Large scale studies on its efficacy are currently limited, with one large multicenter randomized placebo-controlled trial failing to find any change in hair growth or progression of hair loss with finasteride 1 mg/day in postmenopausal women with FPHL over a 1 year follow-up period (
Price et al 2000). However, smaller case reports and case series have demonstrated efficacy for finasteride 1.25 mg/day in 4 cases of FPHL in both pre- and post-menopausal women with hyperandrogenism (
Shum et al 2002), finasteride 2.5 mg/day in 5 cases of FPHL in post-menopausal women without hyperandrogenism (
Trüeb 2004), and finasteride 5 mg/ day in 1 case of FPHL in a post-menopausal woman without hyperandrogenism (
Thai et al 2002). Finasteride does appear to be successful in some patients, but further large scale studies are required to determine optimal dosing regimes.
Finasteride is generally well tolerated. Infrequent side effects in female patients include breast tenderness and increased libido, which are most common in the first year of therapy, reversible on dose reduction, and tend to diminish over time with continued use.
Dutasteride
Dutasteride is a more potent 5α-reductase inhibitor than finasteride, working by inhibiting both type I and type II 5α-reductase. Whereas type II 5α-reductase concentrations are much higher than those of type I 5α-reductase, the additional inhibitory effect on androgen activity produced by dutasteride may translate into greater clinical efficacy. It is commonly used to treat benign prostatic hypertrophy but is not approved by the US FDA for the treatment of either male or female androgenetic alopecia. Significant issues with teratogenicity arise from the long biological half life (months), and this drug is best avoided in women who may become pregnant.
Phase 1 and 2 trials conducted exclusively in men demonstrated that at a dose of 2.5–5.0 mg/day, dutasteride suppresses almost 100% of serum DHT activity, whereas finasteride at a dose of 5 mg/day suppresses only 70% of DHT. Phase 2 preclinical trials showed that after 6 months of treatment, there was a 30% increased improvement in hair count when comparing 0.5 mg of dutasteride with 5 mg of finasteride (
GSK 2006).
Cyproterone acetate
This medication inhibits gonadotropin-releasing hormone (GnRH) and blocks androgen receptors. Other uses include prostate cancer, hirsutism, and severe acne. In Australia, it is commonly used combined with estradiol as an oral contraceptive pill named Diane-35.
A number of studies suggest a role for cyproterone acetate, with some suggesting that this role is greater in patients with evidence of hyperandrogenism. One moderately large study of 25 subjects aged between 31 and 35 years with FPHL showed that Diane-35 used for 6–9 months clearly decreased the loss of hair, hair thinning, and seborrhea
Brzezinska-Weislo 2003). Another study compared 8 control patients with FPHL receiving placebo treatment with 20 patients with FPHL treated with 50 μg ethinyloestradiol plus 2 mg cyproterone acetate daily with additional 20 mg cyproterone acetate on days 5–20 of the menstrual cycle. The authors found that patients receiving active treatment enjoyed reduced hair shedding without actual increased hair regrowth (
Lucky et al 2004). The best study investigating cyproterone actetate was a 12-month randomized trial to compare the use of topical minoxidil 2% and cyproterone acetate in 66 women with FPHL. These authors found that minoxidil 2% was more effective in women without evidence of hyperandrogenism, whereas cyproterone acetate was more effective in those with signs of hyperandrogenism (
Vexiau et al 2002). Comparison of two antiandrogen medications (ie, spironolactone and cyproterone acetate) was undertaken in another study involving 80 women with biopsy confirmed FPHL. The authors found that overall, 88% of women either experienced improvement or had no progression of their hair loss with no significant difference in efficacy between individual medications (
Futterweit et al 1988).
In contrast, there is only one significant randomized study which has shown no benefit for cyproterone acetate. This study compared flutamide, finasteride, and cyproterone acetate in 36 hyperandrogenic women and failed to show a significant response for cyproterone acetate (as well as finasteride-asteride) (
Carmina and Lobo 2003). It would appear that the balance of evidence supports a role for cyproterone acetate in FPHL. Further research would need to be done to clarify whether this medication has a greater role in those patients with evidence of hyperandrogenism.
Treatment doses utilized vary but it appears the most effective is 100 mg/day on days 5–15 of the menstrual cycle supplemented by 50 μg ethinyl estradiol on days 5–25 (
Dawber et al 1982). The side effect profile includes menstrual disturbances, weight gain, loss of libido, depression, breast tenderness, and gastrointestinal upsets.
Spironolactone
Spironolactone is used widely to treat FPHL and hirsutism. It acts as an androgen antagonist by competitively blocking androgen receptors, as well as inhibiting ovarian androgen production (
Shaw 1996). In the USA it is the most widely used antiandrogen to treat FPHL. The usual daily dose is 100–200 mg. Published studies supporting efficacy are limited but as mentioned above, a recent open intervention study concluded that spironolactone 200 mg/day was equally effective in either restoring hair growth or preventing further progression of hair loss compared with cyproterone acetate at a dose of either 50 mg/day or 100 mg/day given for 10 days every menstrual cycle (
Sinclair et al 2005).
The side effect profile of spironolactone is perhaps more varied compared with other medications, due partly to its additional actions as an aldosterone antagonist. These include postural hypotension, electrolyte disturbances, menstrual irregularities, fatigue, urticaria, breast tenderness, and hematological disturbances. Because of these known side effects, it is recommended that women have regular blood pressure and electrolyte monitoring, especially in the first few months of treatment. Further caution with its use needs to be exercised in the patient with renal abnormalities since it can potentially cause serious electrolyte disturbances.
Flutamide
Flutamide is a potent antiandrogen, acting via androgen receptor antagonism. As such, it is commonly used to treat advanced prostate cancer and hirsutism. Being one of the newer antiandrogens, there is limited medical literature on its use in FPHL. One randomized study suggested that flutamide at a dose of 250 mg/day could lead to greater improvements in stemming hair loss after 1 year of treatment compared with finasteride and cyproterone acetate (
Carmin and Lobo 2003). Another randomized controlled trial found a significant treatment advantage for flutamide over spironolactone in the treatment of hirsutism, the reduction of total acne and seborrhea, and the slowing or halting of hair loss (
Sinclair et al 2005).
Adverse effects due to flutamide are potentially severe. These include hepatic dysfunction and breast tenderness, both of which are dose-related. The rate of hepatotoxicity has been estimated at 3 in 10,000 users (
Sinclair et al 2005). It is recommended that serial liver transaminases are monitored in the first few months of treatment, and that flutamide be stopped or not commenced if transaminase levels exceed twice the normal limits.
