| BALDNESS | opINIoN
use for the treatment of baldness was also originally developed for a quite different purpose. Merck & Co’s finasteride is an inhibitor of type 2 steroid 5α‑reductase, and thus inhibits the formation of DHT. It was originally developed for the treatment of benign prostatic hypertrophy (BPH) and is marketed for that use under such brand names as Proscar and Andozac. It is now also marketed for male pattern baldness (at a lower dose) in approximately 40 countries, under such brand names as Propecia and Finastar. It was approved for this indication in the US in 1997. Merck’s sales of Propecia in 2010 were $420 million. Finasteride is used alone or in
combination with topical minoxidil for the treatment of androgenetic alopecia. It increases the ratio of anagen to telogen hairs and increases the growth rate and thickness of hair. In the US, its formal indication is for the treatment of male pattern hair loss in men only; safety and efficacy have been demonstrated in men aged 18–41 years with mild to moderate hair loss of the vertex and anterior mid‑scalp area. It is not indicated in women, and is absolutely contraindicated in women who are or may be pregnant because of its ability to cause abnormalities of the external genitalia of a male foetus. In men, possible side‑ effects include decreased libido, erectile dysfunction, and ejaculation disorder (decreased volume of ejaculate). Recently, Merck has come in for some
criticism after a study published in The Journal of Sexual Medicine (3) suggested that the incidence of sexual dysfunction among men treated with finasteride was higher than previously believed, and that in some cases it was persistent. A lawsuit has been filed in the Federal District Court
in New Jersey on behalf of undisclosed plaintiffs who were prescribed Propecia and who experienced a number of severe side‑effects that were permanent in nature, including loss of libido, erectile dysfunction and depression. A class action lawsuit has also been filed against Merck Frosst Canada. More recently, a second 5α‑reductase
inhibitor, GlaxoSmithKline’s dutasteride (Avodart), has become available for treating male pattern baldness, but only in South Korea so far (although it is widely marketed for treating BPH). Dutasteride differs from finasteride in that it inhibits both type 1 and type 2 forms of the enzyme and is therefore more potent at inhibiting the formation of DHT. Clinically, the effects of dutasteride are similar to those of finasteride, but because it has a longer half‑life in the body, its effects (both desirable and undesirable) are potentially much longer‑lasting. Another proprietary product that has
been used for treating hair loss, although strictly off‑label, is the antifungal ketoconazole (J&J’s Nizoral shampoo). It is not clear how ketoconazole affects hair growth, although it may be through a mild anti‑androgenic effect. No new drug treatments for
androgenetic alopecia look likely to appear on the market for some time. A small number of products are undergoing clinical evaluation, although none has yet entered large‑scale clinical trials (Table 1). These products are also being
developed for other uses: ASC-J9 and CB-03-01 (cortodoxone) are in separate Phase II trials for acne, while the other two products are in early studies for other indications. Also worth a mention is Allergan’s Lumigan/Latisse (bimatoprost), a topical
References
1. Men’s Hair Loss. American Hair Loss Association. Calabascas, CA, USA: 2010. Available at: http://
tinyurl.com/3jw2a2e [Last accessed 20 April 2011]
2. Chumlea WC, Rhodes T, Girman CJ et al. Family
history and risk of hair loss. Dermatology 2004; 209(1): 33–9
3. Irwig MS, Kolukula S. Persistent Sexual Side Effects of Finasteride for Male Pattern Hair Loss. J Sex Med 2011: published online 18 March 2011, doi: 10.1111/j.1743-6109.2011.02255.x.
ophthalmic hypotensive lipid derived from prostaglandins that is used for the treatment of glaucoma and hypotrichosis of the eyelashes. Based on its ability to promote the growth of eyelashes, it is in early clinical trials for the treatment of alopecia.
Conclusions While we are still a long way from a cure for male pattern baldness, there are a number of treatment options, with more on the horizon. The role of stem cells in male pattern baldness has recently come under the spotlight, with evidence being produced to show that, while the scalps of affected men contain a similar number of stem cells to men with no hair loss, a smaller proportion of the cells reach maturity and go on to produce new hairs. If a way could be found to activate these stem cells, it might afford a completely new approach to the condition. Until such time, however, existing products such as minoxidil and finasteride will continue to be the mainstay of medical interventions to reverse hair loss.
Table 1 Drug products being developed for androgenetic alopecia Name
Originator
OSH-101 RK-023
CB-03-01 ASC-J9
OsteoScreen (now licensed to Leo)
R-Tech Ueno Cosmo Pharmaceuticals AndroScience Phase II Phase II Phase I Phase I
Development status (for MPB)
Pharmacology Unidentified Unidentified Androgen antagonist Androgen antagonist
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