It is well-known that androgens have a potent influence on hair growth and the overall physical characteristics of hair [8,9]. For example, at the onset of puberty vellus hairs are converted to terminal hair in various body regions such as the axilla, genital area, legs, chest, and face—the latter two occurring preferentially in males. The contribution of androgens to hair growth is paradoxical, in that they have the opposite affect on the crown of the scalp in certain individuals—leading to male pattern baldness. While there have been studies which show differences in the sensitivity of hair follicles to androgens, it is not clear if the paradoxical response of hair follicles to androgens is mediated locally at the level of the hair follicle, or is the result of systemic androgens, or perhaps more likely, a combination of both.
An anti-androgen approach to treat unwanted facial hair that has been characterized as hirsutism is predicated on the blockade of the androgen receptor using spironolactone (SL). This agent has been successfully used to reduce the growth of androgen-dependent hair, but often requires high doses, as its affinity for the androgen receptor is more than an order of magnitude less than that of dihydrotestosterone (DHT), the potent form of testosterone [8,9]. There are side effects associated with SL therapy that range from milder conditions of gastritis and dry skin [8] to more severe ones such as polyuria and hypotension. In addition, SL is contraindicated in patients with renal insufficiency, hyperkalemia, and pregnancy. While the use of anti-androgens may be suitable for people with severe hirsutism, they are not useful for the control of facial hair that is not androgen-dependent, such as vellus hair.
A similar approach to controlling facial hair includes the use of 5a-reductase inhibitors. This enzyme reduces testosterone to the more potent dihydrotestosterone (DHT). Elevated 5a-reductase activity has been reported to be associated with idiopathic hirsutism [8] and, therefore, therapeutic strategies which block 5a-reductase seem plausible. Finasteride, an inhibitor of Type II 5a-reductase has been successfully developed by Merck & Co. (Proscar) as a systemic treatment for male-pattern baldness. In an attempt to capitalize on the paradoxical effects of androgens on hair growth, finasteride was evaluated as a treatment for hirsutism, but was shown to be minimally effective when compared with anti-androgens [8].
The only topical treatment approved by the FDA for the treatment of unwanted hair growth is eflornithine-HCl, which is marketed as Vaniqa (13.9% eflornithine). The molecule’s mechanism of action involves the irreversible inhibition of ornithine decarboxylase, a rate-limiting enzyme required for the synthesis of polyamines [10]. While originally developed as a novel cancer therapeutic, cancer clinical trials with difluoromethylornithine (eflornithine) showed low efficacy, but was found to be well-tolerated among patients [11]. Increased ODC and DNA synthesis was shown in murine hair follicles [12], and related to the onset of the anagen hair growth cycle stage [13]. These insights gave rise to the notion of hair growth inhibition by polyamine analogs and Shander and Ahluwalia [10] identified the utility of eflornithine (difluoromethylornithine) as a hair-growth inhibitor, which was subsequently brought to the market place through collaboration with Bristol-Myers Squibb.