10.3.4.1 Hormonal Treatments
Women suffering from clinically significant hirsutism, male-pattern hair growth in women [19], generally seek treatments beyond simple cosmetic measures or cosmeceutical products to manage their hair growth. A study conducted by McKnight [20] in a random population of 400 European women asked the question how many felt they have excess amount of unwanted body hair. Nine percent of the surveyed women felt that they were particularly ‘hairy’. The investigator assessment classified this nine percent to be ‘hirsute’. The medical literature estimates that hirsutism occurs in approximately 5% of the population [21,22]. In women, the condition is caused by increased levels of androgens (male hormones) and/or increased hair follicle sensitivity to androgens, and only rarely is it accompanied by any serious underlying medical problem [23-27].
It is generally agreed by both dermatologists and endocrinologists that successful management of the hirsutism condition requires a combination of both medical (anti-hormonal, Rx creams) and cosmetic procedures. Two kinds of products are available, a topical Rx cream Vaniqa that inhibits the rate of hair growth by targeting a hair follicle enzyme ornithine decarboxylase [28], and anti-androgens that work by reducing the androgen-dependent hair growth [29]. For the treatment of clinically hirsute women, drug treatments include systemic use of steroidal and nonsteroidal anti-androgens, including spironolactone, flutamide, cypro – terone acetate, finasteride and cimetidine. In the United States, spironolactone (Aldactone) is the most widely used anti-androgen for this indication [30-35]. Spironolactone interferes with the formation of androgens and androgen receptor binding [26]. Its use in hirsutism is suggested for women with normal ovulatory cycles and normal testosterone levels [30,33]. Cyproterone acetate and flutamide, inhibit the biological activity of androgens by blocking the binding of the androgen to its receptor. The overall efficacy of these drugs is similar to sprionolactone [32,36]. Cyproterone acetate (pianette) is especially recommended for women who exhibit increased testosterone levels or polycystic ovarian syndrome [37-39]; however, the drug is not available in the United States market. Flutamide (Eulexin), is a potent antiandrogen and a receptor-binding agent, and shows efficacy that is similar to spironolactone [40]. Earlier studies used higher doses of the drug, up to 250 mg, that resulted in severe toxici – ties; however, the drug has now been shown to be effective at much lower doses, that is,
62.5 mg with fewer side effects [41,43]. Potential for liver toxicity is still the major issue with this drug [40,44-46]. The most recent drug to be tried for this indication is a 5-alpha reductase inhibitor, finasteride (Proscar). Originally developed for benign prostatic hypertrpohy in men, finasteride inhibits the formation of active reduced metabolites from testosterone. The results from controlled clinical studies with this drug demonstrated clinically significant efficacy with relatively fewer side effects [40, 47]. The treatment did not show any efficacious advantage over sprinolactone [31,33,40]. All four of these oral medications, because of their antiandrogenic activity, have some systemic side effects. The most significant side effect reported is hepatotoxicity [48,44-46]. Overall, the efficacy of anti-androgen treatment is rather limited, they do not provide a “cure” for this condition, and have not been approved by the FPA as treatments for hirsutism.