Ch75 Dermatological Pharmacology

皮肤病药理学

1 Drugs Affecting Hair Growth

影响毛发生长的药物

1.1 Androgenic Alopecia (雄激素性脱发)

雄激素性脱发，通常称为男性和女性型秃发，是 40 岁以上成年人脱发的最常见原因。频率和严重程度随着年龄的增长而增加，一些患者可能在青春期开始。它是一种具有可变表达的遗传性状。在易感毛囊中，二氢睾酮（DHT）与雄激素受体结合，激素-受体复合物激活负责将大末端毛囊逐渐转化为小型毳毛囊的基因。雄激素性脱发的治疗旨在减少脱发和维持现有头发（Varothai 和 Bergfeld，2014 年）。

Androgenetic alopecia, commonly known as male and female pattern baldness, is the most common cause of hair loss in adults older than 40 years. The frequency and severity increase with age and may begin during puberty in some patients. It is a genetically inherited trait with variable expression. In susceptible hair follicles, dihydrotestosterone (DHT) binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles into miniaturized vellus follicles. Treatment of androgenetic alopecia is aimed at reducing hair loss and maintaining existing hair (Varothai and Bergfeld, 2014).

米诺地尔最初是作为抗高血压药开发的，据悉与一些患者的多毛症有关。米诺地尔可增强毛囊大小，使毛干更浓密，并刺激和延长头发周期的生长期，导致头发更长和数量增加。必须继续治疗，否则任何药物诱导的毛发生长都会丢失。磺基转移酶活性升高的患者最有可能对米诺地尔治疗有反应;这可能是将来有用的预测测试（Roberts et al.， 2014）。外用米诺地尔有 2% 溶液和 5% 溶液或泡沫两种形式。可能会发生过敏性和刺激性接触性皮炎，使用药物时应小心，因为毛发生长可能会出现在不良位置。这在停药时是可逆的。应指导患者在使用米诺地尔后洗手。口服低剂量米诺地尔（每天 0.25 – 5 毫克）已超说明书用于治疗雄激素性脱发，推荐剂量为女性每天 0.5 – 2.5 毫克或男性每天 2.5 – 5 毫克。口服小剂量米诺地尔最常见的副作用是多毛症。其他潜在的副作用包括体位性低血压、下肢水肿、心动过速和头痛。

Minoxidil, originally developed as an antihypertensive agent, was noted to be associated with hypertrichosis in some patients. Minoxidil enhances follicular size, resulting in thicker hair shafts, and stimulates and prolongs the anagen phase of the hair cycle, resulting in longer and increased numbers of hair. Treatment must be continued or any drug-induced hair growth will be lost. Patients with increased sulfotransferase enzyme activity are most likely to respond to minoxidil treatment; this may be a useful predictive test in the future (Roberts et al., 2014). Topical minoxidil is available as a 2% solution and a 5% solution or foam. Allergic and irritant contact dermatitis can occur, and care should be taken in applying the drug because hair growth may emerge in undesirable locations. This is reversible on stopping the drug. Patients should be instructed to wash their hands after applying minoxidil. Oral low-dose minoxidil (0.25 – 5 mg daily) has been used off label for androgenic alopecia with recommended dosages of 0.5 – 2.5 mg daily in females or 2.5 – 5 mg daily in males. The most common side effect with oral low-dose minoxidil is hypertrichosis. Additional potential side effects include postural hypotension, lower extremity edema, tachycardia, and headache.

非那雄胺抑制 5α-还原酶的 II 型同工酶，5α-还原酶是将睾酮转化为 DHT 的酶（见第 49 章），存在于毛囊中。与非秃顶区域相比，头皮的秃顶区域与 DHT 水平升高和毛囊较小有关。口服非那雄胺（1 mg/d）在 2 年内不同程度地增加男性的头发生长。非那雄胺被批准仅用于男性，但已被超说明书用于女性型脱发（Varothai 和 Bergfeld，2014 年）。非那雄胺在女性中的使用受到其致畸性的限制。孕妇不应接触该药物，因为有可能诱发男性胎儿生殖器异常。非那雄胺的不良反应包括下降、勃起功能障碍、射精障碍和射精量减少。有上市后监测报告称，停药后持续性功能障碍。与米诺地尔一样，停用非那雄胺后，新的头发生长会丢失。度他雄胺（0.5 毫克/天）是一种 I 型和 II 型同工酶 5α-还原酶抑制剂的组合，具有相似或更高的疗效，但副作用可能更常见（Varothai 和 Bergfeld，2014 年）。

Finasteride inhibits the type II isozyme of 5α-reductase, the enzyme that converts testosterone to DHT (see Chapter 49) and that is found in hair follicles. Balding areas of the scalp are associated with increased DHT levels and smaller hair follicles than nonbalding areas. Orally administered finasteride (1 mg/day) variably increases hair growth in men over a 2-year period. Finasteride is approved for use only in men but has been used off label for female pattern hair loss (Varothai and Bergfeld, 2014). Finasteride use in women is limited by its teratogenicity. Pregnant women should not be exposed to the drug because of the potential for inducing genital abnormalities in male fetuses. Adverse effects of finasteride include decreased libido, erectile dysfunction, ejaculation disorder, and decreased ejaculate volume. There have been postmarketing surveillance reports of persistent sexual dysfunction after stopping the medication. As with minoxidil, new hair growth will be lost when finasteride is discontinued. Dutasteride (0.5 mg/day) is a combined type I and type II isozyme 5α-reductase inhibitor that has similar or greater efficacy, but side effects may be more common (Varothai and Bergfeld, 2014).

螺内酯是一种醛固酮拮抗剂和保留 K+ 的利尿剂;它还具有抗雄激素活性。它用于女性型脱发，剂量为 50 至 200 毫克/天（Varothai 和 Bergfeld，2014 年）。有生育潜力的女性不应在没有可靠避孕措施的情况下接受螺内酯治疗，因为螺内酯可导致男性胎儿女性化。 Spironolactone is an aldosterone antagonist and K+-sparing diuretic; it also has antiandrogen activity. It is used off label for female pattern alopecia at dosages of 50 to 200 mg/day (Varothai and Bergfeld, 2014). Women of reproductive potential should not receive spironolactone without reliable contraception because spironolactone can cause feminization of a male fetus.