Hirsutism, treatment

Hemostatic mechanisms and drugs influencing them Hiccup treatment of Hirsutism treatment of... 

Dihydralazine and minoxidil (via its sulfate-conjugated metabolite) dilate arterioles and are used in antihypertensive therapy. They are, however, unsuitable for monotherapy because of compensatory circulatory reflexes. The mechanism of action of dihydralazine is unclear. Minoxidil probably activates K channels, leading to hyperpolarization of smooth muscle cells. Particular adverse reactions are lupus erythematosus with dihydralazine and hirsutism with minoxidil—used topically for the treatment of baldness (alopecia androg-enetica). 

Unlabeled uses Spironolactone has been used in the treatment of hirsutism (50 to 200 mg/day) due to its antiandrogenic properties. One study suggested that a lower... 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

Cyproterone acetate is a progestational antiandrogen that blocks androgen receptor binding and suppresses androgen-sensitive tissues. It is available in a topical form in Europe for the treatment of hirsutism. 

Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance. The United Kingdom Prospective Diabetes Study demonstrated a marked reduction in cardiovascular comorbidities and diabetic complications in metformin-treated individuals. Metformin has also been used to treat hirsutism in individuals with polycystic ovarian syndrome and may enhance fertility in these women, perhaps by decreasing androgen levels and enhancing insulin sensitivity. 

Currently, production of eflornithine has been stopped because of industrial policy and environmental problems it involves the use of Ereon (CHF2CI) as a reagent in its synthesis (Eigure 8.27). However, production of eflornithine may start again in order to supply the WHO. Another reason is that a topical formulation for the treatment of female hirsutism has recently been launched (Vaniqa). Its synthesis has recently been improved by using the selective catalytic reduction of the cyano group without any cyclization into lactam. ... 

Unlabeled Uses Adjuvant monotherapy after radical prostatectomy in treatment of prostate cancer, female hirsutism... 

Spironolactone is also an androgen antagonist and as such is sometimes used in the treatment of hirsutism in women. Dosages of 50-200 mg/d cause a reduction in the density, diameter, and rate of growth of facial hair in patients with idiopathic hirsutism or hirsutism secondary to androgen excess. The effect can usually be seen in 2 months and becomes maximal in about 6 months. 

It has become apparent that reduction in the dose of the constituents of oral contraceptives has markedly reduced mild and severe adverse effects, providing a relatively safe and convenient method of contraception for many young women. Treatment with oral contraceptives has also been shown to be associated with many benefits unrelated to contraception. These include a reduced risk of ovarian cysts, ovarian and endometrial cancer, and benign breast disease. There is a lower incidence of ectopic pregnancy. Iron deficiency and rheumatoid arthritis are less common, and premenstrual symptoms, dysmenorrhea, endometriosis, acne, and hirsutism may be ameliorated with their use. 

Spironolactone, a competitive inhibitor of aldosterone (see Chapter 15), also competes with dihydrotestosterone for the androgen receptors in target tissues. It also reduces 17a-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. It is used in dosages of 50-200 mg/d in the treatment of hirsutism in women and appears to be as effective as finasteride, flutamide, or cyproterone in this condition. 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

The azasteroids 268 and 269 of potential clinical utility for the treatment of acne, hirsutism or prostatic hypertrophy, have been 14C-labelled in ring A and the t-butyl portion of carboxamide for metabolism and bioavailability studies283. 

In women and children, the main effect will be one of virilization in its various forms, ranging from hirsutism and deepening of the voice to enlargement of the female clitoris and male pattern baldness the effect on the voice rapidly becomes irreversible because of changes in the larynx laryngeal polyps have also been observed (69). In women, menstrual abnormalities are likely. Shortterm treatment can produce increases in estradiol, dihydrotestosterone, testosterone (total and unbound), and the ratio of dihydrotestosterone to testosterone. 

Topical application of testosterone, as a gel or from transdermal patches, can lead to absorption and systemic effects (SEDA-16, 158). Transdermal absorption of testosterone (usually from treatment of vulvar lichen scler-osus et atrophicus) can lead to increased libido, clitoral hypertrophy, pubic hirsutism, thinning of the scalp hair, facial acne, voice change, hirsutism, and even virilization (111). 

However, one needs to be cautious when faced with claims that topical hormonal products are better tolerated than those administered orally or by other routes. Topical testosterone has sometimes been used in women as a treatment for different vulvar conditions, and hirsutism and other signs of virilization have been described by several authors. Clearly, close monitoring is needed (114). 

Townsend KA, Marlowe KF. Relative safety and efficacy of finasteride for treatment of hirsutism. Ann Pharmacother 2004 38(6) 1070-3. 

Bayram F, Muderris I, Guven M, Ozcelik B, Kelestimur F. Low-dose 2.5 mg/day) finasteride treatment in hirsutism. Gynecol Endocrinol 2003 17 419-22. 

Tartagni M, Schonauer MM, Cicinelli E, Petruzzelli F, De Pergola G, De Salvia MA, Loverro G. Intermittent low-dose finasteride is as effective as daily administration for the treatment of hirsute women. Fertil Steril 2004 82 752-5. 

Falsetti L, De Fusco D, Eleftheriou G, Rosina B. Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome Gynaecol Endosc... 

---