Treatment of hyperandrogenism in women

Abstract

In this review the medical therapy of hyperandrogenism is evaluated both by a literature review and by our own experiences at a large outpatient clinic for patients with symptoms of hyperandrogenism. The clinic was established over 15 years ago at the Department of Gynecological Endocrinology and Reproductive Medicine of the University Women's Hospital in Heidelberg, Germany.

In addition to the dermatological aspect, therapy using antiandrogens also contributes to avoiding the development of polycystic ovary syndrome, reducing the increased risk of endometrial cancer in cases of hyperandrogenemia and avoiding the associated cardiovascular complications of hyperandrogenemia. About 25—40% of all women aged between 15 and 25 years suffer from acne vulgaris of differing degrees of severity. Since severe psychological strains caused by this may be expected, especially in young women without adequate therapy, systemic antiandrogen treatment is of particular importance.

The requirement for available and safe substances for use in the therapy of symptoms of hyperandrogenism, particularly with respect to the required long-term treatment, is demanding. The following factors must be considered from a risk—benefit aspect for the currently available therapies: efficacy, unwanted concomitant symptoms and drug safety as documented by the scope of available controlled clinical studies. The most important drugs for the treatment of symptoms of hyperandrogenism are cyproterone acetate, chlormadinone acetate, dienogest, spironolactone, βutamide, corticosteroids and gonadotropin-releasing hormone (GnRH) analogs.

The efficacy and tolerability of βutamide and spironolactone have been shown by a number of studies. However, both substances have no contraceptive effect and have a negative influence on the menstrual cycle. As regards βutamide, there are concerns with respect to its possible hepatotoxic effect. Furthermore, because of the teratogenic effect of flutamide, reliable contraception is necessary during therapy. The combination oral contraceptive/flutamide bears the potential risk of drug interaction, particularly in view of the possible hepatotoxic effect of flutamide.

Combinations of GnRH analogs and estrogens/progestogens may be useful in some cases (polycystic ovary syndrome) but they cannot be considered for long-term therapy since they lack peripheral (androgen receptor) efficacy. Their use is restricted to a group of patients in whom suppression of adrenal and/or ovarian androgen secretion is the primary goal. Spironolactone is an alternative in cases where contraindications for estrogen/progestogen combinations exist, depending on the legal situation (approval by the health authorities) in the particular country. Chlormadinone acetate can be used to treat mild forms of acne, and dienogest might prove to be a promising new drug for mild forms of acne or hirsutism. Cyproterone acetate is one of the most potent antiandrogens and has the advantage of being well tolerated even in higher dosages. Available manufactured dosages of cyproterone acetate allow for adaptation of the administered dose according to the seventy and type of hyperandrogenism (oral: 2, 10, 25, 50 and 100 nig/day; parenteral: 300 nig i.m.). The combination cyproterone acetate/ethinylestradiol exerts good cycle control comparable to that o f other modern estrogen/progestogen combinations.

Following an analysis of efficacy, indications for use and the range of unwanted concomitant symptoms of the products currently used for the treatment of symptoms o f hyperandrogenism, cyproterone acetate, the most potent ant androgen, and with no contraindications for estrogen/Progestogen combinations, is considered the substance of choice for the treatment of hyperandrogenism in women.

Key Words:

• Hyperandrogenism
• Hirsutism
• Acne
• Antiandrogens
• Cyproterone Acetate
• Dienogest
• Spironolactone