Introduction Uses How it works Anti-androgenic drugs Clinical effects Oral contraceptives Spironolactone Cyproterone acetate
Anti-androgen therapy refers to medication taken by women to counteract the effect of male sex hormones such as testosterone on the skin. Anti-androgens are not suitable for skin problems in men.
Anti-androgen medications are used to treat signs of hyperandrogenism, including the following skin and hair disorders:
Anti-androgen therapy may:
Androgen receptor blockers act on the sebaceous gland and base of the hair follicle. They include:
Spironolactone and cyproterone may be effectively combined with cyproterone acetate/ethinyloestradiol or other oral contraceptive agent, partly because they cause menstrual irregularities and partly to prevent pregnancy. The combined treatment is not necessary in post-menopausal women.
Low-dose oral corticosteroid (eg prednisone 2.5 mg in the morning, 5 mg at night) acts to reduce adrenal androgen production. In congenital adrenal hyperplasia, DHEAS levels should reduce to normal.
Limecycline, roxithromycin and ketoconazole (no longer available in New Zealand) are antimicrobial drugs that have also been noted to reduce androgen synthesis.
Drugs acting on ovarian androgen production include:
Excessive prolactin is reduced by bromocriptine, cabergoline and quinagolide.
5-alpha reductase inhibitors include zinc, finasteride, azelaic acid, saw palmetto and other plant extracts. Spironolactone inhibits 5-alpha reductase weakly. Unfortunately, finasteride does not reduce sebum production and is not effective in the treatment of acne. However, we now know that isotretinoin reduces sebum partly by reducing dihyrotestosterone production in the sebaceous gland.
Insulin resistance can be reduced using metformin, mainly prescribed for type 2 diabetes mellitus and obesity / metabolic syndrome. It may also reduce signs of hyperandrogenism. Metformin 250 mg to 2 g daily is safe but can cause diarrhoea and should be taken after food in gradually increasing doses. Rosiglitazone and pioglitazone can cause heart and liver toxicity.
In acne, the effects of anti-androgens include:
They can be combined with other topical and oral treatments for acne.
In hirsutism, the results are:
Physical methods of hair removal such as waxing, shaving, electrolysis or laser epilation, can be used at the same time as anti-androgens are taken. They often work better than prior to the medication.
In female pattern hair loss, the results are:
These effects are not always clinically significant.
Progesterone-only oral contraceptives are not effective in the management of androgen-mediated skin conditions.
Combined oral contraceptives contain two hormones, ethinyloestrodiol 20–35 mcg (an oestrogen) and a progesterone. They prevent pregnancy by suppressing ovulation and changing cervical mucus. There are various kinds of progesterone, which may be androgenic in nature and thus unsuitable for those androgen-mediated skin conditions (particularly levonorgesterol and norgestrel). Anti-androgenic or minimally androgenic progesterones (see above) are indicated in these women.
Their effect in hyperandrogenism is to reduce production of androgens by the ovaries, by the adrenals and at the receptor level in the skin. They also decrease circulating testosterone by increasing sex hormone binding globulin (SHBG).
Combined oral contraceptives are available as 21-day and 28-day packs; start on Day 1 (conventionally, day 1 is the first day of menstruation) and take one a day for 21 days. Then have a 7-day break (21-day pack) or take the placebo tablets for a week (28-day pack) before starting the cycle again. During this time, you can expect a withdrawal bleed (a period).
Combined oral contraceptives can increase the risk of thromboembolism (blood clots blocking blood vessels), especially in those with an inherited tendency ("thrombophilia"), or who smoke. Please refer to the New Zealand Ministry of Health (Medsafe) advice on the use of combined oral contraceptives.
The combined oral contraceptive may be unsuitable if the patient:
Many of these women can instead use progesterone-only contraceptive pills while they are being treated with spironolactone or cyproterone.
Oral contraceptives can sometimes aggravate migraine and are inadvisable in those with significant liver disease. They may occasionally increase the risk of certain uncommon forms of breast cancer. They must not be taken in pregnancy.
On the other hand, the combined oral contraceptive reduces the risk of ovarian and endometrial cancer, benign breast disease, ectopic pregnancy, painful periods, iron deficiency anaemia and pelvic inflammatory disease.
Cyproterone acetate/ethinyloestradiol (co-pyrindiol) should be discontinued in the following circumstances:
As with other oral contraceptives, minor side effects may arise, especially in the first few weeks. These include:
Other medications can interfere with the contraceptive effectiveness.
Combined oral contraceptives with anti-androgenic components have advantages:
Studies have demonstrated that the skin condition continues to improve even after the medication has been taken for a year. Combined oral contraceptives can usually be taken safely for many years.
Unfortunately, the skin condition tends to deteriorate again within a few months after the medication has been stopped.
New forms of oral contraceptive are introduced from time to time, to increase efficacy and reduce side effects.
Please refer to the New Zealand Ministry of Health (Medsafe) advice on the use of combined oral contraceptives.
Spironolactone is a potassium-sparing medication used as a diuretic medication for heart failure, liver disease and high blood pressure. However, it has also been found useful for hirsutism, acne and seborrhoea because it has anti-androgenic properties. Spironolactone mainly works by blocking androgen receptors.
The dose of spironolactone is usually slowly increased from 25 to 200 mg daily, taken at night. It is sometimes prescribed cyclically to reduce menstrual irregularities, eg, for 3 weeks out of every 4 weeks or days 5–21 of the menstrual cycle. It may take six or more months to see improvement in the skin condition.
Side effects of spironolactone include:
Potassium, other electrolytes and creatinine levels in the blood are often monitored in older women, if high doses are prescribed, in patients taking other medicines (due to drug interactions) and in those with heart or kidney problems. Monitoring is not considered necessary in healthy women. Spironolactone should not be taken in pregnancy or during lactation (see Lactation and medications used in dermatology).
Spironolactone is prohibited in athletic competition (requires therapeutic use exemption).
Higher doses of cyproterone acetate are indicated for more severe cases of androgenetic skin conditions. It is effective for 70% of those with hirsutism.
Several different regimes are prescribed with doses ranging from 25 to 200 mg daily. Prior to the menopause, the medication is usually combined with cyproterone acetate/ethinyloestradiol or other oral contraceptive agent:
One system is to take the high dose cyproterone for the first ten days of the cycle.
Postmenopausal women and women who have had a hysterectomy can take cyproterone every day. It may be advisable to have a 7-day break every month. They may also take spironolactone.
Occasional significant side effects include:
Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).
