Hormonal treatment

This page provides information about anti-androgen therapy, i.e. medication taken by women to counteract the effect of male hormones such as testosterone on the skin. Anti-androgens are not suitable for skin problems in men.

Patient information in women that may be caused or aggravated by androgenic hormones include:

• Acne
• Seborrhoea
• Hirsutism
• Female pattern hair loss
• Hidradenitis suppurativa

Hormonal regimes effective for these skin conditions include:

• Cyproterone acetate with ethinylestradiol (Diane™-35, Estelle™ 35)
• Other low-dose combined oral contraceptives
• Spironolactone 100-200 mg daily (Aldactone™, Spirotone™), which is most useful in women over the age of 30 years.
• Low-dose oral steroid (eg prednisone 2.5 mg in the morning, 5 mg at night)
• Cyproterone acetate 50 - 200 mg (Androcur™, Procur™, Siterone™ - available only on a specialist's prescription). This powerful anti-androgen is usually taken on days 1 to 10 of the menstrual cycle (conventionally, day 1 is the first day of menstruation).

Spironolactone and cyproterone may be 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.

These medications suppress release of the pituitary hormone, gonadotrophin, which in turn reduces androgen production by the ovaries. They also have a direct peripheral effect on the sebaceous gland.

In acne, the effects of anti-androgens include:

• Reduced sebum production
• Reduced comedone formation

They can be combined with other topical and oral treatments for acne.

In hirsutism, the results are:

• Slower growth of hair
• Lighter coloured hair
• Finer textured hair

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:

• Reduced hair shedding
• Reduced hair thinning
• Sometimes, restoration of thicker hair

Cyproterone acetate/ethinyleodstradiol and other combined oral contraceptives

Diane™-35 and Estelle™ 35 are similar medications marketed by different pharmaeutical companies. They contain two hormones, cyproterone acetate 2mg (an anti-androgenic progestogen) and ethinyloestrodiol 35 mcg (an oestrogen). This combination is classified as a low-dose combined oral contraceptive - it suppresses ovulation and changes cervical mucus.

Diane™-35 comes as a 21-day pack; 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 before starting the cycle again. During the tablet-free interval, you can expect a withdrawal bleed (a period).

Diane™-35 ED and Estelle™ 35 have the same medicine but come as 28-day packs. There are 7 placebo tablets to take – this makes it easier to remember.

Low dose 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:

• Has had a previous blood clot (thrombosis, embolism or ‘DVT’)
• Has high blood pressure (hypertension) or heart disease
• Smokes
• Is significantly overweight (obese)
• Has recently undergone surgery or trauma or is immobile
• Is undertaking long distance air travel (4 hours or more)
• Has a family member aged less than 50 years who has had blood clots or high blood pressure

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.

Cyproterone acetate/ethinyleodstradiol should be discontinued in the following circumstances:

• Severe migraine (headache, visual disturbance, numb feelings)
• Any form of thrombosis (such as heart attack, stroke) or increased blood pressure
• In case of immobility (including due to surgery) or trauma (eg bad sprains)
• If an increase in number or severity of epileptic seizures occurs, or liver disease arises during treatment
• Pregnancy

As with other oral contraceptives, minor side effects may arise, especially in the first few weeks. These include:

• Breast tenderness (20%) and increase in bra size
• "Spotting" (irregular mild bleeding between periods) occurs in 10% of women in the first month, but only affects 3% by the sixth month. Rarely, periods may stop altogether (amenorrhoea).
• Nausea and loss of appetite
• Headaches
• Increased appetite and weight increase (uncommon)
• Mood changes including depression
• Melasma (facial pigmentation)
• Hair loss (it is more common for hair fall to occur when the medication has been discontinued however)

Other medications can interfere with the contraceptive effectiveness.

• Barbiturates
• Phenytoin
• Rifampicin
• Some antibiotics

On the other hand, cyproterone acetate/ethinyloestradiol has advantages:

• It regulates the menstrual cycle in the majority of women
• Lighter, less painful periods occur in the majority of women
• Iron deficiency anaemia is less common because of less bleeding
• Increased "good" HDL cholesterol may protect against atherosclerosis (hardened arteries predisposing to heart disease)
• A decrease in the number and size of ovarian cysts occurs in polycystic ovarian syndrome
• Sebum production is reduced by 30%, resulting in worthwhile improvement in 80% of those with seborrhoea
• Acne usually improves by 40-50% by the third cycle and by 80-90% by the ninth cycle.
• More than 40% of women with facial hair find it clears within 9 months, and many get worthwhile reduction in hair growth elsewhere.

Studies have demonstrated that the skin condition continues to improve even after the medication has been taken for a year. Cyproterone acetate/ethinyloestradiol 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. Yasmin™ contains 30mcg of ethinyl oestrodiol and 3mg drospirenone. Its effect has been described as similar to spironolactone (see below).

Please refer to the New Zealand Ministry of Health (Medsafe) advice on the use of combined oral contraceptives.

Spironolactone

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 works by blocking androgen receptors.

The dose of spironolactone is usually slowly increased from 50 to 200 mg daily, taken at night. It may take six or more months to see improvement in the skin condition.

Side effects include:

• Nausea, diarrhoea
• Drowsiness (possibly due to high blood potassium levels)
• Headache and dizziness
• Menstrual cycle irregularities including increased frequency of menstruation, bleeding in the middle of the month or stopping periods altogether (amenorrhoea)
• Breast pain

Cyproterone acetate

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:

• To regulate menstrual cycle irregularities caused by the high dose cyproterone
• To prevent pregnancy; there are concerns that cyproterone could harm a male fetus by "feminising" it.

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.

Occasional significant side effects include:

• Liver disturbance
• Tiredness and depression
• Weight increase