Hormonal Treatment for Acne

oral contraceptive pills

I have mentioned in my earlier post “Why should acne be a cause for concern” that hormones play a role in the pathogenesis of acne. Even before the onset of puberty adrenal glands are already producing larger amounts of dehydroepiandrosterone sulfate (DHEAS), which can be metabolized into more potent androgens, leading to cascade of events that trigger acne formation. In women, excess production of androgens by the ovary as a result of Polycystic Ovary Syndrome may also cause acne. These are the reasons behind the use of hormones in the treatment of acne.


Hormonal therapy is most effective in adult females with persistent facial inflammatory papules and nodules. We may have heard of women complaining of acne flare before or during menstruation. Therefore, hormone intervention is an additional option in the therapeutic arsenal for female patients with acne. 


When should hormonal therapy be initiated in acne cases?

• when acne has not responded to standard treatment (topical and oral antibiotics or its combination)
• when there are contraindications to intake of isotretinoin
• when rapid relapse has occurred after repeated courses of isotretinoin
• when menstrual control and/or contraception are required alongside acne therapy

Nevertheless, it is also noteworthy that this kind of treatment can also be very effective in females with acne whether their serum androgens are normal or abnormal. Females with acne have higher levels of serum androgens compared with women without acne, though these levels are mostly within the normal range.

I.           Inhibitors of Adrenal Androgen Production

Glucocorticoids in low doses can suppress the adrenal production of androgens. They are indicated for patients, both male and female, who have an elevated DHEAS level associated with late-onset congenital adrenal hyperplasia, caused by an inherent deficiency of 11-hydroxylase or 21-hydroxylase enzymes. Low-dose prednisolone (2.5–5 mg) or dexamethasone (0.25–0.75 mg) given at night (or alternative nights) can be sufficient to suppress adrenal androgen production and subsequently reduce sebum (oil)production by up to 50% with a concomitant improvement in acne.

Several studies have shown that glucocortioids given alongside cyclical estrogen (i.e., oral contraceptives) can successfully reduce sebum production in recalcitrant acne via reduction in plasma androgen level than with either agent alone.

II.        Inhibitors of Ovarian Androgen Production

1.   Estrogen

Estrogens are particularly valuable in women with clinical evidence of hyperandrogenism ( e.g., hirsutism or excessive hair growth,  menstrual irregularity, acne and oily skin). It shows two-pronged action. First, estrogen increases the hepatic production sex hormone-binding globulin, which binds and thus reduces levels of free circulating testosterone. Second, estrogens suppress the ovarian production of androgens by suppressing gonadotrophin release from the pituitary, resulting in lower serum androgen levels, hence less seborrhea.

The ones recommended for the treatment of acne are usually oral contraceptives with combined preparation containing estrogen (most commonly ethinyl estradiol) and a progestin with anti-androgenic activity.

Oral contraceptive pills containing ethinylestrodiol (oestrogen) and an antiandrogenic progesterone  include cyproterone acetate (co-cyprindiol or Diane™-35, Estelle™ 35, Ginet-84™and Althea), drospirenone (Yasmin™, Yaz™) or dienogest (Valette™).

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.  Minor side effects are breast tenderness (20%) and increase in bra size, Spotting" (irregular mild bleeding between periods) occurs in 10% of women in the first month, nausea and loss of appetite, headaches, increased appetite and weight increase (uncommon), mood changes including depression, melasma (facial pigmentation) and hair loss.

2.   Gonadotrophin-releasing Agonists

Gonadotrophin releasing agonists inhibit ovarian androgen production by interrupting the cyclical release of luteinizing hormone and follicle-stimulating hormone from the pituitary.  Nafarelin, leuprolide and buserelin are included in this group. They all have demonstrated efficacy in the treatment of acne and hirsutism in females both with and without endocrine abnormalities. . However, their use is limited somewhat by the potential for adverse effects including reduced bone mass, headache and menopausal symptoms, caused by the suppression of ovarian estrogen production.

 

III.     Androgen Receptor Blockers

1.   Cyproterone Acetate

Cyproterone acetate  (CPA) is a progestional anti-androgen that directly inhibits the androgen receptor. It  reduces sebum production by no more than 30%, but its success in acne is enhanced by its direct effects on androgen-mediated comedogenesis (i.e. blackhead and whitehead formation). . An overall improvement in acne has been reported in up to 90% of patients treated with higher doses of CPA (50–100 mg/day), with or without ethinyl estradiol.

Is it okay for men suffering from acne to take CPA? It has been demonstrated that 25mg of CPA can  improve acne in males. However, due to its feminization effects, such as reduced libido, gynecomastia (breast enlargemement) and azoospermia (absence of sperm in the ejaculate) this kind of treatment is not recommended for males. General side effects of CPA, although uncommon, include fatigue, headache, nausea, weight fluctuation, liver dysfunction and blood clotting abnormalities.

2.   Spironalactone

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.

                It can reduce sebum production by 30–75% depending on the dose. It is usually prescribed at a dose of 50–100 mg daily with meals, but many women with sporadic outbreaks can be successfully managed with as little as 25 mg daily. As with other hormonal therapies, response is slow and it may take up to 3 months of continuous treatment before any benefit is observed.

Menstrual irregularities, potential hyperkalemia, breast tenderness, fatigue, headache, fluid retention and, rarely, melasma are among the side effects.  Spironalactone should not be prescribed for male patients because like CPA it can also cause feminization. Females should be advised to avoid pregnancy owing to potential abnormalities to the male fetus. All patients should undergo regular monitoring of their electrolytes owing to the potassium-retaining effects of spironolactone on the kidney.

3.   Flutamide

Flutamide is a nonsteroidal potent androgen antagonist, most routinely used in the treatment of prostate cancer. It has been demonstrated to be efficacious in treating androgen-mediated acne and hirsutism when administered at a dose of 125–250 mg daily.

Like all hormonal agents, it should not be prescribed for male patients and owing to the risks of teratogenicity, pregnancy should be avoided.

Fatal hepatotoxicity has been reported with flutamide,  that is why many countries now ban the use of flutamide as a treatment for androgen-mediated acne and hirsutism.

Other skin/hair conditions, aside from acne aggravated by androgenic hormones and therefore hormonal therapy is applicable are:

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

Hormonal therapy carries multiple side effect, thus it requires monitoring. Patients therefore are advised not to self-medicate. Always seek advice from your dermatologist or gynecologist regarding the appropriate medicine for your condition.

References:

1. Treating Acne Vulgaris:Systemic, Local and Combination Therapy. Medscape
2. Hormonal treatment . DermNet NZ

Related articles:

1. What is Hormonal Imbalance?
2. Why should pimples be a cause for concern?