Hormonal Treatments

What is hormonal therapy?

Hormonal therapy is an excellent option for women, especially if oral contraception is also desired. Hormonal therapy generally implies oral contraceptives, either alone or in conjunction with other hormone treatments.

These treatments help woman who have acne either alone or in association with other signs of hormonal imbalance such as increased hair growth on the face or other parts of the body where hair growth is undesirable and for women who have excessive hair loss from the scalp unexplained by other factors, such as thyroid or other conditions, and irregular menstrual periods.

The goal of hormonal therapy is to block the effects of androgens on the sebaceous gland and probably the skin cells that are lining the pores as well. This can be accomplished with the use of estrogens or a class of drugs known as antiandrogens (androgen receptor blockers) or by agents designed to reduce the body’s production of androgens by the ovary or adrenal gland, such as oral contraceptives, glucocorticoids, or gonadotropin-releasing hormone agonist.

Do I need to have my hormones evaluated?

An evaluation of hormones, usually done by an endocrinologist, may be indicated for women with acne who have proven resistant to conventional treatments or if there is a sudden, severe onset of acne.

Other cases in which an endocrine evaluation may be indicated are in women with acne who also have irregular menstrual periods and also increased hair growth in unusual areas such as the face and abdomen. Androgen evaluation may also be indicated for women who relapse shortly after oral isotretinoin therapy. The screening usually involves a physical exam by the doctor and a series of blood tests to measure specific levels of hormones in the blood.

These screening tests are timed to correlate with a certain phase of the menstrual cycle and are usually done within 2 weeks before the next menstrual cycle begins. People on oral contraceptive pills should discontinue he medication for at least 1 month before testing. The tests are designed to try to pinpoint the source of the increased androgen production so that appropriate therapy can be instituted.

It is important to note that hormonal therapy can be very effective in women even if the blood levels of the serum androgens are within normal limits. Although women with acne are more likely to have abnormalities in hormonal evaluations than women without acne, most women with acne who are evaluated for hormonal abnormalities have androgen levels that are within normal limits.

Hormonal therapies seem to work best in adult women and sexually active teens with persistent inflammatory papules and nodules that commonly involve the lower face and neck. These women often report that their acne flares before their menstrual periods and consists of painful, often deep, inflammatory papules and nodules.

The skin may or may not be oily. There are also often comedones on the forehead and chin, especially in teenagers. These women also note that there is little or no improvement in their acne after multiple courses of antibiotics.

In these cases, oral antibiotics can be discontinued in favor of oral contraceptives because they block the production of androgens from both the ovary and adrenal glands. Also, the continued use of oral contraceptive pills is recommended if the addition of other hormonal agents is considered for use in the future.

For optimal results from hormonal therapy, appropriate patient selection is key. Hormonal therapy is useful for women with endocrine abnormalities and for women who have proven non responsive to or unable to tolerate more conventional therapies such as oral antibiotics, topical antibiotics, and retinoids along with BP.

The use of oral contraceptive pills may also be useful for women who require medical treatment to control irregular periods or who would like contraception. It is important to remember that oral contraceptive pills do not protect against sexually transmitted diseases and that a second form of protection is required to reduce the risk of transmission of HIV and other potentially serious sexually transmitted diseases.

The aim of hormonal therapy is to reduce sebum production; however, sebum production is only one component in the pathway to acne. For this reason, hormonal therapy is most effective when used in conjunction with other antiacne therapies, including oral or topical antibiotics, topical retinoids, azelaic acid, salicylic acid, and BP.

For those with concerns about the reduced effectiveness of contraception when oral contraceptive pills are used in conjuction with oral antibiotics, recent evidence suggests that antibiotics do not significantly affect the metabolism of oral contraceptive pills, which means that their effectiveness in contraception should not be reduced.

The following are recommendations for hormonal therapy:

• It is an excellent choice for women who need oral contraception for gynecologic reasons
• It should be used early in female patients with moderate to severe acne or signs of androgen abnormalities
• It is useful as component of combination therapy in women with or without documentable hormonal abnormalities
• It is sometimes used in women with late-onset acne

What hormonal therapy is right for me?

After appropriate evaluation, your doctor will work with you to determine the right medicine or combination of medicines for you.

Estrongens are particularly valuable in women who have oily skin and clear signs of increased sebum production. Any estrogen, if given in high enough doses, will decrease sebum production; however, higher doses of estrogen are necessary than that required for typical oral contraception.

Estrongens suppress the ovarian production of androgens and encourages the liver to increase the production of a product called sex hormone binding globulin that binds the androgen and takes it out of circulation.

For women on estrogen therapy, breast exams and pap smears should be done at least annually, with the recommendations varying from country to country depending on age, sexual activity, family history of breast and other cancers, and other factors.

The incidence of more serious side effects, such as clotting and high blood pressure that can occur in the use of estrogens is fortunately rare in healthy young women; however, the doctor and the patient should be aware of the potential risk of adverse reactions, and the risk/benefit ratio should be carefully considered before starting estrogen therapy.

Recent data suggest that it is not possible to predict the final effect of an oral contraceptive on sebum production based on the amount or type of estrogen it contains. All of the low-dose estrogens tested showed that sebum production was reduced by about the same amount.

Does every oral contraceptive help adult acne?

Oral contraceptives (OC) should only be used in women over the age of 16 because in younger women they can suppress growth. The main way OC’s work to improve acne is by decreasing androgens such as DHEAS and free testosterone, and by increasing sex hormone binding globulin that binds to testosterone and reduces the amount of free testosterone.

In this way OC’s help inhibit sebum production, which is one of the main components of acne production. The two main active ingredients in most oral contraceptives are estrogens and progestins. Estrogens are known to reduce sebum production, with some types of estrogens being more potent than others.

Progestins can increase the androgenic effect, have no effect on it, or decrease it. Some of the progestins increase the effects of androgens directly or can act as antiestrogens, blocking the benefits of the estrogen on reducing sebum production.

Many of the different types of oral contraceptives are effective in the treatment of acne. The only oral contraceptives that can potentially worsen acne are the ones that contain only progestins instead of a combination of progestin and estrogen. Oral contraceptives containing only progestins include levongestrel and medroxyprogesterone. Acne, hirsutism, and hair loss have been associated with certain progestins.

What are other hormone treatments are available?

Antiandrogens

Cyproterone acetate (CA): this drug blocks the androgen receptor. It is combined with an estrogen called ethinyl estradiol in an oral contraceptive formulation commonly used in Europe for the treatment of acne. It is not currently available in the United States. Reports have shown improvement of 75% to 90% in patients taking variations of this medication.

CA works through a dual action of both inhibiting ovulation and blocking the androgen receptors. This drug should be used only in women because of the risk of feminization in men (increased breast size and other effects).

Potential side effects of CA include irregular menstrual periods, breast enlargment, nausea/vomiting, fluid retention (bloating), swelling of the legs, headache, and melasma. It can also be associated with tiredness, liver abnormalities, and rarely blood-clotting disorders.

Chlormadinone acetate: Similar to CA, it is available in several European countries and is only slightly less efficacious than CA.

Spironolactone: Spironolactone functions as both an androgen receptor blocker and possibly also as an inhibitor. In doses of 50 to 100 mg per day, it has been shown to reduce sebum production and improve acne. In countries such as the United States with no effective antiandrogenic medications such as CA, spironolactone may be used for female patients with therapy-resistant acne, although it has not been formally approved for this condition.

 In one study looking at spironolactone therapy in acne, one third of the patients had complete clearing of their acne. One third had marked improvement, and nearly one third showed partial improvement, with less than 10% showing no improvement of their acne.

Side effects are increased at higher doses and include the potential for increased potassium in the blood, a slight lowering of the blood pressure, irregular menstrual periods, breasts tenderness and enlargement, headache, and fatigue. The increased potassium in the blood is rare in healthy young women.

Although breast tumors have been reported in rats treated with spironolactone, this drug has been used for years in humans and has not been directly linked with the development of cancer. There have been no documented cases of breast cancer in more than 30 years of spironolactone usage.

Because spironolactone is an antiandrogen, there is a risk of feminization of a male fetus if a pregnant woman takes this medication. The risk to a fetus and the symptoms of irregular menstrual periods can be improved by combining the treatment with an oral contraceptive.

Side effects can be minimized if treatment is started at a low dose of 25 mg per day and increased every few months as needed because the response can take as long as 3 months, as with other hormonal therapies. Once adequate response is attained, dosage can again be lowered to the minimal dose required to maintain adequate results.

Flutamide: Flutamide blocks the androgen receptor and is approved for the treatment of prostate cancer. It has been used at doses of 250 mg twice a day in combination with oral contraceptives for the treatment of acne or hirsutism in women. In a study comparing Flutamide with spironolactone, Flutamide was shown to be superior in reducing total acne after just 3 months.

Side effects can be serious, including cases of fatal hepatitis, requiring regular blood tests to monitor liver function. As with all antiandrogens, pregnancy should be avoided because of the risk of feminization in male fetuses. The use of Flutamide in acne is very much limited by the side-effect profile and is used very little.

Oral contraceptive pill: These drugs work by blocking ovarian androgens. They contain estrogens, often in conjunction with progestins, to avoid the risk of endometrial cancer associated with the use of estrogens alone. Some progestins also have their own androgenic potential, which can aggravate the acne.

Several generations of progestins are now available, the most recent of which has intrinsic androgenic activity. Many oral contraceptives are available that offer a variety of types, combinations, and dosages of estrogens and progestins. This means that for most women at least one oral contraceptive will have some effect on their acne while also offering contraception.

For a woman who is considering starting an oral contraceptive as a form of birth control, she should also bring up any issues of acne in order to maximize the benefits of the drug. She should at least make sure that the oral contraceptive pill that she is considering would not potentially make her acne worse.

All combination oral contraceptive pills reduce the amount of free testosterone circulating in the blood and have had a positive effect on acne in laboratory tests, although this has for some reasons not always translated to improved acne in people.

The most serious side effect of oral contraceptive pills is thromboembolism (blood clots), most commonly of the deeper veins in the legs. This risk has largely been eliminated by the lower doses of estrogens used in current formulations of oral contraceptive pills. In general, most women tolerate oral contraceptive pills well.

The most common side effects include nausea/vomiting, increased breast sensitivity, headache, spotting or breakthrough bleeding, swelling of leg veins, and with some, weight gain. These are often temporary effects that resolve after the first few months of treatment. There can also be a transient flare of inflammatory acne when oral contraceptive pill therapy is started.

Side Effects of Oral Contraceptive Pills

• Nausea/vomiting
• Breast tenderness
• Headache
• Spotting/breakthrough bleeding
• Swelling of leg veins
• Weight gain
• Irritability/depression/mood swings

Glucocorticoids: Glucocorticoids, such as prednisone or dexamethasone, in low doses can suppress the adrenal production of androgens. They can be used in male or female patients who have an elevation of DHEAS in the serum associated with a decrease in levels of 11 – or 12-hydroxylase.

These are measured through blood tests. Glucocorticoids can also be used in cases of acute acne flare or in very severe cases of acne for a few weeks. Low-dose prednisone (2.5 or 5 mg) or dexamethasone (0.25 to 0.75 mg) can be given by mouth at bedtime to suppress adrenal androgen production. Side effects include other unwanted signs of adrenal suppression and can be followed with specific tests every 2 to 3 months after treatment is started.

The combination of glucocorticoids and estrongens had been used in recalcitrant acne in women with excellent results. The doses of estrogens typically used, however, are higher than the typical dose of estrogen used in oral contraceptives.