Treatment Options for Polycystic Ovary Syndrome

Management of Specific Symptoms of Polycystic Ovary Syndrome

Obesity

It is very important for obese women with polycystic ovary syndrome (PCOS) to commence a supervised weight loss and exercise program as soon as possible. Research has shown that shedding as little as 7% of body weight can initiate the improvement of many symptoms of PCOS. A nutritionist can be very helpful in terms of information about healthy diet and nutrition and helping to set short and long-range goals for an effective weight reduction program. The evidence regarding the effect of treatment with metformin on weight loss is unclear.

Women with PCOS should also consult with the health care provider regarding development of a safe, individualized exercise program.

Hirsutism

The goal in treating hirsutism is to prevent the growth of new hair while controlling the growth of current hair. Hirsutism may be treated with medications or various types of hair removal.

Drug Therapy

  • Oral contraceptives (e.g., Yasmin) - The FDA has not approved any oral contraceptives specifically for the treatment of hirsutism. However, they are widely used and their efficacy is well established.

  • Antiandrogens

    • Spironolactone is highly effective for the treatment of hirsutism but does not have FDA approval for this indication. Some researchers report a 40-80% reduction in hair growth with this medication. It is the most widely used antiandrogen for treatment of hirsutism in the US.

    • Flutamide is effective but may carry the risk of liver toxicity. Its efficacy is very similar to spironolactone.

    • Cyproterone acetate - Cyproterone is a progestin which is effective in the treatment of hirsutism and is often combined with oral contraceptives to enhance its effect. Due to the possibility that it may be teratogenic (cause birth defects) it is not currently available in the US.

    • Ketoconazole - Ketoconazole is an antifungal agent that has some antiandrogenergic properties. It is considered as an alternative drug if a patient cannot tolerate other more effective medications.

  • 5-alpha Reductase Inhibitors

    • Finasteride - This drug is an enzyme inhibitor and interferes with enzymes in the hair follicle. It is comparable with the antiandrogens and is reported to be as effective as spironolactone.

  • Glucocorticoids

    • Dexamethasone is a glucocorticoid which may be used if there is adrenal androgen excess causing hirsutism. It is often given in combination with antiandrogens or oral contraceptives to enhance its effect.

  • Insulin Sensitizing Agents

    • Metformin is a widely used insulin-sensitizing agent. Some research indicated that after 6 months on a regimen of metformin combined with dieting, some patients experienced a 10% reduction on their Ferriman-Gallwey scores. It also helps to prevent the metabolic syndrome.

    • Glitazones - Troglitazone was removed from the market due to hepatotoxicity (liver toxicity) and there is insufficient data at this time regarding the efficacy of rosiglitazone and pioglitazone on hirsutism.

  • Biologic Modifiers of Hair Growth

    • Eflornithine HCL (Vaniqa) - This topical cream inhibits the enzyme in the hair follicle that stimulates hair growth. It is used only on the face and can cause burning and stinging. Improvement is gradual and if no change is noted within 6 months some doctors recommend discontinuing the cream. Reports of success vary with some studies indicating that one-third of women experience moderate or marked improvement but the effect is usually temporary. There have been no clinical studies demonstrating safety and efficacy of this cream for use in adolescents with hirsutism. It can be 6-12 months before benefit is actually seen. In some women, it can take up to 18 months before any improvement is observed.

As mentioned above, the first line of treatment for hyperandrogenism, of which hirsutism is a symptom, is modification of lifestyle, namely weight loss and exercise. If these measures are not sufficient, medications may be introduced. The medications may be taken alone or combined in order to boost efficaciousness, especially for moderate to severe cases of hirsutism.

In conjunction with any treatment for hirsutism, psychological counseling is a very important aspect since the symptoms are so overt and can affect a woman's or adolescent's self-esteem and well being.

Hair Removal

There are several options to physically remove hair that is currently growing. Many women employ these hair removeal procedures while taking medications. Some women prefer to wait 6-12 months before initiating physical hair removal techniques in order to give medications sufficient time to prevent the growth of new hair. This reduces the need for undergoing hair removal procedures a second time.

Each of the methods to remove hair physically has its own advantages and disadvantages. Techniques used for hair removal include:

  • Shaving - this is the least traumatic method of hair removal. Stubble often remains but shaving can easily be repeated. Shaving cuts off the hair at the thickest part of the shaft which may make the hair look darker as it grows out. Shaving does not stimulate new hair growth.

  • Depilatories - these are creams that burn off the hair at the skin line. They can cause skin irritation or allergic reactions but do not stimulate new hair growth.

  • Tweezing/wax stripping - this method is painful and can be done only for small patches of hair. There is also an increased risk of infection of the hair follicles as well as ingrown hairs and distorted follicles. This method stimulates the hair root into the growing phase.

  • Electrolysis - application of electric current to the base of the hair follicle with a fine needle. Electrolysis is highly effective because it permanently removes hair by destroying the follicles through a caustic chemical reaction. Electrolysis is expensive, tedious, and is effective for only small portions of skin. The efficacy of electrolysis for permanent hair loss ranges between 15-50%. It is very important to use the services of a reputable, experienced operator. Electrolysis may cause hyperpigmentation and/or scarring.

  • Laser treatment - this is the newest technique available. The melanin pigmentation in hair follicles absorbs laser light more than the surrounding skin which results in the hair follicles retaining the heat and being destroyed (photothermolysis). It is effective on large areas of hair and results in long-term hair removal in 33% to 66% of women. It is more effective in light-skinned, dark-haired women and less effective in blondes. It is still unclear how long the treatment lasts. Laser treatment may cause erythema (reddening of the skin), hyperpigmentation, and/or hypopigmentation of the skin.

Alopecia

For women who experience alopecia or male pattern balding, effective treatment includes medications such as minoxidil and spironolactone. Spironolactone reduces the rate of hair loss but its effect on hair growth is minimal, if any.

Acne

Acne is often treated with medications either following or concurrently with weight loss and exercise.

Drugs commonly used for acne treatment in women with PCOS include:

  • Oral contraceptive pills - Ortho Tri-Cyclen (norgestimate and ethinyl estradiol) and Estrostep (ethinyl estradiol and norethindrone acetate) have been approved by the FDA for treatment of acne.
  • Spironolactone
  • Retinoids (topical or systemic) - These drugs are teratogenic (can cause birth defects in a fetus) and should not be taken if trying to conceive or if pregnant.
  • Antibiotics (topical or systemic)
  • Topical benzoyl peroxide

If left untreated, acne can lead to scarring and/or abnormal pigmentation.

Hyperinsulinemia

One of the most effective ways to treat hyperinsulinemia is through calorie reduction, weight loss, and exercise. Research shows that a combination of intensive weight loss and exercise significantly reduces or delays the risk of developing Type II diabetes. For some women with PCOS, metformin treatment appears to have a beneficial effect on weight loss but the evidence is inconsistent.

Insulin sensitizing agents are very effective and are prescribed to treat hyperinsulinemia and to improve all of the other aspects of PCOS that are related to the underlying hyperinsulinemia.

Insulin sensitizing agents include:

  • Metformin (most commonly used)
  • Pioglizatone
  • Rosiglitazone

Dyslipidemia

Diet, weight loss, and exercise also significantly influence dyslipidemia. These lifestyle modifications can result in lowering LDL, increasing HDL, lowering triglycerides and lowering total cholesterol. If these steps are not sufficient, there are also cholesterol reducing drugs that are available (statins).

Menstrual Irregularity

Menstrual regularity is crucial for fertility as well as for the overall health of the endometrium. Amenorrhea or oligomenorrhea must be treated to reduce long term risks of endometrial hyperplasia, endometrial cancer, and breast cancer.

As with most other symptoms of PCOS, the first line of treatment is weight loss and exercise. If further treatment is necessary, medications can be used.

Progesterone is the hormone secreted by the ovary during ovulation and it promotes the increase of blood vessels in the uterine lining. If conception does not take place, the uterine sloughs off the excess blood and tissue and a menstrual flow commences. Progesterone levels are often low in women PCOS and increasing their levels usually induces menstruation. One strategy to raise progesterone levels is to regulate the menstrual cycle either by promoting ovulation, which leads to an increased in the production of progesterone, or through the use of progestogen supplementation.

Drugs used to promote menstrual regularity in women with PCOS include:

  • Oral contraceptive pills
  • Medroxyprogesterone (Provera)
  • Micronized progesterone (Prometrium)
  • Insulin-sensitizing agents

Women with PCOS and menstrual irregularity experience a significant increase in regulated menstrual cycles and ovulation with metformin treatment. Some women benefit from the addition of clomiphene citrate to metformin treatment.

Anovulatory Infertility

In many cases, it is possible to restore fertility to women with PCOS. Weight loss and exercise are considered the first-line therapy for overweight women with infertility. Exercise and weight loss also improved the fertility of non-obese women, whether insulin resistant or not. If fertility is not achieved, there are several medications that are used to help increase ovulation and chances for conception. Women who are trying to conceive must stop taking oral contraceptives as well as antiandrogens.

Drugs that are commonly used for the treatment of anovulatory infertility include:

  • Clomiphene citrate
  • Metformin
  • Exogenous gonadotropins
Clomiphene Citrate

Clomiphene citrate (Clomid) is the standard first-line pharmacotherapy in anovulatory women with PCOS. It is initiated at low doses in order to reduce the chances for multiple births, which overall is approximately 6-7%. There are varying reports of the percentages of women who ovulate when taking clomiphene citrate.

At low doses, some research indicates the success rate for ovulation at approximately 50% and at the next higher dosage level, an additional 20% of women ovulate. Other studies estimate ovulation rates to range from 40-85%. For women oligomenorrhea, there is success rate for ovulation estimated at 93-95%. Some studies suggest that possible indicators of success for treatment are body weight and androgen levels.

Estimates are that women with PCOS exhibited conception rates following clomiphene citrate that are comparable to rates of conception in the general population. The majority of pregnancies occur within the first 6 ovulatory cycles. Some reports indicate that more than 70% of pregnancies occur within the first three cycles. If pregnancy does not occur within the first three cycles, some are of opinion that there should be a reassessment of treatment and that treatment should include the addition of either:

  • Metformin
  • Exogenous gonadotropins

Side effects of clomiphene citrate include:

  • Hot flashes
  • Headaches
  • Blurred vision
Metformin

If clomiphene citrate alone is not successful in inducing ovulation, several studies have shown that metformin improves ovulation resulting in enhanced fertility. A meta-analysis of metformin use for anovulatory infertility indicated that ovulation was achieved in approximately 46% of women. When women were given metformin together with clomiphene citrate, 76% ovulated, compared to only 42% of those receiving clomiphene citrate alone.

Currently there is little information regarding the correlation of treatment with metformin with pregnancy rates and live births.

Exogenous Gonadotropins

Exogenous gonadotropins are synthetic drugs that mimic the action of gonadotropins produced by the body.

  • Perganol
  • Humegon

If a woman does not ovulate in response to clomiphene citrate, exogenous gonadotropin therapy may be considered as an option. Because women with PCOS are at a higher risk for ovarian hyperstimulation syndrome, the lowest, effective, possible doses of gonadotropins are prescribed. This strategy also minimizes the chances for multiple pregnancies. Chances for multiple birth with gonadotropin treatment is approximately 16-18%, higher than with clomiphene citrate.

There are various gonadotropin regimens that are used and most involve incremental dosage elevations while carefully monitoring hormone levels. In one study of 269 women with PCOS and anovulatory infertility, approximately 73% experienced ovulatory cycles following gonadotropin treatment and a majority of these women produced only a single follicle. The overall conception rate was 48% resulting in 129 pregnancies and 7 twin births.

Gonadotropin treatment is usually administered for six cycles. Most researchers have found that pregnancies occur within the first three cycles. Miscarriage rate was comparable to that of the general population.

The greatest factor that predicts the outcome of treatment is body mass index (BMI) - the higher the BMI, the less probability for conception and, if pregnancy does occur, there is a higher rate of miscarriage.

Disadvantages of gonadotropin treatment include:

  • Administered by injection which many women find inconvenient
  • Expensive
  • Risk of causing ovarian hyperstimulation syndrome