Polycystic Ovary Syndrome (PCOS)
Conventional Treatment of PCOS
Polycystic ovary syndrome treatment generally focuses on management of the individual main concerns, such as infertility, hirsutism, acne or obesity.
- Oral contraceptive pills, consisting of estrogen-progesterone combinations, are preferably used. Estrogens lower LH levels and androgen production. Progesterone is crucial, as it may increase the liver production of SHBG, reducing free testosterone levels.41
- Another medication called spironolactone (Aldactone) is used as a primary medical treatment for hirsutism and female pattern hair loss since the accidental discovery of its antiandrogenic effects. Spironolactone reduces testosterone production and inhibits its action on target tissues. It also is an effective alternative treatment for acne in women. Spironolactone should not be used in pregnancy since it can disturb the growth and development of the embryo and fetus.42
- Even more promising are insulin-sensitizers like metformin (see text box below), which also holds promise for managing hirsutism in PCOS patients.41
Ovulation induction remains a milestone in the treatment of women with anovulatory infertility.43
- Clomiphene citrate (CC), an oral antiestrogen medication, is considered the first line treatment for inducing ovulation in women with PCOS.43
- Since insulin resistance plays a central role in PCOS, insulin reduction strategies are a possible treatment for infertility in PCOS patients.44 For instance, if CC alone is not effective, metformin can be added to help induce ovulation.45
- If the CC and metformin combination fails, gonadotropins—follicle stimulating hormone (FSH) and luteinizing hormone (LH) medications that are administered by injection—may be another option.43,46
- Aromatase inhibitors, such as anastrozole and letrozole, are a relatively new treatment for ovulation induction.43 Aromatase inhibitors selectively block the peripheral conversion of androgens to estrogens, causing a reaction in the pituitary gland, increasing FSH, and optimizing ovulation. The advantage of aromatase inhibitors is that they avoid the unfavorable side effects seen frequently with antiestrogens.47
- If medication does not work, a surgical procedure called laparoscopic ovarian drilling (LOD) may be considered. During LOD, a surgeon makes a small incision in the abdomen and inserts a tube attached to a tiny camera (laparoscope) providing detailed images of the ovaries and neighboring pelvic organs. The surgeon then inserts surgical instruments through other small incisions and uses electrical or laser energy to destroy the extra, androgen producing follicles on the surface of the ovaries. The goal of the operation is to induce ovulation by reducing androgen levels.
Regulation of the Menstrual Cycle
- Metformin improves ovulation and leads to regular menstrual cycles (see sidebar).
- Birth control pills containing a combination of synthetic estrogen and progesterone decrease androgen production, correct abnormal bleeding, and decrease the risk of endometrial cancer as well. Low-dose birth control pills have been proven effective for regulating the menstrual cycles of those who are not trying to become pregnant.48
- To date, there are no known clinical studies on bioidentical hormone replacement therapy (BHRT) and PCOS.
Long-term PCOS Management
- Managing cardiovascular risks such as obesity, elevated cholesterol, high blood pressure and diabetes is considered the most important aspect of PCOS treatment.
- Since medications such as metformin and thiazolidinedione improve insulin sensitivity, in 2004 Great Britain’s National Institute for Health and Clinical Excellence recommended that women with PCOS that have a BMI above 25 be given metformin when other therapies fail to produce results.49
- This recommendation proved to be well-founded, as Metformin is known to be an effective treatment for both hyperinsulinemia and hyperandrogenism.50-52
- Indeed, metformin may be the most promising conventional medical treatment for PCOS.
Metformin: An Underutilized Treatment for PCOS
- Metformin, a medication currently used to lower blood sugar, is approved by the US Food and Drug Administration (FDA) to manage type 2 diabetes mellitus. Metformin inhibits liver glucose production, though it also decreases intestinal glucose uptake and increases insulin sensitivity in peripheral tissues.53
- Metformin improves the likelihood of ovulation in women with PCOS through a variety of actions, including reducing insulin levels and altering the effect of insulin on ovarian androgen synthesis, theca cell proliferation, and endometrial growth.43
- To increase metformin tolerance, patients start with 500 mg daily with food. After one week, the dose increases to 1,000 mg for another week and then to 1,500 mg daily. Clinical response is usually seen at the 1,000 mg daily dose.54
- Studies have found that PCOS patients who do not respond to metformin at the 1,500 mg dose respond favorably to 2,000 mg.54
- For many years, oral hypoglycemic agents were regarded as teratogenic, and their use was contraindicated during pregnancy. However, the latest data supports the safety of metformin throughout pregnancy. Glueck et al reported that metformin was not teratogenic and did not affect the motor or social development of infants age 3 and 6 months.55 Recently, Tang et al concluded that metformin improves ovulation and pregnancy rates, findings they noted while updating the Cochrane Review of insulin-sensitizing drugs (metformin, rosiglitazone, pioglitazone, d-chiro-inositol) for women with PCOS, oligo/amenorrhea and subfertility.56
- A recent clinical study of 50 PCOS patients reported that metformin exerts a slight but significant deleterious effect on serum homocysteine levels. Therefore, supplementing with folate is considered useful for lowering homocysteine and increasing the beneficial effect of metformin on the vascular endothelium (the inner lining of the blood vessels).57
Side Effects with Conventional Treatments
A pitfall of mainstream approaches to PCOS is that they are often associated with unwanted side effects, for example:
- For trouble conceiving, a doctor typically prescribes fertility drug Clomid. In some women, Clomid causes no side effects. In others, side effects may include mood swings, hot flashes, breast tenderness, abdominal cramps, and nausea. Roughly 30% of women who take Clomid experience the more serious side effects of hostile fertile mucous (HFM, a condition in which the cervical mucus become too thick to allow sperm to penetrate the cervix) and uterine lining thinning. HFM prevents conception and a thin uterine lining decreases the likelihood of implantation and may lead to early miscarriage, both are undesirable effects of using Clomid.
- Birth control pills are still the treatment of choice for irregular periods. However, a 2006 study concluded that birth control pills increase insulin resistance, making the symptoms of PCOS more pronounced and increasing the risk of major heath complications.58
- In fact, many medications used in the treatment of PCOS do not adequately address the lifestyle and hormonal imbalances that are at the root of PCOS, nor do they hold much promise for managing associated cardiovascular risks and type 2 diabetes.