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Metformin is often combined with other drugs such as antiandrogens and oral contraceptives since it works differently than the others and appears to boost their effectiveness. It is usually initiated at low doses and is increased in graduating amounts as needed. It appears that even women who do not show signs of insulin resistance benefit from metformin for most other symptoms of PCOS.

Research reported in the British Medical Journal indicated that women with high blood pressure who were treated with metformin experienced a significant reduction in blood pressure. In a study published in the Journal of Clinical and Endocrinological Metabolism, adolescents treated with metformin experienced a significant improvement of hirsutism, hyperandrogenism, improved glucose tolerance, as well as regulation of menstrual cycles.

Side effects of metformin include:

• Gastrointestinal symptoms - diarrhea, nausea and anorexia)
• Lactic acidosis - the buildup of lactic acid in the body. This is a rare side effect and may be associated with alcohol use
• Poor absorption of vitamin B12

Metformin is not recommended for patients with renal (kidney) disease.

Glitazones

The glitazones are a relatively new class of insulin sensitizing drug used to control type II diabetes. They have been shown in studies to be very effective in reducing hyperandrogenism and improving ovulation. Glitazones improve the glucose uptake in muscle and peripheral tissue and also inhibit the production of glucose by the liver. The use of glitazones is often accompanied by weight gain.

There are three types of glitazones:

• Troglitazone - this drug has been shown to decrease testosterone, decrease fasting insulin levels and improve ovulation rates. However, troglitazone was removed from the market in 1999 due to liver toxicity.
• Pioglitazone (Actos)
• Rosiglitazone (Avandia)

The latter two drugs seem to improve glycemic control and show promise for the treatment of symptoms of PCOS. They may be given either individually or together with metformin or other medications. However, more testing is required before their efficacy and safety can be clearly established.

Glucocorticoids

If spironolactone and oral contraceptives do not adequately suppress levels of testosterone or DHEA-S, low doses of a glucocorticoid called dexamethasone may be given in order to decrease the adrenal production of these hormones. Glucocorticoids may also help in the establishment of ovulatory cycles.

Glucocorticoids are not used often since they cause many other undesirable side effects including:

• Water retention
• Osteoporosis
• Increased susceptibility to infection
• Insomnia
• Mood swings

Glucocorticoids can also affect blood sugar levels so that careful monitoring is required while taking these drugs.

Gonadotropin Releasing Hormone (GnRH) Agonists

GnRH agonists (e.g., Lupron, Zolodex and Synarel) are often used for severe ovarian hyperandrogenism since they cause almost complete suppression of ovarian function. This can lead to menopausal symptoms, including hot flashes and bone mineral loss, which are usually reversible with concurrent use of oral contraceptives. Due to the adverse side effects, as well as being expensive, GnRH agonists are not often used for the treatment of PCOS.

Ovulation Inducing Drugs

Drugs used to induce ovulation in women with anovulatory infertility associated with PCOS include:

• Clomiphene citrate (Clomid, Serophene) - Clomiphene citrate stimulates the release of gonadotropins that stimulate the follicular development of the ovaries.