Poly-Cystic Ovary Syndrome (PCOS) is the most common endocrine problem in women of reproductive age (puberty to menopause). At a minimum, 5% of all reproductive age women have it; some studies have put the figure as high as 10%.
Not only is PCOS the most common endocrine problem in women of reproductive age, it is the most common endocrine problem in infertile women and, overall, is one of the most common reasons for infertility.
There are two criteria that must be fulfilled in order to make a diagnosis of PCOS - the woman must not ovulate (or ovulate very infrequently) and she must have either clinical or laboratory evidence of increased androgen (male hormone) production. The two most common manifestations of increased androgen production are either hirsutism and/or acne.
For women who are trying to conceive, there have been a number of therapies available for many years. The first specific therapy to treat ovulation problems was Clomiphene which was introduced in 1968. Although Clomiphene is an excellent drug for the treatment of the infertile woman with PCOS, and a very substantial number of women will ovulate, only about 40% will conceive.
There are other therapies available, most notably Pergonal and related medications. Unfortunately, for many women, their insurance will not pay for Pergonal and if the Clomiphene doesn't work, they have, to a considerable degree, reached the end of their ability to have their problem successfully treated. However, newer therapies are offering significant hope to these formerly untreatable women.
It has been known for many years that a considerable number of women with PCOS are overweight. People of both sexes who are overweight are often insulin resistant. This is one of the major causes of Diabetes. It has been known for many years that insulin resistance is a major part of PCOS.
Insulin resistance means that the insulin that you are producing does not work as effectively as it ought to and hence, your body must produce increased amounts of insulin to keep your blood sugar normal. This leads to elevated levels of insulin in the bloodstream and these increased levels of insulin stimulate increased androgen production by the ovary. The increased androgen production in turn interferes with development of the egg and further blocks ovulation. As you can now begin to see, the process locks itself into a vicious cycle.
It has also been known for many years that the dose of Clomiphene necessary to induce ovulation is directly related to the woman's weight. Women of normal body weight may require only one or two tablets of Clomiphene daily for five days each month to stimulate ovulation. Women who are significantly overweight may require four or five tablets a day and even then only about 20% of obese PCOS women will ever ovulate on Clomiphene therapy.
The good news is that there are now drugs available which reduce insulin resistance. Reducing insulin resistance means the pancreas has to produce less insulin, thereby reducing serum insulin levels. This should, at least in theory, help reduce the excess androgen production from the ovary.
There are two main classes of drugs which reduce insulin resistance. We call them "insulin sensitzers". The two principal types of drugs that are available are the Thiazolidinediones and the Biguanides. The first thiazolidinedione was Rezulin. This was taken off the market because of rare but sometimes severe liver damage. The 2 newer versions (Avandia and Actos) have so far shown no evidence of liver toxicity. Metformin (trade name Glucophage) is the most commonly prescribed biguanide.
The thiazolidinediones and Glucophage have slightly different mechanisms of action. The former work mainly on peripheral tissues whereas Glucophage works in large part on the liver.
Increasing reports have shown that women placed on thiazolidinediones alone will sometimes ovulate and become pregnant.
Both Glucophage and the thiazolidinediones can be used as a sole treatment for diabetes, particularly in the earlier stages. However, they are usually used in combination with other drugs. On the other hand, they are frequently used alone to treat people who are insulin resistant but not yet diabetic.
A recent study has shown that the combined use of Glucophage with Clomiphene will allow ovulation to occur in women with PCOS, particularly those who are overweight, where therapy with Clomiphene alone had been unsuccessful.
Furthermore, not only was the Clomiphene therapy successful in inducing ovulation, it did so at much lower doses (one or two tablets daily), even in women who had not responded to higher doses.
This is of great importance - first, because it allows women to ovulate with easier and simpler therapies, and secondly, it opens up doors to women whose insurance companies will not pay for Pergonal and who might otherwise therefore be shut out of any effective infertility therapy.
