Sunday, 24 July 2011

Insulin Sensitizers in Polycystic Ovarian Syndrome

Published in Panorama

Insulin Sensitizers in Polycystic Ovary Syndrome

Medication, hitherto effective in treating diabetes, is now being viewed in a new light - as being effective in treating the symptoms of Polycystic Ovary Syndrome (PCOS), reveals Dr. Iyad Ksseiry, Specialist Physician and Endocrinologist, Welcare Hospital, Dubai.

PCOS is the most common endocrine disease in women in the child-bearing ages. About 6-10% of women in the reproductive age suffer from this disorder but it's likely to be much higher in this region because metabolic syndromes are much higher here, opines Dr.Ksseiry. "PCOS is characterized by an excess of male hormones that disrupts normal ovulation, resulting in symptoms which include irregular or absent menstrual periods and small, multiple ovarian cysts. Frequently, women with PCOS are found to be insulin resistant, which means they have a decreased sensitivity to insulin. This means that more insulin is necessary to achieve the same effect. For this reason, individuals who are insulin resistant have higher levels of insulin secretion or hyperinsulinemia. Because women with PCOS are insulin resistant, they are at a greater risk for developing type 2 diabetes. Many women with PCOS are also obese, which adds to their insulin resistance and risk for progression to diabetes. Also the excess insulin that the body produces, causes the ovaries to produce too much of the male hormone, androgen."

With PCO, the body secretes far too much androgen, which disrupts the ovaries' ability to make enough progesterone necessary for a normal cycle. Also, the levels of lutenizing hormone (LH) are higher than usual, working overtime to try to kick-start the cycle, and the androgen levels interfere with the follicle stimulating hormone (FSH). As a result, the follicles, instead of developing normally, turn into small, pea-size cysts on the ovaries. This may lead to an enlargement of the ovaries. In 70% of cases, the elevated androgen levels cause the individuals with PCOS, to develop facial hair and hair on other parts of the body. There may even be a balding problem. Acne is another typical symptom, as well as obesity, although women who are thin or of normal weight can also have PCO.

What causes PCOS and who are the women prone to it? Dr.Ksseiry explains that there is as yet no clear cut identifiable cause, but the causes are multifactorial with heredity playing its role. "But we have to rule out other conditions that look like PCOS. For instance, thyroid, pituitary, and adrenal glands problems could mimic symptoms of PCOS and hence proper diagnosis has to be made before labeling a person as having PCOS. But PCOS is a very common problem among women and it can begin as early as in the teenage itself, with the onset of puberty. However, with timely diagnosis and proper treatment, these individuals can be as normal as normal can be.

What are the symptoms of PCOS? The most common clinical presentation of PCOS is irregular periods or having no periods at all, difficulty in conceiving, infertility, obesity and hirsutism & acne which are caused by excess androgen production.

What can untreated PCOS lead to? Women with PCOS have an increased risk of early-onset heart disease, hypertension, diabetes, reproductive cancers, and a higher incidence of miscarriage and infertility, reveals Dr.Ksseiry.

Dr.Ksseiry adds a word of caution. Not all women with PCOS share the same symptoms and that lacking any of the above-mentioned symptoms does not necessarily preclude a diagnosis of PCOS.
How is PCOS diagnosed? History taking and Clinical examination of the patient is the first step in diagnosis. A blood test may be in order to check hormone levels and this may be followed by an ultrasound to detect the small cysts. However, further diagnosis with laparoscopy may be necessary to exclude endometriosis or scar tissue due to previous pelvic infection, reveals Dr.Ksseiry.

How is PCOS treated? Dr.Ksseiry explains, "If insulin-resistance is causing PCOS as one of its manifestations, then why not treat the condition with insulin-sensitizing agents that would make the body more sensitive to insulin or less resistant to it? This is the premise on which insulin-sensitizing agents, a group of drugs, are being used to help women with the problem, to have more ovulation, implying less infertility. These agents or drugs would also be able to improve the other manifestations related to androgen levels in these women."

One of the recently used diabetes medications, an insulin sensitizer, metformin, has been found to be effective in treating PCOS, reveals Dr.Ksseiry. "Metformin, has been effective in both, reducing excess androgens and promoting ovulation and regular menstrual cycles. The drug does have some adverse side effects which include gastro-intestinal discomfort, some abdominal cramps and diarrhea. These effects usually appear after the individual has taken the drug for some period of time but most people tolerate it pretty well. Also, when taken appropriately with specific monitoring, the benefits mostly outweigh the risks."

What is the duration of treatment with metformin? "Basically we use these insulin-sensitizing drugs to improve the ovulation rate and promote fertility. Usually they are continued until the patient conceives if the objective of treatment is to deal with the infertility aspect. Some women may even continue the medication throughout pregnancy though there are still studies that need to be done before recommending the drug during pregnancy. Where the individuals are taking treatment with the drug to bring down the effects of the symptoms of androgen, the medication is continued till the patient sees some improvement to the conditions. Sometimes, we maintain it for a while even after improvement is seen. Of course, insulin-sensitizing agents are not the best treatment for symptoms of excess androgen production. We treat these symptoms with other agents like estrogen/progesterone pills, if the women are not seeking to become pregnant," explains Dr.Ksseiry.

Are the insulin-sensitizing drugs like to have adverse effects on the foetus? Dr.Ksseiry is candid, "That's why I emphasize that we need further study before we advice continuation of these drugs during pregnancy. The general trend that we are presently following is to stop the medicine as soon as the women conceive; sometimes, even before this, to make sure that the fetus does not get exposed to the drug. Also, there is no clear guideline that we should continue it throughout pregnancy because some studies say that these drugs may in fact, lower incidence of abortion rate. However, there is still not substantial evidence to prove this."

Rosiglitazone a newer kind of insulin sensitizer, does not appear to have the same side effects as metformin but the drug is still under study and we require more evidence.


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