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PCOS: Insulin Resistance, The Metformin Myth and Infertility

Posted Apr 03 2010 8:01am 1 Comment
Insulin Resistance In PCOS Patients

There is no "one size fits all" with this particular syndrome. One of the most important points that was brought up during the show was the question of insulin resistance in PCOS patients. There has been a lot of press coverage regarding "insulin resistance" as being the main cause of polycystic ovarian syndrome. This has led to many, many women being misdiagnosed and mismanaged. As a result, there has been a tendency to automatically prescribe Metformin (Glocophage). In reality, only 30-40% of these women have insulin resistance, and only those patients will have some response. Some will resume normal ovulatory function, and others will become more respondent to fertility medications. It will take 6-8 months to see if the medication works and a minimum dosage of 1500mg per day is required.

When is it appropriate to go this route with a patient? The patient must be evaluated for insulin resistance. This is going to be manifest by an elevated fasting insulin blood test, or abnormal glucose tolerance, that is, when the fasting glucose is elevated, a glucose tolerance test is positive or there is a diagnosis of diabetes. In these cases, the insulin level may be low or normal because the long-standing resistance has caused the pancreas to stop secreting insulin. If a patient is not insulin resistant then Metformin or similar medications are not indicated.

Non-Insulin Resistant PCOS Patients

For non-insulin resistant patients the treatment varies,depending on whether a patient is trying for pregnancy or not. For those who are not trying to get pregnant, the dominant male hormones have to be suppressed, female hormone needs to be increased and the patient needs to have regular cycles. This is done through the use of birth control pills because it does all of the above. My preference is a new pill called Yasmin or the lower dosage version, Yaz, because its progesterone, drospirenone, blocks testosterone receptors and so has a stronger effect in lowering the testosterone effects of PCOS. This also replaces the female hormone so that the person does not suffer the long-term effects from a lack of estrogen.

A Tough Journey To Pregnancy

For those women who have PCOS and want to get pregnant the journey gets a little tougher. My job, as an infertility specialist, is to try to get my PCOS patients pregnant. The goal is to get them to ovulate! We use fertility drugs for this purpose, but it varies as to how a patient responds to these medications. The "fertility drug" is actually stimulating the ovary to ovulate.

The first drug we use is Clomid, but it has to be used in higher dosages than normal because of the ovarian resistance that PCO patients have to Clomid. I use it from 150 mg to 250 mg. Another similar medication called Femara (Letrozole)can also be tried. Some Clomid resistant patients will respond to Letrozole. In the patients that do not respond to either of these medications, I use a combination protocol.

Briefly, it entails starting with Clomid or Femara then adding injectable fertility drugs like Follistim, Gonal-f or Bravelle. This "boosts" the Clomid or Femara effect to stimulate a few follicles to grow. The problem with going straight to the injectables is that most PCO ovaries will have a hyper or exaggerated response to the medication, because these ovaries are more sensitive to these drugs, causing the formation and/or ovulation of 10 or more follicles. When that happens the cycle is often converted to an IVF cycle in order to prevent a super-multiple pregnancy to occur, or the cycle is cancelled. With the combination protocol we are trying to give the patient the opportunity to get pregnant using a natural means such as intercourse or IUI. Of course it may take several attempts before pregnancy occurs, since the body has to go through many steps to become pregnant naturally. The medication is just trying to make the ovaries act like normal ovaries.

We have been pretty successful at getting some of our patients pregnant with this protocol. Keep in mind, most PCOS patients are young with fertile eggs. It can be merely a matter of persistance with them, of trial and error with their treatment until success is hopefully soon achieved. But, just like national statistics show that up to 80% of PCOS patients have to progress to IVF, we also see a high number of patients having to go in that direction. The combination protocol is just one option to try to achieve pregnancy through an easier means.

Do patients come to me for "damage control"....not only for OHSS but for recurrent miscarriages. It is not really "damage control" but recurrent failures, or looking for a different option. I have seen many, many patients that have been put on Metformin and/or Clomid for long periods of time and not get pregnant. Many of these patients have just been given a prescription with multiple refills and told to take that for 6-8 months. They never get checked to see if they are even responding to that dosage. In some the dosage is slowly increased up to 150 mg but again they are not checked, by ultrasound, to see if they are responding. So, when they come to me, we have to take a more aggressive tact, and the patient gets to the protocol that will lead to success.

I hope that I was able to help clarify some of the issues regarding Polycystic Ovarian Syndrome, as well as debunk some of the myths surrounding this difficult illness.
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A couple of additional notes regarding PCOS and fertility drugs are worthwhile.  While Clomid does work for some patients, even if ovulation is improved it is important to follow up with a post-coital test after intercourse to ensure that the sperm are surviving, as Clomid has been known to have the adverse effect of creating an environment that isn't hospitable to sperm.  It's better to be aware of this sooner than later in case the protocol needs to be changed.  Women with PCOS may also want to know that a new technology called IVM can stimulate the growth of immature egg follicles in the laboratory, after which in vitro fertilization can take place.   This technique works well for women whose ovaries do not respond to fertility drugs.  Ironically, it can be cheaper, too -- the injectables like Follistim are among the most expensive components of your typical IVF protocol.

Good luck to all women with PCOS who are trying to get pregnant.  Check here for more information on how to conceive with PCOS:


Anna Short 

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