Saturday, February 27, 2010

Interview on PCOS Challenge Talk Radio Part Two: Insulin Resistance, The Metformin Myth and Infertility

Again, it was a pleasure being interviewed by Sasha Ottey of on her radio show. We covered a lot of ground, although I probably could have gone on for another hour since this is such an important subject for many of you PCOS sufferers out there. You can still listen to the show in it's entirety at We left off in the last blog at defining the characteristics of a typical woman who suffers from polycystic ovarian syndrome. I would now like to touch upon one of the hot topics of the PCOS community:

Insulin Resistance In PCOS Patients

Sasha and I went over how PCOS treatment protocols need to be tailored to the specific individual. 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.

Lastly, Sasha asked me if patients come to me for "damage control"....not only for OHSS (as I blogged on February 20th) 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 with these last couple of blogs and through the radio show, 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.

Thank you!


  1. I will say that I saw success with only 50mg of Clomid, on my very first cycle. I'm a PCOS patient without insulin resistance, who was completely annovulatory... So there is hope for the lower dosages working.

    I was also not monitored as here in Canada, ultrasounds are much harder to come by... But I am now 16 weeks pregnant with our first, so something must have gone right :)

    I am curious though - I have always responded very, very poorly to birth control pills - gaining huge (60+ lbs) of weight, getting irritable and depressed, etc.

    What is an option for a PCOS patient who is not insulin resistant once the baby is born, who responds poorly to birth control? Is diet & exercise the only option?


  2. The purpose of the birth control pill in the treatment of PCOS is to correct and over-ride the hormonal imbalance that exists with this disorder. It is not just to give regular cycles. There is no other treatment that can do this. In your case, where there are side effects from previous birth control pill usage, what you will need to do is, through trial and error, try different types of pills until you find one that works for you. The pill I recommend for PCOS are the new pills, Yasmin and Yaz (lower dose) that have a new type of progesterone, called drospirenone. This is an analog of the diuretic aldosterone that is used in the treatment of hirsuitism (facial hair) because it blocks testosterone at the receptor. Drosperinone has similar properties. Increased testosterone levels is part of the hormonal imbalance in PCOS.

    Most of the side effects that women get from birth control pills are from the progesterone. This one may work better for you. The progesterone type is what makes each pill different and that is why you have to try different ones. I've had a good response from my patients using this pill.

    The weight gain, unfortunately, is an estrogen effect. Estrogen will increase your appetite, and if you follow that urge and eat more, you will gain weight. On the other side, you also have to burn off the increased calories so that comes with increased activities such as exercise. Remember, our metabolism also decreases with age, so we inherently burn less calories as we get older.

    I hope this answers your question.

  3. I am an Type i diabetic for 26yrs now aged 30yrs , have PCOS abd hirsutism, is Yaz suitable for me to try to reduce the hair growth , will it help with the insulin resistance and what about weight increase and lipid alteration. thank You Elspeth

  4. Yaz is an appropriate treatment for PCOS and insulin resistance patients. If you have diabetes, that would be in addition to your diabetic management with insulin, oral hypoglycemics or Metformin. The progesterone in YAZ is an aldosterone analogue and block testosterone receptors, which will help to reduce the increases testosterone levels in PCOS patients. The Estrogen will help to overcome the production of testosterone and also suppress the ovarian production of testosterone as well. It has the potential to help with weight by correcting the abnormal hormonal situation caused by PCO, and has the potential to help lipids because of the estrogen but that is not an absolute.

  5. I am 25 years old. My intravaginal ultrasound showed 12 follicles in the right ovary (0.5*0.5cm) and left ovary had less than 12 follicles(1.1*0.9cm) on day 11 of my cycle. testosterone level was 42.88, Prolactin 17.5, Fsh 2.13, Lh 1.60, Dhea 396, Androsten 1.98, random glucose 100, tsh 4.59 and insulin of 4.77 (these tests i did few days before getting my period) i weight 140 pounds at 5'2 height so i was diagnosed with pcos and my doctor put me on metformin. i got pregnant at first month of trying and had a early miscarriage at 6 weeks. continued the use of metformin, ascard, thyroxine and prenatals, did not lose any weight in fact gained more. after 3 months of waiting i got pregnant again on the first try but this was a chemical pregnancy. Although this time i was taking progesterone orally and vaginally. Before the chemical pregnancy my LH was 2.74 and FSH was 7 (at day 3 of the cycle) testosterone had gone down to 24.80 and tsh 2.32



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