Monday, August 1, 2011

New 2011 Study Questions Routine Metformin Use In All PCO Patients

Dear Readers,

A recent study published in the medical journal "Clinical Endocrinology" Frans S., Clinical Endocrinology. [Oxf], 2011; 74:148-151, brings into question the routine use of Metformin in PCO (polycystic ovary) patients. The study showed a small improvement for ovulation but not clearly better than weight loss. It also showed no improvement in pregnancy outcomes, except in patients with diabetes. It showed no benefit or improvement in hirsuitism, acne or hair loss resulting from PCO (polycystic ovary). Alone, it showed no improvement in pregnancy rates but did show some improvement in combination with Clomiphene (Clomid), yet there was no increase in the live birth rate. The authors therefore concluded that there was no real evidence to draw any conclusions regarding Metformin’s treatment in PCO, and that its only benefits may be in patients with diabetes or impaired glucose tolerance.

As you have seen through reading my blog, PCO (polycystic ovaries) is a very common problem among infertility patients. I have participated in numerous posts, have had several on-line, television and radio discussions regarding this problem, and I have given my opinion regarding the diagnosis, management and treatment options associated with this problem. One of the main problems that I face, almost on a daily basis within the medical community, is the mistreatment of PCO patients with Metformin. I see this commonly done by second tier providers such as Nurse practitioners and Physician Assistants, as well as, Physician providers such as Family Medicine practitioners and general Ob/Gyns. Many of these providers have mistakenly latched onto Metformin as the ultimate drug for the treatment of PCO, much the same as they have latched unto Clomid is the ultimate treatment for infertility. As a result, they automatically treat all suspected PCO patients with Metformin. This practice is unfounded and this recent study shows that treating all PCO patients with Metformin may be misguided. In fact, it brings into question whether there is any benefit at all.

I would not say or conclude that there is no benefit, but there is selective benefit. There are certainly studies that show benefit in a sub-population of PCO patients, just as this study shows benefit in patients with impaired glucose tolerance. These are patients that have been found to have an elevated insulin level or diabetes from insulin resistance. Not diabetics who do not produce insulin. Decreasing this level, either through weight loss or Metformin, will often return the ovary to normal function in these patients, or make their ovaries more responsive to fertility medications.

But clearly, it does not benefit all PCO patients and therefore should be selectively used, not, as many of these aforementioned providers do, used for all PCO patients. There is not a good way to know exactly which patients will respond or not respond to this medication, but here are three requirements that I abide by.\:

*First, a fasting insulin level should be taken to see if it is elevated. If not, then skip the Metformin.

*Secondly, if Metformin is going to work, it can take several months, some authors state 6-8 months, to see if there is any effect. The effect should be noticed by resumption of normal ovarian function i.e. regular menstrual cycles or decrease of the fasting insulin levels.

*Thirdly, a minimum dosage of 1500 mg per day is required. I have seen some patients taking only 500 mg. That is a total waste. If you are going to use this medication then you have to use it in the clinically effective dose.

The exact cause of PCOS is not understood. Some thought it was elevated insulin, but that clearly is not the case in all patients. Some thought it was increased weight, but that also is not the cause. It is clearly some inherent pathway within the ovary that is dyfunctioning, and it is clear that there are many forms of this disorder. It may be a multi-factorial condition where there is not one presentation or one treatment. In is imperative that patients and Physicians understand this and not latch onto one treatment modality for all. Treatments have to be specific to the patient.

Which brings me to my final point regarding the patient-doctor relationship:

This is exactly why Medicine can never be dictated by a cookbook method. People are all different, present differently and must be treated differently. We call that the art of medicine, and this is what makes some doctors better or worse than others, makes some doctors decide to specialize, an option which, unfortunately, is quickly disappearing from medicine as we look to less trained and less costly practitioners.

Edward J. Ramirez, MD, FACOG
Medical Director
The Fertility & Gynecology Center
Monterey Bay IVF


  1. My DR had previously put me on Metformin for my IF. She did not take my insulin levels or any other test. The only thing she could visibly see was I was overweight. Finally after being referred to an Infertility Clinic I was diagnosed with Polyps and after having them removed and doing IUI did acheive a positive pregnany result twice. Both times ended in miscarriage due to one polyp returning. But I still am upset at how the first DR just dismissed doing any tests and just told me to start taking the Metformin.

  2. Hello,

    I am sure that many many patients have been treated the same.As the saying goes, "its spilled milk" so there is no sense in being upset about it. My hope is that it will make patients more diligent in questioning the expertise and qualifications of the doctors that they see so that they receive the best medical care. I am seeing a deterioration of that as more an more patients accept non-specialists for specialty care, and non-Physicians for their general health care. Ultimately, it is patients that drive the quality and availability of health care!

  3. Well this is a topic close to my heart! I'm somebody who is debating taking metformin very hard. I come from a family of type 2 diabetics, though both my fasting glucose was great and I passed the 2 hour GTT with flying colors. Yet,I have some presentations of PCOS: multicystic ovaries (AFC is over 30), high DHEAS, high AMH(5.1-5.6) and extremely mild hirsutism(my ferriman gallway score would be around 7-8). My testosterone is low, my FSH:LH ratio is perfect, I'm skinny, and ovulate regularly. I get pregnant with no medications, each time I've tried. I've also had 2 first trimester losses, the first time with a normal XY karyotype and the second time with Turner's syndrome.

    The other issues I have are low positive anti-thyroid antibodies and a vitamin D deficiency (now corrected). And the possible PCOS- I think I barely qualify by the Rotterdam Criteria.

    Nothing is clear cut with the research, but everybody seems to be utterly in the dark regarding the physiology of glucose metabolism and its relationship to infertility. My bottom line is that I want to leave no stone unturned and will do everything in my power to avoid a 3rd loss. If it involves taking metformin, how can it hurt? Yes it has unpleasant side effects and can deplete B12, but women would happily crawl over broken glass if it meant that they'd get a baby for it:(

    There is no evidence to show it does harm, does it?

  4. Thank you Dr. Ramirez for the information.

  5. Hello Jay,

    I understand your dilemma and pain, however, I think your logic for using Metformin is not sound. Metformin is not a miracle drug for PCO patients. That is what the study showed. There is a down side. It is an insulin inhibitor, which means that if your insulin levels are normal and your cells are using it appropriately, the medication will deprive your body of adequate insulin. This will lead to higher glucose levels, altered metabolism and possibly diabetes. Metformin is NOT treating the PCO. It is meant to treat a condition that seems to be more prevalent on some PCO patients i.e. elevated insulin.

    So, although I do understand your desire to throw everything in to achieve a pregnancy and have a child, this is not only not reasonable, but may cause some harm. Treatments have to be specific for the problem that it is trying to treat. I would not recomend "crawling over glass" if it does nothing to help you get pregnant. On the other hand, if doing that does help you get pregnant, then I will certainly be the first to add that to my protocols.

  6. Thank you for your response. When I first was faced with this quandary, I was concerned whether it might cause hypoglycemia, if I actually had no overt problems metabolizing glucose. Multiple sources had said this is not the case and one doctor had claimed that it can have a benefit even in non-insulin resistant individuals. I'm a scientist (an immunologist) myself, I have a good idea about how much variability there can be between studies, how little drug actions are understood, and how much in the dark everybody really is about the physiology of glucose metabolism. Everybody, at the end of the day, is just going with what we think is an informed opinion, but nobody has the right answer.

    I'm going to have to do a lot of reading on this before I decide one way or the other, but right now, I am leaning towards not taking metformin. Thank you for your input!

  7. Dr. Ramirez - Thanks for your refreshing approach to managing PCOS. So many doctors take a cookie cutter approach. I took Metformin to conceive my second child. I swore I would never take it again after the GI issues I experienced. Since I concieved over 9 years ago I have been successfully managing my PCOS symptoms through diet and lifestyle change. So much so, I had a little "surprise" 2 years ago and now have a beautiful daughter. I share what I have learned and help coach women with PCOS to take on their health and life on and on facebook at I would be thrilled if you would consider guest blogging on my site about this very topic. Please contact me at

  8. Hello Amy,
    Thank you for your comments and for taking the time to read my blog! Glad to hear that you have been able to manage your PCOS!

    I am always a little pressed for time, as you might imagine, but if you have a specific topic that you and your followers would like further clarification on re PCOS, I would be happy to write a short piece for you. I will email you the contact informtion. Have a good day!



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