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The Last Word on PCO, For Now.

Wow, this turned out to be a great topic, thanks for all the comments. I want to just finalize a few things. I received a lot of great questions. Rather than answering them all here I will get to them eventually as part of other answers or new blogs.
I just want to go back to the first blog. I basically said if you have PCO get on Clomid, and most of your problems will be solved. Why didn’t I get right into the big metabolic issues? Because in my practice there are not many patients with metabolic issues. Most of my patients see a doctor regularly and know if they have diabetes. I may check a few, but always come up empty-handed. Most are not obese and have normal thyroid, prolactin and 17-hydroxy progesterone levels. The long term endocrine issues are not critical because I have a fertility practice, and getting my patients pregnant is the primary issue. So for the woman reading this who does not have access to the most advanced medical and fertility care, it’s a few tests and then Clomid all the way. Most women will have early success. If they don’t then it’s time to get more serious.

As far as the HSG and sperm tests are concerned, I do think they are important. Please remember the information here is for the average patient, and the average patient does not have multiple issues. If pregnancy is not occurring despite a few months of ovulation from Clomid, the other tests become mandatory. Of course, the patient has the option of getting all of the tests before going on Clomid.

I just can’t use Femara. I think it’s a really good drug, especially in women who don’t respond to Clomid. Because of the warning however, I don’t use it. The drug is very bad for an early pregnancy, even in low doses.
LH. We have no idea why the LH is high in many (not all) women with PCO. Yes, there are tons of theories, but no one really knows. It is this high LH that interferes with the ovulation predictor kit. Some women with PCO can not use the kits because the baseline LH is very high and there is always a color change even when not ovulating.
The bottom line is that if you have PCO, you are probably very fertile. You may need a little of the doctor’s help, but in the end, most patients do very well.
I am sure more PCO topics will sneak into other blogs. Please see disclaimer 5/17/06. Dr. Licciardi

References:

  • Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7 (also Fertil Steril 2004;81:19-25)
  • Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356(6):551-66.
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008;23:462-77 (also in Fertil Steril 2008;89:505-22.)
  • Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91:456-88.
  • Goldzieher JW, Axelrod LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril 1963; 14:631-53.

Even More about Polycystic Ovaries

Should every PCO patient be on a drug like Metformin? This is up to you and your doctor. If you are diabetic or borderline diabetic, Metformin may be just what you need. What if you are a little overweight and have high cholesterol? This is more debatable.
What if you are trying to get pregnant? Say you are normal weight or above weight, no diabetes, don’t ovulate and were told you have PCO. Here, the early studies said yes; as very high rates of ovulation and pregnancy were reported. In fact, some studies showed pregnancy rates from Metformin were higher than Clomid. Many doctors went with this information and gave their patients Metformin rather than Clomid feeling that lowering the insulin levels was the key to natural ovulation.
And then as more studies were published, the results looked less favorable. Metformin did not allow for normal ovulation as often as advertised. I realize there are some of you who took Metformin, ovulated, got pregnant and swear by that system. I am very happy for you, but most people did not have your experience. Most ovulated rarely or never. I noticed this in my practice and found I was just extending the infertile time for my patients.
The New England Journal of Medicine recently published an excellent paper on PCO, written by members of the Cooperative Multicenter Reproductive Medicine Network. The title is “Clomiphine, Metformin or Both for Infertility in the Polycystic Ovary Syndrome”, published February 8, 2007. I hate to get too scientific, but I want to say a few words about this because the findings surprised even some of the authors. Most studies that are published are not of high enough quality to make doctors change they way they practice medicine. There are many reasons for the low quality including a low number patients studied, non-randomization, flaws in the statistics, and the list goes on and on. This paper is of very high quality. In summary, while 24.9% of the patients taking Clomid never ovulated; the rate was 44.7% in women taking Metformin. There was a 22.5% live birth rate in women taking Clomid, a 7.2% live birth rate in the Metformin group. Rates with Clomid were not increased by adding Metformin. So Clomid was clearly better for becoming pregnant than Meformin.
Now this is just one study and treatment needs to be individualized. I just wanted to present the case that as of 2/08/07, Metformin is being questioned as a reliable primary method of conceiving. I’ll finish up with PCO next time, and remember speak to your doctor and read the disclaimer 5/17/06.

References:

  • Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7 (also Fertil Steril 2004;81:19-25)
  • Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356(6):551-66.
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008;23:462-77 (also in Fertil Steril 2008;89:505-22.)
  • Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91:456-88.
  • Goldzieher JW, Axelrod LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril 1963; 14:631-53.

Polycystic Ovaries and Insulin Resistance

Thanks for all the comments. I would like to address the very important comment about insulin resistance and PCO. I need to start by saying that, as with many things in medicine, we though we had this figured out but in the end, we may be a little off the mark.
What is the definition of PCO? 2/3 of the following:
1) no or infrequent ovulation
2) physical signs of excess androgens, or high levels of androgens in the blood.
3) polycystic ovaries on ultrasound (12 or more little follicles on each ovary)

The physical signs of PCO vary considerably. Some women are thin and just don’t ovulate, and have polycystic ovaries on ultrasound. The opposite is women who are heavy, abnormally hairy, have high levels of androgens; testosterone and the other male hormones. Even normal women have these hormones, but not in excess.
So your PCO may be completely different that your friend’s PCO. And the treatment of your PCO may also be different.
Now let’s get to PCO and insulin resistance.
Insulin is the hormone made by the pancreas that allows us to use sugar. Sugar (glucose) needs to get from our food, into the circulation and then into our cells. Cells can not function without glucose. It’s the insulin that allows us to properly use the glucose. No insulin, no proper glucose utilization, no life.
Diabetes is a condition where there is a problem with insulin. Without insulin, blood levels of glucose rise to dangerous levels. Type 1 diabetics don’t have insulin, and need to take insulin by injection.
Type II diabetics make some insulin. Some Type II diabetics make a small amount and need a little help with medications to improve the action of insulin. However, most Type II diabetics make more that enough insulin, but for some reason the insulin doesn’t work well and glucose levels rise. So they have high levels of insulin and glucose. These patients are “insulin resistant”. They also take medications to improve the actions of insulin.
Some women with Type II diabetes have PCO, some women with PCO have Type II diabetes. A number of decades ago, researchers noticed this relationship and started asking if PCO was related to diabetes and some progress was made in the area of insulin resistance. That is to say, it was determined that some women with PCO also have insulin resistance.
When all this came about, researchers were quick to say that all women with PCO have some degree of insulin resistance. They may not be diabetic, but their insulin levels are high. By the way, insulin resistance is not in the definition of PCO.
Here comes the most important point of this blog. Because insulin also acts a growth hormone, it can make people bigger and fatter. People who are insulin resistant, have higher levels of insulin and may be bigger. (Now I know that some of you are type II diabetics and have normal weight, but most type IIs are at least a bit overweight.) The idea was if we lower the insulin (with medications that help insulin work more efficiently) patients will lose weight, and ovulation will occur normally. And it’s not just about the weight, there may be other benefits of lowering the insulin levels that help women with PCO. Lowering insulin levels also may lower the androgen levels. Metformin, aka Glucophage, is the most commonly used drug for this purpose. We will get into this next time.

References:

  • Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7 (also Fertil Steril 2004;81:19-25)
  • Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356(6):551-66.
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008;23:462-77 (also in Fertil Steril 2008;89:505-22.)
  • Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91:456-88.
  • Goldzieher JW, Axelrod LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril 1963; 14:631-53.