1999 AIA PCOS Conference Summary

by Ellen Friedman Bender

On October 17, 1999, the American Infertility Association (AIA) held its inaugural conference devoted to Polycystic Ovarian Syndrome (PCOS): Understanding Polycystic Ovarian Syndrome: A Reproductive and Metabolic Disorder. The conference was attended by over 150 people and featured talks by several of the leading medical professionals and nutrition writers in the field. I co-chaired the conference and in between introducing the speakers took notes on most of the lectures, although, unfortunately, I could not attend the break-out sessions. The following are summaries of my notes. They are not verbatim transcripts of the lectures and have not been reviewed by the speakers for accuracy. In addition, as with any information on the internet, this summary is not intended to be a substitute for a thorough consultation with your own doctor.

The Basics of PCOS - Rogerio Lobo, M.D., Columbia Presbyterian Medical Center

After welcoming remarks by Pamela Madsen, Executive Director of AIA and Ellen Friedman Bender, co-chair of the conference with Beth Kushnick, the first speaker was Dr. Rogerio Lobo, Chairman of the Department of Obstetrics and Gynecology at Columbia Presbyterian Medical Center. Dr. Lobo spoke about "The Basics of PCOS." Dr. Lobo began by noting that as many as 7% of women of reproductive age suffer from PCOS but that the syndrome affects different women differently. Dr. Lobo said that PCOS is diagnosed by signs and symptoms. Although the syndrome is associated with polycystic appearing ovaries (approximately 80% of women with polycystic appearing ovaries have PCOS), he cautioned that one cannot make the diagnosis solely based on polycystic appearing ovaries. Dr. Lobo emphasized that women with polycystic appearing ovaries do not necessarily have PCOS. He said that approximately 16% of the population had polycystic appearing ovaries (as opposed to the approximately 7% with PCOS).

Dr. Lobo said that he looked for the following three clinical manifestations in making the diagnosis:

Hyperandrogenic Chronic Anovulation: A More Appropriate Name?

Dr. Lobo has suggested that a more appropriate name for the syndrome is "hyperandrogenic chronic anovulation" though he conceded that this name would need a strong lobby if it were to become universally accepted. "Polycystic ovaries," on the other hand, is clearly incorrect since one can have polycystic appearing ovaries and not have the other features of the syndrome. Likewise, "polycystic ovarian disease" is also incorrect because a disease has characteristic features. In contrast, a syndrome -- like polycystic ovarian syndrome -- is a set of symptoms or symptom complex.

Dr. Lobo said that while the classic presentation of PCOS includes hyperandrogenism, chronic anovulation and polycystic appearing ovaries, there was a wide spectrum of presenting symptoms. Indeed, because of the heterogeneity of the syndrome, even the experts do not necessarily agree on the diagnostic criteria for the syndrome. For example, at a 1990 NIH meeting on PCOS, when asked for the criteria used in making a diagnosis of PCOS, the participants responded as follows:

  • Hyperandrogenism
  • Menstrual dysfunction       
  • Elevated LH/FSH            
  • Polycystic ovaries by ultrasound
- 64%
- 52%
- 55%
- 52%

Dr. Lobo said that LH (or lutenizing hormone) tends to be elevated in women with PCOS but that if one depends on LH levels to make the diagnosis one will be misled since levels varies and it is elevated in only 70% of women with PCOS. Dr. Lobo said that testosterone (an androgen, or male hormone), particularly free testosterone, is the culprit but he also said that approximately 50% of women with PCOS also have elevated adrenal levels.

PCOS Cuts Across Race and Ethnic Lines

Dr. Lobo said that he believes that PCOS is a disorder for the generalist in that it affects at least 6% of women of reproductive age. PCOS cuts across race and ethnic lines. One study found that 3.4% of African American women and 4.7% of white women had the syndrome. Another study looked at women with PCOS in the United States (Los Angeles), Tokyo and Sicily to see whether the disorder was the same across borders. He said that the body weight of the women in the United States was higher, that of the women in Sicily was slightly higher than normal and the body weight of the Japanese women was normal. He said that testosterone levels were elevated for all three populations but that the Japanese women had normal skin and the other two groups had skin manifestations of hyperandrogenism such as hirsutism and acne.

Polycystic Appearing Ovaries Found in 6 Year Old Girls

Dr. Lobo said that he thought that the ovaries may well be at the root of the syndrome rather than the hypothalamus as had previously been suspected. He pointed to a study by Dr. Howard Jacobs of Middlesex Hospital in London which found polycystic appearing ovaries in girls as young as 6 and 7 years old. Dr. Lobo said that if this is true then some women are born with polycystic appearing ovaries irrespective of any endocrine disturbances. Dr. Lobo speculated that normal ovaries, through either a genetic or environmental cause, develop into polycystic appearing ovaries. Then something else -- perhaps puberty or a significant weight gain -- acts as an insult, bombarding the woman or her ovaries and causing the full blown syndrome to develop. Dr. Lobo emphasized again that there is a broad spectrum of PCOS, ranging from subtle manifestations to the full blown syndrome. Dr. Lobo said that PCOS develops when one or more insults exist -- whether it be a substantial weight gain or the emotional stress of puberty. Significantly, he said that there is evidence that increased psychological stress is a factor in whether a woman develops PCOS.

Genetics of PCOS

Dr. Lobo said that there is now strong evidence that there is a genetic susceptibility to developing polycystic appearing ovaries or PCOS, though he said that there was no single gene responsible. The susceptibility for developing PCOS is an autosomal dominant trait, the male counterpart of which is premature baldness.

Central Role of Insulin in Pathophysiology of PCOS

Dr. Lobo emphasized that insulin is a major culprit in determining the severity of the disorder. While in the study involving Japanese, American and Italian women, the fasting insulin levels of the Japanese women were normal, a careful evaluation of how insulin acts in the body revealed that the levels were substantially the same in all three populations even though the Japanese women were significantly leaner. Thus, even in lean women with PCOS, there is evidence of insulin resistance. Interestingly, he said that there was a slight increase in insulin resistance even in women with polycystic appearing ovaries but without the full blown syndrome.

PCOS as a Life Long Metabolic Disorder

Dr. Lobo emphasized that along with insulin resistance, PCOS carries with it significant long term health risks for women. Women with PCOS have been found to have higher triglycerides, lower HDL (the "good" cholesterol) and elevated total cholesterol and LDL (the "bad" cholesterol). There is evidence to suggest that this is related to higher insulin levels. In a study of women in Thailand who were relatively lean and on relatively low fat diets, the women still had higher lipoproteins. Another study of women in Sweden who had undergone wedge resections (where parts of their ovaries are removed) found that the women were more likely to have hysterectomies and entered menopause later. Significantly, the studies showed that there was a persistence of androgen abnormalities and hyperinsulinemia and a higher rate of metabolic disease such as hypertension and diabetes.

Risk for Myocardial Infarction (Heart Attacks) in PCOS

At least one study has shown that women with PCOS are seven times more likely to suffer from heart attacks than women in the rest of the population. However, that data was challenged recently by Howard Jacobs in a study in England. Jacobs suggests that while women with PCOS have a higher incidence of diabetes, their mortality from heart disease is not necessarily increased.

Prevalence of Diabetes Mellitus in Women with PCOS

In a study by Dr. Richard Legro of 254 women ranging in ages from 14 to 44, 31.1% had impaired glucose tolerance and 7.5% had diabetes. The numbers were lower for non-obese women. In that group, 10.3% had impaired glucose tolerance and 1.5% had diabetes.

Hirsutism and Other Skin Issues

Dr. Lobo explained that the extent to which PCOS will lead to hirsutism is determined by how an individual's skin recognizes the elevated testosterone in a woman's system. For example, Japanese women with PCOS do not have an increase in body hair despite the fact that they have elevated androgens.

PCOS and Fertility

Dr. Lobo said that PCOS related infertility is largely due to anovulation. He said that women with PCOS ranged from anovulatory to oligovulatory. He suggested that even women with PCOS who reported "normal" ovulatory status were probably still sub-ovulatory. In addition to their problems with ovulation, women with PCOS are two times as likely to suffer a miscarriage, even after ovulation induction. Dr. Lobo suggested that this twofold increase in the miscarriage rate was due to the abnormal metabolic environment caused by the high insulin levels which could effect the development of the egg. Accordingly, Dr. Lobo said that his first line of treatment for PCOS related infertility is to recommend weight loss to get insulin down to acceptable levels.

Dr. Lobo said that his preferred order of treatment options for a PCOS patient with infertility is : diet/weight loss, followed by clomiphene citrate, gonadotropins (follistim, fertinex, pergonal), ovarian diathermy, in vitro fertilization (IVF), then unstimulated IVF. He said that there was a study out of Norway involving electrocautery (in which a laser makes holes in the ovary) with a fairly impressive pregnancy rate. He said that this might be an option for women who were resistant to other treatments. Dr. Lobo referenced a 25% pregnancy rate for an unstimulated IVF cycle using immature oocytes (eggs).

Ovarian Cancer Risk in Women With PCOS

It has long been known that women with PCOS have a higher risk of endometrial cancer but Dr. Lobo said that there was early research pointing to the possibility that the risk for ovarian cancer was also higher in women with PCOS -- as much as 2.5 times the normal rate. He said that there was evidence that oral contraceptives (birth control pills) offered some protection. Women with PCOS who were not on oral contraceptives had the highest rate of ovarian cancer. Data suggested that leaner women were at greater risk.

Editors Note: This article will continue with a discussion of PCOS and Infertility based on notes of the talk given by Dr. Alan Copperman at AIA's 1999 PCOS Conference.

Ellen Friedman Bender is a member of the board of directors of the American Infertility Association. She co-chaired AIA's 1999 symposium on PCOS. She has appeared on national and local media to discuss PCOS.