I want to share what I learned with those of you who were unable to attend, so I thought I would put my notes from the conference online. These are all paraphrases and my own interpretations of the lectures. All rights of the material presented here are to the authors of the presentations. These are only fragmented notes, and I take full responsibility for any errors in these summaries. Soon you will be able to order the full transcripts from the PCOSA.
Screaming to Be Heard, Elizabeth Lee Vilet
PCOS: Poignant Problems
- weight gain
- acne
- facial and body hair
- marked mood swings
- severe insomnia
- altered hormone levels
Behavioral problems and PCOS: when free androgens are so high, then there are major problems with mood and behavior.
Estrogen dominance in PCOS: role of estrogen in fat tissue and ovary and estradiol. We need to better evaluate the relationship to estradiol and fat.
One patient, a teen, has been successful with a treatment of Ovcon 35, spironolactone, and metformin.
Not enough to just change your diet. You must have other interventions. If a person eats too few calories, then you'll really gain weight, because your body will think that it is starving. Also, the fibroid hormone becomes inactive.
Low progestin pills work better for PCOS.
Combination birth control pills are very successful in reducing testosterone.
Possible signs of a heart attack in women:
- shortness of breath
- severe fatigue
- insomnia
- mood swings
- dropping estradiol levels can caus spasms of the body and the arteries
Estrogen replacement therapy may be useful when nothing else worked. We must think about PCOS beyond a gynecological problem.
Overmedication
We must look at the whole picture. We must get women healthy and think about the power of hormones. You must check with a detailed cholesterol profile. Taking too many meds can make the problems much worse. Increased risk of estrogen problems, an increased risk of heart disease with PCOS. Wellbutrin and other antidepressants can make the problem much worse. Avoid Efexor! Worst profile for withdrawal of any psychotropic drug.
PCOS Myths, Mythstakes, Mythconceptions, and Mythed Opportunities, Dr. Mark Perloe
Dr. Perloe's IVF website can be found at www.ivf.com. He has been to all of the PCOS conferences. His now famous quote about PCOS: "Like pornography, I can't define it but I know what it is when I see it."
Teenage years with PCOS tests character.
Women with PCOS are often taken less seriously in the doctor's office, because of their bodies and issues of low self-esteem.
We also need to treat the other aspects of PCOS:
- endometrial cancers
- heart disease
- sleep disorders
- depression
Complications for treating PCOS:
- medical knowledge is constituted with a few published physicians
- patients with certain criteria only could get treatment
- money and medical care--reduced access to care
- medical economics reduces health care and possibilities for patient doc relationship--one patient is the same as the next patient
- realities of medical expenses
What we need is a patient-centered system that focuses on the needs of the patients, rather than the paternalistic dictators we have known in the past.
Metformin is cheaper (much less than injectables).
There is no excuse for docs not to prescribe IR meds for PCOS.
Make a difference in another cyster's life!
PCOS: Origins in Early Childhood, Dr. Selma Witchel
PCOS is familial and begins in childhood and adolescents.
Early Puberty (Premature Adrenarche)
- due to premature adrenal maturation
- early pubic hair development
- 3-8 years of age
- diagnosis of exclusion
- skeletal age may be normal or slightly accelerated
Classification of Diabetes in Children and Adolescents
- Two types--type one and type two
- both are increasing in children
- warning signs: obesity, family history of diabetes, decreased exercise levels
Testing Method: fasting plasma glucose every two years.
Does premature pubarche represent the 1st manifestations of PCOS? circumstantial evidence suggests yes. Studies done in Spain and New England found that 1/2 of the participants with early pubic hair became women with PCOS.
IR may be the primary manifestation of PCOS.
How does obesity affect the condition of PCOS?
Twelve obese girls with PCOS and twelve obese girls without PCOS were studied. The obese girls with PCOS were found to have:
- decreased peripheral tissue insulin sensitivity
- hepatic insulin resistance
- hyperinsulemia
Perhaps weight gain during this time (after pubic harir has developed) might predict (prevent) outcomes. So control of weight gain could prevent or just stave it off.
She feels that PCOS is multigentic and that a threshold of genes are responsible for the development of PCOS.
P12A variant of PRAR gene may be genetic marker indicating risk for obesity persisting into adolescence. Girls who carried the variance became very much more obese. Lifestyle changes can be a powerful intervention.
Factors that influence outcomes
- obesity
- lifestyle (diet and exercise)
- genetics
Does it begin in utero? low birth might indicate PCOS. Insulin is a major intrauterine growth factor. Poor intrauterine nutrition affects the development of PCOS and genes. Poor insulin action=low birth=PCOS.
Can we intervene? Yes. Good diet and exercise can be very beneficial. People with IR who lost weight have been found to not become diabetic.
Survival Advantage of PCOS--Thrifty genotype; genes are taking advantage of our bad lifestyles; slightly impaired fertility because of PCOS. We've always had the genes for PCOS, but until our lifestyles changes, these genes were suppressed or used in other ways. PCOS and diabetic genes probably overlap.
You can be overweight and malnourished at the same time. Too much "junk" food can rob your body of essential vitamins and minerals.
Update on INS-1 d-chiro inositol (Only Drug Being Designed Specifically for PCOS)
This presentation was given by Dr. William Jacobson from Insmed, the manufacturers of INS-1. INS-1 (aka d-chiro inositol) is good for PCOS treatment for several reasons:
- excellent safety profile
- currently in Stage 2
- first drug specifically designed for the treatment of PCOS
In clinical trials, 90% of the women treated with INS-1 ovulated.
In hyperandrogenic women with PCOS:
- INS-1 improves ovulatory function in a dose responsive manner
- ovulation is accompanied by a reduction in androgens
Two studies of the use of INS-1 with PCOS proved that it was quite successful in treating ovulation. When used in conjunction with chlomiphene citrate, it increasing the response of the chlomiphene.
If you want to become involved in the INS-1 studies, check out the Insmed website for a location nearest you. Also, their site is a really good resource for understanding insulin action.
Throwing the Book at PCOS, Dr. Ronald Feinberg
Dr. Ronald Feinberg, medical director for the conference, presented his latest ideas about PCOS during lunch. He referred to himself as "a philosophical endocrinologist." He began by going all the way back to Stein and Leventhal's 1935 article in which they presented their argument about PCOS. He then took the audience on a journey back in time to the 1930s and 40s and presented proof from textbooks at the time that revealed that doctors knew that there were connections between insulin and the ovaries.
He said that he does not think that PCOS is necessarily genetic. He feels that lifestyle has a lot to do with it.
Since 70% of the women with PCOS want the name to be changed, he thinks that an appropriate name might be Syndrome O.
Why Syndrome O?
- not an ovarian disease
- better than female X syndrome
- most want a name change
- PCOS concepts are hard to teach patients
Syndrome O basically involves four principles:
- ovulation disruption
- ovarian confusion
- overproduction of insulin
He offers a strategy for dealing with PCOS, which he calls SOS. It involvolves the following components:
- Strategy of Organization
- Strategy of Optimization
- Strategy of Offering
Beta-Cell Dysfunction in PCOS, Dr. David Ehrmann
Dr. Ehrmann said that "35% of all women age 28 or so have impaired glucose tolerance." Not all women with impaired glucose tolerance will develop diabetes. Up to 10% of all women with PCOS are diabetic. Pima Indians have the highest rate of diabetes. Close to that of PCOS women.
Normal glucose tolerance is less that 140. 140 to 200 indicates impaired glucose tolerance.
Dr. Ehrmann believes that fasting glucose is not an indicator of IGT. You must do a GTT.
Pathogenesis of Type 2 Diabetes
- insulin resistance (not equivalent to or necessarily a precursor to type 2 diabetes)
- hyperinsulimia
Beta Cells, located in the Island of Langerhans in the pancreas, there must be dysfunction of the beta cells in women with PCOS.
Theca Cell makes androgens. LH important regulator. Insulin can directly cause testosterone to be produced.
When insulin levels are high SHBG goes down. There's more free testosterone, therefore more hair. If you give them estrogen, there is less SHBG, therefore less hair.
PCOS women with no family history of diabetes are less impaired than women with a family history of diabetes.
Waist/hip ration is a marker of metabolic obesity.
Glycohemoglobins are higher, SHBG lower, DHEAS: family history of diabetes have a greater chance of developing diabetes and are more insulin resistant.
Dexamethasone (DEX) induces/exacerbates insulin resistance.
Women with PCOS have a higher rate of getting diabetes.
Insulin-sentizing agents can reverse--temporarily--the effects of impaired glucose tolerance.
Women with PCOS have a high risk of gestational diabetes and vice versa. PCOS is a diabetic condition.
Modest weight loss can reduce the risk of developing diabetes.
Insulin levels and alopecia correlation is not direct. Testosterone is more likely.
What's Good About PCOS?, Dr. Samuel Thatcher
Spelling errors are common in the translation process during genetic transciprtion. Some changes are going on for good, toehr for bad. 10% to 30% of thepopulation has PCOS. It is a very prominent genetic problem
Man different names for PCOS:
- Ovarian Syndrome or an Ovary Problem
- Polycystic Ovarian Spectrum
- Ovarian Dismetabolic Syndrome
- Hyperandrogenic Chronic Annovulation
We are watching the transformation of PCOS and how it is treated.
The entire female body is set up to produce an egg. Women are not supposed to have annovulation. Is annovulation better? Could be.
Why do women see docs for PCOS?
- menstrual cycle disturbance/infertility
- problems with body image
- metabolic derangements
No physician can see a patient for all of these.
Infertility is only part of PCOS. 80% of PCOS patients cannot get pregnant. Miscarriage can be seen positively, however, because most people who miscarry will eventually have a viable pregnancy.
Edometreois, Fibroids, and PCOS?
- Common
- Proliferation processes
- estrogen related
- familial tendency
- frequent causes of pain, bleeding, and infertility
PCOS, Age, and Cycle Length--cycles tend to become more regular with age because FSH increases, so cycle become more regular.
Age and Testosterone Levels
- decrease somewhat, but are very high in menopausal women
- testosterone to low is very bad
- no, it can be good for PCOS
Osteoporsis
- kills 4 times more women than breast cancer
- related to diet and calcium intake
- with PCOS, osteoporosis is significantly reduced
Ovarian Cancer Facts
- there is no real relationship between PCOS and ovarian cancer
- 1% lifetime risk
Cancer Variables
- oral contraceptive use protects against it as much as 50%
- pregnancy
- breastfeeding
- hysterectomy
- hormonal replacement therapy
- fertility therapy
Ovarian Cancer Theories
- genetics
- environmental
- incessant ovulation
- gonadotropin
- antibiotics cancause cancer
PCOS represents a lethal combination of genes.
Cardiovascular Diseases and PCOS
- dyslipidemia (high LDL, low HDL, high triglycerides)
- diabetes
- insulin resistance
- impaired fibrinolysis or increased coagulation
- obesity
- family history
- smoking
Greater risk of cardiovascular disease, but not greater disease.
Become fit. Weight loss is important, but you do not need to be thin to be healthy. Just become as physically fit as you possibly can.
Insulin Resistance: What Is It? Why Is it Important? How Does it Cause Coronary Heart Disease?, Dr. Gerald Reaven
PCOS is a manifestation of insulin resistance.
How can insulin action differ so much from people with the same GTT? normal people with insulin response.
IR=being overweight is simply not true. There are a number of people who are IR, but not overweight.
Body Mass Index <25 is normal; 25-30 is overweight; >30 is obese.
The relationship between BMI and IR--25% of the variability is due to differences in BMI. 75% is not due to that. So, weight is not an indicator for IR.
Physical fitness is vital in the treatment of PCOS and IR.
Break down of factors contributing to IR:
- 50% genetic
- 25% body weight
- 25% fitness level
Many of IR manifestations are due to the presence of tissues that are IR. Not all tissues are IR.
Salt-sensitive hypertension is correlated to IR.
What is Syndrome X? IR and compensatory hyperinsulemia. People with X are normally hyperandrogenic as well.
50% of patients with hypertension have IR.
Syndrome X patients have high levels of fibrinogen, which makes clots, and high levels of PAI-1, which can't break up clots.
PCOS is the ovary responding to IR.
IR is highly predictive of alot of bad things. IR and coronary heart disease.
High triglycerides and low HDL--syndrome X.
Low triglycerides and High HDL--not syndrome X.
Smoking and syndrome X=coronary heart disease.
Why high triglycerides and IR? Adipose tissue IR, high insulin/high fatty acid levels; liver increases TG concentrations
Myth--there is something magical about the location of adipose tissue. It doesn't matter where it is located, it is still problematic for IR. Nothing about the placement of fat indicates IR.
"Low HDL cholesterol is the best indicator of IR."
Rosiglitazones--very powerful and helpful with improving insulin sensitivity. There are ways of improving insulin sensitivity.
If you lose weight, you have a 100% chance of becoming more insulin sensitive.