Polysyctic Ovary Syndrome
Polycystic Ovary Syndrome (PCO) is one of the most common disorders affecting young women. It is estimated that about 7.5% to 10% of women of child bearing age (about 5 million women in the U.S.) suffer from Polycystic Ovary Syndrome.
Unfortunately most patients with PCO remain undiagnosed. Even those who are diagnosed with this disorder generally do not receive the optimal treatment.
Symptoms of Polycystic Ovary Syndrome
Polycystic Ovary Syndrome has a variety of signs and symptoms:
1. Less frequent Menses: Most women with Polycystic Ovary Syndrome have less frequent menses, although some apparently have normal menses. (There are several other causes of irregular menses, including thyroid disorder, high prolactin level and severe emotional stress.)
2. Excessive Hair Growth: Most women with Polycystic Ovary Syndrome also have excess hair. This excess hair usually occurs in areas such as the chin, sideburns, upper back and around the nipples.
3. Acne: Acne, either on the face or on the upper back, is also a fairly common symptom of women with Polycystic Ovary Syndrome.
A severe amount of excess hair, especially over the abdomen,as well as male pattern baldness, deepening of the voice and an enlarged clitoris raises the possibility of ovarian or adrenal cancer and must be evaluated by a experienced endocrinologist.
4. Infertility: Polycystic Ovary Syndrome is the most common cause for infertility in the U.S., although many women with this disorder are able to have children.
5. Obesity: Patients with Polycystic Ovary Syndrome are usually obese, although it does occur in non-obese individuals as well.
6. Premenstrual Syndrome and Uterine Fibroid: Many experts in this field (including the author) believe that premenstrual syndrome (PMS) and uterine fibroids are also manifestations of this syndrome.
Do I have Polycystic Ovary Syndrome?
There's a good chance that you have Polycystic Ovary Syndrome if:
1. You have irregular menses for a long period of time (usually less than 8 menstrual periods in a year).
2. You are over-weight, although women of normal weight do have this condition as well.
3. You have excess hair on your face or upper body.
4. You have acne.
5. You have severe PMS.
6. You are infertile.
What is the diagnostic testing for Polycystic Ovary Syndrome?
The diagnosis of Polycystic Ovary Syndrome is a clinical one, ie. the diagnosis is based upon the clinical history and findings at the clinical examination. The author carries out the following diagnostic testing in patients suspected of having Polycystic Ovary Syndrome, primarily to rule out other medical conditions.
Blood test for
2.Thyroid function test
The blood level of testosterone is elevated in almost all patients with Polycystic Ovary Syndrome.
A frustrating practical problem is that most laboratories have an erroneously high normal range for testosterone. In most normal women, the blood level of testosterone is usually less than 30 ng/dl.; However, many laboratories report under 60 ng/dl as normal. Often I see a patient with clinical features of Polycystic Ovary Syndrome whose testosterone is about 50 ng/dl.; They have been told by their physician that their testosterone is in the normal range and that they do not have Polycystic Ovary Syndrome. Wrong! In a woman with clinical features of Polycystic Ovary Syndrome, a testosterone level more than 30 ng/dl is high and is in line with the diagnosis of Polycystic Ovary Syndrome.
If a woman’s testosterone level is too high, ie. more than 100 ng /dl, there is a possibility of an ovarian or adrenal tumor. Further testing, such as vaginal ultrasound of the ovaries and a CT scan of the adrenal glands, should be carried out in these patients.
A low TSH usually indicates that you have overactive thyroid gland, which should be further evaluated by an endocrinologist.
If the prolactin level is elevated, a pituitary tumor may be present. An appropriate evaluation by an endocrinologist should be carried out in these patients, possibly including a MRI of the brain.
Ultrasound of Ovaries
Sometimes I see patients with Polycystic Ovary Syndrome who have undergone an ultrasound of their ovaries, which is not necessary and not recommended by most authorities in this field. The reason is that sometimes ovarian cysts are seen in normal women and many patients with Polycystic Ovary Syndrome have cysts too small to be seen on an ultrasound. Therefore, an ovarian ultrasound does not aid in this diagnosis and certainly can cause a lot of confusion.
The root cause of Polycystic Ovary Syndrome
In the past fifteen years, there has been extensive research in the field of Insulin Resistance Syndrome. Now it is well established that Polycystic Ovary Syndrome is primarily due to insulin resistance.
Other components of Insulin Resistance Syndrome include abdominal obesity, low HDL cholesterol, high triglycerides, high blood pressure, high insulin level and high glucose level.
In an excellent study published in Metabolism in 2003, 138 women with PCO syndrome were analyzed for different components of Insulin Resistance Syndrome.
Abdominal obesity was present in 98%, low HDL cholesterol in 95%, high blood pressure in 70%, high triglycerides in 56% and high glucose level in 11% of these patients.
Researchers at the University of Chicago recruited 122 women with PCO syndrome. These women were given an oral glucose tolerance test. The test was abnormal in 45% of these women; 35% had impaired glucose tolerance and 10% had diabetes.
Another study, carried out at the Division of Endocrinology, Diabetes and Hypertension at UCLA, showed that in patients with PCO syndrome, insulin resistance was closely associated with testosterone level, abdominal obesity, low HDL, high triglycerides and high blood pressure.
What is Insulin Resistance and how does it cause
Polycystic Ovary Syndrome?
Insulin resistance is a genetic disorder and is further exacerbated with aging, obesity and decrease in exercise level.
Insulin resistance means that there is resistance to the action of insulin. One of the actions of insulin is to drive glucose from the blood into the cells. As insulin resistance develops, glucose tends to stay in the blood. However, the body can produce large amounts of insulin to compensate for this resistance, thereby keeping blood glucose in the normal range. This large amount of insulin however, is not good for the body and causes an increase in the production of testosterone by the ovaries.
A high level of testosterone interferes with ovulation and results in irregular menses and infertility. An increased testosterone level also affects the skin and causes increased hair growth and acne formation.
What are the long term complications of
Polycystic Ovary Syndrome?
Patients with Polycystic Ovary Syndrome are at an increased risk for prediabetes, diabetes, high blood pressure, heart attack and uterine cancer.
Insulin resistance, the underlying mechanism for Polycystic Ovary Syndrome, continues to increase as time goes by. After several years, the body is unable to keep up with the demand of increased insulin production due to insulin resistance. At this point, the blood glucose level starts to rise and the patient develops prediabetes and eventually diabetes.
Insulin resistance also decreases HDL cholesterol (the good cholesterol) and increases triglycerides level. It makes LDL cholesterol (bad cholesterol) particles small and dense, which are more harmful for the bloods vessels.
A high level of insulin due to insulin resistance also raises blood pressure. An excellent study from the Texas Institute for Reproductive Medicine and Endocrinology showed that young women with a testosterone level more than 30 ng/dl had a higher risk for high blood pressure.
Prediabetes, diabetes, low HDL cholesterol, high triglycerides level, small dense LDL cholesterol and high blood pressure lead to narrowing of the blood vessels and eventually many patients have a heart attack.
Patients with the Polycystic Ovary Syndrome have infrequent menses, usually less than eight per year. Between the menses, there is extensive buildup of the lining of the uterus. It is this repeated excessive build-up of the lining of the uterus that can lead to development of uterine cancer. Insulin promotes growth. The high levels of insulin probably play a role in promoting the growth of cells in the lining of the uterus.
Screening Testing in Patients with Polycystic Ovary Syndrome.
In view of these long term complications of Polycystic Ovary Syndrome, these patients should have the following screening tests every couple of years.
1. Oral glucose tolerance test to diagnose prediabetes/diabetes.
2. Cholesterol panel, which should include HDL cholesterol, triglycerides and LDL cholesterol.
3. Blood pressure check-up
4. Pap smear
Old treatment approach for patients with
Polycystic Ovary Syndrome
In the past, most patients with Polycystic Ovary Syndrome were treated with Birth control pills and Aldactone (spironolactone).
The rationale for using Birth Control Pills are: Birth control pills ensure withdrawal bleeding every month, and therefore prevent the build-up of the uterine lining and thus prevent uterine cancer.
Birth control pills may decrease the free testosterone level and therefore, helps to decrease excess hair growth and acne.
The rational for using Aldactone (spironolactone): Aldactone (spironolactone) decreases the testosterone level and therefore, helps to decrease excess hair growth and acne.
The main disadvantage of this old approach is that it does not address insulin resistance, which is the underlying mechanism of the disease. Therefore, these patients continue to be at high risk for prediabetes, diabetes, high blood pressure and heart attack.
Birth control pills also usually cause weight gain and a number of other side-effects, including mood swings and migraine headaches in certain individuals.
Aldactone (spironolactone) may increase blood potassium, which can be a life-threatening situation. Therefore, blood potassium should be monitored with a blood test periodically.
New treatment approach for patients with
Polycystic Ovary Syndrome
Now we understand that insulin resistance is the root cause of Polycystic Ovary Syndrome. Therefore, treatment must target reducing insulin resistance.
A low carbohydrate diet is recommended for these patients,
because it decreases the amount of insulin. This diet also
helps to lose weight, as most patients with Polycystic Ovary
Syndrome are over-weight. Please refer to “ Dr.Z’s diet.”
Aerobic exercise for at least 30 minutes per day is
recommended as it has been shown to decrease insulin
resistance. Regular exercise also helps to promote weight
loss and prevent lost pounds from coming back.
A. Metformin( Glucophage). Metformin reduces insulin resistance. Metformin has been shown to be effective in treating Polycystic Ovary Syndrome and also appears to reduce the risk for prediabetes, diabetes, and heart attack.
In one study, 6 months of Metformin therapy was effective in reducing weight, triglycerides, blood pressure and insulin level. Several other studies have confirmed the beneficial effects of Metformin in reducing testosterone level, normalizing menses and improving fertility in women with PCO syndrome.
B. Pioglitazone (Actos) belong to the newer class of drugs, known as TZD (short for thiazolidinediones ). It reduces insulin resistance and is quite effective in treating patients with Polycystic Ovary Syndrome. It also appear to reduce the risk for prediabetes, diabetes, and heart attack.
In an outstanding study, pioglitazone (Actos) was added to Metformin in obese women with PCO syndrome who did not respond adequately to Metformin alone. Pioglitazone plus Metformin was found to be more effective in normalizing irregular menses. In addition, this combination was also more effective than Metformin alone in reducing insulin resistance, insulin level, glucose and DHEA-S (dehydroepiandrsterone –sulfate) and in raising HDL cholesterol.
Alert: At the present time, metformin as well as pioglitazone are not approved by the FDA for the treatment of Polycystic Ovary Syndrome. However, a number of endocrinologists are using these drugs to treat their patients with Polycystic Ovary Syndrome.
The potential side-effects of metformin include nausea, abdominal pain, diarrhea, vitamin B12 deficiency and lactic acidosis.
The gastrointestinal side-effects can be minimized by starting at a small dose and increasing the dose slowly.
Lactic acidosis ia a rare side-effect of metformin, which is a life-threatening condition. This risk of lactic acidosis is seen primarily in patients with kidney failure and liver disease. In healthy young women, it is a pretty safe drug.
The potential side-effects of pioglitazone include weight gain of a few pounds in a few patients and congestive heart failure in some patients.
As these drugs reduce the testosterone level, patients usually resume ovulation and may become pregnant if they are not using contraception.
Birth control pills can be used in combination with these drugs.
These drugs must be discontinued if you become pregnant.
I frequently start my patients with Polycystic Ovary Syndrome on pioglitazone and metformin in addition to diet and exercise.
In patients with severe excessive hair growth and/or acne, I also add Aldactone.
Occasionally I also add Birth control pills to the above regimen for the sake of contraception and also to ensure monthly withdrawal bleeding in those patients who continue to have irregular menses.
The following are actual case studies from my practice.
Case Study #1
A 23 years old female consulted me for fatigue and weight gain. On questioning, she told me that she had irregular menses for many years. She believed that her gynecologist had taken care of this problem by placing her on birth control pills as she now had menstrual bleeding every month.
Family history was positive for diabetes in her father and coronary artery disease in her maternal grandmother.
Blood pressure = 110/70
Weight = 127 (she was 12 labs overweight)
Diagnosis: I diagnosed her with Polycystic Ovary Syndrome as she had a long standing history of irregular menses.
I ordered an Oral Glucose Tolerance test, the result of which are following:
Blood Glucose Levels
Fasting = 85 mg/dl
1 hour = 139 mg/dl
2 hour = 142 mg/dl
These values are consistent with the diagnosis of Impaired Glucose Tolerance (Pre-Diabetes) which would have remained undiagnosed if she did not take the Glucose Tolerance test as her fasting blood glucose was normal.
I placed her on my Diet and regular aerobic exercise for at least 30 minutes every day.
I also put her on Glupride (multivitamin) and Actos to treat her insulin resistance which is the root cause for Polycystic Ovary Syndrome as well as Pre-Diabetes.
She has done well on this regimen.
Case Study #2
A 19 year old female was referred to me by her gynecologist for elevated DHEA-S of 476 (65-368 microgram/dl) on a recent blood test. In the same blood test, her testosterone was also elevated at 78 . Her gynecologist was not concerned about her elevated testosterone as it was in the normal range per the laboratory (14 – 80 ng/dl).
She had irregular menses for many years. Her gynecologist had placed her on birth control pills. The patient had been gaining weight throughout her teenage years. In the previous 5 years, she gained 36 pounds.
She also had excessive facial hair. Her gynecologist did a pelvic ultrasound and told her that her ovaries were fine and the problem seemed to stem from from adrenal glands and therefore, she should see an endocrinologist.
Family history was positive for hypertension and gestational diabetes in her mother. Positive for diabetes, hypertension and stroke in maternal grandmother.
Blood pressure = 110/80
Weight = 186 Lbs (75 Lbs overweight)
Diagnosis: I diagnosed her with Polycystic Ovary Syndrome as she had irregular menses, excessive facial hair, obesity and an elevated testosterone level.
Increased DHEA-S was also on the basis of Polycystic Ovary Syndrome and not due to an adrenal problem.
Pelvic ultrasound of ovaries may be normal in these patients with Polycystic Ovary Syndrome as was the case in this patient.
I ordered Oral Glucose Tolerance Test result of which were as follows:
Blood Glucose Levels:
Fasting = 80 mg/dl
1 hour = 139 mg/dl
2 hour = 157 mg/dl
These values are consistent with the diagnosis of Impaired Glucose Tolerance (Pre-Diabetes) which would have remained undiagnosed if she did not take a Glucose Tolerance test as her fasting blood glucose was normal.
Other lab values:
Total Cholesterol = 197 mg/dl
HDL cholesterol = 38 mg/dl
Triglycerides = 191 mg/dl
LDL cholesterol = 122 mg/dl
Impaired Glucose Tolerance, low HDL cholesterol and high triglycerides are due to insulin resistance which is also the root cause for Polycystic Ovary Syndrome.
I placed her on my Diet and regular aerobic exercise for at least 30 minutes every day.
I also put her on Glupride (multivitamin), Glucophage and Actos to treat her insulin resistance which is the root cause for Polycystic Ovary Syndrome as well as Pre-Diabetes, low HDL and high triglycerides.
On this treatment, she has done well.
This article was written by Sarfraz Zaidi, MD, FACE. Dr. Zaidi specializes in Diabetes, Endocrinology and Metabolism.
Dr. Zaidi is a former assistant Clinical Professor of Medicine at UCLA and Director of the Jamila Diabetes and Endocrine Medical Center in Thousand Oaks, California.
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