Kathryn Jean Lucas, MD
611 N 35th St
Morehead City, North Carolina 28557

inside health

THE DILEMMA OF THE POLYCYSTIC OVARY SYNDROME

By: K. Jean Lucas, M.D.

Because Kathy had always been a scrawny child, her mother had to force her to eat and worried that she might always stay too thin. When puberty started, however, Kathy began gaining weight. At first, everyone was happy for her because she was finally beginning to fill out. Over time, however, the situation escalated. Her weight continued to increase, especially in her waist area, causing her clothes to be too tight. No matter what she ate or how much she exercised, her weight just kept going up.

Her menstrual periods began normally at age 13- the age her weight began to increase. After one year of regular periods, she started skipping periods. The cycles were totally unpredictable. She might go as much as 6 months without a period. Although she did not mind the absence of periods, she knew something was wrong.

The precise moment that she began to want help with this problem occurred several years later when she noticed, to her horror, dark thick hairs on her chin. She would pluck them out at first, but the hairs continued to spread. She was not able to keep up with them unless she spent hours by the mirror. The quantity of hair began to cover her face in the image of a man's beard. Her scalp hair began to thin on top. The hair changes as well as the deepening of her voice made her think she was transforming into a man.

The first gynecologist she saw put her on birth control pills to regulate her menstrual cycle. Her periods became regular. She was relieved by that development but she still worried about the weight and the excessive hair growth. She now had to shave twice daily to get rid of the hair.

Despite the daily routine of shaving and heavy makeup to cover up her hair, she managed to do well in high school and college. Being on a soccer team helped with controlling her weight, although it was still too high. She became engaged. Her husband did not think less of her because of her facial hair. She stayed on the birth control pills and her periods continued to be normal. She developed a false sense of security that her body was getting back to normal after the hormonal surges of puberty.

When she and her husband decided to have children, she stopped the birth control pills. Her periods were regular for the first 2 months and then they stopped. She immediately thought she had gotten pregnant, but multiple pregnancy tests were negative. She and her husband tried for two years without success to have a baby. She went to an infertility specialist who tried her on Clomid and then on Pergonal without success. In vitro fertilization was the next step but she was loath to pay over $10,000 per cycle with only limited guarantee of success. No one had ever explained to her why she could not become pregnant.

Her electrologist who had worked with her for years to remove her facial hairs permanently, suggested that she see an endocrinologist. Kathy asked what an endocrinologist did. The electrologist told her that an endocrinologist was a physician who specialized in hormone imbalances. The electrologist revealed that her treatments were not controlling the hair growth. The ineffectiveness of the electrolysis may mean that Kathy made too much male hormone. Male hormones from the ovary and the adrenal gland stimulate hair growth in women in the same places that men typically grow hair.

The endocrinologist diagnosed Kathy as having the Polycystic Ovary Syndrome (PCOS). Even though she had no history of ovarian cysts, the endocrinologist explained that the only three criteria for diagnosing this syndrome are: irregular periods, obesity, and excessive facial or body hair. Cysts in the ovary do not have to be present for the patient to have the syndrome. Any condition that causes a patient to not have periods and not produce eggs on a monthly basis can cause cysts in the ovary. The endocrinologist explained that the cause of the problem was genetic and involved insulin resistance. People with PCOS may eventually develop diabetes. Many of these women have a family history of diabetes. 

The pancreas, a gland which sits directly behind the stomach, makes insulin. Insulin regulates the blood sugar. This hormone keeps the blood sugar from increasing after a meal containing carbohydrates. It blocks the liver from making and releasing too much sugar at night when one is not eating. Insulin stores excess calories as fat in the middle of the body. Insulin helps keep supplies of sugar stored in the liver and muscle to provide energy when the person is not eating and/ or exercising.

When insulin resistance is present, the body requires much more insulin than normal to keep the blood sugar normal. The pancreas may need to make four to seven times more insulin than normal to keep the blood sugar in the normal range. This high level of insulin is required to allow the sugar in the bloodstream access to each cell. The cells use sugar for energy.

High insulin levels cause the accumulation of fat primarily in the upper part of the body which leads to the so-called "apple" shape. The excessive body fat makes estrogens which can interfere with menstrual periods. The estrogens made from fat (estrone) can be converted by the adrenal gland into weak male hormones.

In addition to the effects of the increased fat deposition, insulin has a direct effect on the ovaries. The ovaries are not insulin resistant. High insulin levels cause the certain cells in the ovary to produce high levels of testosterone, a male hormone. The elevated testosterone levels can lead to acne, increased facial hair, male pattern hair loss on the scalp, and irregular periods. The skin may turn dark and thick around the intertriginous areas under the neck and under the armpits. In women, excessive male hormone leads to an increase in the upper body size. The waist to hip ratio increases. The normal for women is 0.8 and the normal ratio for men is 1.0. Above these measurements, the health of the individual is compromised by the increased risk of diabetes, heart disease, high blood pressure, strokes, and certain types of cancer.

Since the PCOS patients cannot complete a normal menstrual cycle, they do not ovulate and have extreme difficulty becoming pregnant. Clomid stimulates the production of estrogen, but the estrogen may not be enough to overcome the deleterious effect of the male hormone. Pergonal (FSH) stimulates the production of eggs but may not completely normalize the cycle leading to failure to maintain the pregnancy.

PCOS and Diabetes

The treatment of PCOS is important not only for enabling pregnancy to occur but also to prevent the development of diabetes.

Diabetes occurs as two major distinct entities. People with type 1 diabetes do not produce insulin. Antibodies attack the islet cells (insulin producing cells of the pancreas) and gradually destroy them. These patients are required to take insulin throughout their lives and will die if they are not unable to take it.

Type 2 diabetes is a genetic disorder caused by insulin resistance. Over time, the pancreas will not be able to continue its high insulin production. When the pancreas slacks off from its high insulin production only slightly, the blood sugar begins to increase. The insulin level may still be high even though the blood sugar is starting to rise. When the blood sugar is fasting (prior to eating the first meal of the day) is greater than or equal to 126 and any other blood sugar is greater than or equal to 200, the diagnosis of diabetes is made.

The insulin resistance is present, however, most of the person's adult life. This high insulin level leads to obesity and upper body fat. This type of obesity continues to perpetuate the cycle of increasing obesity from high insulin levels leading to more insulin resistance from the fat accumulation. Women with PCOS may develop diabetes earlier than most because of their very high insulin levels.

 Treatment of PCOS

The two goals of treatment are to reduce the insulin resistance and correct the underlying hormonal imbalance.

In the past, the only way to decrease insulin resistance was exercise and weight loss. Exercise has been shown to reduce insulin levels and prevent diabetes by improving insulin resistance. Exercise increases the burning of calories and improves the metabolic rate. Exercise causes the muscle to use sugar without needing more insulin to help the sugar get inside the muscle cells. Individuals that exercise drastically decrease their risk of diabetes.

Weight loss is difficult in patients with insulin resistance because they may have sugar cravings from the increased insulin level. They may have low blood sugar if the high levels of insulin are released later than normal from the pancreas.

If diet is to be used with exercise in PCOS patient, it should be composed of foods which do not need as much insulin to be used by the body. Lean meats such as fish and chicken, vegetables, and salads are the preferred foods. Fruits and starchy foods should contain more fiber the delay the absorption of carbohydrates and subsequently cause the delay in the absorption of the carbohydrate and less of an insulin release from the pancreas.

With a genetic disorder, pharmaceutical therapy should be considered. In the past three years, two medications have been introduced for the treatment of diabetes. They involve reducing the resistance to insulin. Their potential for delaying or preventing the onset of diabetes by lowering the insulin resistance and conserving pancreatic function is ongoing in studies but should not be underestimated.

Glucophage (metformin) has been used in Europe for over 30 years with great success in treating diabetes. The medication lowers the liver's production of sugar by making the liver more sensitive to insulin. The medication is given with each meal by gradually increasing the dose by one additional pill every week up to a maximum of five of the five hundred milligram tablets daily. The gradual increase in the dose is used to minimize the side-effects; the most common is diarrhea. Diarrhea may occur in up to 30% of the people taking this medication. The nausea may not be present at all. One beneficial side-effect is decreased appetite. Most of the patients with insulin resistance tend to be hungry and crave sweets. This medication helps lower these cravings. It has also been shown to decrease the upper body mass and reduce the waist to hip measurements. One can often see a change in the waist measurement before a change in the overall weight.

Rezulin (troglitazone) is from a totally new class of medicines called thiazolinediones. This medication was introduced in March 1997. Rezulin binds to the genetic material of the cell and causes more insulin receptors to be made. These additional receptors cause improvement in the resistance to insulin. Side-effects are usually rare but include dizziness and swelling. Very rarely, this medication can cause liver damage. A patient's liver blood tests need to be monitored monthly during the first eight months of therapy and every 3-6 months thereafter. Rezulin may also decrease the effectiveness of birth control pills. Since it also improves the hormonal imbalance, the patient may find it much easier to become pregnant even though she may be on birth control pills. This medication has been used in a study to help women with PCOS become pregnant. It has been successful. Other medications are being developed in this drug class of thiazolinediones. The next one to be released is Avandia (rosiglitazone).

No other medication for diabetes available at the present time has helped insulin resistance; therefore, the medication will not help PCOS. Many other compounds are being tested to improve insulin sensitivity. Many are in the same family as Rezulin. Another compound is chiro-inositol. This sugar alcohol when given to patients magnifies the signal that insulin gives to cells leading to less insulin being required in the body.

Because hirsutism (excessive facial and body hair in male hormone dependent areas) is such a problem, other medications are often needed to lower the testosterone and decrease the effectiveness of the testosterone on the hair follicle. Spironolactone blocks the effect of male hormone on the hair follicle causing a decreased growth rate of the hair. It will decrease the thickness and pigmentation of the new hairs. Electrolysis, which chemically and electrically destroys the hair follicle, will speed up the process. Laser treatments may also prove to be useful once the technique is perfected.

Proscar (finasteride) blocks an enzyme called, 5- alpha reductase. 5-alpha reductase is an enzyme found only in the hair follicles and the prostate gland. In men this medication has been used to shrink the size of the prostate and improve the hair growth in male pattern baldness. In the latter function, the dose is lower and the name of the medication is Propecia.

In women, the medication decreases the growth of facial hair and male pattern hair loss. Finasteride and spironolactone may be used together for the same problems because they work by two different mechanisms. A female taking this medication needs to avoid becoming pregnant on either of these medications.

Hirsutism may slightly improve with the correction of insulin resistance but usually requires additional medication. After being stimulated by large amounts of male hormone, the hair follicles become very sensitive to small amounts of male hormone. The hair may continue to grow even when the hormone imbalance has improved.

Male pattern hair loss may also be an effect of the high male hormone production. Genetics determine whether or not one will develop this complication of excessive male hormone. Finasteride may also help in this problem. Women who could become pregnant should not take this medication or spironolactone because of the potential effects on the male fetus. These medications may block the development of the male genitals in the fetus. Contraception should be used by any woman of child-bearing potential when taking these medications.

 Who is at Risk to Develop PCOS?

If Type 2 Diabetes is present in one parent, the risk of diabetes is 50% in the offspring. If both parents have diabetes, the risk is 90% that that person will develop diabetes sometimes in her life. Diabetes and PCOS are genetic conditions resulting from insulin resistance. If the family history is positive for diabetes, one should work on increasing exercise throughout life starting at an early age as well as avoiding excessive carbohydrate consumption and weight gain.

At puberty, the PCOS symptoms should be diagnosed before excessive testosterone and weight gain can occur.

Testing with a two hour glucose tolerance test to check both sugar and insulin levels can be done once the symptoms of PCOS begin. The GTT will determine if the symptoms are caused by insulin resistance or by another disorder.

The degree of male hormone production can be determined by measurement of the free testosterone levels. The free testosterone is the active form of the hormone and is a more accurate determination of the level of the active hormone in the system. The adrenal gland can also be the site of excessive male hormone production and these hormones should be checked out as well.

Prolactin, a pituitary hormone, may also cause irregular periods, hirsutism, and infertility. Thyroid abnormalities may cause changes in body weight and irregular periods. Excessive abnormal production of cortisone or prolonged use of prescribed cortisone such as Prednisone may also lead to irregular periods and hair growth.

A complete physical examination from the physician should include a pelvic exam, a waist to hip ratio, determination of your body mass index, and a blood work evaluation should be done to rule out other diseases which may cause the same symptoms. PCOS is a group of symptoms and not a distinct disease entity. Insulin resistance is the genetic disorder which leads to the constellation of symptoms known as PCOS. Since this condition is so important for the development of diabetes later, its early detection should be encouraged. Many physicians including gynecologists may not know about the insulin resistance components of the treatment of PCOS. They may not be familiar with the new medications for PCOS since these medications are only approved by the FDA for use in diabetes.

Future research will be needed to determine the precise cause of the varying amounts of insulin resistance present in different patients. Currently, many pharmaceutical companies are looking at new medication for this disorder and are trying to gain FDA approval for the use of their medications in PCOS. Hopefully, as more physicians are aware of this problem, more patents will be recognized early and treated so that they may lead a more normal life and avoid the development of diabetes.

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