PCOS

Polycystic Ovarian Syndrome (PCOS) is also known as: polycystic ovaries; sclerocystic ovarian disease; polycystic ovarian disease (PCOD); Stein-Leventhal Syndrome. PCOS stands for Polycystic Ovarian Syndrome. PCOS is actually a misnomer, because it onlyrefers to one of many symptoms associated with this disorder. It affects between 5 to 10%of all women and is one of the leading causes of infertility.

WHAT ARE THE SYMPTOMS?

Symptoms can be mild or severe, and can vary widely from woman to woman. This is part of the reason doctors often miss the diagnosis. Someone with PCOS may have one or all of the following symptoms in varying degrees:

- irregular periods: abnormal, irregular, heavy or scanty (oligomenorrhea)
- absent periods (amenorrhea)
- ovarian cysts
- hirsutism (excess facial and/or body hair)
- alopecia (male-pattern hair loss)
- obesity
- acne
- skin tags
- acanthosis nigricans (brown skin patches, often found on the nape of the neck)
- high cholesterol levels
- high blood pressure
- exhaustion and/or lack of mental alertness
- decreased sex drive
- excess "male" hormones, such as androgens, DHEAS, or testosterone
- infertility
- decreased breast size
- enlarged clitoris(rare)
- enlarged ovaries
- enlarged uterus

Note that symptoms can worsen over time or with weight gain.

I THINK I HAVE PCOS - WHAT NOW?

Go straight to an endocrinologist. They specialize in glandular disorders; in this case, the gland in question is the pancreas, which is overproducing insulin. Seeing an OB/GYN is only really useful if you are trying to get pregnant and, even then, a reproductive endocrinologist would probably be better informed.

TESTING FOR PCOS

There is no *one* truly definitive test yet, but rather a set of tests can be used to diagnose PCOS:

1. A glucose tolerance test (GTT). Note that for the GTT you should have about 200g of carbs daily for the three to four days leading up to the test -- but of course fasting for 10 to 12 hours right before the test! -- otherwise the results will not be accurate. Also, smoking or exercise for 8 hours before or during the test can affect results.

2. Cholesterol Levels. Not just total cholesterol, but also triglycerides, HDL cholesterol, LDL cholesterol.

3. Testosterone, LH, FSH, and androstenedione levels. Some doctors will advocate more or fewer tests, but the ones listed above are the most common. Other tests may include urine 17-ketosteroids, laparoscopy, ovarian biopsy, serum HCG (pregnancy test), and basal fasting insulin.

In addition, some physicians will also suggest an ultrasound to check for ovarian cysts, which is of course what the syndrome is actually named after. However, some women with PCOS do *not* have ovarian cysts and some women who do not have PCOS do, so an ultrasound alone is not enough for a firm diagnosis.

WHAT CAUSES PCOS?

The root of PCOS is an inability to respond properly to insulin, the hormone produced in the pancreas that allows your body's cells to absorb energy from the food you eat. This means your cells don't respond to the normal amount of insulin, so the pancreas pumps out even more. That's what insulin resistance is and it happens when the body turns carbohydrates, both simple and complex, into glucose that surges into the bloodstream. Insulin travels to the muscle cells, telling them to take glucose from the bloodstream and store it in the liver. As
insulin levels in the blood increase, glucose levels in the blood decrease. When blood glucose falls below a certain level, the brain, which needs glucose to function, calls out for more by telling you to eat again. If it doesn't get glucose, the result is drowsiness or lack of mental alertness. This glucose shortage is also known as low blood sugar or hypoglycemia. When hypoglycemia strikes, the liver is unable to replenish bloodglucose from its stored supply because eating a carbohydrate-rich meal or drinking a sugary beverage creates an exaggerated
insulin response that prevents delivery of the glucose. So, insulin remains in the bloodstream,sending messages to store more body fat and preventing the release of already-stored fat, and glucose remains in the liver instead of going to the brain. In addition, the high levels of insulin stimulate the ovaries to produce large amounts of the male hormone testosterone, which may prevent the ovaries from releasing an egg each month, causing infertility. High testosterone levels in women also cause acne, male-pattern baldness, and excess hair growth. Last but not least, it is the insulin problem that puts us at increased risk for diabetes as well as heart disease.

WHAT IF I HAVE PCOS?

If you are currently overweight, the first step is to lose the excess pounds, because many symptoms of PCOS improve or even disappear entirely at normal weight. Since the cause of all the problems is insulin resistance, the key seems to lie in restricting carbohydrates and exercising regularly, for physical activity also helps regulate insulin production. The most popular of the low-carb diets are 'Dr Atkins' New Diet Revolution' by Robert Atkins and 'Protein Power' by Michael and Mary Eades. Another popular approach is the 'Carbohydrate Addicts Diet' by Rachel and Richard Heller. Even at normal weight, it is still critical to moderate
carbohydrate intake as well as exercise. This is simply going to have to be a way of life, since PCOS cannot be cured, only held in check. Although many women have reported great success through low-carbing and exercise alone, a growing number of women with PCOS are now being treated with so-called diabetic drugs, such as Metformin (AKA Glucophage). There have been several studies reporting good results in treating PCOS with Metformin. However - and this is very important! - Metformin is only meant to be taken temporarily. The goal is to use
Metformin in conjunction with diet and exercise to lose excess weight.

STANDARD THERAPIES
Many therapies target specific symptoms of PCOS, but may not address the underlying cause.

Oral contraceptives. Traditionally, physicians have prescribed oral contraceptives (birth control pills) to regulate menstrual periods in women with PCOS. Oral contraceptives contain a combination of hormones (estrogen and progesterone). Used properly, oral contraceptives can assure that women menstruate every four weeks.

Because they cause women to menstruate regularly (and, thus, shed the endometrial lining), oral contraceptives as treatment for PCOS help to reduce a woman's risk of endometrial cancer.

Anti-androgens. Anti-androgenic agents, such as spironolactone, block the effect of androgens (male hormones , including testosterone). In high doses, anti-androgens can reduce unwanted hair growth and acne.

Treating infertility. Many assisted-reproduction techniques are available for women who have difficulty conceiving because of PCOS. Through our experts in reproductive endocrinology, the Center for PCOS offers a full spectrum of standard and innovative fertility therapies: from oral and injectible medications that stimulate ovulation, to advanced methods of in vitro fertilization including use of donor eggs.

NEWER TREATMENTS
Rather than focusing on relieving specific symptoms, the newer treatments aim at what may be the root cause of PCOS, ie insulin resistance. Many of these new therapies are designed to lower insulin levels and, thus, reduce production of testosterone.

Investigational Therapies
New evidence suggests that using medications which lower insulin levels in the blood may be effective in restoring menstruation and reducing some of the health risks associated with PCOS. Lowering insulin levels also helps to reduce the production of testosterone, thus diminishing many of the symptoms associated with excess testosterone: hair growth on body, alopecia (hair loss), acne, obesity and cardiovascular risk.

Troglitazone (Rezulin®). Troglitazone is an insulin-sensitizing agent that improves glucose tolerance and insulin resistance. The drug was approved by the Food and Drug Administration (FDA) as a treatment for diabetes, but because of concern regarding the potential for liver damage, troglitazone is no longer available.

Early results from clinical trials showed that troglitazone dramatically lowered insulin levels and, therefore, testosterone levels in women with PCOS.

Pioglitazone (Actos®) and Rosiglitazone (Avandia®) are two medications in the same class as troglitazone and may hold promise for the treatment of PCOS. It is important to note, however, that neither is approved by the FDA for this purpose.

Metformin (Glucophage®). Metformin is an insulin lowering drug. It is approved by the FDA as a treatment for diabetes, but is not yet FDA-approved for use in treating PCOS.

In clinical trials conducted at the University of Chicago Hospitals and other medical centers, metformin achieved mixed results. Roughly half of the women achieved relief from symptoms, whild the other half did not.

NON MEDICAL APPROACHES
Many non-medical approaches can relieve or reduce specific symptoms. These include:

Weight loss. Because of excess testosterone and insulin resistance, losing weight can be quite challenging for women with PCOS. These women truly have a metabolic cause for their extra weight. Many women with PCOS follow a low-carbohydrate diet designed to lose or maintain their weight.

However, weight loss achieved through dietary changes and exercise can help women with PCOS in several ways. Like men and women without PCOS, losing weight reduces a person's risk of cardiovascular disease and non-insulin dependent (type 2) diabetes. Weight loss also helps to lower the level of insulin which, in turn, reduces the ovaries' production of testosterone.

Electrolysis. Electrolysis can eliminate or decrease unwanted hair. During electrolysis, individual hair follicles are destroyed by using an electric current. The University of Chicago Center for PCOS is one of the few medical centers in the U.S. which provides certified electrolysis services on-site for patients. Electrolysis service is provided by the staff of M.G. Institute.

Laser Hair Removal. The removal of body hair through the use of laser treatment appears to be both effective and permanent. This service is now available by appointment at The University of Chicago Center for PCOS and is provided by the staff of M.G. Institute.

Alternative therapies. Some women with PCOS find relief from symptoms through alternative therapies such as herbs, acupuncture, homeopathic remedies and other alternative approaches. Please note that many herbal therapies are not regulated by the government, so you must be careful about the source of the herb.

PCOS and Infertility

Do all women with PCOS suffer from infertility?

The answer to this depends on the criteria used to diagnose PCOS. If a main criterion is anovulation, then by definition women with PCOS would have fertility problems. It is possible to have the appearance of polycystic ovaries and be fertile, but having the syndrome usually does impact fertility adversely.

Is it possible to have regular cycles without ovulating?

Yes, but the reasons for this happening are poorly understood. Some women seem to have a regular bleed regardless of ovulation, so one should look beyond cycle length to determine ovulation.

Are basal body temperatures reliable in women with PCOS?

Women with PCOS who are mostly anovulatory will have erratic BBTs — some say it will look like the Rocky Mountains. If a woman with PCOS has an ovulatory cycle, the BBT chart should show a thermal shift, but it may be a bit harder to read. Some doctors see more value in charting than others, and one should follow their own physician's advice.

Are ovulation predictor kits reliable for women with PCOS?

It depends on whether the woman has high LH levels. A woman with elevated LH may consistently get positive tests or get erratic readings. Most women will show some kind of line in the result window of a test since LH is always present — it is important to note that a positive result is as dark or darker than the control line. The Clearplan Fertility Monitor notes that it is unreliable for women with PCOS. It's a good idea to check with one's doctor for suggestions on home monitoring.

Will losing weight jumpstart fertility in overweight patients with PCOS?

It may, but it doesn't always. There are lean women with PCOS. Weight loss may help reduce insulin resistance, resulting in spontaneous or improved ovulation. Quick weight loss may cause more harm than good, so slow weight loss is best. Losing 10 percent of one's body weight should be enough to show some improvement in symptoms.

Is it safe to follow a low carbohydrate diet while trying to conceive?

It depends on the diet plan followed. Most doctors would stress a lifestyle change — a change in types of food consumed — over a reduced-calorie diet. Several of the more popular plans are outlined in the weight section below.

Does Clomid work for women with PCOS?

Clomid may work for PCOS women, but only about 40 percent of those who ovulate on it will get pregnant. A good trial is three to four ovulatory cycles. Most doctors would recommend not doing more than six cycles total of Clomid.

Which injectable fertility medications work best for women with PCOS?

Many doctors will suggest FSH-only medications for women with PCOS as LH levels are already elevated.

Does PCOS lower egg quality?

It is possible that PCOS may reduce egg quality — perhaps because of abnormally high insulin levels, or because of the delayed ovulation (to which insulin resistance may contribute).

What is the benefit of adding steroids such as dexamethasone or prednisone to ovulation induction medications?

The steroids are used to help lower androgen levels, particularly DHEAS. This may help ovulation induction. However, use of steroids should be carefully implemented, since insulin resistance is generally worsened by these medications.

Is progesterone support needed in women with PCOS?

Women with PCOS frequently have low progesterone levels. The best solution is to strengthen ovulation, as opposed to progesterone supplementation alone without investigating follicle development through ultrasound monitoring and estradiol levels. Supplementation may still be desirable as it probably cannot hurt, and might help.

Can insulin-sensitizing medications be used in conjunction with ovulation stimulation drugs?

Yes. The use of insulin-sensitizing medications while trying to conceive is becoming more common, and many doctors will introduce ovulation stimulation medications such as clomiphene citrate, FSH-only injectables, or FSH/LH injectables. The greater debate right now is when to stop the medications when pregnancy is achieved.

How long a trial should one give insulin-sensitizing medications before adding ovulation stimulation medications?

A good trial period for insulin-sensitizing medications is 3-6 months. Someone with borderline insulin elevations may require a shorter duration of therapy than a woman with a strikingly high level. If ovulation does not resume after 3-6 months, or pregnancy is not obtained, one might consider adding fertility medications. It may also make sense to re-check fasting glucose and insulin levels to see if the insulin-sensitizing therapy is working or if adjustments in treatment should be made.

Do insulin-sensitizing medications improve egg quality in IVF?

The follow-up for women taking insulin-sensitizing agents who subsequently undergo IVF/ET is currently limited. No controlled data exist (yet) that proves whether or not normalization of insulin levels has an important effect on oocyte quality, but some generalizations suggest this may indeed be the case. It does appear that use of metformin may increase the number of mature eggs retrieved.

For example, among many diabetics both insulin and glucose are elevated. The incidence of congenital anomalies is well known to be higher in these patients. This means something is adversely affecting development with bad perinatal results. At the gamete (egg) level, similar blocks to normal growth may also exist.

Should metformin be discontinued before doing a hysterosalpingogram (HSG)?

Patients should go off metformin for several days prior to any x-ray procedure in which iodinated compounds will be used, including the hysterosalpingogram where contrast dye is injected into the uterus (note: this is a different procedure than a sonohystogram where saline is injected into the uterus before an ultrasound).

The reason for this recommendation is that the kidneys clear both the dye and metformin. It should not be a problem if renal function judged by creatinine and blood urea nitrogen (BUN) tests is normal. Renal function testing should be performed before metformin is started, and periodic screening is prudent. Many of the users of metformin are older diabetics with altered kidney function, and this is added precaution.

Does PCOS increase the risk of ovarian hyperstimulation?

Yes. Because of the tendency for women with PCOS to produce many small follicles, the trick to avoiding hyperstimulation is getting a few follicles to mature without an army of smaller ones. Caution should be used with medications, starting at the lowest doses, and follicle production should be monitored by ultrasound and estradiol levels. It is possible that the use of metformin with gonadotropin-induced ovulation may reduce the risk of hyperstimulation.

Should women with PCOS who are trying to conceive take baby aspirin?

This is something that should be discussed with one's doctor, but there is some research indicating that pregnancy continuation rates in PCOS may be improved with low-dose (81 mg/d) aspirin therapy. The aspirin is used to help prevent blood clotting in the uterine lining and help increase blood flow.

What is in vitro maturation (IVM) and is it beneficial for women with PCOS?

In vitro maturation is a process in which immature eggs are harvested from a woman early in her cycle and matured in a laboratory using gonadotropins, rather than medicating the patient in order to stimulate follicle growth prior to egg retrieval (IVF). After the eggs are matured, they are fertilized and resulting embryos are transferred to the uterus. While gaining publicity recently, the procedure is not really that new. It isn't widely used because the pregnancy rate with IVM is low, and the miscarriage rate is high. The primary advantages of the process are that it may work for women who are poor responders to medications, the risk of hyperstimulation is eliminated, and it reduces costs by lessening the amount of medications and monitoring needed. Fertilization rates in PCOS patients may be improved if they are given an hCG injection 36 hours prior to egg retrieval.

Is there a relation between PCOS and endometriosis?

Endometriosis has been reported in about 30 percent of infertile women. PCOS is the most common cause of lack of ovulation and certainly a leading cause of female infertility. Statistically, it would seem that many women would have both and this is probably the case. Both of these disorders appear to have a genetic predisposition. However, whether endometriosis is more or less common in PCOS patients and PCOS in those with endometriosis is not known. Certainly, everyone that has one of these disorders does not necessarily have the other.

The leading theory on the origin of endometriosis is a back flow of blood from the uterus through the tubes and out into the pelvis (retrograde menstruation). This theory can only partly explain the origin of endometriosis because most women have this "backward flow" each month, but endometriosis is not seen universally. The second theory of endometriosis is that the cells lining the pelvis and ovaries are transformed into endometrial cells by some internal or external stimulus. Perhaps, blood and all the growth factors it contains is a good candidate. It can easily be seen how these two theories could work together.

In one way, the PCOS patient who has very infrequent bleeding should have a decreased chance of endometriosis. In another way, estrogen levels may be chronically elevated to a level lower than those near ovulation, but high enough to cause the endometrium to proliferate as it remains unopposed by progesterone. Endometriosis can be thought of as a fire. The fuel for the fire is estrogen.

What is Luteinizing Unruptured Follicle Syndrome (LUFS) and how does it relate to PCOS?

Luteinizing unruptured follicle syndrome occurs when the follicle develops but changes into the corpus luteum without releasing the egg. It may be more likely to occur in women with polycystic ovaries since the ovaries become tougher and it is harder for the egg to escape the follicle and the ovary. In some cases of LUFS, a thermal shift will be visible on a BBT chart, and a progesterone draw seven days after suspected ovulation may show a borderline response (between 5 and 15 ng/ml). The only absolute test of ovulation is pregnancy. The use of non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen sodium (Advil and Aleve), as well as adult-strength aspirin, may contribute to LUFS. Therapeutic low-dose aspirin, also called baby aspirin, should not effect ovulation.

What is an ovarian drilling or wedge resection?

The purpose of both surgeries is the same, to reduce androgens and restore menses, but the wedge resection is rarely done anymore. The success of the wedge resection may be higher than that of ovarian drilling, but the drilling is a less invasive procedure with less risk of scarring.

The wedge resection involves doing a laparotomy (a major abdominal surgery where a long cut is made along the bikini line), and then cutting a portion (wedge) out of the ovary and stitching the ovary back together. The procedure is known to result a significant reduction in LH and androgen production. Some studies noted establishment of regular menses in more than 75 percent of patients and a pregnancy rate of about 60 percent. Unfortunately the risk of adhesions, sometimes severe, is around 30 percent.

The more common procedure today is ovarian drilling (microcautery or diathermy) done by outpatient laparoscopic surgery. A small needle is used to make 4-20 punctures in the ovary. An electric current is passed through the needle and a small portion of the ovary destroyed. Often a small amount of cyst fluid can be seen escaping as the puncture is made. Alternatively, lasers have been used for the same effect with the potential disadvantage of greater surface injury and scar tissue formation.

The success rate for ovarian drilling is generally less than 50 percent, maybe less than 25 percent, but the best answer is to ask the doctor's statistics and what outcomes are associated with his/her particular technique. The risk of adhesions still exists, but is much lower in ovarian drilling than in wedge resection. One advantage is that the surgery may be combined with diagnostic laparoscopy, chromotubation (also called chromopertubation or hydrotubation) and/or hysteroscopy.

Surgical therapy for PCOS should not be considered as a first step in treatment in part because it is unclear what the long-term effects might be. A good time to consider it would be when making preparation for a diagnostic laparoscopy or considering in vitro fertilization.

What is hyperprolactinemia and what can be done to treat it?

Hyperprolactinemia is an elevation of prolactin levels in the blood that may appear more often in women with PCOS. The elevated levels may cause breast discharge and may contribute to irregular menses. In some cases it is caused by a tumor on the pituitary gland. The first step in diagnosis is usually a blood test, and elevated levels may indicate further investigation through MRI. If the tumor is large and pressing on adjacent brain structures, it may be removed and all problems are solved. A small tumor might be treated with medications such as bromocriptine (Parlodel) or cabergoline (Dostinex — which is also shown to improve uterine perfusion. Cabergoline is often tolerated better than Parlodel, and doses are taken less frequently.