WOMEN'S HEALTH
April 21, 2011

The Most Common Hormone Disorder in Women

D.A. Dumesic, M.D., M. Goodarzi, M.D., Ph.D., G. Chazenbalk, Ph.D., D. Geller, M.D., and D.H. Abbott, Ph.D.
PCOS can interfere with fertility and make pregnancy risky. Worse, it brings long-term health problems.
D.A. Dumesic, M.D., Professor and Division Chief of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Associate Professor, Director of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center; G. Chazenbalk, Ph.D., Associate Researcher, Department of Obstetrics and Gynecology, Ronald Reagan UCLA Medical Center; and D. Geller, M.D., Associate Professor of Pediatrics, Ahmanson Department of Pediatrics, Cedars-Sinai Medical Center, all at the University of California Los Angeles, Los Angeles, CA; and D.H. Abbott, Ph.D. Professor, Wisconsin National Primate Research Center and Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI.

Polycystic Ovary Syndrome (PCOS) affects millions of women in the U.S. It is estimated that between 5-10% of women suffer from PCOS, making it the most common hormone disorder that exists in women of childbearing age. PCOS is often diagnosed early in a woman’s life, during the transition into puberty, or it may only apparent when a woman is trying to get pregnant but finds she has difficulty conceiving.

A Hormone Disorder with Many Faces

The symptoms of PCOS are well-known, and all arise from the fact that levels of the reproductive hormones in the PCOS patient are altered. Women may experience a range of symptoms, including irregular or missed periods, heavy periods, difficulty becoming pregnant, excess or male-pattern hair growth, weight gain, acne, and cysts on the ovaries.

The appearance of many small "cyst-like" follicles on the ovaries on ultrasound gives the condition its name. Many women experience a combination of several symptoms, and the pattern of symptoms can vary greatly from woman to woman. Over the years, experts have evaluated and reevaluated how to define and diagnose the condition.

Because there are many other disorders involving the sex hormones, distinguishing between PCOS and other related conditions can sometimes be tricky, particularly since some conditions have overlapping symptoms. For this reason, it is important to visit your doctor if you believe you may have PCOS or another hormone disorder, so a specific diagnosis can be made.

Genetics seems to play a strong role in who develops the condition. Many women who suffer from PCOS also have an immediate female family member with the disorder. PCOS is thought to be the product of an imbalance of sex hormones. Sometimes an excess of the naturally-occuring "male" hormones – androgens – may be present in a woman’s body. All women produce small amounts of androgens, like testosterone, but sometimes the body may produce too many. When this happens, the body gets mixed signals from the altered hormone environment, and PCOS may develop.

PCOS may also be due to too much insulin circulating in the body: insulin is the hormone that helps sugar gain entry into the body’s cells from the blood stream. Indeed PCOS has many similarities to insulin-related health issues like insulin resistance, metabolic syndrome, and diabetes.

Because PCOS affects so many women, it is a condition of which all women should be aware. One reason for this is that it is important to be diagnosed and treated for the syndrome if you suffer from it, in order to minimize symptoms and any complications that might arise. It is important to manage PCOS because it can put women at higher risk for other conditions, like high cholesterol, high blood pressure, heart disease, and diabetes.

There are many effective treatment options available these days — from lifestyle changes to hormone therapies to blood sugar medications. We will outline the symptoms, causes, and treatments for PCOS, including information about being or becoming pregnant if you already have PCOS. Though research continues to be done, we know a lot more about the condition than we did even a decade ago, and the development of more effective treatments has led to vast improvements in quality of life for many PCOS patients.

The Symptoms of PCOS: Every Woman Has a Different Story

Women who suffer from PCOS can have very different experiences, and may initially visit their doctors with various constellations of symptoms. Many women develop PCOS around the time of puberty, or even prior to it, as the hormone environment in the body is dramatically shifting. But for others it doesn’t become apparent until later in life, often after years of suffering from irregular periods or after they find they are having difficulty getting pregnant. Sometimes, it develops after a large weight gain, perhaps triggered by the change in hormone levels that may follow an increase in body fat. To be diagnosed with PCOS, a woman must experience two of the following three symptoms:

  • Menstrual Irregularity. Many women who are diagnosed with PCOS have irregular or missed periods, often with 35 days or more between periods. Menstrual irregularity is a common symptom of PCOS.
  • Excess Androgen. PCOS patients have too much androgen ("male" hormones) circulating in their bodies. This is responsible for male-pattern hair growth, often on the face, back, chest, or stomach. Acne, or other skin problems, is another common symptom of PCOS, which may develop as a result of excess androgen.
  • Polycystic ovaries: The ovaries may develop small but numerous "cyst-like" follicles, which doctors can spot with an ultrasound. However, at least one of the other two symptoms should also be present, because it is possible to have cystic ovaries without actually having PCOS.

Other PCOS symptoms may include pelvic pain, skin tags (small, benign flaps of skin), sleep apnea (where one stops breathing for brief periods while asleep), and depression. Because the body is producing too much androgen, male-pattern baldness (thinning of the hair above the forehead and at the crown of the head) may also occasionally be experienced. Patches of dark skin may also be seen around the neck, underarms, groin, and breasts, which is related to insulin resistance.

Fertility Problems
One of the most difficult aspects of PCOS for some women is that conception can be very difficult. Because the brain may not producing hormones in correct amounts to signal egg production, or the ovaries may not be producing enough hormones themselves, ovulation may not occur consistently – or at all – in some women. Some PCOS patients may only have menstrual cycles every 60 or 90 days, which makes the window of opportunity for getting pregnant much narrower than in unaffected women. There are some fertility treatments that can increase a PCOS patient’s chances of getting pregnant, which will be discussed in more depth below.

Signs in Adolescence
Some women suffer from PCOS from the time they are very young, with symptoms arising well before puberty. For example, some young patients may have signs of pubic hair and an adult-like body odor as young as five years old. In healthy people, the development of pubic and underarm hair occurs during a hormonal change called adrenarche, which happens before (and is distinct from) puberty.

Many girls who go through early or premature adrenarche (PA) do go on to develop PCOS: some studies have estimated that 10-20% of girls with PA will develop PCOS. (Because there are also other causes for PA, girls who experience it should visit their doctors.) Acne and weight gain, despite attempts to lose weight and exercise, may also develop in adolescence, along with irregular periods. As for adults, hormone, insulin, and blood glucose tests may reveal that a teenage patient is suffering from PCOS, when all other possibilities have been ruled out.

Often, being born at a low birth weight can put a girl at higher risk for PCOS and for developing other metabolic problems later in life. As mentioned earlier, though the evidence is a little mixed, having a mother or sister with PCOS appears to put a girl at a 5-times higher risk of having PCOS herself. Just having a family member with PCOS can also put a young woman at a higher risk of developing other hormone and metabolic problems.

Testing for PCOS
As mentioned, a woman must experience two of the three symptom categories listed above, to be diagnosed with PCOS. In addition to using ultrasound to look at the ovaries, doctors will need to do several types of blood tests in order to determine hormone levels. These tests may include measures of several hormones, including follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and androgens from the ovaries and adrenal glands. Because insulin levels are often affected in PCOS, a glucose test performed before and 2 hours after drinking a sugar solution may also be done to check for insulin resistance, along with tests for blood fat levels like cholesterol and triglycerides (more on this later). Once a doctor has evaluated all of one’s symptoms and blood work, and ruled out all other possible diagnoses, a diagnosis of PCOS may be made.

PCOS and the Risk for Other Health Problems

Since PCOS affects the sex hormones and reproductive health, it can make becoming pregnant difficult; it may also increase one’s risk during pregnancy. Since PCOS also affects insulin levels and metabolic health, having the condition can put a woman at greater odds for developing complications like type 2 diabetes, obesity, heart disease, high blood pressure, and high cholesterol and blood fats (triglycerides). Women who ovulate at least some of the time may have lower risk for developing these conditions than women who never ovulate. For all women with PCOS, it is very important to work with one’s doctor to manage it well, in order to minimize the risk for developing one or more of these related conditions.

PCOS Can Make Pregnancy Riskier
A central issue with PCOS is that it can make pregnancy riskier due to too many androgens and insulin circulating in the blood stream of the mother. PCOS patients who do become pregnant may be at higher risk for pre-eclampsia, a potentially dangerous condition of high blood pressure during pregnancy, which may require early delivery for safety of the mother and infant. Women may also have higher odds of developing gestational diabetes, high blood pressure, and giving birth prematurely. Newborns of PCOS mothers are frequently in the neonatal Intensive Care Unit, may have a higher death rate, and also may have low birth weight. Despite the risks involved with pregnancy, it is possible for PCOS patients to give birth to a healthy child. The patient and her doctor must keep an especially close eye on all aspects of the patient’s – and fetus’ – health.

Insulin Resistance and Type 2 Diabetes Are More Likely with PCOS
Aside from the reproductive challenges and risks associated with PCOS, the condition also makes it more likely to develop other conditions, particularly those that are insulin-related and metabolic. Up to 70% of women with classic PCOS are insulin resistant, especially women who are overweight or obese. When obesity occurs along with PCOS , insulin resistance may be even worse. Another potential contributor to insulin resistance may be the use of oral contraceptive pills, which are commonly prescribed for PCOS patients.

Most PCOS patients with insulin resistance have increased insulin production, leading to too much insulin circulating in the blood. This creates a vicious cycle, in which insulin actually stimulates the production of testosterone from the ovaries, which suppresses ovulation. Higher levels of testosterone also lead to the darkening of the skin in certain areas, skin tags, fatty liver disease (non-alcohol related), and sleep apnea.

But most importantly, the insulin resistance that can occur with PCOS puts a woman at a much higher risk of developing type 2 diabetes. This happens when the body does not produce enough insulin to compensate for the insulin resistance that can develop with PCOS. Women with a family history of PCOS are much more likely to develop type 2 diabetes. The risk of developing type 2 diabetes for PCOS patients in general is about 10%, which is considerably higher than healthy women of the same age, whose risk is only about 3%. One’s doctor will determine the best way to screen for type 2 diabetes, and possibly repeat testing every couple of years to keep a close eye on the situation.

PCOS Patients May Suffer from High Cholesterol and Blood Fats
Along with the metabolic risks that PCOS can pose is the risk of high cholesterol and triglycerides — the blood fats. Problems with cholesterol and triglycerides occur in 70% of PCOS patients in the U.S. (the rate is lower in countries where the average body weight is less). PCOS patients often suffer from high triglyceride levels, high LDL ("bad") cholesterol, and low HDL ("good") cholesterol. This happens because insulin resistance compromises the ability of insulin to break down the blood fats, so they are able to leave the fat cells where they normally reside and free to roam the blood stream. The increase in LDL cholesterol can happen in women of any weight, while problems with other forms of blood fats, like triglycerides and HDL, are more likely to occur in overweight and obese PCOS patients.

Metabolic Syndrome and Cardiovascular Risks
Excess insulin in the blood stream can increase one’s risk for metabolic syndrome, which is a group of risk factors including high blood sugar, high blood pressure, high triglycerides, low HDL cholesterol, and carrying more fat in the belly region (abdominal fat). Metabolic syndrome can occur in as many as 30-45% of PCOS patients, which is much higher than the general population, in which only 5% suffer from metabolic syndrome. Metabolic syndrome is a major risk factor for cardiovascular disease. PCOS patients have several increased risk factors for cardiovascular disease: in addition to the issues mentioned above, other risk factors may include dysfunction of the blood vessels, thickened arteries, and increased inflammatory markers. Some of these risk factors get better with treatments for insulin resistance, which suggests the large role that insulin resistance plays in heart risk. Some studies have found that the number of heart attacks may be higher for PCOS patients than for the general population.

Treating Women with PCOS over the Long Term

Improving Fertility
There are a number of ways to induce ovulation and boost one’s changes of conceiving if you are a woman with PCOS and wish to get pregnant. A drug called clomiphene citrate is generally considered the first-line therapy for women who are not ovulating. This drug is known to stimulate the hormone (FSH) that stimulates growth of the ovarian follicle. Another drug, letrozol, is also used to boost ovulation, but more studies are needed to demonstrate its benefits more clearly.

Over the long-term, the diabetes drug metformin may also increase ovulation by reducing insulin levels. However, at least six months of metformin may be needed to have an effect on ovulation. For this reason, clomphene citrate is generally the first choice among doctors, although a combination of metformin and clonphene citrate may be favored under certain circumstances. Metformin, combined with diet and exercise, may be used if the need for conception is less urgent, and has the advantage of being associated with a lower rate of multiple births.

Injections of hormones called gonadotropins may also be used to increase fertility. These help egg mature and stimulate ovulation. Laparoscopic ovarian surgery may also be used to destroy ovarian cells that produce excess androgen. Both methods are considered second-line treatments if clomiphene (or combined clomiphene/metformin) are unable to induce ovulation.

in vitro fertilization, or IVF (in which the egg and sperm are placed together in a laboratory dish to be fertilized), is usually considered a third-line treatment; but it can be an earlier option for certain couples, so it is important to talk to your doctor about which options are appropriate for your situation.

There is also the risk of having multiple births with medical therapies for infertility, including IVF. Unlike medical therapies which allow the sperm and eggs to fertilize in your body, however, IVF might be a reasonable option for some PCOS women who fail clomiphene therapy because the sperm and eggs are fertilized in a dish and only one embryo can be transferred into your uterus.

Managing Metabolic and Cardiovascular PCOS Symptoms
Some women may find that weight loss and exercise do a lot to manage metabolic syndrome that is associated with PCOS. Nowadays, certain treatments that improve insulin sensitivity and reduce insulin levels are very common in the management of PCOS. The most-used and safest drug therapy is metformin, the common diabetes medication mentioned earlier. Metformin improves insulin resistance by reducing the release of glucose from the liver. In PCOS patients, the use of metformin not only reduces insulin levels, but it can also reduce testosterone levels, improve one’s cholesterol profile, and as mentioned above, may help improve one’s chances of conception. Using metformin may also prevent full-blown type 2 diabetes from developing, as well as lower the risk for cardiovascular disease.

Statins may also be prescribed for some women who need extra help managing cholesterol levels. Depending on the severity of your symptoms, your doctor will determine the best management plan for you. Taking part in the lifestyle changes (caloric restriction – diet – and exercise) that have been shown to help manage PCOS symptoms and treating any other PCOS-related health issues will be the best way to improve your health and reduce your risk for complications over the long term.

Managing PCOS in Adolescents
Things are not too different for young women affected with PCOS. Diabetes medications like metformin and thiazolidinediones (TZD) are commonly used to improve metabolic problems such as insulin resistance. These treatments have the added benefit of helping regulate a young woman’s menstrual cycle and restoring ovulation. They can also be helpful for girls who experience premature adrenarche, mentioned earlier, and who are therefore at higher risk for PCOS. It is important to note that at this point in time, metformin use for adolescent PCOS patients is not approved by the FDA, even though it has been shown to be extremely safe. Use of TZD in adolescents has been more controversial, since it is associated with certain risks, such as cardiovascular problems. Many doctors favor trying metformin in adolescent patients, since the risk of developing metabolic syndrome down the road is much higher for adolescent PCOS sufferers, and irregular periods are likely to continue into adulthood. Again, if you suspect that you or your daughter may have PCOS (or another hormone dysregulation), it is important to see a doctor who can diagnose it appropriately, and treat it effectively.

Summary

PCOS is the most common hormone disorder in women in the U.S. Typical symptoms include irregular or absent menstrual cycles, male-like hair growth, acne, and ovaries with multiple cysts visible on ultrasound. Looking at the patient’s history, symptoms, and blood work, a doctor can rule out other hormone disorders that share symptoms with PCOS.

Most PCOS patients have insulin resistance (disproportionate to their body weight), and several of the risk factors associated with cardiovascular disease, including high cholesterol/blood fat levels, abdominal obesity, high blood pressure, and glucose intolerance, insulin resistance, or type 2 diabetes. A subset of PCOS patients also experience infertility due to hormone imbalances. Fertility treatments like IVF may help PCOS patients become pregnant if they wish to start a family, although they may not be effective in all patients. Once pregnant, it is certainly possible for a PCOS patient to carry a fetus to term, though there are certain risks involved.

Researchers are still working to understand the underlying causes for PCOS, and to develop effective treatments to manage both the metabolic and the reproductive symptoms associated with PCOS. Working closely with one’s doctor to determine the best management plan, which can include lifestyle changes, hormone therapies, and diabetes medications, is the best way to improve one’s quality of life and reduce odds of developing complications down the road.

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