POLYCYSTIC OVARIAN SYNDROME

Introduction

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine (hormonal) abnormalities of women in their reproductive years (ages 13 – 45) and affects 6 – 15% of women worldwide. It was first described in 1935 by Drs. Irving Stein and Michael Leventhal, two Chicago physicians, that described a series of 7 women with menstrual disturbances, male-pattern hair growth and enlarged polycystic ovaries. For many years this was referred to as the Stein-Leventhal Syndrome and is now replaced with the term polycystic ovarian syndrome or PCOS. In their original report Drs. Stein and Leventhal described women who had amenorrhea (a complete absence of menstrual periods) and subsequent infertility. We now realize that PCOS can also present with a range of menstrual disturbances including amenorrhea (no periods) to irregular and unpredictable periods that vary from very light to very heavy menstrual flow. Polycystic ovarian syndrome (PCOS) can be a very worrisome condition since affected women often worry whether or not they will ever be able to become pregnant. Others are concerned why their reproductive system isn’t functioning properly and how this might otherwise affect their health.

Why is it called a “syndrome” and not a “disease”?

In medicine we often use the word “syndrome” to describe a variety of signs and symptoms that tend to occur without a definitive understanding of a central cause. Women with PCOS, understandably, wish to know “what caused it”—and in most cases we can identify the diagnosis and even correct many of the symptoms, but the truth is that, unlike many other abnormalities or “diseases”, physicians cannot explain why certain women get it and others don’t. What’s more frustrating for many women is that there is no simple single test—imaging or blood—that absolutely defines PCOS. Instead, the diagnosis of PCOS is based on a constellation of signs and symptoms listed below. In 2003 an international group of physicians established what are known as the Rotterdam Criteria for the diagnosis of PCOS. The diagnosis of PCOS is made if a woman fulfills 2 of the following 3 criteria:

1. Infrequent or a complete lack of ovulation. Most women will ovulate 12-13 times a year. Women with PCOS, however, may not ovulate at all or have only infrequent ovulations. The result is either the complete absence of menstruation or irregular and unpredictable periods that have no “rhyme or reason.”
2. Excessive androgen (male hormone) activity. This can manifest itself as increased facial and/or abdominal hair OR the finding of increased levels of male hormones known as androgens.
3. Features of polycystic ovaries found on ultrasound (Figure 2). Ultrasound may indicate the presence of many immature follicles. The follicle is where egg production occurs. In normal, ovulating women, one typically finds follicles of varying sizes. Some of these follicles get large (about an inch in diameter) just before they release an egg. However, in women with PCOS there are many follicles present, but they don’t “mature” and ovulate. Figure 1 shows normal ovulation on the left-hand side and how this compares to women with polycystic ovaries who produce many follicles that don’t mature and release an egg.

What are the signs and symptoms of Polycystic Ovarian Syndrome (PCOS)?

Women with PCOS often have a constellation of signs and symptoms. The signs (something that a physician can measure) include ultrasound evidence of polycystic ovaries (Figure 2), abnormal androgen (male hormone) production, and a male pattern of hair growth on the face and abdomen. Other signs which suggest PCOS include metabolic abnormalities which include insulin resistance, type-2 diabetes, elevated triglycerides and hypercholesterolemia. The symptoms of PCOS include increasing growth of facial hair and body hair, male pattern loss of scalp hair, unwanted weight gain, and irregular or absent periods.

Why is the diagnosis of PCOS important?

The diagnosis of PCOS may be important since women with this diagnosis, in addition to having menstrual abnormalities, may anticipate difficulty in achieving a pregnancy. Additionally, the metabolic abnormalities noted above also puts them at increased risk for type 2 diabetes, cardiovascular disease and strokes. Finally, women with polycystic ovarian syndrome are at a markedly increased risk for developing endometrial hyperplasia and even endometrial cancer.

Before you get anxious!

Although these “signs and symptoms” and their medical implications sound scary the truth is that they can all be managed. For instance, the menstrual abnormalities can be managed depending on whether or not you are trying to become pregnant at the present time. Infertility, as well as other symptoms such as increased unwanted hair growth, are also manageable. Since women with PCOS are at increased risk for developing diabetes and related conditions these problems can be screened for and managed. Finally, because of the increased risk endometrial or uterine cancer, screening for this risk should be regularly performed since, in most cases, endometrial cancer is avoidable.

How can I tell if I have PCOS?

The diagnosis of PCOS is often suspected whenever a women of reproductive age (13 -45 years old) presents with a history of absent or irregular periods and symptoms of excessive male hormone production (hyperandrogenemia). Symptoms of excessive male hormone production can include acne, excessive hair growth (facial and body hair), male-pattern baldness and central obesity. Therefore, using the criteria listed above—the Rotterdam Criteria—if you are between the ages of 15 and 45 and experiencing symptoms of excessive male hormone production AND irregular or absent periods you are likely—but not certain–to have PCOS.

What kind of tests can confirm the diagnosis of PCOS?

The most useful single “test” for PCOS is a complete history and physical examination. By itself, the history and physical exam is imperfect but can be supplemented with many of the following tests. It should be kept in mind, however, that none of these tests, by themselves, is absolutely diagnostic of PCOS. One can have PCOS without abnormal laboratory tests. Moreover, abnormal laboratory findings may indicate other irregularities.

Ultrasound examination—A transvaginal ultrasound often indicates somewhat enlarged ovaries that contain multiple small ovarian cysts (Figure 2).

What is typically abnormal about the ultrasound is the large number of immature ovarian cysts (Figures 1 and 2) and the absence of a maturing or mature ovarian cyst that shows signs of ovulation.

Blood Tests:

A variety of blood tests are helpful in determining whether you have PCOS or another abnormality that can mimic it.

Total and free testosterone—Often, women with PCOS show slightly higher levels of either total or free serum testosterone. These elevated values often explain why women with PCOS develop excessive growth of facial and abdominal hair. However, one can still have PCOS and male pattern hair growth without this laboratory finding. The measurement of total and free testosterone is also important in terms of ruling out other causes of testosterone elevation such as androgen-secreting tumors.

Sex steroid binding globulin (SSBG)— although this lab test is often not performed, it is frequently low in women with PCOS.

DHEA-sulfate— this hormone is made largely in the adrenal glands with a small percentage of it produced by the ovaries and in brain. Mildly elevated levels are often found in women with PCOS. Very elevated levels of DHEA-sulfate are consistent with something called congenital adrenal hyperplasia (CAH).

17-hydroxyprogesterone—Although this blood test isn’t required for the diagnosis of PCOS it is often helpful to distinguish PCOS from an abnormality known as congenital adrenal hyperplasia (CAH). In CAH the abnormal production of androgens (male hormones) comes from the adrenal gland rather than the ovaries.

Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, thyroid stimulating hormone (TSH) and Prolactin—These other hormones are often drawn in order to seek out other explanations and causes of menstrual disorders.

Why is it important to know if I have PCOS?

The diagnosis of PCOS is important for several reasons:

• First, it helps to rule out other abnormalities of menstrual disturbances such as premature ovarian failure, abnormal thyroid function, a hormone secreting pituitary tumor, an adrenal tumor and other causes of menstrual abnormalities. These other conditions require different medical or surgical management.
• Second, the diagnosis of PCOS often guides your treatment which depends on whether or not the goal is to improve the menstrual outcome or to achieve a pregnancy.
• Third, women with PCOS should be periodically checked to see if they are developing any signs of endometrial hyperplasia or cancer. This risk can be sharply reduced with appropriate management.
• Fourth, women with PCOS should be periodically screened for the metabolic abnormalities that often coexist. This includes insulin-resistance, type 2 diabetes, hyperlipidemia and hypercholesterolemia. Knowledge of these metabolic abnormalities are important in order to avoid the long-term complications of PCOS which include the development of diabetes, hypertension and heart disease.

How is polycystic ovarian syndrome treated?

The treatment of PCOS can be divided into short-term goals and long-term goals. The short-term goals include control of the menstrual abnormalities––amenorrhea (lack of periods altogether), irregular menses, and heavy or painful periods. The long-term goals include avoiding endometrial hyperplasia and endometrial (uterine) cancer, diabetes, abnormal lipids, and other complications associated with worsening obesity––hypertension and cardiovascular disease. Another long-term goal includes the control of excessive hair growth and acne.

Please note that some of the short-term goals–such as menstrual control and control of excessive hair growth and acne—also overlap with the long-term goals.

Treating the short-term goals:

The short-term goals will vary for women who are trying to become pregnant and those women who are not trying to become pregnant.

For women who are attempting to achieve a pregnancy the goal is to accomplish regular ovulation. Most women ovulate approximately 13 times a year (think of the lunar calendar). However, women with PCOS include those that do not ovulate at all (anovulatory) as well as those with infrequent and unpredictable ovulation (oligoovulatory).

This goal—to ovulate–is often achieved with medications. These medications include oral agents such as letrozole or clomiphene as well as injectables such as human menopausal gonadotropins (hMG), human recombinant FSH (hrFSH) and human chorionic gonadotropins (hCG). These ovulation-inducing agents are generally administered by Reproductive Endocrinologists who specialize in Fertility. By increasing the likelihood and frequency of ovulation, women with PCOS are often able to achieve a pregnancy. Since these medications are expensive and carry some risks they are generally used only when women are actively attempting to conceive.

For women who are not attempting to achieve a pregnancy the goals are very different.

1. Regulation of periods. This can be achieved with either oral contraceptives (which contain a combination of estrogen and a progestin) or with hormone containing IUDs (which do not contain estrogens). Women who utilize oral contraceptives can take them in such a fashion as to have light cyclic and predictable periods or, if they wish, they can also take them in such a fashion that they have no periods at all. Women who utilize a hormone-containing IUD (such as Mirena, Liletta, Skyla or Kyleena) will typically have no periods.
2. Reduce unwanted and worsening hair growth. It must be emphasized that the medications used will not reverse unwanted hair, but will slow the rate of progression of future hair growth. These goals are often achievable with medications known as “testosterone blockers,” such as spironolactone. Additionally, oral contraceptive pills, when appropriate, can also be helpful with reducing future hair growth. Existing unwanted hair is typically treated cosmetically with techniques such as laser hair removal.
3. Reduce/eliminate Cystic acne. This can often be accomplished by using a variety of medications which include estrogen-containing oral contraceptives (when desired), testosterone blockers, and other medications including antibiotics and topical retinoids, such as Tretinoin.

Treating Long-Term Goals

1. Reducing the long-term metabolic complications of PCOS In women with PCOS who are also overweight or have abnormal glucose metabolism (insulin-resistance) it is very important to address lifestyle changes in order to prevent the long-term complications which include hypertension, diabetes, sleep apnea, cardiovascular disease and strokes. Clinical studies have shown that reducing 5-7% of body weight can improve menstrual function and decrease the risks of cardiovascular disease and diabetes. If insulin resistance is already present the use of such medications as metformin can also be helpful in preventing the development of diabetes.
2. Mood changes. Numerous authors have suggested that there is a relationship between depression, anxiety and PCOS. Oftentimes, addressing the symptoms and other health related issues associated with PCOS can reduce many of these symptoms.

Conclusions

Polycystic ovarian syndrome (PCOS) is a common gynecologic and metabolic disorder that affects a large number of women–some estimate as many as 20%–around the globe. Most clinicians agree that the syndrome consists of a combination of irregular (which can be light or heavy) or absent menses, in combination of signs of excessive male hormone production (hyperandrogenism), as well as ultrasound evidence of polycystic ovaries. The treatment of PCOS should include management of both short-term and long-term goals. It is also very important that women with PCOS are screened for type 2 diabetes, abnormal lipids (cholesterol and triglycerides), and hypertension since these metabolic and other abnormalities often accompany PCOS and they place affected women at increased risk for heart disease, strokes and chronic renal disease. Finally, PCOS places women at an increased risk for endometrial (uterine) cancer. All of these issues can be addressed with a combination of lifestyle changes and—in some instances—medications, so that PCOS-affected women can lead a normal life.