Polycystic Ovarian Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) has lately become a hot topic of discussion. In the past two years, no other condition in the field of reproductive medicine has been more popular in both the lay-press and Internet. It was once rarely recognized by people apart from those affected, infertile women who received treatment from Reproductive Endocrinologists. Now, individuals are learning about the condition on their own more than many physicians know. Almost daily, I am asked questions by a patient regarding what they have read on the web, heard from a friend, or learned from a women’s magazine. It has been fascinating to observe how the educational waves of the mass media have empowered patients with knowledge to recognize and seek treatment for this important disorder.

What is PCOS?
Polycystic ovary syndrome affects about 4% of all reproductive-aged women in the United States, or approximately 5 million women. It is the most common hormone disorder in reproductive-aged women, making it the leading cause of female infertility. It also is one of the most treatable forms of infertility, yet patients often suffer from it too long because it is undiagnosed or mistreated. Many patients are surprised to learn that there are effective treatments available for virtually every symptom associated with the condition.

PCOS was first described by Drs. Stein and Leventhal in 1935 as a disease characterized by amenorrhea (no menses), hirsutism (i.e., excessive body hair growth), obesity, and the presence of polycystic ovaries. The condition was subsequently referred to as “polycystic ovary syndrome” since the polycystic ovary was a distinguishing characteristic. It could also have easily been called the “amenorrhea, hirsutism syndrome” since these are the clinically important features, but PCOS became the standard.

The polycystic ovary contains many small cysts, 2 – 6 mm in diameter. In the past, it was diagnosed during surgery when the ovary could be revealed. Now, an ultrasound examination can show the polycystic nature of an ovary. Since using ultrasound, polycystic ovaries have been observed in 25% of normal women. Therefore, it is important to distinguish the findings of polycystic ovaries and PCOS. Polycystic ovaries are a common characteristic in patients with PCOS, but they do not define the condition. For example, a running nose is a common symptom of a cold, but does not mean that a person with a running nose has a cold. Other conditions can cause one’s nose to run, such as allergies, sniffing pepper, crying, etc. An individual with a cold can be met with a multitude of symptoms. Women with PCOS can also be met with a variety of symptoms. Polycystic ovaries are merely one finding of the polycystic ovary syndrome.

PCOS is a clinical diagnosis based on irregular ovulation and signs of excessive androgen (male-type hormones) effect. It is called a syndrome because it constitutes a constellation of clinical symptoms. The diagnosis cannot be determined by a single symptom or clinical test alone. Individuals will have an extreme variety of manifestations. The spectrum can range from a thin woman with occasionally skipped menses to an overweight woman with no menses who suffers from hirsutism, acne, diabetes, balding, skin pigmentation, and the inability to lose weight no matter how well she diets.

Symptoms of PCOS
Irregular menses are a hallmark for an individual who does not ovulate regularly. Since the lack of ovulation is a main feature of the syndrome, many patients will suffer from infertility. Due to the heterogeneity of the syndrome, guidelines have been made to diagnose the condition. In the United States, we diagnose the condition when a patient has irregular menses and symptoms of hyperandrogenemia, like hirsutism, acne and/or oily skin.

What causes PCOS?
The syndrome is a result of a functional hormonal disorder that throws off normal ovarian function. It is best defined as an imbalance of hormones that control the ovary’s ability to mature and release an egg. Normally, the pituitary gland in the center of the brain releases follicle stimulating hormone (FSH), which travels to the ovaries through the blood stream and tells them to mature or “grow” an egg. An ovary complies by stimulating a follicle’s growth. A follicle is a cyst containing an egg and many “nursing” granulosa cells. The follicle starts as a small cyst less than 2 – 6 mm in diameter. As it matures, the follicle fills with fluid until it measures over 20 mm in diameter. This takes approximately 14 days. This time frame is known as the follicular phase of the menstrual cycle. Once mature, the follicle sends a signal back to the brain indicating it is ready for ovulation. Then, the pituitary gland sends out a pulse of luteinizing hormone (LH), telling the ovary to release or ovulate the egg. The follicle ruptures (i.e., the cyst pops), releasing the egg to the surface of the ovary where the fallopian tube should pick it up. PCOS is present when the hormonal signals are not carried through. As a result, follicles do not grow and release the egg, but instead stay small 2 – 6 mm in diameter each month. Over time, these small follicles accumulate resulting in an ovary packed with multiple small cysts.

It is not well understood why the ovary fails to respond to the FSH. It is believed that there are elevated “resistance factors” that obstruct the ovaries ability to function normally. Some of these resistance factors include the androgens and insulin-like growth factors. These hormones raise the threshold at which the ovary will respond to FSH. If the FSH does not reach that threshold, the follicles become delayed in the early part of growth. The ovary remains in a steady state of no ovulation, which is the hallmark of PCOS.

These resistance factors are evident in other areas of the body. Androgens in the skin cause hirsutism or male-type distribution of hair growth on the face, chest, and abdomen. Increased activity in the oil gland of the hair follicle may also cause oily skin and/or acne.

Some degree of insulin resistance is seen in nearly 70% of patients with PCOS. Insulin is a hormone released into the blood stream by the pancreas. It works to propel blood glucose into cells. Insulin resistance means that more insulin is required to achieve the same result as a person without PCOS. Patients with type II diabetes have the same condition. Indeed, PCOS patients are at an increased risk of developing type II diabetes. The reason for this insulin resistance is the subject of intense research. Currently, it is believed to be related to an inherent defect within the cells signaling mechanism to allow glucose to come into the cell. Due to the cellular resistance, PCOS patients have elevated levels of insulin and/or insulin-like growth factors, which can then negatively affect the ovary. In addition, insulin encourages growth or body mass/weight retention. Because of this, PCOS patients have trouble losing weight regardless of how much they diet and exercise.

Commonly known stimulants to both elevated androgen levels and insulin resistance include excess body weight and obesity. Since insulin resistance causes elevated insulin levels that promote further weight gain, an overweight individual becomes stuck in a vicious cycle. The more weight she gains, the worse the condition becomes. All the symptoms of PCOS, including hirsutism, anovulation, and difficulty losing weight, become more difficult to reverse. Consequently, excess weight can exacerbate PCOS and, in some individuals, can even be the sole cause of the condition.

How is PCOS treated?
The most important aspect in treating PCOS is first determining what you desire to treat. Since it is a multifaceted disorder, a number of different treatments are available depending on the symptom you wish to improve. This is similar to over-the-counter medicines for the common cold. The drugstores must stock an entire shelf with the variations of available cold remedies. Some are aimed at treating a specific symptom, while others comprise combination medications to cover a multitude of symptoms. The medicinal treatments for PCOS can be directed at a specific symptom or combined to treat several complaints. But first, the therapeutic goals must be decided by the patient and physician.

Generally, the therapeutic options are directed at one or more of the following: 1) Restoring regular menstrual cycles, 2) Minimizing symptoms of excess hair growth or oily skin, 3) Restoring normal fertility, 4) Weight reduction.

Oral contraceptive pills (OCPs) are the most effective method to correct # 1 and improve # 2. Naturally, they are counterproductive for both # 3 and # 4. OCPs contain estrogen and progesterone, which are the hormones produced by the ovary governing the normal menstrual cycle. Furthermore, estrogen acts as an antagonist to the androgen effects seen in PCOS.

There are several options available to effectively treat # 2. Besides OCPs, a common anti-androgen is the diuretic, spironolactone. Others include finasteride, flutamide, and cyproterone acetate. Since hair growth and turnover occur over a long time, the results of decreasing hirsutism with these agents sometimes takes 3 – 6 months to show results.

Returning the FSH effect to a predominant role on the ovary is required to restoring fertility (# 3). This can be achieved by either reducing the “resistance factors” or merely increasing the FSH until it reaches the elevated threshold needed for follicles to grow. The most effective agents for reducing insulin resistance are insulin sensitizing ones. These include metformin, rosiglitazone, and D-chiroinositol (not yet commercially available). These agents are very efficacious for treating # 4. By reducing insulin levels, the weight promoting stimulus is reduced, and the patient finds it easier to lose weight through diet modification and exercise.

The cells in the center of the ovary produce both the androgens and insulin-like growth factors. Therefore, suppressive and destructive treatments are available to reduce these cells. Drs. Stein and Leventhal described the “ovarian wedge resection” as a treatment for PCOS. This surgery removed a section of the ovary in an attempt to debulk the resistance-factor producing cells of the ovary. Currently, this has been replaced by laparoscopic ovarian drilling. Because it is invasive and could potentially cause adhesion which could compromise fertility, surgery is considered a last resort for the treatment of PCOS. The drug, Lupron, is the most effective suppressor of ovarian activity. It is also viewed as a measure of last resort since it is very expensive and associated with many side-effects.