Diagnoses: Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a set of clinical findings and not a disease itself. There are many abnormalities which may collectively produce the findings which characterize PCOS.

Originally the syndrome was termed Stein-Leventhal Syndrome after the investigators who published papers on the clinical findings in 1935.

With the advent and availability of ultrasound, the term polycystic ovaries became more common. This name refers to the characteristic ultrasound appearance of the ovaries. Due to abnormal follicular development, the ovaries have multiple small follicles usually measuring < 5mm dispersed around the periphery of the ovary in a pattern often referred to as a "string of pearls".

Symptoms

This ultrasound appearance alone does not mean you have polycystic ovarian syndrome. The clinical findings which comprise the syndrome include:

• Polycystic appearing ovaries
• Hyperandrogenism (increased testosterone)
  • Hirsuitism (male pattern hair growth such as facial hair)
• Hyperinsulinemia (increased insulin secretion)
  • Insulin Resistance
• Abnormal uterine bleeding
  • oligo-ovulation (irregular ovulation)
  • amenorrhea (absence of uterine bleeding)
• Infertility
• Obesity
  • Not clear if this is a cause or an effect
  • Not all patients with PCOS are overweight
• Laboratory findings
  • Elevated LH
    • Reversal of the LH/FSH ratio as LH becomes higher than FSH throughout the menstrual cycle
  • Elevated:
    • Testosterone
    • DHEAS - dehydroepiandrostenendione sulfate (adrenal gland)
    • 17-OHP - 17 hydroxyprogesterone
    • estrone - a form of estrogen
• Skin abnormalities
  • Acanthosis Nigricans (darkened scaly like rash commonly on patients neck)
  • Skin tags
• Possible long term effects
  • Increased risk of cardiovascular disease from increased lipids
  • Increased risk of endometrial cancer
  • Increased risk of breast abnormalities
  • Increased risk of developing type II diabetes

Many of these findings are inter-related in a complex system of cause and effect.

Again, these are all clinical findings and are not necessarily related to the cause of the syndrome. The exact etiology of the syndrome is unknown. There are several theories as to the underlying cause or causes.

Causes

Obesity

Obesity alone can not account for all of the findings of PCOS, however, it does worsen the degree of insulin resistance. Weight-loss can often lead to a reversal of the clinical manifestations.

Patients have been able to reduce the effects of the elevated androgens as well as resume normal ovulation with weight loss alone.

Insulin Resistance

Resistance to the effects of insulin produces an increase in insulin production and circulating levels (hyperinsulinemia) and can lead to skin disorders and elevated androgens (hyperandogenism).

The elevated androgens like DHEAS and testosterone can lead to male pattern hair growth and acne. The androgens cause an increase in free estrogen (by reducing sex hormone binding globulin which binds both estrogens and androgens) which results in a decrease in follicle stimulating hormone (FSH).

The follicles are initially stimulated to grow but do not have enough FSH to continue to grow. This results in the polycystic appearance of the ovaries. Because follicles are not developing normally women will not ovulate normally and will not have normal menses.

Other names which have been used to refer to this syndrome include Insulin Resistance Syndrome and Hyperestrogenic Anovulation. It is most likely this syndrome does not represent one disease process but several disease processes which result in a similar clinical presentation.

PCOS and Infertility

PCOS is associated with infertility. The most likely cause of infertility is anovulation or lack of ovulation. Ovulation can be induced by gonadotropins or by correction of insulin resistance.

Some investigators have reported a lower than normal fertilization rate during in vitro fertilization in women with PCOS. There may also be a higher miscarriage rate in women with PCOS also, but this has been debated.

Women with PCOS are at increase risk of ovarian hyperstimulation (OHSS) when taking gonadotropins.

A history of PCOS or irregular menses should be reported to your physician before taking any fertility medications.

Diagnosis

While the appearance of multiple small follicles on ultrasound can be suggestive of PCOS it is insufficient evidence that someone has PCOS. The same is true for anovulation.

Multiple findings taken together can be used to classify someone as having polycystic ovarian syndrome but this is not a diagnosis of a disease. As mentioned earlier, PCOS is a set of clinical findings associated with an underlying abnormality so it is technically incorrect to say someone is diagnosed with PCOS.

There has been much attention given to the documentation of insulin resistance in patients with PCOS over the last few years. Newer findings are demonstrating insulin resistance can be detected before the appearance of other clinical findings of PCOS. Patients with PCOS findings, and in some cases patients with only anovulation, are being tested for insulin resistance.

Our current testing includes a 12-hour fast followed by a 75g glucola challenge (sugar solution commonly used to test for gestational diabetes in pregnancy).

Blood work is drawn before the glucola (fasting) and at one and two hours after the glucola. The blood is evaluated for insulin and glucose. Normally the fasting blood work will demonstrate a normal range glucose and a low insulin level.

After a dose of sugar the blood glucose level increases as well as an increase in secreted insulin. Abnormal values can indicate insulin resistance, and in some cases, diabetes.

Insulin resistance is defined by a 1 hour post glucola insulin level greater than 23. Values below 23 are considered normal. These values may be different at different clinics or labs.

Glucose values over 200 at any point may indicate diabetes and further testing may be needed to confirm the diagnosis of diabetes. Often patients with diabetes will have elevated fasting glucose levels which again is evidence for diabetes.

Some investigators have reported a fasting glucose to insulin ratio is accurate enough to predict insulin resistance. Using this approach any fasting glucose to insulin ratio 4.5 or less is indicative of insulin resistance.

Treatment

Treatment of polycystic ovarian syndrome has two distinct directions. Patients not desiring pregnancy at the time of treatment will be managed differently than patients actively seeking pregnancy.

For patients desiring pregnancy there are several approaches. The more modern approach in younger patients involves the use of insulin sensitizing agents. These medications allow for a better response to the insulin in the circulation. Very frequently the manifestations of PCOS will demonstrate resolution. Many women begin to ovulate and have a return of normal menses. Many clinics have been successful at achieving pregnancy by using insulin sensitizing agents alone. These medications are discontinued after achieving pregnancy.

In some patients, ovulation induction using Clomid, and subsequently gonadotropins, may be required. Because of the risk of ovarian hyperstimulation and multiple gestation associated with COH, this approach is used as a secondary treatment.

Patients not seeking pregnancy are generally treated with oral contraceptive pills which allow the endometrium to cycle normally (reducing the risks of endometrial cancer and hyperplasia), reduce acne, and reduce hair growth.

Additional therapy may be required to decrease the androgenic effects of PCOS. Such agents include finasteride (Proscar, Propecia), reglan, and spironolactone. Current trends to treat these patients with insulin sensitizing agents are gaining more popularity.

Insulin sensitizing agents include metformin (Glucophage) and Avandia (rosiglitazone). Metformin is known to cause gastrointestinal upset in a large percentage of patients and should be started slowly and tapered to a therapeutic dose. Avandia seems to be better tolerated and is our primary choice of treatment at this time.