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”.
Ultrasound demonstrating a polycystic appearing ovary
This ultrasound appearance alone does not mean the patient has polycystic ovarian syndrome. Other clinical findings which comprise the syndrome include:
- Polycystic appearing ovaries
- Hyperandrogenism . Increased:
- DHEAS – dehydroepiandrostenendione sulfate (adrenal gland)
- Hirsutism (male pattern hair growth such as facial hair)
- Hyperinsulinemia (increased insulin secretion) and Insulin Resistance
- Abnormal uterine bleeding oligo-ovulation (irregular ovulation)
- Amenorrhea (absence of uterine bleeding)
- Infertility Obesity. Not all patients with PCOS are overweight.
- Laboratory findings
- Elevated LH and reversal of the LH/FSH ratio as LH becomes higher than FSH throughout the menstrual cycle
- Estrogen and testosterone elevation
- 17-OHP – 17 hydroxyprogesterone
- Skin abnormalities
- Acanthosis Nigricans (darkened scaly like rash commonly on patients neck)
- Skin tags – small outgrowths of skin
- 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
- Increased risk of heart disease
Many of these findings are inter-related in a complex system of cause and effect. The exact etiology of the syndrome is commonly considered “unknown”. There are several theories as to the underlying cause or causes.
Obesity alone cannot 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.
Resistance to the effects of insulin produces an increase in insulin production and circulating levels of insulin (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 FSH. The follicles are initially stimulated to grow but do not have enough FSH to continue to grow and are also affected by the elevated LH. The disturbance in follicular growth 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 physiologic abnormalities which result in a similar clinical presentation. Recently there has been growing acceptance that insulin resistance is the primary abnormality associated with PCOS. PCOS seems to worsen with weight gain, high carbohydrate diets, age, and genetic influences. The medical literature has not been able to agree on a common etiology, however, there is a lack of consensus in insulin assays, methods of testing, and interpretation of studies of varying quality. Overall methods to reduce insulin resistance such as weight loss, diet modification, and metformin have been shown to improve insulin resistance and the clinical effects of PCOS. California IVF physicians use dietary modification as a primary means to improve pregnancy and reduce the risk of miscarriage.
PCOS is associated with infertility. The most likely cause of infertility is anovulation or lack of ovulation. Ovulation can be induced by oral medications such as clomid, letrozole (Femara), or gonadotropins. Ovulation can also be restored for many women with PCOS by correcting of insulin resistance through diet, exercise and Metformin. Some investigators have reported a lower than normal fertilization rate during IVF in women with PCOS and is likely do to a reduction in egg quality. There may also be a higher miscarriage rate in women with PCOS also, but this has been debated.
Women with PCOS are at increased risk of ovarian hyperstimulation when taking gonadotropins. A history of PCOS and/or irregular menses should be reported to your physician before taking any fertility medications. Fortunately, recent advances in how injectable fertility medications are used with patients at risk for ovarian hyperstimulation have led to a minimal risk of ovarian hyperstimulation and improved rates of pregnancy.
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. 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. 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, however, due to a lack of consensus and standardized testing, there isn’t a single test that is used clinically to determine if a patient is insulin resistant. In research settings, it is likely that giving fixed doses of glucose and monitoring insulin responses over time is a useful method for documenting a person’s insulin status.
Glucose values over 200 at any point may indicate diabetes and further testing may be needed to confirm the diagnosis of diabetes. Hemoglobin A1C levels are also used frequently to determine if there is an elevated risk of fetal malformations due to chronically elevated glucose levels. Often times patients with diabetes will have elevated fasting glucose levels which again is evidence for diabetes. Diabetes can occur when the pancreas does not make sufficient levels of insulin to regulate blood sugar. Diabetes may be successfully managed in a similar manner to insulin resistance described above.
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 dietary modification, exercise, and occasionally insulin sensitizing agents. These medications allow for a better response to the insulin in the circulation. Very frequently, the manifestations of PCOS will improve or resolve. Many women begin to ovulate and have a return of normal menses as insulin resistance improves. Many patients have been successful at achieving pregnancy by using diet alone. When insulin sensitizing medications are used, they are usually discontinued after achieving pregnancy. In some patients, ovulation induction using Clomid, and ocassionally gonadotropins, may be required. Because of the risk of ovarian hyperstimulation and multiple gestation associated with ovarian stimulation, 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. Medications that can be used to treat androgen excess of PCOS include finasteride (Proscar, Propecia), reglan, and spironolactone. Current trends to treat these patients with insulin sensitizing agents are gaining more popularity. Diet and exercise are usually the most effective approach for all aspects of PCOS.
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 seemed to be better tolerated though after several warnings, Avandia is not commonly used any longer.
See more information on hyperinsulinemia and insulin resistance here.
Dietary modification and exercise can be a very effective treatment for PCOS and insulin resistance. Click Here.