Polycystic Ovary Syndrome: Facts and Treatments

by Walter Futterweit, MD, FACP

What is Polycystic Ovary Syndrome?

Polycystic ovary syndrome (PCOS) is the most common endocrine problem in women, affecting 5 to 7.5 percent of reproductive-aged women, yet it is only in the past decade that ideas about its causes and treatment are being pieced together. Although what causes it remains unclear, the main cornerstones of diagnosis and treatment are well established. While the syndrome has a wide spectrum of clinical presentations, in most cases it causes the ovaries to become enlarged with multiple small cysts. This condition eventually results in the secretion of excess androgens, mostly testosterone. The endocrine abnormality is marked by erratic menstrual cycles and infertility. The excess androgens also exert effects on the hair follicles and sweat gland unit of the skin (pilosebaceous unit), often leading to acne, excessive facial and body hair growth (hirsutism), and thinning of scalp hair (alopecia).

Many of the latter features are variable, and the characteristics of the classical symptom complex described above may occur either singly or in combination. For example, menstrual abnormalities may occur early at puberty and vary over time, while other women present with persistent acne even in their 30s in association with abnormal menstrual cycles. Obesity is present in about 50 to 60 percent of patients and there is a frequent tendency for fat to take on a central distribution (apple-shaped, rather than pear-shaped obesity). The resulting increase in the so-called waist-to-hip ratio (WHR) is a marker that often indicates the potential for metabolic or cardiovascular complications.

Characteristics of PCOS

The cause of polycystic ovary syndrome is still unclear, but several characteristics are now firmly established:

  • There is a strong genetic component to the syndrome and several cases of PCOS in the same family is commonplace.
  • There is an association between PCOS and increased blood levels of insulin (hyperinsulinemia), which is amplified by obesity. The increased blood levels of insulin cause a number of effects, some of which may lead to glucose intolerance or frank type 2 diabetes mellitus.
  • Normal ovarian function relies on the selection of a follicle in the ovary, which is largely a response to an appropriate signal from substances called follicle-stimulating hormone and luteinizing hormone-two hormones secreted by the pituitary gland. In PCOS, there's a hypersecretion of pituitary luteinizing hormone (LH) and the high levels of both LH and insulin appear to stimulate the ovary to produce excessive male hormones (androgens). Obesity magnifies this effect.
  • Intrinsic enzymatic abnormalities have been demonstrated in the ovaries as well as the adrenal glands, which are a significant factor in the syndrome.
  • The higher centers in the brain may be implicated in the characteristics of the disease. Both hypothalamic and pituitary dysfunction have been reported (e.g., Abnormal hypothalamic stimulation to the pituitary gland leads to increased pulses of luteinizing hormone).

The frequent presence of insulin resistance (IR) may be at times selective, (i.e., lean or normal-weight women who tend to have more regular cycles tend to be less likely to have insulin resistance) so that not all patients demonstrate the major consequences of hyperinsulinemia.

Diagnosis of Polycystic Ovary Syndrome

It should be noted that polycystic ovary syndrome is a syndrome, not a disease, and authorities have differed on the definition of the entity. The classic findings that most doctors agree on include the following:

  • Chronic anovulation (erratic menses).
  • Signs of male hormone excess alone or in combination with biochemical evidence of androgen excess.
  • The exclusion of other problems that can mimic the syndrome. Syndromes and diseases that can be easily confused with PCOS include adult onset adrenocortical hyperplasia, or what is often referred to as nonclassical congenital adrenal hyperplasia (NCCAH), excess prolactin states, thyroid disorders, and others.

Although insulin resistance is often present in most women with PCOS, it's not a distinct requirement for diagnosis of the syndrome. In PCOS, pelvic ultrasound scanning frequently reveals multiple follicular cysts present under the outer cortex of normal-sized or enlarged ovaries. However, even this finding is considered to be nonspecific.

Certain laboratory tests are useful in diagnosing and tracking the progression of the syndrome. These include testing the levels of the following:

  • Serum testosterone (T)
  • Serum biologically free testosterone (the active fraction of testosterone)
  • Serum luteinizing hormone and follicle stimulating hormone (Often there is an increased ratio of LH/FSH)
  • Serum dehydroepiandrosterone sulfate (DHEAS) (An androgen that is a precursor to testosterone; this is useful in evaluation of the significance of the role of the adrenal cortex in the syndrome)
  • Serum 17-hydroxyprogesterone as an initial screen for NCCAH; fasting plasma insulin and a blood glucose level
  • Serum prolactin

It has been reported that about 10 to 20 percent of PCOS patients have high levels of prolactin. This should be recognized early, since management of women with high prolactin levels may differ from that of other women with the syndrome. Once PCOS is considered, lipid studies including total cholesterol and its sub-fractions (HDL, LDL), as well as serum triglycerides should be obtained. A number of authorities also recommend that patients take a two-hour glucose tolerance test to assess the extent of insulin dysregulation. An ultrasound of the pelvis is also useful to find changes relating to treatment as well as potential complications, such as uterine changes and the development of benign ovarian growths (usually dermoid cysts, with an incidence ranging from 5 to 15 percent).

Potential Complications of PCOS

Menstrual dysfunction and associated infertility, as well as skin and scalp manifestations are often what brings patients to their physicians. However, it's the potential of metabolic and cardiovascular complications that pose the greatest risk to those with PCOS. There's a wealth of data indicating that hyperinsulinism and the associated insulin resistance (often accompanied by an increase in the waist-to-hip ratio) not only allows for androgen excess, but also may lead to a higher incidence of type 2 diabetes mellitus and the possibility of cardiovascular events later in life. Additionally, a small but convincing series of reports suggest that hypertension and premature calcifications in the carotid arteries may already be present at a relatively early stage in life (30s and 40s).

Obesity and PCOS
There is no question that there is a significant incidence of abnormal glucose tolerance in 40 percent of obese patients with PCOS and 10 percent in normal-weight women with the syndrome. Some of these patients may already be diabetic (approximately 10 percent of the obese women with PCOS). With time, the incidence increases. The associated risk factors such as lipid abnormalities, high triglyceride levels, and increased clotting factors may predispose these patients to coronary heart disease. Studies assessing the long-term complications of these symptoms are currently in progress. Whether newer treatments for PCOS and lifestyle modifications may mitigate these risks remains to be seen.

There are data also indicating an increase in uterine hyperplasia (an increased number of normal uterine cells) and neoplasms (cancerous cells) in women with PCOS. Data for an increased breast cancer risk is as yet unproven. Another well recognized complication of PCOS is the relatively high miscarriage rate, possibly through an adverse effect of luteinizing hormone on maturation of the oocyte (egg). The long-term effect of ovulation induction treatments on the development of ovarian carcinoma will require years of more prolonged study.

Treatment of PCOS

Medical treatment of PCOS depends on a number of factors, mostly related to the patient's main complaint(s) of

  • erratic menstrual cycles and/or infertility
  • concern over the skin manifestations of the syndrome (acne, hirsutism, and alopecia)

Weight reduction employing a low-carbohydrate diet and changes in lifestyle, including exercise, are essential components of all treatments. Weight reduction alone (five to seven percent of the total body weight) is associated with reduced androgen levels, reduced hyperinsulinism, and frequently, improvement in menstrual cycles and skin appearance.

Many patients will require medical therapy to control symptoms. Often a low dose of combined oral contraceptive is effective. It is ideal to avoid an oral contraceptive pill containing androgenic progesterone, such as levonorgestrel, as this may exacerbate some symptoms. For this reason, new third-generation contraceptives, which have a lesser male hormone effect of the progestin in the formulation, are preferred. Other drugs used to manage the symptoms of PCOS include: anti-androgens such as spironolactone and cyproterone acetate (which is not FDA approved in the USA), glucocorticoids, and drugs that improve insulin sensitivity, such as metformin.

How Do You Treat the Skin Manifestations of this Syndrome?

In women who are plagued by cystic acne, the first line of treatment appears to be a combination of oral contraceptives and spironolactone. The use of contraceptives alone is often effective in mild to moderate acne cases, but combined treatment of these two agents is useful and effective in the vast majority of patients.

Similarly, hirsutism rarely improves with OCP (oral contraceptive pill) therapy alone and the combination of OCP and spironolactone is often effective in reducing and lightening unwanted hair. Glucocorticoids, like prednisone, often have no effect on excessive hair growth and in some patients may worsen the condition. In addition, the tendency to increased insulin resistance makes this choice less appealing. Women with alopecia have some improvement in reducing hair loss with combination therapy of OCP and up to 150 to 200 milligrams a day of spironolactone in divided doses. Outside of the USA, cyproterone acetate in combination with OCP is equally or, in some instances, more effective in the treatment of hirsutism and male pattern baldness than combined treatment of OCP and spironolactone.

Women with abnormal menstrual cycles, and mild skin manifestations may be treated with oral contraceptives alone. In obese women, although there are indications for OCP use, infertility or increasing weight gain may be an indication for using insulin sensitizing therapy. Metformin, in a dosage of 1,500 to 2,000 milligrams a day in divided doses with meals, and given in small increments, frequently improves menstrual cycles and tends to enhance weight reduction.

There are several reports indicating that metformin, used in combination with clomiphene citrate, leads to a higher rate of ovulation. The mechanism is not clear, but it appears that insulin sensitizers, including a new non-FDA drug D-chiro-inositol (which is almost ready for Phase III of FDA trial) may be useful in treatment of women with PCOS, and perhaps reduce some of the long-term unfavorable effects of the syndrome. However, the use of insulin sensitizer drugs should not be viewed as a reflex response of treatment for all women with polycystic ovaries. More studies are underway to define the role that such agents should play in treatment strategies.


PCOS is a common endocrine disorder that should be considered in any woman with irregular menses, infertility, and skin manifestations of male hormone excess. The potential of metabolic complications such as diabetes mellitus and lipid disorders, as well as the long-term risk of cardiovascular disease, makes it imperative that a diagnosis be established. It is possible to effectively treat many of the skin manifestations of the syndrome as well as the menstrual dysfunction in most women with PCOS. Moreover, with the advent of insulin sensitizer therapy, some of the other complications may also be modified. Further studies are needed however, to fully appreciate the role of these newer treatments.

Dr. Walter Futterweit is Clinical Professor of Medicine of the Division of Endocrinology of the Mount Sinai School of Medicine, New York, NY. He is also Chief of the Endocrine Clinic at the Mount Sinai Medical Center, and Attending in Medicine. He is board certified in Internal Medicine and Endocrinology and Metabolism. His main interest has been the study of polycystic ovary syndrome (PCOS) for the last 25 years, and has written extensively in this area and wrote the first textbook on the subject, "Polycystic Ovarian Disease", in 1984. His extensive practice which comprises mostly of patients with PCOS has allowed him the means to study insulin dynamics as well as recent genetic studies of the syndrome. As an international expert in the field of PCOS, he is invited to speak at many meetings, and still maintain his busy practice and teaching committments at the Mount Sinai Medical Center.

Copyright © Walter Futterweit. Permission to republish granted to Pregnancy.org, LLC.