Polycystic Ovarian Syndrome (PCOS)

Polycystic ovarian syndrome, or Stein-Leventhal Syndrome, is the most common endocrine disorder in women of reproductive age, afflicting between 5-10% of premenopausal women (almost 20% of women at The Fertility Center). It was identified almost 80 years ago and still today we are puzzled regarding its cause. Since PCOS includes a spectrum of disorders rather than a single, discrete disease, women may experience a variety of signs and symptoms. Invariably some women are misdiagnosed with PCOS and others fail to be diagnosed.

Multiple features such as ovulation dysfunction, elevated androgen production, an abnormal ratio of pituitary gonadotropins (LH and FSH), insulin resistance and polycystic ovaries can characterize the disorder. Recently a PCOS consensus workshop recommended that a diagnosis of PCOS should be based upon the findings of at least 2 of the following 3 criteria: (1) oligo- and or anovulation (infrequent or absence of ovulation, respectively), (2) polycystic ovaries on ultrasound, and (3) hyperandrogenism (elevated levels of androgens or “male hormones”).

Insulin Resistance

Insulin facilitates the utilization of glucose as a source of energy for the cells in the body. In some patients the cellular response to circulating insulin is inadequate; therefore insulin synthesis is increased to compensate for the deficiency in glucose metabolism. Through the years this over production may exhaust the pancreas and lead to diabetes. Additionally, the inefficient use and absorption of glucose together with high levels of insulin causes an increased storage of fat, hence the increased obesity seen in many women with PCOS. However, a large proportion of thin women with PCOS can exhibit a degree of insulin resistance. The variation in insulin resistance is dependent upon age, body mass index (BMI), body fat distribution and family history of diabetes.

The effect of PCOS on fertility

In order to completely appreciate PCOS and its heterogeneous presentation, it is important to understand the dynamics of follicular growth within the ovary. The follicle which houses the oocyte, or egg, is composed of layers of cells which support the growth of the oocyte through the follicular phase of the menstrual cycle. One cell type, the theca-interstitial cells, responds to LH to produce androgens. Androgens are then converted to estrogens by the granulosa cells in response to FSH. The ovarian response to the gonadotropins is modulated by both ovarian derived and peripheral factors. One such regulator, insulin, augments androgen production by the theca cells and also promotes the proliferation of these cells within the ovary. Although peripheral tissues exhibit resistance to insulin (thus stimulating overproduction), the ovary, however, has an increased sensitivity to insulin and when combined with elevated LH produces the high androgen levels and polycystic ovaries observed in some women. The conversion to estrogens is not as efficient in the PCOS patient therefore the estrogen concentration per follicle is lower than normal. However, the abundance of small follicles together produces an elevated estrogen level. As the development of the oocytes within the ovarian follicles is subject to even the slightest alteration of hormonal environment, the quality of the oocyte(s) and thus resulting embryo(s) can be compromised. This may influence the predisposition of the PCOS patient to experience early pregnancy loss.

The effect of PCOS on long term health

For many years PCOS was dismissed as a cosmetic problem, one interfering with the reproductive processes only. PCOS is now known to have long-term ramifications on women’s health including an increased risk of diabetes, hypertension and cardiovascular disease, due to the impact of androgens on the lipid profile. Lifestyle modifications both in diet and exercise can not only lead to an improved quality of life but also reduce the risks of the long-term sequelae of PCOS. Moreover, the infrequency of ovulatory and consequently menstrual cycles causes an increased frequency of endometrial growth from simple changes (hyperplasia) to cancer.

Treatment

Effective treatment of PCOS addresses specific and general symptoms that patient’s may experience. These include excessive hair growth, irregular periods, infertility and insulin resistance status. It should be emphasized that while many therapies target specific symptoms of PCOS, they usually do not address the underlying cause. These therapies include:

Oral contraceptives: Many physicians prescribe oral contraceptives (birth control pills) to regulate menstrual periods in women with PCOS. Oral contraceptives contain both estrogen and progesterone that with appropriate use can guarantee menstruation monthly. The regular shedding of the uterine lining can reduce the risk of developing endometrial cancer. Provera (pure progesterone) may also be employed to regulate the menstrual cycle.

Oral contraceptives reduce the concentration of active circulating male hormone therefore also very effective against excess hair growth. Also, certain anti-androgenic agents such as spironolactone are effective in preventing new hair growth and reducing acne.

Weight loss: The relationship between obesity and insulin resistance makes weight loss an essential part of any treatment plan. Dietary restriction and exercise are both key to success. In many cases weight-reduction will not only improve insulin resistance will also help regulate menstrual cycles, reduce male hormone levels, lower the risk of heart disease and restore fertility. Weight loss will also reduce the excess of female hormones produced in the fat tissue and consequently the risk for uterine cancer.

Use of insulin sensitizers: Rather than focusing on relieving specific symptoms, newer treatments concentrate on the biochemical abnormalities (abnormal insulin levels) of the PCOS patient. Insulin sensitizers such as Glucophage are used to reduce the levels of circulating insulin and thus the level of insulin at the ovary. This class of agents enhances insulin action at its target site, thus causing a decrease in circulating insulin levels. This approach diminishes many of the symptoms associated with excess testosterone. Within two to three months many have reported a decrease in hair loss, diminished facial and body hair growth, regular menstruation, weight loss and normal fertility.

Options for assistance in conception

Although not common practice today, surgical ovarian drilling may be employed to reduce the amount of ovarian derived androgens. This procedure involves destruction of some of the theca tissue. Because of the tendency for formation of significant scar tissue following this procedure, a more conventional methodology is preferred.

Clomid (ovulatory drug) is typically the first line of intervention with >75% success with ovulation and a 40% singleton take home baby rate, however failure to respond to Clomid necessitates the consideration of insulin resistance and circulating androgen levels. Clomid resistance can be approached by co-administering insulin sensitizers such as Glucophage and/or addition of low levels of Dexamethasone, which will reduce androgen production from the adrenal gland. For patients resistant to this treatment, gonadotropin stimulation (Gonal-F, etc.) may be prescribed. This option, however, is not without risks and challenges.

The PCOS Healthy Lifestyles Program at the Healthplex (click here for brochure) is a comprehensive health and fitness program designed by Dr. El-Roeiy for patients with PCOS. For more information on this specific program please contact Shannon Donovan-Halter, MA for more information at (610) 447-2727.