Polycystic Ovary Syndrome – More Than a Fertility Problem
By Patricia D. Maningat, MD, MSC, FPCP, DPSEM
Polycystic Ovary Syndrome (PCOS) is the most common hormonal disorder in reproductive-age women affecting between 4-12 percent in this age group. The name of this disorder is quite misleading because not all women with multiple cysts in the ovaries have PCOS.
What is PCOS?
By definition, a syndrome is composed of a group of signs and symptoms that identify patients with a particular disorder. For PCOS, although the cause is not yet clearly established, the key features include androgen (male hormone), excess insulin resistance (ineffective insulin function and high insulin levels) and abnormal gonadotropin (reproductive hormone) dynamics. It is recognized as an important metabolic and reproductive disorder with increased risk for developing type 2 diabetes mellitus. PCOS impacts several aspects of a woman’s life including physical appearance, fertility, morbidity and quality of life.
During a normal menstrual cycle, the hormonal milieu causes the stimulation and development of a dominant follicle in the ovary, followed by ovulation in mid-cycle, and then by either pregnancy when the egg is fertilized by a sperm; or menstruation when no fertilization occurs. It is thought that in PCOS patients, the ovaries are extra-sensitive to the stimulus of reproductive hormones, producing more androgens compared to estrogen.
Because of this imbalance, several follicles are stimulated with no dominant follicle, leading to failure of ovulation. The presence of several follicles on the surface of the ovaries lead to the term multiple cysts or “polycystic ovaries.” High levels of androgens lead to development of acne and hirsutism (malepattern of hair distribution) and can induce or worsen insulin resistance. Conversely, high insulin levels and insulin resistance exacerbate androgen production and lead to metabolic abnormalities.
How can you tell it’s PCOS?
There is no definite test to diagnose PCOS and our best guide to date is based on recommendations given by three expert committees (National Institutes of Health (NIH), Rotterdam group, and the Androgen Excess Society).
The NIH requires the presence of menstrual abnormalities and hyperandrogenism clinically or by laboratory tests, and does not require the presence of polycystic ovaries. The Rotterdam criteria requires two out of three signs be present: hyperandrogenism, menstrual abnormalities, and/or polycystic ovaries. The Androgen Excess Society requires hyperandrogenism plus either abnormal menses or polycystic ovaries. Although lacking a consensus, they share a common focus on PCOS as an ovarian disorder. And because PCOS may share similar signs and symptoms with other conditions such as adrenal gland disorders, ovarian tumors, steroid excess from Cushing’s syndrome, and hormonal imbalances due to thyroid or pituitary problems, all three expert groups advocate that other causes must be ruled out before making a diagnosis of PCOS.
The signs and symptoms of PCOS vary among patients but women consult for three primary reasons: menstrual irregularities, infertility, and symptoms associated with androgen excess (hirsutism and acne). The diagnosis is often made based on clinical history and physical examination while laboratory exams are done to exclude other causes mentioned above. The initial onset of PCOS is around puberty and progresses slowly during the reproductive years. Therefore if a woman develops these signs and symptoms rapidly, another cause should be sought.
Having menstrual periods that are few and far between (longer than 35 days, or fewer than eight cycles/year) may be clues to having anovulatory cycles. However, some women with PCOS may have normal menses. Signs of androgen excess may be absent in some women, but when present, include acne and hirsutism or sometimes malepattern baldness (androgenic alopecia).
Hirsutism is the presence of coarse hair in a male pattern of distribution (sideburn area, chin, upper lip, around the nipples, chest, lower abdominal midline and inner thigh). There is still some debate about whether the diagnosis of high androgens should be based on laboratory values of circulating androgens (free or total testosterone) or on clinical signs and symptoms alone. Problems with using laboratory values as the sole basis for diagnosing hyperandrogenism are that the normal range of testosterone in different populations has not been adequately validated; the available testing methods are imperfect, and some women with PCOS have testosterone levels within normal. Thus, this area is still ripe for research.
Some women may have enlarged ovaries discovered on ultrasound. Ovaries are considered polycystic when eight or more follicles per ovary are seen and follicles are less than 10mm in diameter. These ultrasound findings are present in majority of women with PCOS, but also in up to 25 percent of normal women which is why not all experts agree that this should be a criterion for diagnosis of PCOS.
Some PCOS women have normal menstrual cycles, but typically PCOS patients have their first period at a normal age, then gradually develop irregular periods, often leading to absence of menstruation. PCOS is the leading cause of infertility caused by anovulation.
The laboratory abnormalities in reproductive hormones include elevated levels of testosterone and LH (luteinizing hormone) or an increased LH to FSH (follicle stimulating hormone) ratio. However, because LH and FSH are secreted in a pulsatile manner throughout the day, a single determination of the level of these hormones may not be accurate, thus they are not used in the diagnosis of PCOS. Your doctor may request for other more specific tests to exclude some of the disorders mentioned above.
What links PCOS, diabetes, and other disorders?
Why discuss PCOS here? Is it related to diabetes and other medical conditions? There is an intricate and complex relationship between PCOS and metabolic conditions like diabetes, insulin resistance and abnormal lipid profiles. Many women with PCOS are obese, more commonly with central obesity having a waist to hip ratio more than 0.85. high androgen levels are thought to drive the development of central obesity.
Independent of obesity, women with PCOS may have insulin resistance accompanied by high insulin levels, glucose intolerance (tested by checking blood sugars during fasting and two hours after drinking a sugar drink) and abnormal lipid levels (low HDL and high triglycerides).
The evidence linking PCOS with cardiovascular disease directly is still lacking, but because both insulin resistance and abnormal lipids increase the risk for cardiovascular disease, it is plausible that PCOS increases cardiovascular risk as well. Therefore it is important that women with PCOS be screened for glucose and lipid abnormalities.
Persistent anovulation and irregular menses lead to unopposed estrogen stimulation to the uterus, which increases the risk for endometrial hyperplasia (thickening), and endometrial cancer. Women with PCOS have three times the risk of developing endometrial cancer. Obesity is also associated with increased risks for these disorders.
How is PCOS treated?
Because the primary cause of PCOS is still unknown, treatment is directed at the symptoms of the patient. There is no therapy that addresses all the aspects of the syndrome, and treatment decisions are dependent on whether or not fertility is desired because many treatments to address hirsutism, obesity, and acne may be contraindicated in pregnancy.
Treatment approaches for chronic anovulation for those desirous of pregnancy should start with screening both male and female partners for causes of infertility before starting medical therapy. Medication options include clomiphene citrate, an antiestrogen that results in ovulation induction in women with PCOS. Those who do not respond to clomiphene may be given secondline agents of injectable gonadotropins or reproductive hormones. Surgery (e.g. ovarian wedge resection, drilling) is offered when medical therapy is not successful.
For those who do not want to get pregnant, the goal is to maintain a normal endometrium to decrease the risk of endometrial cancer. Combination oral contraceptives, medroxyprogesterone or leuprolide can be used with the goal of normalizing menstrual bleeding.
For those with high androgens, combination oral contraceptives are used to treat hirsutism and acne. Other agents that can be used are spironolactone, flutamide, and finasteride. A new treatment for unwanted facial hair is eflornithine hydrochloride cream, which is applied on the affected areas and has been shown to decrease hair growth. Mechanical and cosmetic means such as shaving, waxing, electrolysis, and laser hair removal are effective means for controlling the appearance of unwanted hair.
It is also important to address the metabolic disturbances associated with PCOS, especially insulin resistance, diabetes, and abnormal lipid profiles. Lifestyle changes including diet, exercise and weight reduction for those who are overweight or obese are cornerstones of management, whether or not drug therapy is started.
Smoking cessation and reduction of alcohol intake are important to decrease the risk for cardiovascular disease. Metformin is the medication of choice and reduces insulin resistance and has been shown to decrease the risk of developing diabetes in the general population, although there is no data on PCOS in particular. It has also been shown to reduce levels of androgens in circulation. Many studies have shown that metformin restores menstrual cyclicity and may increase ovulation rates. However, it has not consistently been shown to increase live birth rates.
Each of these therapies has their own risks and benefits and should be assessed and discussed by the patient and physician. Treatment goals must be agreed upon as well. With more research and better understanding of this syndrome, we may one day be able to target therapies toward the specific cause.