Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome – PCOS

by Sandy Goodman, M.D.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder occurring in women 10 to 45 years old.  Approximately 5–10% of women (3.5 to 5 million women) in the United States are affected.  Females with PCOS often experience irregular, heavy or absent menstral bleeding, facial, abdominal or lower back hair growth (hirsutism), hair loss from the top of the head, acne, obesity and infertility.  Irregular menstral bleeding can manifest by menstral cycles that are longer than 35 days apart or by bleeding episodes shorter than 21 days apart.  Both patterns suggest a disruption in the ovulation (egg development and release) process.

Etiology

The cause of PCOS has not been completely determined although genetics likely play a role.  A family history of diabetes, obesity, irregular menses or hirsutism is common.  The majority of patients have a higher than normal amount of luteinizing hormone (LH) in relationship to follicle stimulating

hormone (FSH) produced by the pituitary gland (a small gland located at the base of the brain).  Additionally, numerous studies have linked hyperinsulinemia (high blood levels of the hormone insulin) with PCOS.  Elevation in the amount of LH produced decreases the chances that an egg will develop and be released.  The ovary continues to produce estrogen as well as an excess male hormone including testosterone.  Continual estrogen production stimulates growth of the uterine (endometrial) lining.  In females who ovulate regularly and do not have PCOS, estrogen is counter balanced by progesterone which is released after ovulation.  Progesterone stabilizes the endometrial lining.  In PCOS women, without ovulation, progesterone is  not produced.  The resultant unopposed estrogen causes the development of  a thickened and irregular endometrial lining that can result in abnormal bleeding, hemorrhage, or pre-cancerous changes which can eventually development into uterine cancer.  Excessive production of male hormones further disrupts the menstral cycle and causes acne as well as male pattern hair growth in areas including the face, chest, abdomen and lower back with hair loss in the front and top of the head.  Additionally, up to 80% of women with PCOS have some degree of insulin resistance which results in the release of higher amounts on insulin into the blood than normal.  Insulin stimulates ovarian as well as adrenal androgen secretion, further worsening hair abnormalities and acne.   Excessive levels of androgens and insulin can affect metabolism and weight.  Ultimately, insulin resistance can develop into actual diabetes.  Women with PCOS often experience problems with weight control, frequently observing that they gain weight easily but experience significant difficulty losing weight.

Unfortunately, obesity has significant adverse effects on PCOS by worsening insulin resistance and glucose intolerance and increasing the amount of active male hormone.  Numerous studies have demonstrated that even a 10% weight loss can have a significant, positive effect on the PCOS metabolic and hormone profile including improvement in insulin resistance, decline in male hormone levels and improvement in menstral cycle regulation.  Women with untreated PCOS are at increased risk for developing anemia, (low red blood cell count), endometrial hyperplasia/cancer, hypertension (high blood pressure) diabetes, lipid (cholesterol) abnormalities and cardiovascular (heart) disease.  PCOS is a common cause of infertility and is also associated with pregnancy complications.  First trimester (weeks 4 to 11) pregnancy loss rates have been noted to be as high as 30-40% for women with PCOS, in comparison to the 10-15% rate reported in the general population.  Additionally, PCOS women are at increased risk for developing diabetes and hypertension during their pregnancy.

Diagnosis

Both the symptoms as well as the long-term health consequences of PCOS can be altered through a combination of lifestyle changes and medical management.  All preteens, teenagers and woman with irregular menses in combination with either abnormal hair growth or acne should see their physician and request an evaluation for PCOS.   Children may present as early as age 10 with hair growth or the disorder may not manifest until the 20’s or 30’s, often in association with weight gain.  A physical exam should include assessment of height, weight with BMI (body mass index) calculation and blood pressure.  Signs of excess hair, male pattern baldness, obesity and acanthosis nigricans (darkening of the skin behind the neck, under the arms, and on the inner thighs which indicates insulin resistance) may be visualized.   Appropriate laboratory testing includes measurement of fasting glucose (blood sugar), insulin, FSH, LH, DHEAS, total testosterone, TSH, prolactin and lipid profile.

Treatment

Therapy for PCOS is determined by your goals in terms of desire for pregnancy or treatment of abnormal hair growth, acne, or obesity.   Educating yourself about your health and actively participating in your care is essential for getting your PCOS under control.  Regulation of the menstral cycle is essential in avoiding long-term complications of heavy or prolonged uterine bleeding and endometrial hyperplasia/cancer.  The cornerstone of therapy involves lifestyle changes incorporating dietary modifications and exercise.  As noted, weight reduction of even 10% has been demonstrated to improve insulin resistance, reduce blood levels of male hormones, and improve lipid abnormalities.  A high fiber, reduced carbohydrate diet has been beneficial to many PCOS women in achieving weight loss.  Counseling with a nutritionist who has an interest in treating PCOS is recommended.  Exercise has been demonstrated to improve insulin sensitivity as well as weight loss.  After consultation with your physician, begin slowly but unless contraindicated, your goal should be cardiovascular aerobic exercise in which your heart rate is accelerated to between 120-140 beats per minute for 45 to 60 minutes daily.  Unfortunately there is no magic pill currently available to cure PCOS but you can do your part to gain control through diet and daily exercise.

Insulin sensitizing agents have become an increasingly common element in the treatment regimen of PCOS.  Metformin (glucophage) has been used to treat diabetes mellitus for more than 40 years and is currently the most widely used sugar lowering agent for women with PCOS.  Metformin indirectly improves insulin resistance by decreasing the production of glucose (sugar) by the liver.  In comparison with diet alone, metformin added to a low calorie, reduced carbohydrate diet has been demonstrated to result in greater reduction in body weight, abdominal fat, hirsutism, insulin resistance and androgen levels.  Gastrointestinal side effects including bloating, nausea and diarrhea are the most frequent cause of drug discontinuation.  Starting at a low dose with slow increases over time will minimize these side effects.   Also, foods/drinks with high carbohydrate or simple sugar content worsen GI side effects.  Evaluate your diet before giving up on the metformin/glucophage therapy.  Some women tolerate the extended release formula better so ask your physician about that option if you can not tolerate the regular formula.  You should not take metformin if you have kidney, liver or severe heart disease.  In addition, the medication should be temporarily discontinued before surgery, procedures requiring intravenous iodinated contrast media (such as hysterosalpingogram, IVP or CAT scan) and during a severe febrile (high fever) or dehydrating illness.   The combination of weight loss and use of metformin may allow women who are not ovulating, but desire pregnancy,

to become ovulatory and conceive.  Specific medications are available to stimulate ovulation for PCOS women who wish to conceive, including clomiphene citrate, letrozole (both taken orally) and gonadotropins (FSH or FSH/LH hormones) that are given by injections under the skin surface. Surgical treatment of PCOS by a method known as ovarian diathermy or drilling has been described in the medical literature.   The procedure involves the use of a cautery needle to puncture the ovarian capsule during laparoscopy with the goal of reducing the amount of ovarian androgen producing tissue in order to improve the frequency of ovulation.

Birth control pills (OCP’s) have been the mainstay of treatment for girls and women with PCOS who are not pursuing fertility.  OCP’s increase the release of sex hormone binding globulin which binds up the free/active male hormone, thereby lowering the testosterone level, decrease LH release which also decreases testosterone production and regulates the menstral cycle.   Although OCP’s have a role in the treatment of hirsutism, more than 60% of hirsute patients do not find OCP’s alone to be sufficiently effective in treating existing hair growth.  In addition to androgen (male hormone) suppression from OCP’s, androgen blockers can be added to the treatment regimen for women struggling with hirsutism that does not adequately respond to OCPs.  The principle medication used for this purpose in the United States is aldactone/spironolactone.  Antiandrogenic medications are potential teratogens (are harmful to the unborn fetus/baby) and should be used in combination with reliable contraceptives, optimally with OCP’s and are not appropriate for use by women who are sexually active without the use of reliable contraception or who are desiring pregnancy.

Mechanical reduction of unwanted hair by tweezing, shaving, depilatories, electrolysis or laser hair removal are effective.  Eflornithine hydrochloride (Vaniqua) has been available for use on facial hair.  Vaniqua is applied to the skin and works by inhibiting an enzyme that effects hair growth and reverses the terminalization of the hairs being produced, making the facial hair lighter and less course.  Skin irritation, cost and need for daily application are the most common reasons for a high discontinuation rate.   Other than laser therapy, all mechanical methods are temporary and are best used in conjunction with androgen lowering medications.  Laser hair removal is the most affective method but even with that treatment, control of the hormones with medication is important to allow the technique to be maximally effective.

PCOS remains a difficult and frustrating disorder with variable presenting signs and symptoms.  Diagnosis is essential to allow for appropriate education and intervention.  Menstral irregularities, hirsutism and infertility should be addressed.  Long-term health disorders including diabetes mellitus, endometrial cancer, hyperlipidemia and cardiovascular disease may be mitigated or avoided by lifestyle modifications in combination with appropriate medications.

Resources:

American College of Obstetricians and Gynecologists (ACOG)   www.acog.com

American Society for Reproductive Medicine (ASRM) www.asrm.org

American Association of Clinical Endocrinology (AACE) www.aace.org

Polycystic Ovarian Syndrome Society (PCOS) www.pcosupport.org

This brochure has been written by Sandy B. Goodman, M.D. and is the sole property of The Reproductive Medicine Group, Tampa, FL.