The NP spends time talking with Beth about her concerns, completes a physical exam, and suggests diagnostic testing. Ultimately, the results of the interview, exam, and laboratory studies confirm Beth’s suspicions. She has PCOS.

After discussing the diagnosis with Beth and her parents, the NP begins to develop a plan of care with Beth. The NP knows that the main concerns in caring for Beth are twofold. The first is to better control her irregular periods, and the second is to develop a plan to avoid the potential long-term effects of PCOS.

A complex disorder

First described by U.S. gynecologist Irving S. Stein and gynecologist/obstetrician Michael L. Leventhal in 1935, PCOS was formerly known as Stein-Leventhal Syndrome, and was considered a benign gynecologic disorder characterized by the formation of multiple ovarian cysts. Since then, much has been learned about PCOS, leading to a growing awareness that PCOS is actually a complex, multisystem disorder with potentially serious long-term implications. Because there is significant variation in presenting signs and symptoms, PCOS is often misdiagnosed or goes unrecognized in women and can often lead to serious long-term conditions.¹ Nurses and especially NPs can play a key role in identifying patients with PCOS, helping to manage symptoms, prevent complications, and provide education and support.

More common than you think

PCOS may be the most common endocrine disorder in women of reproductive age, with estimates from 4% to 12% of women between ages 14 and 50 being affected.² Approximately 625,000 new cases are diagnosed each year with patients presenting a widely diverse group of symptoms, most of which relate to excessive androgen release (hyperandrogenism), higher than normal luteinizing hormone (LH) levels, and irregular or absent menses.² PCOS is thought to be the underlying problem associated with approximately 75% of cases of infertility related to anovulation and more than 90% of patients with hirsutism.⁶ In addition to reproductive problems, approximately 30% to 40% of those women and adolescents diagnosed with PCOS show evidence of impaired glucose tolerance or type-2 diabetes.³ Among obese women with PCOS, 25% to 40% are likely to develop noninsulin-dependent diabetes by age 50. Patients with PCOS also have increased risk for impaired lipid metabolism, premature cardiovascular disease, and a threefold risk of developing endometrial or breast cancer from prolonged exposure to excessive amounts of unopposed estrogen, i.e., estrogen without the balancing effects of progesterone.³

Disturbing symptoms

Typically, PCOS has a subtle onset and can occur at any age. Symptoms, usually first noticed during adolescence, are often erratic. Frequently, patients complain of menstrual irregularities and symptoms of hyperandrogen release, such as excessive growth of body hair, weight gain, and acne. However, diagnosis and treatment can easily be delayed or ignored until adulthood with clinicians attributing symptoms to normal adolescent development. Different healthcare providers may treat signs and symptoms as they appear with no one recognizing the overriding pattern of PCOS.

Initially, complaints of menstrual irregularities often bring women to their healthcare provider. Patients frequently report that their previously regular periods have become less frequent, much heavier, or persist longer. Many report complete cessation of periods over time. Patients may describe increased growth and pigmentation of body hair, especially on the upper lip, chin, chest, lower abdomen, and inner thighs requiring hair removal treatments, such as waxing, electrolysis, tweezing, or shaving. A velvety, hyperpigmentation of the skin, acanthosis nigricans, may also be present, especially in the axilla, at the nape of the neck, under the breasts, and in the groin. Some patients also report masculinization of their facial features and frontal hair loss, as in male-pattern baldness. Many complain of weight gain, especially around the abdomen and trunk. As patients try to cope with self-image issues related to these symptoms, they may become psychologically troubled. Recent studies report a fourfold increased risk of depressive disorders in women with PCOS along with frequent reports of fatigue, poor sleep, appetite changes, and loss of interest in normal activities.⁷

A multisystem situation

Although the exact mechanism of PCOS development remains unknown, a disturbance between three interrelated systems — the hypothalamic-pituitary-gonadal systems — cause metabolic and reproductive effects.

In the normal ovulating woman, the anterior pituitary gland stimulates release of gonadotropic hormones, follicle-stimulating hormone (FSH), and luteinizing hormone(LH). FSH is primarily responsible for stimulating the ovaries to secrete estrogen, and LH is primarily responsible for stimulating progesterone production. Balance of the two hormones is, in part, regulated by a feedback mechanism. For example, elevated estrogen levels in the blood inhibit FSH secretion, but promote LH secretion.

During menstruation, midcycle fluctuations of LH, estrogen, and androgens occur as the follicle is released from the ovary. In the patient with PCOS, an abnormally high ratio of LH to FSH exists with no hormonal fluctuations, and the growth of the follicle is abnormally delayed or completely stops. Instead, an abnormal steady state of high levels of estrogen, androgen, and LH exists. Constant stimulation of the endometrium and breast tissue by LH and simultaneous decreased levels of FSH lead to amenorrhea or oligomenorrhea, resulting in anovulation and infertility. In addition, multiple benign ovarian cysts may develop when the follicles do not mature. Continuous production of estrogen without the opposing production of progesterone leads to thickening of the endometrium, and over time, may lead to development of endometrial cancer.³ While the exact mechanism of the pathophysiology is unclear, it appears that with the loss of the normal midcycle surge of balancing hormones, androgens are continuously produced, particularly testosterone, causing an abnormal production of body hair, possible male-pattern baldness, overproduction of sebum resulting in acne, voice changes, central obesity, and in rare instances, enlargement of the clitoris.⁹

In addition, the current view of PCOS suggests an underlying metabolic abnormality of insulin-resistance, causing difficulty with the movement of glucose into body cells. Since glucose cannot effectively move into the tissue, the pancreas compensates by releasing more insulin, causing hyperinsulinemia, a potential precursor to the development of type-2 diabetes mellitus. An elevated LH, along with excess insulin secretion, cause the ovary to increase production of androgens (in response to the insulin), which, in turn, results in arrested development of healthy follicle and anovulation.⁵ Further release of dehydroepiandrosterone sulfate (DHEA-S) by the adrenal glands leads to enhanced androgenic effects, such as obesity, hypercholesterolemia, and hypertension. The combined effects of insulin resistance, obesity, high cholesterol, and elevated blood pressure can lead to significant associated cardiovascular disease, especially as women enter their mid to late 30s.¹⁰

Since the majority of women with PCOS do not ovulate, achieving a successful pregnancy is often difficult. Clomifene citrate (Clomid), an oral estrogen antagonist that raises FSH and induces growth of the follicle in most women, can be used. Women with PCOS who do conceive are at a 30% to 50% higher risk for miscarriage in the first trimester¹ and gestational diabetes. Women with a history of diabetes related to PCOS fall into the high-risk category during pregnancy.⁶ The addition of metformin (Fortamet) throughout the pregnancy can reduce the risk of early miscarriage.¹

Pieces of the PCOS puzzle

Three different methods — history and physical exam, serum testing and sometimes, pelvic ultrasound — usually determine the diagnosis.

History and physical exam: A history and physical exam set the wheels in motion for diagnosing women with PCOS. Nurses can assist with finding these individuals by identifying at-risk patients through a thorough personal and family history of gynecological disorders. Of particular interest is any history of problems in conceiving or sustaining a pregnancy in either the mother or sister of the patient, since an estimated 40% of mothers and 50% of sisters of patients with PCOS have some form of the syndrome. Included in the history should be the onset, pattern, and frequency of menstrual periods and information on contraceptive methods. If the patient has conceived, the number and length of each pregnancy, any miscarriages or abortions, and number of sexual partners should also be included. The nurse should also ask about weight gain, especially in the upper body; abnormal hair growth or loss; and skin or voice changes. The social history includes dietary habits, exercise patterns, and levels of daily stress that may contribute to amenorrhea. A urine and/or serum pregnancy test is necessary to rule out pregnancy as a cause of amenorrhea.

Along with the usual physical assessment and exam, close inspection of the skin and patterns of hair growth provides essential clues. Pelvic and bimanual exam are necessary to check for masses of the uterus or ovaries.

Pelvic ultrasound: Transvaginal and transabdominal ultrasound can measure endometrial thickness and determine the size and appearance of the ovaries, including the presence of any masses or cysts.³ Not all patients with PCOS have cystic ovaries so the use of pelvic ultrasound is somewhat controversial. The ultrasound cannot confirm the diagnosis of PCOS. In addition, about 22% of normally menstruating women have cystic ovaries, but are not affected by PCOS.⁶

Laboratory Testing: The patient should be prepared for laboratory testing that includes a pregnancy test for women of childbearing age, baseline serum levels of FSH and LH, estrogen and androgen levels, total and free testosterone, and DHEA-S levels. In addition, serum chemistries are drawn for fasting serum glucose, fasting and postprandial insulin levels, and a lipid profile to establish a baseline and identify other treatable problems associated with PCOS, such as hyperlipidemia. Other lab tests such as prolactin levels and thyroid-stimulating hormone levels help rule out other endocrine disorders that may mimic PCOS symptoms.⁴

A treatable problem

Treatment goals usually relate to controlling symptoms associated with the excessive production of androgens, improving reproductive function, and minimizing future risk for cardiovascular disease, diabetes, and breast and/or endometrial cancer.

Treatment of PCOS varies depending on the severity of symptoms and the women’s desire to conceive. Typically, women with irregular or absent menses who do not wish to conceive immediately are treated with combined low-dose oral contraceptives (OCs) containing both estrogen and progesterone. OCs help to reduce androgen excretion and restore regular menstrual cycles that allow regular shedding of the endometrium. In addition, some OCs may also reduce some of the androgenic effects, such as acne. The clinician may add antiandrogen therapy to reduce the effects of hyperandrogenism, especially hirsutism.¹⁰ Spironolactone (Aldactazide) and finasteride (Proscar) are two drugs with antiandrogenic properties. However, patients need to realize that it may take up to six months on these drugs before they see any improvement.

Likewise, discontinuing either the OCs or antiandrogen drugs may result in a relapse. Women who are either not candidates for OCs or do not respond to standard treatment may be placed on cyclic oral progesterone to allow for regular shedding of the endometrium, thus preventing endometrial hyperplasia. Patients who wish to conceive may be prescribed a fertility drug such as clomiphene citrate (Clomid) or menotropins (Pergonal). If these therapies don’t lead to pregnancy, the patient may choose to undergo specific surgery, such as wedge resection of the ovaries or laparoscopic laser surgery of the ovary to improve the frequency and regularity of ovulation.

Recent studies indicate that use of metformin (Glucophage), an insulin-sensitizing agent, may also be helpful in treating patients with PCOS, regardless of whether diabetes is evident or not.¹⁰ While Food and Drug Administration approval is still pending for use of metformin in the treatment of PCOS, it is believed to be beneficial for several reasons. Most notably, metformin reduces circulating androgens. It also reduces hyperinsulinemia by increasing peripheral muscle glucose uptake, and reducing glucose release from the liver. This results in weight loss in some obese patients; it may also improve ovulatory response to fertility drugs.^1,10 By decreasing symptoms related to overproduction of androgens and restoring ovulation, metformin may also reduce cardiovascular and diabetes risk factors and help restore a positive self-image.^1,10

Patients need to be prepared for possible adverse effects of metformin, which often occur during the early stages of treatment, but usually subside thereafter. To reduce some of the adverse effects, metformin is usually started at 500 mg/day for two weeks and gradually increased to 1 gm twice a day. Adverse effects include gastrointestinal symptoms, such as nausea, diarrhea, anorexia, and abdominal discomfort. Treatment with metformin may take up to three months before antiandrogenic effects appear.

Control of excessive hair growth can be accomplished with mechanical methods such as tweezing and shaving or with use of laser or electrolysis treatments. Eflornithine HCL (Vaniqa) has also been found to slow the growth of excess facial hair.¹

Support and education

Nurses also have a critical role in providing support and education about PCOS, its treatment, and prevention of long-term health problems. Although PCOS is a chronic illness, patients can manage it with lifestyle changes and medications. Some areas for teaching and counseling for patients with PCOS include —

• Medication doses, uses, adverse effects, and interactions.
• Strategies for preventing long-term problems caused by PCOS, including the importance of treatment regimens; reporting symptom changes; and maintaining routine preventive screenings, such as annual physical exams, regular blood pressure screenings, and monitoring of laboratory values.
• Lifestyle changes that include daily weight control, including a high-fiber diet that is low in fat, refined carbohydrates, and calories (1,000 to 1,200 calories/day) for weight reduction and management of hyperinsulinemia.
• Moderate but sustained exercise. Exercise not only assists with weight loss, but also raises high-density lipids (HDL), which is helpful in reducing the incidence of cardiovascular disease. Some studies suggest that in obese women, even a moderate weight loss of 13 kg to 15 kg may help in reducing peripheral estrogen production, improving insulin resistance, and reducing ovarian androgen production.
• Methods for hair removal. Laser treatments or electrolysis can permanently remove hair, although the cost may be prohibitive for some patients because it is not generally covered by medical insurance. Nonpermanent methods of hair removal include depilatory creams, waxing, plucking, and shaving, but they do not lend themselves to facial hair removal. One approach may be a short-course of electrolysis for removal of obvious facial and mustache area hair combined with over-the-counter depilatory cream for less obvious sites.
• Oral or topical antibiotics for acne treatment, along with OCs that specifically control acne (e.g., OrthoTriCyclen). Patients with resistant acne may need referral to a dermatologist.
• Counseling recommendations for couples/partners with concerns about infertility.

A solution for Beth

During that first visit, the NP learned that Beth had her first menstrual period at age 13, with fairly regular menses until recently. Over the last eight months, Beth had gained 20 pounds and found hair growth on her face, arms, and abdomen. She has also had some facial and shoulder acne treated by a dermatologist with topical antibiotics. Beth told the NP that her two older sisters also had irregular periods and facial hair.

Laboratory tests confirmed that Beth was not pregnant. Her androgen levels were mildly elevated. Oral glucose tolerance was normal. Insulin levels were also normal. Cholesterol levels revealed low HDL and mildly elevated LDL levels; triglycerides were normal. A pelvic ultrasound showed no signs of ovarian cysts or any other GYN problem.

After the diagnosis of PCOS was established, Beth started on oral contraceptives with a nonandrogenic progestin used to treat menstrual irregularities, also useful in treating acne. Metformin was not recommended at this time since her insulin and glucose levels were normal. However, the NP recommended that Beth have the lab tests repeated at least annually, as well as after a substantial weight gain or pregnancy.

The nurse practitioner met with Beth several times to discuss the symptoms and treatment options. They reviewed a plan for a 1,200-calorie diet and moderate daily exercise to slowly reduce her weight. The goal was to lose approximately 2 lb to 3 lb a month for the next four months. Since Beth was still in high school, she joined the intramural volleyball team to increase her daily exercise and to help manage weight loss.

Recommendations for treating the hirsutism included information about options available for permanent and semipermanent hair removal. After a discussion with her parents, Beth chose electrolysis to remove the facial and lip hair. She also opted to try a course of spironolactone for a period of six months. A follow-up appointment with the NP was scheduled in six months to evaluate the effects of therapy. The NP also encouraged Beth to call if she had any questions about her symptoms, medications, or treatments. Recommendations for further information and support were also made available to Beth. Online resources include Polycystic Ovarian Syndrome Association at www.pcosupport.org, PCOS.NET at www.pcos.net, and www.youngwomenshealth.org/pcosinfo.html.