We know that excess male hormones, secreted mostly by the ovaries, cause PCOS symptoms. Every woman has both female and male hormones, and her health and well-being depend on the balance between them. When the level of male hormones exceeds the normal range, a woman begins to have physical and emotional problems. This happens in PCOS, but PCOS is not the only condition that causes such problems. Several other hormonal conditions can easily be confused with PCOS because of similar symptoms.
Obviously, when misdiagnosed or not diagnosed for some other reason, your PCOS continues more or less untreated. The best way to avoid such a situation is by finding the right doctor and having the right diagnostic tests performed.
If you think you may have PCOS, you need to find a knowledgeable physician whose diagnosis you can trust. A PCOS diagnosis is not easy to make, particularly for a doctor who does not specialize in hormonal medicine. As you already know, PCOS is a collection of signs and symptoms, any one of which could be caused by other disorders. For example, the symptom that most strongly suggests the presence of PCOS is irregular periods— something that can also be caused by frequent intense exercise without any associated serious medical disorder at all. There is no single symptom that can pinpoint PCOS as the cause of your health problems.
Because of the potentially serious diabetic and cardiovascular risks of most women with PCOS, you need to find a clinical endocrinologist to make a diagnosis. Although skin and hair problems may be making your life difficult, preventing the possible development of diabetes and heart disease later in life is what makes finding a diagnosis urgent. Finding a remedy for your irregular periods or for your skin and hair problems is not the same as finding a remedy for PCOS, because irregular periods and skin and hair problems are a result of PCOS, not its cause. When you discover and treat the underlying cause, annoying symptoms can almost miraculously diminish and sometimes can disappear altogether.
Ask your regular or family doctor or other health professionals for a referral to an endocrinologist. You can research an endocrinologist’s background and credentials by calling the referral service of a university-affiliated hospital or organizations involved with endocrinology (see Resources). The Internet may have information on an endocrinologist’s position and papers published in the PCOS field. If you happen to know of a local endocrinologist who is knowledgeable about PCOS, ask your doctor to refer you to that physician.
Almost inevitably, the endocrinologist will require blood samples for lab tests. It’s best to have your blood drawn in the morning, because later in the day your hormone levels are likely to be increasingly variable, due to normal hormonal changes. You need to fast for ten to twelve hours before giving a sample, so giving a blood sample in the morning means that you can sleep during much of the fasting period.
Try to schedule your appointment during days four through nine of your menstrual cycle (day one is the first day of bleeding) if your menstrual cycle is not highly irregular.
The endocrinologist usually begins with detailed questioning about your current symptoms and medical history, including prior illnesses and treatments, and your family history. At this time, or prior to the appointment, give the doctor any earlier lab test results or other data that you have from visits to physicians, even if you think they may not be relevant. In particular, bring any actual films of ultrasound or other imaging examinations that you have had done previously for whatever reason.
In the physical examination that follows, the doctor evaluates the extent of any acne and abnormal hair growth, the degree and distribution of hair loss, and the textures of your scalp hair and skin. The distribution and degree of excessive hair are usually plotted on a diagram, which is later used for reference in evaluating the results of treatment. The doctor also checks for the presence of acanthosis nigricans and skin tags, particularly on your neck. Some consultants use digital photography as a baseline assessment of the degree of skin changes of the acne, hirsutism, and scalp hair loss.
Routine measurements include those of your height, weight, blood pressure, and the ratio of your abdominal circumference to your hip circumference. The latter, also called the hip-to-waist ratio, is an important measure of the central distribution of body fat. Centrally distributed or visceral fat is associated with more health problems than an all-over generalized fat distribution, though this is not to underplay the risks of any kind of excess weight. A hip-to-waist ratio greater than 0.8 indicates a central distribution of fat associated with insulin resistance and probable development of the insulin resistance syndrome. Measurements of 0.80 to 0.845 may represent a potential risk for diabetes and other complications. When the hip-to-waist ratio exceeds 0.85, it should be regarded as a health warning.
Jessica had always been a happy child, excelling in both sports and schoolwork. When her periods began, she had very painful cramps. To help with the pain, her doctor put her on an oral contraceptive. As months passed, Jessica had worsening depressive moods. The four doctors her parents took her to all suggested antidepressants. None questioned whether she might be reacting to the contraceptive pill. Her parents took her off the pill, and Jessica’s depression vanished.
Within two months, however, she began to gain weight rapidly, lose hair from her scalp, and grow extensive body hair. In spite of exercise, she gained ten pounds in a single week. The doctors thought stress might be responsible.
Jessica’s parents desperately searched for information. They had never heard of PCOS, but the writings of a doctor on women’s hormonal problems seemed to describe some of the symptoms that their daughter was suffering from. Although they lived in Southern California and the doctor’s office was in Arizona, they made an appointment for a diagnostic examination for Jessica. From Jessica’s history and lab tests, the doctor diagnosed her with PCOS. Her mother felt deep relief that at least now she knew what illness her daughter had and that something could be done about it.
At this writing, Jessica is sixteen. Seven months after her diagnosis, she is feeling much better and is taking spironolactone, metformin, and a different oral contraceptive. After five months on metformin, her body has begun returning to its former shape. Jessica still has bad days, and her mother regards her recovery as “a work in progress.”
Her mother praises the Polycystic Ovarian Syndrome Association (at http://www.pcosupport.org) for valuable emotional support. Her advice to parents of teens with PCOS is to take action; find a doctor who can help; keep a detailed history of your daughter’s health; believe in your judgment as a parent. You can find help. Don’t give up.
FACTORS OFTEN IMPORTANT IN DIAGNOSIS
Age
Weight
Ethnicity
Family medical history (PCOS, diabetes, hirsutism, alopecia, cardiovascular problems, blood lipid abnormalities, high blood pressure)
Oral contraceptive use, present or past
Rapid weight change, recent or past, and its relationship to symptoms
Polycystic ovaries on sonograms of the pelvis
An endocrinologist considering whether you have PCOS bases the final decision on a number of factors. The following three factors are regarded by many endocrinologists as the most significant.
1. History of irregular periods and lack of ovulation, with onset at puberty. These signs are often associated with abnormal skin changes, and as excessive hair growth. However, it is possible that almost one in four women with PCOS actually has regular periods, without ovulation necessarily taking place. The symptoms that your primary doctor is most likely to notice are your skin and hair problems. It may be these that cause an inquiry about the regularity of your periods.
2. Lab tests that show elevated levels of male hormones. These include total and free testosterone, as well as other ovarian and adrenal male hormone levels. They also include evidence of an abnormal ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH), which occurs in two out of three women with PCOS. However, oral contraceptives can change any of these levels.
3. Exclusion of other hormonal disorders as causes of the symptoms. Before diagnosing PCOS, an endocrinologist needs to eliminate the possibility that the following disorders, which often have similar symptoms, may be present: adult-onset or congenital adrenal hyperplasia, hyperprolactinemia, adrenal or ovarian hormone-producing adenomas, hyperthecosis, hirsutism from unknown causes, and Cushing’s syndrome. We will talk more about these disorders later in this chapter.
We will now look at these three diagnostic criteria in more detail.
A history of irregular periods is the first and most significant criterion of PCOS diagnosis. Most women later diagnosed with PCOS experience a normal onset of puberty and menstrual cycles at twelve to thirteen years of age. Some who are overweight or obese as girls have an earlier onset of menstrual cycles. Like those of the majority of young girls, their periods for the first couple of years are often somewhat irregular and are usually painless. As they grow into their mid-teens, their periods continue to be infrequent (oligomenorrhea), but not always painless. They may have two successive periods on time and then not have another for two to six months or longer. They often have no typical symptoms of an approaching period: no bloating, breast tenderness, or pelvic discomfort in the few days before bleeding.
A gradual increase of weight, and particularly a rapid weight gain, may result in intervals of three to six months or longer between periods. An interval of greater than four to six months is called amenorrhea and requires medical attention, regardless of a teenager’s weight. One obvious explanation of a lack of periods that must always be excluded is that the young woman has become pregnant.
Some young women have prolonged episodes of bleeding (dysfunctional bleeding), lasting more than six or seven days, and this should be investigated. These bleeding episodes can result from thickening of the endometrium, which is almost continually bombarded by estrogens from the ovaries, adrenal glands, and peripheral stores of body fat cells in a woman who is not ovulating. An ultrasound of the pelvis, with careful attention to the uterus, may show endometrial thickening, which can be measured accurately by the ultrasonographer. At times, there may be ultrasound evidence of polyp formation or other abnormalities. An iodine study of the endometrium (hysterogram) or perhaps a diagnostic biopsy or scraping by the gynecologist may be needed for evaluation of the abnormal bleeding.
Polycystic ovaries are detected by ultrasound in 90 percent of women with PCOS who have not recently taken oral contraceptives or similar medications. In sonograms of such women, the ovaries may be normal in size or enlarged, and ten to twelve follicles or cysts, measuring 4 to 9 millimeters, are frequently seen under the ovarian capsule. Imaging of a polycystic ovary would seem to be good evidence of PCOS, except that almost one in four apparently asymptomatic healthy women also have some features of polycystic ovaries on their sonograms. From this, we know it is possible for you to have polycystic ovaries without PCOS. Ultrasound studies of the ovaries alone are not sufficient for a diagnosis of PCOS, and need to be backed by a history of irregular periods and evidence of an oversecretion of male hormones, which are far more reliable diagnostic indicators. In addition, other hormonal disorders can result in very similar sonograms. These disorders include congenital and adult-onset adrenal hyperplasia, hyperprolactinemia, Cushing’s syndrome, and some cases of hypothalamic amenorrhea.
Although ultrasound sonograms cannot diagnose PCOS with any certainty, they provide a valuable pretreatment picture of the ovaries. Your doctor can later judge how well treatment is working by comparing before and after sonograms for ovarian size, follicle number, endometrium, and cysts or other growths (up to 10 percent of women with PCOS develop them). Early recognition helps avoid the loss of an ovary if a cyst enlarges rapidly. The endometrium can be assessed for thickness and other changes that can play a role in infertility or episodes of heavy menstrual bleeding. A thickened endometrium suggests excess stimulation by estrogen and a potential for endometrial hyperplasia and carcinoma.
Sonograms can even show that you’ve ovulated in a particular menstrual cycle. The sonographer can see a corpus luteum cyst—the remains of the bust follicle that recently released an egg.
An experienced ultrasonographer can test young girls with the scanning device placed against the abdomen (a transabdominal sonogram), but for post-teens a transvaginal sonogram provides a more accurate picture. The best time to have an ultrasound is on days 4 to 8 of a menstrual cycle—whether it’s a regular cycle or one induced with progesterone.
Although lab tests that show elevated levels of male hormones are the second of three criteria for PCOS diagnosis, there is no agreement among professionals on which male hormone lab tests work best. The following are the tests most frequently ordered by endocrinologists. They serve to confirm a PCOS diagnosis, and also to evaluate your glucose intolerance and cardiac risks.
Many of my patients are surprised at the number of lab tests required at my initial evaluation. Not to worry—it only takes one relatively painless stick and six to eight small tubes of blood for a thorough evaluation. Your blood samples should be drawn in the morning, while your are fasting, and if possible during days 4 to 9 of your menstrual cycle. Your doctor could miss early morning spikes in the levels of male hormones, prolactin, and adrenal hormones if your blood is drawn later in the day.
Your lab test results may vary with the regularity or irregularity of your menstrual cycles. Individual responses to hormones vary also. For example, hormone receptors can become sensitized, so that a lower level of male hormones produces the same effect as the higher level once did. The sebaceous glands in hair follicles can become sensitized in much the same way, sometimes resulting in excess body hair even when male hormone levels are at or close to normal.
Testosterone level. Most endocrinologists agree that measurements of total and free testosterone levels are vital in the evaluation of PCOS. Several measurements may be needed of total and free testosterone, or a free androgen index performed by a competent laboratory. Value ranges differ with laboratories, but your doctor is familiar with the lab processing your test. If you take oral contraceptives or other medications, your testosterone level may be difficult to assess.
Most of your testosterone comes from your ovaries, with much smaller amounts coming from your adrenal glands. Free or unbound testosterone, which is only a small fraction of total testosterone, affects the sebaceous glands inside hair follicles, causing cystic acne, hirsutism, and thinning of scalp hair. You can have a normal total testosterone level while having a high level of free testosterone. Much depends on genetic factors, ethnicity, body weight, and individual responses and sensitivity to the male hormones produced. Your total testosterone level is often a good indicator of your male hormone levels. Most women with PCOS have a total testosterone level above 60 to 70 ng/dL, depending on the laboratory used and its normal range. This may in part be due to effects of insulin on the sex hormone binding globulin (SHBG), which dictates the amount of free testosterone measured in the blood. Women with male hormone secreting tumors, HAIRAN syndrome, or hyperthecosis (see section in this chapter called Exclusion of Hormonal Disorders Similar to PCOS) may have varying total testosterone levels of 70 to 150 ng/dL or higher.
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. An LH/FSH ratio greater than 2 is found in 60 to 70 percent of women with PCOS, and is more likely to occur in women who are not obese. If you take oral contraceptives or a similar medication, your LH and FSH levels will be difficult to assess because the hormones in contraceptives suppress them.
Sex hormone binding globulin (SHBG) level. Women who are obese or have the insulin resistance syndrome also have reduced SHBG levels. Reduced SHBG levels result from excessive insulin production and lead to an increase in free testosterone, which in turn causes many of the symptoms of PCOS. Prolactin level. An elevated prolactin level may be present in 10 to 20 percent of women with PCOS. About one in three of these women have an associated milky breast discharge and other signs of PCOS.
Dehydroepiandrosterone sulfate (DHEAS) level. DHEAS and other male hormones (androgens) such as androstenedione are weaker than free testosterone, but they are good makers of increased adrenal male hormone production. (DHEAS comes almost exclusively from the adrenal glands.) In initial assessments, most women with PCOS have elevated levels of total testosterone, free testosterone, androstenedione, and/or DHEAS.
17-alpha-Hydroxyprogesterone (17-OHP) level. Doctors test for this female hormone to exclude the possibility that overactive adrenal glands are at the root of the problem (congenital and adult-onset adrenal hyperplasia).
Lipid profile. Your HDL (“good”) and LDL (“bad”) cholesterol levels and particularly your triglyceride level are good indicators of insulin resistance. In addition, they are a good measure of your risks for diabetes and cardiovascular disease.
Glucose level. A fasting morning glucose level is a guide to your blood sugar status: normal, impaired glucose tolerance, or a clear case of diabetes. Although it is more convenient, this test is not as reliable as the two-hour glucose tolerance test described below.
Insulin level. Because of the technical difficulties involved, this test often has unreliable results. Additionally, a test result showing an elevated insulin level does not always mean you are insulin resistant or have the insulin resistance syndrome. Similarly, having a normal insulin level does not exclude the possibility of having insulin resistance.
Measuring your insulin level, however, is an important part of your evaluation. A persistently high insulin level often indicates a need for the pancreas to release more insulin due to a defect or inability of organs to respond normally to this hormone (insulin resistance). If your insulin level is high or if you have a family history of diabetes, you should definitely have a two-hour glucose tolerance test.
Two-hour glucose tolerance test. For this test, your glucose and insulin levels are measured prior to consuming a 75-gram glucose drink and again two hours later. If you have any symptoms of hypoglycemia (such as nausea or dizziness) during this test, be sure to tell your doctor. Consider carefully if these symptoms are similar to episodes you may have experienced after eating a carbohydrate-rich meal. A similarity between them suggests that you may have hyperinsulinism leading to episodes of low blood glucose levels.
This glucose tolerance test is recommended as a screen for diabetes for all women suspected of PCOS, even those in their teens, regardless of their weight. Since type 2 diabetes evolves over time, any woman who has passed the screening glucose tolerance test needs to be retested periodically over her lifetime.
Other diagnostic tests. Routine thyroid function tests include 1-thyroxine (T4) and thyroid-stimulating hormone (TSH). If your doctor suspects overactive adrenal glands, you may require a cortisol suppression test or an adrenal stimulation test employing adrenocorticotropic hormone (ACTH). A complete blood count, electrolytes, and kidney and liver function should be included in your evaluation. Tests checking for potential risk factors often include homocysteine and C-reactive protein blood levels, as well as a urine microalbumin level.
The third of the diagnostic criteria for PCOS is the exclusion of other hormonal disorders that can produce symptoms and signs similar to those of PCOS. Such disorders do not occur nearly as frequently as PCOS. Of women who appear to have PCOS, 10 to 15 percent of them turn out instead to have one of the following disorders.
An experienced physician excludes these relatively infrequent hormonal disorders through a careful analysis of your medical history, a physical examination, lab tests, and imaging. Treatments for the following disorders can vary dramatically from those for PCOS.
Congenital and adult-onset adrenal hyperplasia. Congenital adrenal hyperplasia, a hormonal condition of the adrenal glands, can cause symptoms that look very similar to those of PCOS. Hyperplasia involves an increased growth of normal cells that enlarge but maintain the shape of the original organ. Although it is relatively uncommon, this disorder runs in some Ashkenazi Jewish, Eskimo, and Hispanic families. The adult-onset type of the disorder can be initially diagnosed by a suspiciously high blood level of 17-alpha-Hydroxyprogesterone (17-OHP), together with an increase in testosterone level. If you have a menstrual cycle that appears to be ovulatory, you not only have an associated rise in serum progesterone, but also of 17-OHP, in the second (luteal) phase of your cycle. Thus it is necessary to measure this hormone in the early or follicular stage of the menstrual cycle—or at any time, if you have infrequent cycles. A diagnosis of congenital adrenal hyperplasia is confirmed by a marked increase of 17-OHP following a safe, one-hour morning intravenous ACTH-stimulation test (Cortrosyn test) in your endocrinologist’s office.
Ovarian hyperthecosis. On ultrasound, the ovaries of women with this condition usually look thick and lack the follicles found under the ovarian capsule in women with PCOS (see the Imaging Tests section earlier in this chapter). Women with ovarian hyperthecosis often have significant insulin resistance and high testosterone levels. Many are diabetic and obese, and some may even be fertile. Some experts in this field consider this to be a PCOS subgroup.
Idiopathic hirsutism. A woman whose excessive hair growth has no known medical cause is said to have idiopathic hirsutism. Regularly menstruating women who have excess body hair characteristic of an ethnic group receive this diagnosis, as do regularly menstruating women with excess hair caused by increased sensitivity of the hair follicles to male hormone levels. Such women show no evidence of elevated testosterone levels, even on repeated testing, and their menstrual cycles are regular and frequently ovulatory. The incidence of idiopathic hirsutism in a large group of hirsute women has been put at 5 percent.
HAIRAN syndrome. Hyperandrogenism-insulin resistantacanthosis nigricans (HAIRAN) syndrome results in symptoms of excess body hair, marked insulin resistance, and areas of skin pigmentation. About 3 percent of hirsute women have this syndrome. The changes occur early in puberty, typically with very high insulin levels and very dark acanthosis nigricans, particularly on the nape of the neck, under the arms, and in the groin area. This syndrome may be genetically associated with very severe insulin resistance, for which early diagnosis and treatment can be helpful.
High prolactin level (hyperprolactinemia). Women with hyper-proclactinemia and PCOS are regarded by some physicians as a subgroup. The incidence of significant hyperprolactinemia in PCOS varies from 7 to 20 percent. The hormone prolactin, secreted by the pituitary gland, stimulates milk production after childbirth. It also stimulates progesterone production by the corpus luteum in the ovary. A high prolactin level results in overproduction of milk and can disrupt the menstrual cycle by blocking the action of FSH or LH. Some drugs can cause a high prolactin level, and your doctor will explore that as a possible cause. If the prolactin level is sufficiently high, an MRI of the head can exclude the presence of a small prolactin-secreting pituitary growth (adenoma). The drugs bromocriptine (Parlodel) and cabergoline (Dostinex) have been used successfully for hypersecretion states of prolactin. The effects of excessive production of prolactin may cause menstrual abnormalities, the absence of periods, acne, hirsutism, and occasional hair loss, all of which are readily treatable.
Cushing’s syndrome. Any fairly rapid weight gain of more than twenty-five to thirty pounds in a year; high blood pressure; wide, violet-colored stretch marks; development of a significant fat pad on the back of the neck; round facial features; possible diabetes; acne; hirsutism; muscle weakness; and a lack of periods can be caused by excessive production of the stress hormone cortisol by the adrenal glands. This is called Cushing’s syndrome. Extensive testing by an experienced endocrinologist is required for its diagnosis.
Testosterone-secreting neoplasm of ovaries or adrenal glands. A rapid weight change, markedly increased hirsutism or acne, thinning scalp hair, deepening of voice, a noticeable increase in muscle mass, and usually an absence of periods indicate a possible testosterone-secreting neoplasm (usually benign) of the ovaries or adrenal glands. The testosterone level is usually very high (greater than 150 mg/dL, and often greater than 200 mg/dL). A pelvic ultrasound is needed to check the ovaries for any sign of a growth. A CT scan of the adrenal glands using iodine contrast can help locate the neoplasm. Some doctors recommend an MRI of the abdomen, but it’s of little practical help in defining subtle changes in the ovaries that show up much better on ultrasound performed by an experienced radiologist.
Thyroid function abnormality. Thyroid function tests are used routinely in health assessments of women of reproductive age. They have limited usefulness, however, in helping to establish a diagnosis of PCOS. An underactive thyroid may cause heavy menstrual cycles and hair loss. On the other hand, an overactive thyroid is often associated with a decrease in menstrual flow, longer intervals between cycles, skin itchiness, hyperactivity, palpitations, and some hair loss.
Other conditions. Changes in weight and eating patterns can frequently cause hormonal changes. Drugs and moderate or severe stress can also affect hormones. Low levels of the ovary-stimulating pituitary hormones LH and FSH, usually with a low estrogen level, can indicate hypothalamic amenorrhea. This condition is characterized by reduced ovary stimulation by brain hormones and can have various causes, including poor eating habits and excessive exercise. On the other hand, high LH and FSH levels, with a low estrogen level, can be characteristic of women who have a relatively early onset of menopause, with symptoms such as hot flashes, insomnia, and lack of periods.
Many women spend years suffering from their symptoms while searching for an adequate diagnosis and appropriate treatment. Early recognition of PCOS and immediate treatment by a specialist can save women much heartbreak and wasted effort. Diagnosis is difficult, however. It’s no surprise that endocrinologists familiar with the condition are the most likely to recognize it at an early stage as well as the warning signs of insulin resistance and the insidious approach of type 2 diabetes.
Detection and treatment of blood lipid abnormalities are the first steps in avoiding cardiovascular disease. If you have unhealthy cholesterol or triglyceride levels, your specialist will probably suggest dietary measures and exercise. If they don’t work, you may need a statin (for example, Lipitor), fibrate (Tricor), or niacin.
High blood pressure is called a silent killer because it often shows no symptoms, goes undetected, and can be dangerous. Your specialist can detect and treat it. Insulin resistance, blood lipid abnormalities, and high blood pressure can interact as a complex network of risk factors in the insulin resistance syndrome, to which women with PCOS are especially vulnerable.
When you know for certain that PCOS is responsible for your infertility, your specialist can almost certainly remedy the situation with highly successful medications, as discussed in chapter 10. Likewise, when your specialist knows that your skin or hair problems are caused by PCOS, he or she can prescribe medications for the symptoms that have been highly successful in clinical practice. We discuss these medications in chapter 11.
An experienced specialist will emphasize controlled eating patterns and exercise, offer you encouragement when you need it, and monitor your progress over the course of treatment. He or she will explain why lifestyle modification is essential to easing symptoms. You can make a good start with the PCOS diet program in the next chapter.