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Who Gets PCOS?

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THE PREVALENCE OF PCOS, using the NIH criteria, ranges from 6 to 9 percent, with a strikingly similar rate globally.¹ Using the Rotterdam criteria, that rate is about 15 to 20 percent of women. This makes PCOS the most common endocrine (hormonal) disorder of young women by far. Approximately one in 15 women in the United States are affected, with similar proportions in Spain, Greece, and the United Kingdom. An estimated 105 million women of childbearing age are afflicted worldwide.

GENETICS AND PCOS

TO TRY TO understand why some people develop PCOS and others don’t, researchers usually begin by looking for genetic influences. A large Dutch study comparing sets of identical twins with sets of fraternal twins found that approximately 70 percent of PCOS may be attributed to genetic influences.² A U.S. study found that sisters of patients diagnosed with PCOS are more likely to have symptoms, with an estimated 22 percent also fulfilling the full diagnostic criteria.³ A further 24 percent of sisters had hyperandrogenism but regular menstrual cycles, likely indicating that they too had mild PCOS. In a separate study, mothers of patients with PCOS had higher androgen levels, insulin resistance, and metabolic syndrome.⁴ First-degree relatives, male or female, are more likely to have evidence of insulin resistance. Despite these strong genetic tendencies, no single gene has been identified as the causative factor. This indicates that PCOS is a complex genetic disorder with multiple genes contributing small degrees of risk.

HEALTH RISKS ASSOCIATED WITH PCOS

IF PCOS WERE just about acne and a few missing periods, then it would not be so bad. Unfortunately, PCOS is associated with many health concerns, reproductive as well as general.⁵ The reproductive issues include

·anovulatory cycles,

·infertility,

·disorders of pregnancy, and

·fetal concerns.

Other significant health concerns include

·cardiovascular disease,

·non-alcoholic fatty liver disease (NAFLD),

·sleep apnea,

·anxiety and depression,

·cancer,

·type 2 diabetes, and

·metabolic syndrome.

These are some of the deadliest conditions in the world, including the top two causes of death in America, cardiovascular disease and cancer. PCOS is not merely a nuisance; it is an important warning of risk. For this reason, it’s worth taking a look at each of these conditions in more detail to try to understand their link with PCOS.

Reproductive concerns

» Anovulatory cycles

Most women with PCOS suffer from infrequent or absent menstrual periods, mostly caused by anovulatory cycles (ovulation is missed). PCOS accounts for 80 percent of cases of anovulation leading to infertility.⁶

» Infertility

If you do not ovulate, you can’t conceive: no egg, no baby. Anovulatory cycles account for approximately 30 percent of visits to an infertility clinic, mostly due to PCOS. The Australian Longitudinal Study on Women’s Health, a community-based survey of young women, found that a heartbreaking 72 percent of women with PCOS considered themselves infertile, compared with only 15 percent without PCOS. However, women with PCOS usually have difficulty conceiving rather than being completely infertile. The use of fertility hormones in the PCOS group was almost double that of the non-PCOS group. That is, the 5.8 percent of women identified as having PCOS constituted a whopping 40 percent of those seeking fertility treatments. Obviously, PCOS contributes heavily to overall use of costly fertility treatment.⁷

The financial costs of infertility are depressing. Costs in the United States range from relatively inexpensive hormonal treatments (approximately US$50 per treatment cycle) to very expensive in vitro fertilization (IVF), which in 2005 was estimated to cost upward of US$6000 to $10,000 per round of treatment. With millions of women suffering from PCOS, the total cost for infertility treatment alone in the United States is an estimated US$533 million.⁸

The possibility of being unable to conceive a child can cause severe anxiety. Celebrity chef Jamie Oliver and his wife, Jools, have spoken openly about their struggle with PCOS. They now have five children. Jools went through many rounds of hormonal treatments, and even one round of IVF, but at least two of their children were conceived spontaneously. Fertility medications such as clomiphene have been relatively successful at inducing ovulation. However, these treatments often have serious side effects—physical, psychological, and financial. While clomiphene may help women get pregnant, the PCOS-related reproductive problems don’t stop there.

» Disorders of pregnancy

Losing a pregnancy can be absolutely devastating, especially if it was difficult to conceive in the first place. Spontaneous abortions occur in an estimated one-third of women with PCOS. Studies suggest that PCOS is associated with up to twice the rate of miscarriage.⁹

Rates of all pregnancy-related complications are increased among women with PCOS. Gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia risks are approximately tripled. Risk of preterm birth is increased by an estimated 75 percent when compared with women in general or women who have overcome PCOS.¹⁰ Women with PCOS are more likely to deliver by cesarean section, which itself comes with complications.

Fertility treatments may double the risk of multiple pregnancies, with all their attendant complications. Pregnancy with twins, for example, has up to 10 times the risk of the babies being small for gestational age at birth and six times the risk of delivering prematurely.¹¹

» Fetal concerns

Babies of mothers with PCOS may be large for their gestational age, since hyperinsulinemia (excess insulin in the blood) is associated with increased nutrient availability. Both small and large gestational age at birth are associated with admissions to the neonatal intensive care unit (NICU), stillbirths, and perinatal mortality (infant death in the first week after birth)¹² as well as metabolic complications (type 2 diabetes, obesity, and hypertension) later in life.¹³ Hyperinsulinemia in utero may affect the child’s intellectual and psychomotor development too.¹⁴

Associated health conditions

» Cardiovascular disease

Some studies estimate that women with PCOS may have seven times the risk of developing cardiovascular disease over women without PCOS.¹⁵ Large epidemiological studies like the Nurses’ Health Study, which comprised 82,439 women, found a correlation between irregular menses (as a proxy for possible PCOS) and a higher risk of heart disease during 14 years of follow-up.¹⁶ Although one study showed no risk,¹⁷ a 2010 consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society estimated the increased risk at 70 to 95 percent.¹⁸

PCOS is a marker of greater cardiovascular risk. The association with type 2 diabetes, obesity, and cholesterol problems accounts for much of the heightened risk. Insulin resistance develops in 40 percent of women with PCOS¹⁹ and typically gets worse with age. Women with PCOS also tend to have poor cholesterol panels. Since cardiovascular disease is already the leading cause of death in older women, this effect is especially concerning.

» Non-alcoholic fatty liver disease

The most common form of liver disease in the world, non-alcoholic fatty liver disease (NAFLD) affects an estimated 30 percent of the general population. The liver is an organ that should not normally store fat: fat should be stored in fat cells. Excessive alcohol consumption is a common cause of fat accumulation in the liver, but this can also happen in people who drink minimal alcohol. For many years, one of the leading causes of liver failure (cirrhosis) was termed “cryptogenic,” which means “from unknown cause.”²⁰ Now we know that cryptogenic cirrhosis was largely due to undiagnosed fatty liver disease. Patients with NAFLD have an estimated 2.6 times the risk of death compared with the general population, and the disease is intimately linked to type 2 diabetes and metabolic syndrome.

The first case linking PCOS and NAFLD was reported in the medical literature in 2005.²¹ A 24-year-old woman diagnosed with PCOS but otherwise healthy was investigated because her bloodwork showed evidence of liver damage. A long needle was inserted into her liver and a biopsy taken. Under the microscope, to everybody’s surprise, the pathology showed severe fatty infiltration.

Since then, many other studies have confirmed the tight correlation between the two diseases. Women with PCOS have two-and-a-half times the prevalence of NAFLD compared with women without PCOS.²² Approximately 30 percent of women with PCOS have evidence of liver damage by blood tests. In women of reproductive age investigated for NAFLD, 71 percent also had PCOS. Like PCOS, the occurrence of NAFLD is highly associated with metabolic syndrome.²³

NAFLD is often underdiagnosed because there are virtually no symptoms of the disease. It is really only through blood tests that the condition is discovered. Thus, it is important to screen for this condition.

» Sleep apnea

Obstructive sleep apnea (OSA) is a condition in which the upper airway collapses during sleep. Patients cannot breathe for an instant, which causes them to wake up momentarily, though they usually don’t remember. Regular sleep patterns are disrupted and sleep architecture is fragmented. The main symptoms of this disease include snoring and excessive daytime sleepiness.

The rate of OSA in women with PCOS is an astounding five to 30 times higher than in women without PCOS.²⁴ Like PCOS, the occurrence of OSA is highly linked to metabolic syndrome.

» Anxiety and depression

Both anxiety and depression are common among patients with PCOS, and a high index of suspicion should be maintained. Abnormal male-pattern hair growth, acne, obesity, and menstrual irregularities destroy self-esteem, especially during adolescence. Depression, anxiety, and other psychological abnormalities are more prevalent among younger women with PCOS.²⁵ Depression is also common among women suffering from infertility as well as chronic illnesses associated with PCOS (type 2 diabetes, cardiovascular disease, and cancer).²⁶

Weight loss and lifestyle changes may improve the symptoms of PCOS as well as feelings of depression and anxiety.²⁷ Clinicians should regularly assess for psychological well-being.

» Cancer

Women with PCOS are three times more likely to develop endometrial cancer and two to three times more likely to develop ovarian cancer when compared with the general population.²⁸ Since there is a significant overlap between PCOS and obesity/hyperinsulinemia, it is no surprise that women with PCOS are also at higher risk of obesity-related cancers (such as breast cancer and colorectal cancer), which now make up 40 percent of all cancers as classified by the World Health Organization.²⁹

» Diabetes

Perhaps the disease most closely associated with PCOS is type 2 diabetes, a disease of excessive insulin resistance, a trait shared by PCOS patients as well. An estimated 82 percent of women with type 2 diabetes have multiple cysts on their ovaries, and 26.7 percent fulfill the diagnostic criteria for PCOS.³⁰ Women with PCOS have three times the risk of developing type 2 diabetes by menopause when compared with the general population. I was one of these women. A glucose tolerance test confirmed that I had developed type 2 diabetes.

Among women with PCOS, 23 to 35 percent will have prediabetes and 4 to 10 percent will have type 2 diabetes.³¹ This rate of prediabetes is three times higher than in women without PCOS. The rate of undiagnosed type 2 diabetes is 7.5- to 10-fold higher. As in the general population, the rate of type 2 diabetes among women with PCOS rises with increasing Body Mass Index. PCOS is recognized by the American Diabetes Association as a risk factor for diabetes.

Women with PCOS, particularly if obese, have a higher incidence of gestational diabetes and insulin resistance, a rate estimated to be about twice that of otherwise healthy women.³² Gestational diabetes increases the risk of miscarriage and delivering by cesarean section or induced birth, due to the increased size of the fetus.³³ Developing diabetes during pregnancy increases a woman’s risk of developing type 2 diabetes, cardiovascular disease, and metabolic syndrome in the future. Maternal obesity also increases the baby’s risk of developing childhood obesity and PCOS.

Women with type 1 diabetes who are being treated with insulin are also at risk of PCOS, with an estimated 18.8 percent³⁴ to 40.5 percent³⁵ affected, compared with only 2.6 percent in the control group. PCOS is six to 15 times more common among women with type 1 diabetes, probably due to the frequent high dosage of insulin.

Women with PCOS should be screened for type 2 diabetes using an oral glucose tolerance test every three to five years. Measuring fasting glucose alone may miss the diagnosis of up to 80 percent of prediabetic patients and 50 percent of diabetic patients. If cardiovascular risk factors exist, the screening should be done annually so the disease can be diagnosed at an early stage when lifestyle measures such as dietary changes can prevent damage to the body’s major organs.

» Metabolic syndrome

In 1988, Dr. Gerald Reaven of Stanford University termed syndrome X as a group of conditions with an unknown common factor, “X.” These conditions included central obesity, high blood pressure, high triglycerides, and high blood glucose. Reaven and Dr. Ami Laws (also of Stanford University) published the book Insulin Resistance: The Metabolic Syndrome X³⁶ linking insulin resistance to metabolic syndrome and calling it the common factor in all these seemingly separate conditions.

In 2002, a National Institutes of Health report³⁷ defined a patient as having metabolic syndrome if three of the following five conditions are present:

·Abdominal obesity: over 40 inches (102 centimeters) for men; over 35 inches (89 centimeters) for women

·High blood glucose: over 100 milligrams/deciliter (mg/dL), or taking medication

·High triglycerides: over 150 mg/dL, or taking medication

·Low high-density lipoprotein (HDL): below 40 mg/dL for men, below 50 mg/dL for women, or taking medication

·High blood pressure: over 130 mmHg for the systolic (top) number, over 85 mmHg for the diastolic (bottom) number, or taking medication

General obesity, albeit commonly associated, is not one of the criteria. Approximately 25 percent of metabolic syndrome patients are non-obese individuals. Interestingly, high low-density lipoprotein (LDL or “bad” cholesterol) is also not a criterion, even though many doctors and professional guidelines obsess about LDL and statins.

The prevalence of metabolic syndrome in the adult American population is now estimated at 88 percent³⁸—leaving only 12 percent as metabolically healthy—and this comes with an increased risk of cardiovascular disease, stroke, cancer, NAFLD, obstructive sleep apnea, and PCOS.

The link between metabolic syndrome and insulin resistance makes it a reversible dietary condition, not a chronic progressive disease.

UNDERSTANDING THE LINK BETWEEN PCOS AND ITS ASSOCIATED RISKS

PCOS MUST BE considered more than merely a disorder of excess facial hair, acne, and abnormal reproduction. Patients with PCOS have double the chance of being hospitalized compared with those without the disease. The United States spent an estimated $4 billion in 2004 on health care related to treating PCOS³⁹—an amount equal to the entire gross domestic product of Barbados. Much of this cost (40.4 percent) is due to the associated type 2 diabetes.⁴⁰

Even more sobering, this number likely underestimates the true costs, because it takes into account only the reproductive years and not the associated health risks such as type 2 diabetes, heart attacks, strokes, and cancer that may arise in the future. These diseases typically occur in a woman’s post-menopausal years and are many, many times more expensive than simply treating PCOS.

Furthermore, PCOS is one of the main causes of infertility, which often leads to women seeking in vitro fertilization (a multi-billion-dollar industry). As we’ve seen, women with PCOS who do become pregnant are at increased risk of obstetrical complications such as gestational diabetes, pregnancy-induced hypertension (high blood pressure), and pre-eclampsia.

Though they are not part of the formal definition of PCOS, obesity leading to metabolic syndrome and insulin resistance leading to type 2 diabetes have been frequently noted in patients and affect an estimated 50 to 70 percent of women with PCOS. The close link to obesity and type 2 diabetes suggests that all three conditions have the same underlying root cause. All three are now understood as metabolic diseases, putting women with PCOS at high risk later in life for cardiovascular disease, strokes, and cancer.

Perhaps the most important associated disease is a history of weight gain that often precedes the diagnosis of PCOS. Of the obese women referred to one clinic, 28.3 percent were diagnosed with PCOS.⁴¹ PCOS can be more common as severity of the obesity increases, but more importantly, weight loss has also been proven to reduce testosterone, improve insulin resistance, and decrease hirsutism (more on this later).

Figure 3.1. The three metabolic diseases have a root cause

PCOS, obesity, and type 2 diabetes are variable manifestations of the same underlying problem. But what is that problem? To start answering this question, we need to know what causes obesity. Once we figure that out, we can gain a clue as to the root cause of PCOS.

GABRIELLA

Gabi’s story is a simple, clear-cut case of PCOS, but there’s always a twist. In early 2016, Gabi decided to start a family. She had been dating Hugo for many years, and now they were going to marry. She stopped taking the birth control pill, which she had used consistently since age 18.

Once off the pill, Gabi did not have a period for many months. For the first time in her life, she developed acne, and she also gained 8 pounds (4 kilograms). Gabi saw her doctor for a check-up, expressing her concerns. Besides her weight gain, she had headaches that lasted for days and that she could manage only by taking painkillers constantly. Her bloodwork showed increased androgen (male hormone) levels, which explained the acne and missed periods. An internal ultrasound confirmed multiple small ovarian follicles and the diagnosis of PCOS. Her doctor informed her it would be difficult to get pregnant, though not impossible. She felt devastated and discouraged.

At this point, Gabi asked for my help. She had been my patient and friend in Mozambique since 2009, and she knew I’d experienced the same situation. Like me, Gabi was a young, thin woman with PCOS. At 138 pounds (62 kilograms) and 5 feet 6 inches (1.7 meters) tall, she had a BMI of 23, which was perfectly normal. I reassured her that PCOS is a reversible condition related to hyperinsulinemia and insulin resistance and that the treatment was changing her diet. We discussed the diet of low-carbs and high healthy fats, which she knew from South Africa as the Banting Diet. She started immediately.

The next month her menstrual cycle went from 73 to 56 days. Considering that a normal menstrual cycle comes every 25–30 days, she had improved tremendously, but there was still work to be done. In just one month, her headaches were nearly gone, she stopped taking painkillers, and her skin cleared up. After two months on the new diet, Gabi felt less bloated, finally lost some weight, and started to ovulate. She continued on the low-carb diet and stopped snacking completely, even on “low-carb-friendly” foods. She also began some 24-hour intermittent fasting.

By January 2017, just over four months into her new way of eating, Gabi’s menstrual cycle had almost completely reverted to normal. Almost. She was late by a couple of weeks. Out of curiosity, she did a urine pregnancy test, which came out positive. She did a blood test right away. In Mozambique, doing a blood test is as easy as driving to the lab, ordering the test, and paying for it. This test, which is meant to be more accurate than the urine test, came back negative. She was devastated.

But something was not right. Her breasts were swollen and she had serious back and muscle cramps. Two other urine pregnancy tests were positive. We were worried. Could it be an ectopic pregnancy? Did she have a miscarriage? The very next day, she was able to get an appointment in nearby South Africa with her sister’s gynecologist. That blood test and an internal ultrasound confirmed she was five weeks pregnant and all was well! Low-carb works. Insulin resistance is reversible.

I encouraged Gabi to stick with her low-carbohydrate diet during pregnancy to prevent gestational diabetes, knowing that women with PCOS are more prone to this and other gestational conditions. She and the baby remained healthy and well throughout the pregnancy, and Beautiful Banting Baby was born in October 2017.