The PCOS Plan. Jason Fung

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,