The PCOS Plan. Jason Fung

and insulin resistance increased from one in 1980 to about 12,000 in 2011⁸

      In 2003 the second international conference on PCOS was held in Rotterdam, the Netherlands. Two new features were added to the NIH criteria. First, the mention of polycystic ovaries was introduced. It took a mere 14 years to correct that little oversight! Second, PCOS was recognized as a spectrum of disease in which not all symptoms may appear in all patients, and it was decided that a patient could be diagnosed with PCOS if they showed two of three criteria. The updated criteria, published in 2004, became known as the Rotterdam criteria:

      1.Hyperandrogenism: literally, a state of too many androgens. The prefix “hyper” means “too much” and the suffix “ism” means “a state of.”

      2.Oligo-anovulation: literally, few or no ovulatory menstrual cycles. The prefix “oligo” means “few” and the prefix “a” means “absence of.”

      3.Polycystic ovaries: literally, many cysts in the ovaries. The prefix “poly” means “many.”

      Figure 1.4. Diagnostic criteria⁹

      In 2006 the Androgen Excess Society (AES) recommended that hyperandrogenism be considered the clinical and biochemical hallmark of PCOS. Without evidence of hyperandrogenism, they suggested, a person simply could not receive a diagnosis of PCOS. The AES recommendation of making hyperandrogenism a necessary criterion for PCOS diagnosis focused researchers and doctors on the underlying cause of disease rather than merely on the presence or absence of polycystic ovaries.

      Today, the NIH criteria are rarely used. In 2012, an NIH Expert Panel recommended that the Rotterdam criteria be used for diagnosis. And being fairly similar to those criteria, the AES 2006 recommendations are commonly used as well.

      Table 1.1. Criteria for the diagnosis of polycystic ovary syndrome¹⁰

NIH/NICHDa 1992	ESHRE/ASRMb (Rotterdam criteria) 2004	Androgen Excess Society 2006
Exclusion of other androgen excess or related disorders Includes all of the following: •Clinical and/or biochemical hyperandrogenism •Menstrual dysfunction	Exclusion of other androgen excess or related disorders Includes two of the following: •Clinical and/or biochemical hyperandrogenism •Oligo-ovulation or anovulation •Polycystic ovaries	Exclusion of other androgen excess or related disorders Includes all of the following: •Clinical and/or biochemical hyperandrogenism •Ovarian dysfunction and/or polycystic ovaries

      ^a National Institutes of Health/National Institute of Child Health and Human Development

      ^b European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine

      It is important to note here that although obesity, insulin resistance, and type 2 diabetes are commonly found in association with PCOS, they are not part of the diagnostic criteria.

       The PCOS Spectrum: What PCOS Is and Is Not

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      TO CONFIRM A diagnosis of polycystic ovary syndrome (PCOS), clinicians must confirm the presence of two out of the three following conditions: hyperandrogenism, menstrual irregularities, and polycystic ovaries. Because some women will present with all three criteria and others will have only two, PCOS represents a spectrum of disease. The Rotterdam criteria recognized this continuum and grouped patients into four different phenotypes:

      ·Frank or classic polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and polycystic ovaries—3 of 3 criteria)

      ·Classic non-polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and normal ovaries—2 of 3 criteria)

      ·Nonclassic ovulatory PCOS (regular menstrual cycles, hyperandrogenism, and polycystic ovaries—2 of 3 criteria)

      ·Nonclassic, mild PCOS (chronic anovulation, normal androgens, and polycystic ovaries—2 of 3 criteria)

      The frank phenotype represents the most severe disease and is associated with metabolic diseases like obesity and type 2 diabetes and with cardiovascular risk factors like high blood pressure and cholesterol. In contrast, women with nonclassic, mild PCOS are at the lowest risk of metabolic disease.¹ Why some women with PCOS present with hyperandrogenism as opposed to anovulatory cycles is unknown.

      While women may have genetic or other factors that predispose them to PCOS, lifestyle—and particularly Body Mass Index—likely determines their position on the spectrum. Weight gain moves women toward the severe end of the spectrum.² Weight loss, in contrast, moves women toward the less severe end of the spectrum by improving fertility, ovulatory cycles, and hirsutism.³

       MAKING THE DIAGNOSIS

       Hyperandrogenism

      Male sex hormones, called androgens, are normally present in both men and women, but the normal levels for men are far higher than for women. Testosterone is the best-known androgen and contributes to many of the physical factors that distinguish men from women. It is produced in the testes in men and in the ovaries in women. Small amounts are also produced in the adrenal glands that sit above the kidneys. Testosterone helps regulate sex drive, fat distribution, and bone mass. More than 80 percent of women who present with symptoms of hyperandrogenism will eventually be diagnosed with PCOS.⁴

      Common features of hyperandrogenism include

      ·increased facial and body hair growth (hirsutism),

      ·male-pattern baldness,

      ·acne,

      ·lowered tone of voice,

      ·menstrual irregularities, and

      ·clitoral enlargement (in severe cases).

      The feature most commonly associated with PCOS is hirsutism, which affects an estimated 70 percent of women with PCOS. Just as with men, more testosterone increases the growth of facial and body hair in certain areas, such as the face, legs, chest, back, and buttocks. At the same time, higher levels of testosterone can cause hair loss on the scalp, which leads to crown-pattern or male-pattern baldness. In women with hyperandrogenism, this hair gain and loss becomes very obvious.

      An estimated 15 to 30 percent of PCOS patients develop acne, though it has only recently been recognized as a symptom of hyperandrogenism. Among women who complain of acne, 40 percent are eventually diagnosed with PCOS, so it is important to keep it in mind.⁵ Deepening of the voice and enlargement of the clitoris indicate severe hyperandrogenism.

      Serum androgen levels can be measured through blood testing. The most useful blood tests for hyperandrogenism determine levels of serum testosterone and DHEA-S (dehydroepiandrosterone sulfate), another type of androgen. These hormones fluctuate throughout the day and throughout the menstrual cycle, making it harder to define normal and abnormal ranges. Nevertheless, 75 percent of women with PCOS will have an abnormal value, if you look hard enough. Because high testosterone levels are not part of the diagnostic criteria (only clinical manifestations of it are), most clinicians do not bother to administer these blood tests.

      It is worth noting that androgens also act as precursors to female sex hormones (estrogens) in both men and women. Excess adipose (fat) tissue can convert testosterone into estrogen, causing breast enlargement in both men and women. This process accounts for the very obvious “man boob” phenomenon seen in some older and obese men; it is much less