The PCOS Plan. Jason Fung

are ethnic differences in sensitivities to androgens, with white people being the most sensitive and Asians being the least.

       Menstrual irregularities

      Dr. John Nestler from Virginia Commonwealth University estimates that “if a woman has fewer than eight menstrual periods a year on a chronic basis, she probably has a 50 to 80 percent chance of having polycystic ovary syndrome based on that single observation.”⁶ Irregular, absent, or rare menstrual cycles are all common symptoms of PCOS. An estimated 85 percent of women with PCOS suffer menstrual irregularities.⁷ During the normal menstrual cycle, the human egg develops from the primordial follicle. It grows during the first half of the menstrual cycle and then is released into one of the fallopian tubes to be carried to the uterus, where it awaits fertilization by the sperm. Ovulation is the release of the egg from the ovary. Irregular menstrual cycles are caused by the failure of ovulation. In PCOS, the main menstrual problems are anovulation and oligo-ovulation. Anovulation means a complete lack of ovulation and oligo-ovulation refers to a lower-than-normal rate of ovulation.

      Figure 2.1. Follicle development in a normal menstrual cycle

      When normal ovulation does not occur, then menstrual cycles may be completely absent (amenorrhea) or may last longer than usual (oligomenorrhea). But even having a regular cycle does not mean that ovulation has occurred normally, especially in women with other evidence of hyperandrogenism. Twenty to 50 percent of women with signs of excess testosterone and regular periods still have evidence of anovulation. This lack of ovulation will result in difficulty conceiving and infertility. PCOS is associated with recurrent miscarriages, and it is the most common cause of infertility in industrialized nations.

      When I was trying to conceive, I often bought over-the-counter ovulation prediction kits that use urine strips to test for luteinizing hormone (LH). This hormone spikes just before a woman ovulates and indicates that it’s baby-making time! During many of my infertile months, I noticed the same thing as many of my infertile patients do. Even when I had a menstrual cycle, whether it was regular or not (much longer than 28 days), I did not have an LH surge. In other words, I was not ovulating.

       Polycystic ovaries

      Follicles are collections of cells in the ovary. During a normal menstrual cycle, many follicles begin to develop and one eventually becomes the human egg that is released into the uterus at the time of ovulation. The other follicles usually shrivel up and are reabsorbed into the body. When these follicles fail to shrivel up, they become cystic and show up on an ultrasound as ovarian cysts.

      The Rotterdam criteria define polycystic ovaries as being the presence of 12 or more follicles measuring 2 to 9 mm in diameter in each ovary. Two main factors influence the number of cysts. Small (2–5 mm) follicles are related to the serum androgen level and larger (6–9 mm) follicles are related to both serum testosterone and fasting insulin levels. Because 20 to 30 percent of otherwise normal women may have multiple cysts on their ovaries, the mere presence of cysts is not enough to make the diagnosis of PCOS. And there is no correlation between the number of cysts and the severity of PCOS.

       WHEN WHAT LOOKS LIKE PCOS IS NOT

      DESPITE THE REASONABLY clear diagnostic criteria for PCOS, certain populations present with symptoms that fit the Rotterdam criteria but do not necessarily indicate PCOS. Certain conditions, too, can look a lot like PCOS but have completely different causes and associated treatments.

       Misdiagnosis in adolescents

      Making the diagnosis of PCOS in adolescents is particularly tricky because irregular cycles, hyperandrogenism, and polycystic ovaries can all be found during normal puberty.

      When girls first begin to menstruate (called menarche), their cycles are commonly irregular and may not always be accompanied by ovulation. In the United States, the median age of menarche is 12.4 years. The period of irregular cycles often lasts for two years or more, and the cycle intervals typically range from 21 to 45 days (average of 32.2 days). This average is quite close to the 35-day cycle that is defined as oligomenorrhea, or infrequent menstrual cycles in women of childbearing age.

      Normal puberty and the irregular cycles seen in PCOS overlap significantly. To avoid overtreatment and unnecessary worry, clinicians should generally wait until the third year after menarche to confirm a diagnosis of PCOS in teens. By that time, 60 to 80 percent of girls have cycles that are 21 to 34 days long, which is typical of a normal adult cycle.

      Blood testing of androgens in adolescents does not distinguish unusually high levels, because normal levels are not well defined in this age group. During puberty, there is a normal physiological increase in testosterone levels that peaks a few years after menarche. This increased testosterone leads, for example, to the familiar problem of acne during teenage years that improves or disappears in later adult years. The presence and the severity of this temporary increase in acne do not predict a later diagnosis of PCOS.

      Polycystic ovaries, too, are difficult to diagnose during adolescence. In adult women, a transvaginal ultrasound, in which the ultrasound probe is inserted into the vagina, provides the clearest images of the ovary. However, this technique is usually avoided in adolescent girls, which makes the radiological diagnosis more difficult. In studies where ultrasounds were performed, 26 to 54 percent of asymptomatic adolescent girls had polycystic ovaries by imaging.⁸

      Special care must be taken in labeling a patient with PCOS during their teen years, and it is often prudent to wait until after adolescence to make the diagnosis since it is not an urgent condition. If there is evidence of obesity or type 2 diabetes, these associated conditions should be treated earlier. Obesity is known to be associated with increased insulin levels, and this effect is magnified during early puberty. Fasting insulin is more than three times higher in the obese group. This effect is also seen during late puberty and adulthood, but not with such a marked difference. Testosterone levels are also likely to be higher in overweight adolescents. For example, in one study, 93.8 percent of obese preteens were found to have elevated testosterone levels versus 0 percent of the non-obese group.⁹

       Differential diagnoses

      Hyperandrogenism and polycystic ovaries are not exclusive to PCOS, so other diseases that mimic PCOS must be excluded by history or by physical or laboratory examination before the diagnosis can be confirmed. While most of these conditions are rare, they may be serious and require entirely different treatments, which makes the distinction important. The list of similar conditions includes

      ·pregnancy,

      ·hyperprolactinemia (prolactin excess),

      ·thyroid disorders,

      ·nonclassic congenital adrenal hyperplasia (NCAH),

      ·Cushing’s Syndrome, and

      ·hyperandrogenemia (androgen excess, tumor/drug-induced) Let us consider some of these other conditions.

      » Pregnancy

      Pregnancy is by far the most common cause of menstrual irregularity. Obviously, a simple pregnancy test, either a home test or laboratory confirmation, is mandatory before confirming the diagnosis of PCOS. It would be very embarrassing to miss this simple diagnosis.

      » Hyperprolactinemia

      Prolactin is a hormone normally secreted by the pituitary gland in the brain that enables mammals, including humans, to produce milk. Prolactin levels normally increase toward the end of pregnancy for proper breast development in preparation for breastfeeding. Excessive prolactin in the blood when a woman is not pregnant is known as hyperprolactinemia.

      A wide range of conditions may lead to hyperprolactinemia, including chronic kidney or liver disease, drug use, and thyroid disease. Another common cause is a small tumor (microadenoma) of the pituitary gland, which may oversecrete prolactin into the blood. The diagnosis of hyperprolactinemia is made by measuring the blood level