PCOS and Insulin Resistance: Part 4.2 Evaluation of Diagnostic Features of PCOS

In the second part of the Diagnosis of PCOS, I would like to dissect the clinical evaluation of its diagnostic features. A proper diagnostic protocol will determine firstly, who has PCOS, secondly, how many women worldwide actually have this condition, and lastly, lead to a proper treatment plan.

PCOS is a diagnosis given by exclusion. This means that for a physician to diagnose a woman with PCOS, he/she must first exclude other conditions that mimic PCOS, i.e. Differential Diagnosis. In theory, when a woman presents with the common complaints of PCOS, a clinician would need to rule out conditions such as “…nonclassic adrenal hyperplasia, Cushing’s syndrome, androgen-producing tumors, … drug-induced androgen excess… thyroid dysfunction … hyperprolactinemia, as well as pregnancy …” In practice, I am not sure if this is so 100% of the time. A woman would have to undergo an extensive check up, including blood, imaging and other diagnostic and screening tests. In my case, this didn’t happen.

It seems that medicine hasn’t yet successfully implemented a specific protocol, and there are no specific tests that are done to diagnose PCOS. Most women in this process may or may not go through a physical exam, some blood tests and an ultrasound. As you now know, to be diagnosed with PCOS you must present with at least 2 of the 3 diagnostic criteria: 1) androgen excess, 2) PCO, Polycystic Ovaries, 3) Anovulation. This was the criteria chosen based on “expert opinions”. As such, women with PCOS present with varying phenotypes, or expressions, of this same condition. I hope the challenges of coming up with the PCOS diagnosis, and determining its prevalence and treatment, are becoming more and more apparent.

Evaluation of the Diagnostic Features

The evaluation of the 3 criteria can be based on clinical signs and symptoms, and/or diagnostic tests (blood, imaging, etc).

1. Hyperandrogenemia, i.e. high levels of male hormones, present as hirsutism (excess facial and body hair), acne (adolescent and/or adult), and androgenic alopecia (male-pattern baldness). These are clinical signs and symptoms. Blood analysis of free Testosterone, DHEAS, and SHBG assays are available. Problem here is that “There are no clear cutoffs for abnormal levels, and levels decline with age. The clinical meaning of isolated elevation in DHEAS is uncertain.”

Figure 1: Physical signs of PCOS

In my case, I presented with severe acne and hirsutism, since my mid teens, and later (early thirties) developed sudden and severe hair loss in the frontal scalp area. Clear physical signs of hyperandrogenemia. No blood tests were done to determine this.

2. PCO, Polycystic ovaries, on ultrasound present as “enlarged and contain numerous small fluid-filled sacs which surround the eggs”.

Figure 2: Ovarian cysts on ultrasound

Ultrasound is the most common used diagnostic tool for determining PCO. MRI can also be used, but currently it is only used for research purposes. When I started to notice severe scalp hair loss, I asked my doctor for a thyroid test and an ultrasound. This is when I was diagnosed with PCOS. The presence of PCO on ultrasound and the physical appearance of androgen excess sufficed to make the diagnosis that I had been waiting for.

3. Anovulation

Of the 3 diagnostic criteria, ovulation might be the most difficult to determine. Nonetheless, “All major classifications of PCOS include ovulatory dysfunction as a component…”. Ovulation is difficult to evaluate mostly because even the normal ovulatory cycle is not well understood. Women with normal menstrual cycles may have ovulatory dysfunction, presenting as chronic anovulation or oligo-ovulation (irregular ovulation). Clinicians may perform a blood test, “serum progesterone level during the suspected midluteal phase of the cycle and presume that the cycle is oligo-anovulatory if the level is lower than 3–4 ng/mL.” Over-the-counter ovulation prediction kits rely on urine strips to test for LH (Leuteinizing Hormone) spikes. LH surges just before a woman ovulates (the egg passes through the ovary wall and travels down the Fallopian tube). Baby-making time! I used many of these urine strips during my infertile months… I noticed the same thing that many of my patients do. Even during months that I had a menstrual cycle, regular or not (much longer than 28 days), many of those months, I did not have an LH surge. No ovulation. As such, in my case, I checked all 3 boxes for the diagnostic criteria of PCOS. Hyperandrogenemia, check! PCO, check! Anovulation, check!

In summary, PCOS is a diagnosis of exclusion, and to be diagnosed, 2 of the above 3 criteria must be met…nowhere in the definition of PCOS nor in its diagnostic criteria does it state insulin resistance or obesity. Most medical articles on the matter state that insulin resistance is highly associated with PCOS, present in at least 40%-70% of the time, and that at least 50%, and as many as 80% of women with PCOS are obese.

The Mayo clinic states that in order to be diagnosed with PCOS, as part of the panel, some blood tests are often recommended. Among these are “several hormones to exclude possible causes of menstrual abnormalities or androgen excess that mimic PCOS. Additional blood testing may include fasting cholesterol and triglyceride levels and a glucose tolerance test, in which glucose levels are measured while fasting and after drinking a glucose-containing beverage.” I was never tested for any of this, but knowing what we now know, it makes since to test for Metabolic Syndrome.

Figure 3 Prevalence of metabolic syndrome in women with PCOS

Testing for hyperinsulinemia, or insulin resistance, however has its own challenges. “Attempts to quantitate the prevalence of insulin resistance in PCOS are limited by the methods used to determine insulin sensitivity.” In other words, if you can’t easily and readily diagnose insulin resistance in these women, then we can’t really say how many women with PCOS have insulin resistance, although it is estimated to be between 40-70%. “… it is clear that some women with PCOS have normal insulin sensitivity. Thus, defects in insulin action on glucose metabolism are not a universal feature of the syndrome.” Although it is true that some PCOS phenotypes seem to present with normal insulin sensitivity, such as in the case of PCOS women who ovulate, and those that don’t ovulate but have normal androgens levels, these are thought to be transient phenotypes. In other words, there is the possibility that these women may eventually develop insulin resistance in the presence of certain key conditions.

Obesity too is a common feature of PCOS, but not part of the diagnostic criteria. It is estimated that 20-50% of women with PCOS may initially present with a lean phenotype. This lean phenotype may also be a transient one. Lean PCOS women may be of the ovulatory phenotype or those with normal androgen levels. These women present with a normal metabolism. Obesity is determined by BMI (Body Mass Index) based on weight vs. height. A better measurement might be one that considers body fat percentage and distribution (calipers, densitometry, etc). Lean women with PCOS may be at an increased risk for central obesity in relation to lean women without PCOS. This is what happened in my case. I was lean, by BMI standards, but had a growing central obesity concern and eventually became anovulatory. Interesting to note that in my case, the PCOS phenotype did evolve. I did eventually develop all 3 diagnostic criteria, as well as obesity and insulin resistance. I went from having PCOS with a normal metabolism to developing metabolic syndrome and reproductive concerns.