HJAR Jul/Aug 2024

HEALTHCARE JOURNAL OF ARKANSAS I  JUL / AUG 2024 25 izing in diagnosing and treating insulin resis- tance, prediabetes, and PCOS, while ordering somewhat obscure tests like DHEA sulfate and testosterone levels in women and while also prescribing metformin routinely in a way that was outside the evidence-based boundaries of my own training, I was indeed skeptical that it could just be another example of doctors going down a path of monetizing conditions where they deem there is a niche to create and capture value for themselves dispropor- tionately to the value they create for patients. I was and am right about the medical quack- ery of chronic Lyme disease but could not have been more wrong about PCOS. Not only did I not properly allocate my time to attempt to stay up to date, I also lacked the curiosity to better explore a condition that would have al- lowed me to help 10% of my female patients. Getting it right would have required me to be vulnerable and admit that my medical knowl- edge was beginning to get out of date while also being curious enough to devote some of my precious time to exploring it further. Understanding polycystic ovary syndrome (PCOS): It’s not just about the ovary The name of the condition is a bit of a mis- nomer because having polycystic ovaries on ultrasound imaging is not even a necessary criterion for diagnosis. While being over- weight or obese is common in PCOS, it also is not an essential criterion. Pathophysiology is complex, but insulin resistance plays a cen- tral role. Women can have tremendous diffi- culty succeeding with intentional weight loss even if they are modifying their dietary and exercise patterns. Similar problems exist in post-menopausal women for a variety of rea- sons that we can explore more fully in the next article, but age, genetics, and reduced estro- gen levels all play key roles in the hormone- metabolism connection, making weight loss after menopause quite challenging. In PCOS, these hormone-metabolism issues occur well before menopause, though. And conventional thinking fails these women badly. I underwent medical training in the 1990s when dogma er- roneously likened conditions such as obesity or being overweight with that of gluttony. The assumption of that time was that weight loss was a function of “calories in versus calories out,” and to effectively lose weight, all you had to do was eat less and/or exercise more. We now of course know it is not nearly so simple. A brief review of physiology concepts is in or- der. Metabolism involves chemical processes of energy expenditure, or, more simply, the rate at which we burn calories from the food we con- sume to sustain life. Hormones are the chemi- cal messengers that control various metabolic processes throughout the body. Hormones are akin to musicians that are responsible for a veri- table symphony of these metabolic processes, and if they had a conductor, it would be the pituitary gland, which is often labeled as the master metabolic gland. The pituitary gland is situated anatomically very close to the hypo- thalamus in the brain and is connected to the brain by both nerves and blood vessels. Two of its hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are respon- sible for regulating the male hormone testos- terone, and the female hormones estrogen and progesterone. And like any orchestra, if even one musician gets out of whack, it risks disturb- ing the performance of the entire orchestra. Such is the case with hormones as it relates to PCOS. It could be a failure of the conductor itself or perhaps it is due to one of the many musicians, in this case the hormone insulin. While we still do not know the exact patho- physiology underlying PCOS, there are two major hypotheses. It could be due to disor- dered hypothalamic function driving the pitu- itary gland, the conductor, to release excess LH over FSH. High levels of LH then trigger the production of excess androgens, or “male” hormones like testosterone, that could cause abnormal patterns of hair growth in women while also inhibiting normal follicle develop- ment in their ovaries, thus resulting in irregular menstrual periods and potential infertility. The second possibility is that of a rogue musician disrupting the entire orchestral performance. Insulin resistance may very well be the driving factor behind PCOS. Insulin can directly stimu- late cells within the ovary, causing increased male hormone production. Under this second hypothesis, insulin circulates through the hy- pothalamus in the brain to drive increased pulses of gonadotropin-releasing hormones from the pituitary gland, causing increased production of LH over FSH, thus impacting normal ovarian function. Insulin also indirectly increases the amount of “free” or active tes- tosterone, which in turn inhibits normal follicle development and the resulting irregular men- strual periods and infertility issues. Lastly, it is the insulin resistance that contributes to cen- tral weight gain and difficulty losing weight. I’ve spoken before about one of the origi- nal sins of healthcare being that somewhere along the way, we divorced mental health from physical health; but another sin is that we also divorced gynecologic health from inter- nal medicine and primary care. As a male in- ternist and primary care physician, I was more than happy to defer gynecologic issues to my gynecology colleagues. And for many issues, it is very reasonable or even necessary to do so. They have acquired an area of expertise for women’s health issues that I could never hope to replicate. But the discipline of endocrinol- ogy resides firmly within the knowledge do- main of internal medicine, and insulin, the hor- mone secreted by the pancreas to help control blood sugars, is clearly an endocrine concept. During those years in private practice, I knew of the importance of insulin resistance as it related to diabetes and metabolic syn- drome but knew little of the intricacies of its relationship to PCOS. Insulin resistance may very well be the driving factor behind PCOS. So, those new clinics that were measuring DHEA sulfate and testosterone levels in wom- en while routinely prescribing metformin, an insulin-sensitizing agent that helps the insulin in your body work better — i.e., reduces in- sulin resistance — was not medical quackery but rather cutting-edge medicine in an area where my own knowledge was woefully lacking. Diagnosing and managing PCOS Diagnosing PCOS begins with the single most important interaction in healthcare, albeit one that is not at all highly valued by traditional transaction-based healthcare financing mecha- nisms — listening to and talking with patients. To start, we need to know about a woman’s last menstrual period and whether she is experienc- ing menstrual irregularity. Anovulatory men- strual cycles, where a woman fails to ovulate because of the overproduction of testosterone respective to estrogen, results in infertility. So, asking about possible infertility is equally im- portant. A woman who has not been using con- traception for years and who has not yet got- ten pregnant may very well be suffering from PCOS. Asking about hirsutism — abnormal