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And now to a much more practical subject: have you heard about “PCOS diets”?

They suddenly have become a hot topic all over the Internet. But looking a little closer into the wisdom that is being offered, it quickly becomes apparent that practically nobody is addressing the immunological HH-PCOS. Universal attention is given only to the metabolic H-PCOS. Because H-PCOS patients usually are overweight, everybody is talking about weight loss; and because these patients even at younger ages already often suffer from insulin resistance, everybody is recommending avoiding refined carbohydrates since those promote insulin resistance. Recommended foods are high-fiber vegetables and fish. What, therefore, really happens when most so-called PCOS diets are offered, they are weight loss diets (and, yes, of course in combination with exercise), derived from the basic assumption that all PCOS patients must be struggling with overweight. But, as we already know from the preceding section, this is, of course, not true: a good number of PCOS patients are “lean” women and the last thing they need is further weight loss. As HH-PCOS patients they, however, may benefit from an anti-inflammatory diet since, as noted before, ca. 85% demonstrate autoimmunity and/or inflammation if appropriately tested. This kind of diet involves avoidance of wheat/gluten, dairy and sugar and active use of anti-inflammatory spices like cumin. The Mediterranean diet, heavy on olive oil, grains, and fatty fish, is widely considered anti-inflammatory as well.

This is basically the same diet also recommended for another major inflammatory infertility diagnosis in women,- endometriosis. PCOS diets,” per-se, therefore, really do not exist; once diagnosed with PCOS, changing one's eating habits may, however, make sense, but only if the underlying PCOS condition has been identified. Just as losing weight makes no sense with HH-PCOS, an anti-inflammatory high calory diet may do absolutely no good in a H-PCOS patient. Which brings us to another important point of difference, we previously addressed on several occasions in this newsletter: Infertility patients, and especially PCOS patients, are frequently taking a variety of supplements and/or medications. Among the former is myoinositol (or related inositols), which has been well established as effective in H-PCOS patients who, as noted above, usually are hyperandrogenic.

Most HH-PCOS patients by the time they are in fertility treatments are, however, already hypo-androgenic and requires supplementation with androgens rather than further reductions. Myoinositol in HH-PCOS patients, therefore, is contraindicated. A frequently prescribed medication in PCOS is metformin. It usually is prescribed for four reasons: (i) to lower blood sugar levels (it also is a primary treatment for diabetes); (ii) to lower androgen levels; (iii) to regulate the usually irregular menstrual periods of H-PCOS women and, (iv) to help with weight loss. But once again, these potential benefits apply only to H-PCOS patients. Prescribing metformin to HH-PCOS patients, therefore, makes little sense. Finally, allow us to take this opportunity to also introduce a little bit of cutting-edge science to this subject: One of the most interesting new areas in medicine is the study of biota (innate bacterial populations in bodily cavities). The largest and biologically most important biome in our bodies is that of the gastrointestinal tract, now well recognized to have enormous impact on practically all organs in the body, including the brain. Though research of biota regarding infertility is just at the beginning, some studies suggest that gut microbiota may have significant effects on PCOS. For example, a very recent mouse study in a leading science journal suggested that an axis consisting of gut microbiota, bile acid and interleukin-22 “orchestrates” PCOS.1 Once again it is, however, important to point out that the PCOS model used only reflected H-PCOS. Human adolescents with PCOS demonstrated altered biodiversity and relative abundance in gastrointestinal microbiota in comparison to obese adolescents without PCOS.2 A systematic review recently summarized current knowledge on the subject. 

Why does all of this have relevance to the subject of “PCOS diets”? Because gut microbiota can be easily manipulated. In a rat model of PCOS, Chinese investigators recently, for example, demonstrated that an anti-androgenic contraceptive pill (Diane-35) in combination with probiotics restored abnormal diversity of gut microbiota, improving the PCOS rats’ reproductive function. In contrast the sugar- and lipid-lowering supplement Berberine drastically reduced species specificity and amount of gut microbiota without having positive effects on PCOS.4 A directed dietary impact through the gut microbiome, therefore, can be expected in PCOS, though will unquestionably be different for H-PCOS and HH-PCOS. A recent study in Cell, for example, beautifully demonstrated how dietary interventions with plant-based fiber and especially fermented foods (like kimchi, yogurt, etc.) targeting gut microbiota influence immune function.5 Considering the likely genomic differences between H-PCOS and HH-PCOS one, therefore, can foresee simple but varying interventions into gut-health in these two forms of PCOS.

REFERENCES 1.QI et al. Microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med 201925(8):1225-1233

2.Jobira et al. Obese adolescents with PCOS have altered biodiversity and relative abundance in gastrointestinal microbiota. J Clin Endocrinol Metab 2020;105(6):e2134-e2144

3.Guo et al. Gut microbiota in patients with polycystic ovary syndrome: a systematic review. Reprod Sci 2021; doi: 10.1007/s43032-020-00430-0

4.Zhang et al. Diversity of the gut microbiota in dihydrotestosterone-induced PCOS rats and the pharmacologic effects of Diane-35, probiotics, and Berberine. Front Microbiol 2019;10:175 5.Wastyk et al. Gut-microbiota-targeted diets modulate human immune status. Cell 2021;184(16):4137-4153

Norbert Gleicher, MD, FACOG, FACS Norbert Gleicher, MD, FACOG, FACS, is an infertility specialist specializing in autoimmune diseases at the Center for Human Reproduction in the Upper East Side of Manhattan in New York City.

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