PCOS & Weight Loss Resistance
Sixty percent of people with Poly Cystic Ovarian Syndrome (PCOS) struggle with a co-occurring disorder of obesity. And, because of this, they also are at risk for heart disease, metabolic syndrome, type 2 diabetes, and a myriad of other disorders. Thus, the care of these people is nuanced, complex, and the care needs to be patient-centered with an empathetic approach.
A study done in 2022 found that people with PCOS had a higher rate of weight gain than people without PCOS - 0.26 kg of weight gain a year after controlling for lifestyle factors (Awoke). What was interesting about this study is that for all people, there were positive associations between weight gain and energy intake (calories), sitting time and stress, and inverse associations with fiber intake and physical activity - so it is imperative these lifestyle pillars become optimized for the person diagnosed with PCOS. Furthermore, each BMI unit increase in people with PCOS was associated with a 9.2% increase in a PCOS diagnosis.
For people with PCOS, weight loss can be a real struggle. Insulin resistance affects up to 50% of all people with PCOS, and 70-90% of people with PCOS and obesity. The theorized reasons why weight loss is so hard for people with PCOS is because they tend to have impaired glucose utilization, reduced postprandial thermogenesis, fatigue, and a reduced energy expenditure. They also tend to be hyperinsulinemic and have a harder time metabolically clearing their insulin (Tosi). They also tend to have more hypoglycemia episodes driving cravings. Reduced ghrelin, leptin resistance, and lower NPY all affect these people and how hungry and satisfied they are with meals.
People with PCOS tend to struggle with having a higher circulating volume of Free Fatty Acids (FFA), which contribute to worsening insulin resistance and inflammation. When there is excess adipose it reduces adiponectin, thus directly impacting insulin sensitivity in this population. In addition, FFA also induces hepatic insulin resistance, leading to decreased sex hormone binding globulin, which leads to more free testosterone those promoting the hyperandrogen component.
Lifestyle modifications were studied in people with PCOS, and they found weight loss induced by dietary interventions did seem to improve PCOS-related chronic inflammation and hyperandrogenism.
GLP-1 agonists (Semaglutide and Liraglutide) were found to promote hormone regulation, reduce testosterone, waist circumference, triglycerides, and improve hyperinsulinism, normalize total testosterone, total cholesterol, and HOMA-IR markers.
Evidence-based practice would suggest that a combination of exercise, diet, and pharmacological interventions are the most effective means for weight loss, improving ovulation, and normalizing the androgen levels of women. Interestingly, exercise combined with diet and ovulation inducers produced the highest ovulation rate improvement for people with PCOS.
People with PCOS have many co-occurring disorders they are at risk for because of how the biology of PCOS works and affects their metabolic process. Optimizing lifestyle modifications and using medication to help reduce the effects of obesity, metabolic syndrome, type 2 diabetes, and so many other co-occurring disorders should become the priority for these patients to be taken care of in an integrative and holistic way.
References
Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89:453.
Awoke MA, Earnest A, Joham AE, Hodge AM, Teede HJ, Brown WJ, Moran LJ. Weight gain and lifestyle factors in women with and without polycystic ovary syndrome. Hum Reprod. 2021 Dec 27;37(1):129-141. doi: 10.1093/humrep/deab239. PMID: 34788426.
Teede HJ, Joham AE, Paul E, Moran LJ, Loxton D, Jolley D, Lombard C. Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women. Obesity (Silver Spring). 2013 Aug;21(8):1526-32. doi: 10.1002/oby.20213. Epub 2013 Jul 2. PMID: 23818329.
Tosi F, Dal Molin F, Zamboni F, Saggiorato E, Salvagno GL, Fiers T, Kaufman JM, Bonora E, Moghetti P. Serum Androgens Are Independent Predictors of Insulin Clearance but Not of Insulin Secretion in Women With PCOS. J Clin Endocrinol Metab. 2020 May 1;105(5):dgaa095. doi: 10.1210/clinem/dgaa095. PMID: 32119099.
Bril F, Ezeh U, Amiri M, Hatoum S, Pace L, Chen YH, Bertrand F, Gower B, Azziz R. Adipose Tissue Dysfunction in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023 Dec 21;109(1):10-24. doi: 10.1210/clinem/dgad356. PMID: 37329216; PMCID: PMC10735305.
Alenezi SA, Elkmeshi N, Alanazi A, Alanazi ST, Khan R, Amer S. The Impact of Diet-Induced Weight Loss on Inflammatory Status and Hyperandrogenism in Women with Polycystic Ovarian Syndrome (PCOS)-A Systematic Review and Meta-Analysis. J Clin Med. 2024 Aug 21;13(16):4934. doi: 10.3390/jcm13164934. PMID: 39201076; PMCID: PMC11355208.
Austregésilo de Athayde De Hollanda Morais B, Martins Prizão V, de Moura de Souza M, Ximenes Mendes B, Rodrigues Defante ML, Cosendey Martins O, Rodrigues AM. The efficacy and safety of GLP-1 agonists in PCOS women living with obesity in promoting weight loss and hormonal regulation: A meta-analysis of randomized controlled trials. J Diabetes Complications. 2024 Oct;38(10):108834. doi: 10.1016/j.jdiacomp.2024.108834. Epub 2024 Aug 20. PMID: 39178623.
Ruiz-González D, Cavero-Redondo I, Hernández-Martínez A, Baena-Raya A, Martínez-Forte S, Altmäe S, Fernández-Alonso AM, Soriano-Maldonado A. Comparative efficacy of exercise, diet and/or pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity: a systematic review and network meta-analysis. Hum Reprod Update. 2024 Jul 1;30(4):472-487. doi: 10.1093/humupd/dmae008. PMID: 38627233; PMCID: PMC11215161.
