Figure 4 Pathophysiological heterogeneity in patients with PCOS Figure 4 | Pathophysiological heterogeneity in patients with PCOS. Polycystic ovary syndrome (PCOS) is the result of the interaction of a primary abnormality in androgen synthesis (manifesting as androgen excess) with other factors, such as abdominal adiposity (red and white targets), obesity and insulin resistance. At one extreme (*), the disorder in some patients is severe enough to result in PCOS even in the absence of triggering factors (light-blue-shaded woman on the left). At the other extreme (**), a very mild defect in androgen secretion is amplified by the coexistence of abdominal adiposity, obesity and/or insulin resistance (pink-shaded woman on the right). Between the two extremes, there is a spectrum in the severity (range of blue-shaded to pink-shaded women in the middle) of the primary defect in androgen secretion, providing an explanation for the heterogeneity of patients with PCOS with regards to the presence of obesity and metabolic comorbidities. However, all patients share a primary defect in androgen secretion. Adapted with permission from Refs 36,114, Elsevier and Oxford University Press, respectively. Adapted with permission from Escobar-Morreale, H. F. & San Millan, J. L. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol. Metab. 18, 266–272 (2007), and Escobar-Morreale, H. F., Santacruz, E., Luque- Ramirez, M. & Botella Carretero, J. I. Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum. Reprod. Update 23, 390–408 (2017), respectively. Escobar-Morreale, H. F. (2018) Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment Nat. Rev. Endocrinol. doi:10.1038/nrendo.2018.24