Role of classic C19 and 11-oxygenated C19 steroids on androgens excess and metabolic profile of women with Polycystic Ovary Syndrome

• Grant number: 17/21567-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2020
• End date: April 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Larissa Garcia Gomes
• Grantee: Larissa Garcia Gomes
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Helena Panteliou Lima Valassi

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common metabolic endocrine disorder in women of reproductive age, with a prevalence of 8% to 13%. It´s a complex disease that affects multiple aspects of women's health. Women with PCOS have a greater risk of glucose intolerance and type 2 diabetes mellitus, non-alcoholic fatty liver disease, metabolic syndrome, mood changes and endometrial cancer when compared to healthy women. Androgen excess androgens and metabolic dysfunction can occur heterogeneously in women with PCOS, and there is a positive correlation between hyperandrogenism and poor metabolic profile. In this context, the correlation between hyperandrogenemia, obesity and insulin resistance is bidirectional, and androgen excess appears to be the main marker of metabolic risk in PCOS patients. However, studies that correlated androgen concentrations with anthropometric, biochemical, and inflammatory markers are controversial. The recent discoveries of the potential androgenic role of C19 11-oxygenated steroids in human hyperandrogenic disease raised the possibility that these steroids are the best marker of clinical hyperandrogenism and metabolic complications in PCOS patients. Our hypothesis is that C19 11-oxygenated androgens behave heterogeneously in the different PCOS phenotypes and are potential biomarkers of insulin resistance, metabolic dysfunction and inflammation in women with PCOS. Thus, our primary objective is to measure the classic steroids - DHEA, total testosterone and androstenedione, and the C19 11-oxygenated steroids - 11OHA4, 11OHT, 11KA4 and 11KT by LC-MS / MS, and to correlate these hormone levels with clinical, anthropometric, metabolic and inflammatory parameters of PCOS patients at reproductive age compared to healthy and BMI matched controls. Fifty-one patients with PCOS and 32 control women were evaluated in a pilot study. Patients with PCOS have a mean age of 28.8 years, BMI 31.8 kg / m² and increased abdominal circumference (mean of 103 cm). Approximately 10% of these women have type 2 diabetes, 73% have dyslipidemia and 8% have high blood pressure. Initially 45/51 patients with PCOS fulfilled criteria for classic phenotype and the remaining 6/51 patients corresponded to the normoandrogenic phenotype. We established a collaboration with the University of Birmingham, UK, and samples were sent for measurement of classic C19 and 11-oxygenated androgens in 38 PCOS and 16 control women, by LC-MS / MS. In absolute values, the serum concentrations of classic C19 and 11-oxygenated androgens are higher in PCOS patients compared to controls. In addition, the evaluation of classic C19 serum concentrations by LC-MS / MS identified hyperandrogenemia in 4 of 6 patients with normoandrogenic phenotype. However, sample size needs to be expanded to assess which androgens correlate better with hyperandrogenic, metabolic and inflammatory manifestations in PCOS patients. (AU)