Differential Effects of Various Androgens on Polycystic Ovary Syndrome

Abstract

The hyperandrogenism in polycystic ovary syndrome (PCOS) is associated with the risk for the future development of the cardiovascular disease. The objective of the study is to verify whether different androgens have the same harmful effect. This cross-sectional study enrolled 823 women with PCOS: 627 (76.2%) with biochemical hyperandrogenism and 196 (23.8%) with normal androgen levels. The role of individual androgen was evaluated using univariate and multivariate logistic regression. In normoandrogenemic PCOS (NA-PCOS), free androgen index (FAI) predicted significant abnormality in visceral adipose index (VAI, OR=9.2, p=0.002) and dehydroepiandrosterone (DHEA) predicted against alteration in β-cell function (OR=0.5, p=0.007). In hyperandrogenemic PCOS (HA-PCOS), FAI predicted derangements in waist triglyceride index (WTI), VAI, and lipid accumulation product (LAP) (OR ranging from 1.6 to 5.8, p<0.05). DHEA weakly predicted against VAI (OR 0.7, p=0.018), dehydroepiandrosterone sulfate (DHEAS) tended to predict against the conicity index (OR=0.7, p=0.037). After multiple regression, FAI retained significant strength to predict various anthropometric and metabolic abnormalities (OR ranging from 1.1 to 3.0, p<0.01), DHEA was kept as a protector factor against WTI, LAP, and VAI (OR ranging from 0.6 to 0.9; p<0.01) and DHEAS against the conicity index (OR=0.5, p<0.001). In conclusion, the free androgen index was the most powerful predictor of anthropometric and metabolic abnormalities of polycystic ovary syndrome. Conversely, DHEA and DHEAS demonstrated protective effects against disorders in some markers of obesity and abnormal metabolism.

Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women

“…Our results also go in line with Cai et al [41] who observed that FAI was positively associated with WC, BMI, TG, TC and LDL-C and negatively associated with HDL-C. Recently, de Medeiros et al [42] reported a positive association of FAI with most anthropometric and metabolic biomarkers in PCOS women. Al Kindi et al [43] recommended the use of FAI than testosterone alone in the routine investigation for hyperandrogenism in women.…”

The interplay between androgens and the immune response in polycystic ovary syndrome

“…In PCOS, androgens have deleterious impacts on adipose tissue function. The influence of androgens on adipocyte function is determined by levels of circulating androgen, “androgen receptor density and affinity,” [ 16 ] and the enzymatic activity of local steroids. The ability of adipocytes to modulate steroidogenic enzyme activity is of particular importance in the progression of hyperandrogenism in PCOS due to the conversion of weak androgens to strong androgens.…”

“…For this reason, the interrelation of hyperandrogenism and obesity in women with PCOS may originate from increased adipocyte steroidogenesis. With regards to androgen receptors, which are present on preadipocytes as well as mature adipocytes, androgens can affect gene expression, cell differentiation, and proliferation, “and carbohydrate and lipid metabolism” [ 16 ]. Androgens also increase the transcription of androgen receptors on mononuclear cells allowing for the release of adipocytokines, and the concentration of adipocytokines is further increased through production by immune cells.…”

“…The 2022 study conducted by De Medeiros et al [ 16 ] reviewed published studies from 1983 to 2021. The researchers highlighted that androgens on androgen receptors act as transcription factors that modulate gene expression, which is controlled by several factors, including “peroxisome proliferator activated receptor gamma and the mitogen activated protein kinase cascade” [ 16 ]. The researchers conveyed that androgens repress the differentiation of adipocytes epigenetically through lowered transcription of peroxisome proliferator activated receptor gamma.…”

“…In PCOS patients, adipocytes produce higher than average amounts of androgens. Not only are androgens damaging to adipocytes, but they also stimulate the secretion of steroidogenic cells [ 16 ]. Studies have suggested that abnormalities in steroidogenic cells contribute to the hypersecretion of androgens in PCOS [ 17 ].…”