Influence of Body Mass Index on Measured and Calculated Androgen Parameters in Adult Women with Hirsutism and PCOS

Abstract

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

“…These phenomena support the hypothesis that the definition of PCOS in the revised 2003 Rotterdam criteria identifies a different subset of women who have different endocrine profiles, whether they are hyperandrogenic or not. We recently reported that the BMI is associated with significantly lower SHBG levels in women with hirsutism and PCOS, resulting in significantly increased calculated free testosterone and FAI levels, which were appropriate markers for assessing hyperandrogenemia in these women (54,56).…”

The association of body mass index and biochemical hyperandrogenaemia in women with and without polycystic ovary syndrome

“…Changes in SHBG concentrations lead to an alteration of androgen and estrogen delivery to target tissues. Reduction of circulating SHBG determines an increase in the metabolic clearance rate of circulating SHBG-bound steroids, specifically testosterone, dihydrotestosterone, and androstenediol, the principal active metabolite of dihydrotestosterone [13]. This effect is compensated, however, by a consequent elevation of production rates.…”

“…Several studies suggest that adiposity is associated with hyperandrogenaemia [9][10][11], but this link between increasing BMI and hyperandrogenism may be mediated by insulin resistance [12]. There are studies that have failed to demonstrate a direct link between obesity and hyperandrogenism [13,14].…”

Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance

“…In brief, after the glucose and insulin levels had been measured, the following mathematical models were used to assess IR: the homeostatic model assessment of insulin resistance (HOMA-IR) (18), the quantitative insulin sensitivity check index (QUICKI) (19), and the insulin sensitivity index (ISI) (20,21). The defined cutoff points for the different insulin resistance indexes used were HOMA-IR R 2.5 (14,22), QUICKI % 0.33 (23,24), and ISI % 5 (25,26). Calculation of IR has been described in detail elsewhere (27).…”