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Androgen Levels as a Risk Factor for Metabolic Syndrome in Adolescent Girls with Polycystic Ovary Syndrome« Back to Volume 22, Issue 4, December 2006 - Table of Contents Polycystic ovary syndrome (PCOS) is a frequent disorder in adolescent girls; it is a leading cause of glucose intolerance combined with insulin resistance (IR), mostly in obese individuals. As observed in women with PCOS, it is likely that the girls are at risk for developing metabolic syndrome (MBS). Coviello et al investigated whether adolescent girls with PCOS had increased prevalence of MBS. They also tested the hypothesis that an increase in circulating androgen levels was a distinct risk factor for developing MBS. The cross-sectional control study included 49 adolescent girls with PCOS and 165 girls from a national (United States) survey population. The criteria for MBS included waist circumference, systolic and diastolic blood pressure, fasting blood triglycerides, HDL-cholesterol, and glucose according to reference studies by de Ferranti et al1 and Cook et al.2 The prevalence of MBS was evaluated and found to be significantly increased with increasing free-testosterone (uT) quartile when groups were analyzed according to 2 distinct criteria for MBS. MBS was found in 37% of adolescent girls with PCOS compared with only 5% in the control group (mean age 17 ± 2yrs [range 12-19 yrs] and from non-Hispanic, white origin). In addition, the risk of MBS was higher in girls with PCOS compared to the general adolescent population after adjusting for body-mass index (BMI [P<0.01]); they were 4.5 times more likely to have MBS than their age-matched control group. The mean uT level was higher in girls with PCOS and MBS. This difference remained significant after adjusting for IR and BMI. The prevalence of MBS increased with increasing androgen levels as expressed by uT quartile and decreased with increasing SHBG quartile. It was also shown that the high prevalence of MBS in these girls could not be accounted for by the severity of obesity alone. In prospective studies, BMI and waist circumference have been shown to be predictive of MBS and cardiovascular risk in adolescents. They reflect increased visceral adiposity which is associated with IR and is thought to be the primary cause of MBS–a common feature of PCOS in adults. It appeared in this study of an adolescent population that MBS could not be accounted for by the central obesity (as expressed by waist circumference). It was shown that the odds of developing MBS was independently and strongly associated with the level of androgen (largely ovarian) as expressed by the level of circulating uT (but not total testosterone [T], Figure). As a consequence of these findings, the authors considered a specific intervention in these patients aiming at reducing their hyperandrogenemia using antiandrogens in addition to insulin sensitizers, diet, and increased exercise. These data would go along with some evidence that intra-abdominal fat development may be influenced by androgens. It seems important, therefore, to focus on circulating androgens when investigating girls with PCOS, regardless of their BMI. Bioavailable Testosterone Quartile. The prevalence of the metabolic syndrome increased with increasing uT quartile (χ 2 test for trend, P<0.001) with both sets of proposed criteria. Reprinted with permission: Coviello AD, et al. J Clin Endocrinol Metab. 2006;91:492–497. Copyright © The Endocrine Society. 2006. All rights reserved. Editor’s CommentHyperandrogenemia, with minor clinical features, is observed in girls during puberty when the first menstruation is delayed or followed by a prolonged period of irregular menstruations, indicating the absence of normal cyclic activity. Some of these girls develop clinical PCOS within a few years. There is also evidence that obesity prevalence in this age population has dramatically increased, leading to an increased prevalence of MBS. It is also well recognized that PCOS is frequently associated with an increased BMI in adolescent girls. In an editorial, Marshall3 focused on elevated circulating androgens, essentially of ovarian origin, as central actors in the development of future MBS. The androgens exert actions at several levels: 1) accelerate follicular atresia in the ovary; 2) impair regulation of GnRH secretion with elevated LH levels and rapid frequency of GnRH pulse secretion; and 3) impair the normal inhibitory feedback of progesterone and estradiol in the hypothalamus. These effects synergize with elevated plasma insulin levels to maintain elevated circulating androgens. In addition, hyperandrogenemia is more pronounced in girls with predominant visceral adiposity. Weight loss in these adolescents reduced the metabolic features. Interestingly, antiandrogen therapy also reduced the MBS. This approach of the PCOS metabolic consequences puts an emphasis on hyperandrogenemia as a component that should probably be dealt with by specific therapeutic agents, in addition to weight loss programs and insulin sensitizers. Raphaël Rappaport, MD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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