Session: OR46-Hyperandrogenemia: Influences & Implications
Room 121 (Moscone Center)
Hyperinsulinemia by increasing activity of ovarian cytochrome P450c17α ,a key enzyme in the biosynthesis of ovarian androgens, plays a central role in the pathogenesis of obese and lean women with polycystic ovary syndrome (PCOS). Increased P450c17α activity is evidenced by exaggerated serum 17α-hydroxyprogesterone (17α-OHP) response to stimulation by gonadotropin-releasing hormone (GnRH) agonist. In obese PCOS women, weight loss improves insulin resistance and hyperandrogenism, resulting in improvement of clinical symptoms. Since lean PCOS women do not have the option of weight loss, we investigated whether composition and meal timing distribution may influence glucose metabolism, ovarian P450c17α activity and serum free testosterone
Objective: The objective of this study was to compare the effects of two isocaloric maintenance diets with different meal timing distribution on insulin resistance and hyperandrogenism in lean PCOS women.
Methods: Sixty lean PCOS women (mean age 31.9 ± 0.7 yrs, mean BMI 23.7 ± 0.2 kg/m2) were randomized into two isocaloric (~1800kcal) maintenance diets with different meal timing distribution: a breakfast diet (BF) (980 kcal breakfast, 640 kcal lunch, 190 kcal dinner) or a dinner diet (D) (190 kcal breakfast, 640 kcal lunch, 980 kcal dinner) for 90 days. We assessed (in the follicular phase) ovarian P450c17α activity (by measuring the response of 17α-OHP to a GnRH agonist, fasting serum steroids, serum sex hormone-binding globulin (SHBG) and indices of insulin resistance by OGTT that were measured at baseline, and after 90 days.
Results: As expected, no change in BMI occurred over 90 days. In the D group, the area under the curve (AUC) of glucose and AUC insulin by day 90 showed no significant change over time. In contrast, in the BF a significant decrease was observed in both AUC glucose (17274 ± 159 mg/dl/min vs. 13918 ± 81, p<0.0001) and AUC insulin (7251 ± 142 μU/L/min vs. 3774 ± 94, p< 0.0001) respectively. In the BF group, serum free testosterone decreased by 50% from 3.4 ± 0.2 to 1.7 ± 0.1 ng/ml (P < 0.0001), and SHBG increased from 2 ± 0.1 to 4.1 ± 0.2 µg/dL (p< 0.0001). These values did not changed in the D group.
Basal serum 17α-OHP decreased from 9.4 ± 0.7 to 6.2 ± 0.4 ng/dl (p < 0.01), GnRH-stimulated peak of serum 17α-OHP decreased from 421.5 ± 5.2 to 255.6 ± 5.7 ng/dl (P < 0.0001) and the AUC of serum 17α-OHP curve response to GnRH agonist decreased from 7153 ± 84 to 4428 ± 108 (p < 0.0001). Serum 17α-OHP values did not change in the D diet group
Conclusion: In lean PCOS women a high caloric intake at breakfast with reduced intake at dinner results in improved insulin sensitivity indices, reduced ovarian cytochrome P450c17α activity and ameliorates the hyperandrogenism. Meal timing and distribution of breakfast diet group may facilitate the therapeutic management of lean women with PCOS.
Nothing to Disclose: DJ, MB, JW, OF
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