Retention of estradiol negative feedback relationship to LH predicts ovulation in response to caloric restriction and weight loss in obese patients with polycystic ovary syndrome

Van Dam, Eveline W. C. M., Ferdinand Roelfsema, Johannes D. Veldhuis, Simone Hogendoorn, Jos Westenberg, Frans M. Helmerhorst, Marijke Frolich, H. Michiel J. Krans, A. Edo Meinders, and Hanno Pijl. Retention of estradiol negative feedback relationship to LH predicts ovulation in response to caloric restriction and weight loss in obese patients with polycystic ovary syndrome. Am J Physiol Endocrinol Metab 286: E615-E620, 2004. First published December 16, 2003; 10.1152/ajpendo.00377.2003.--The present study tests the hypothesis that specific endocrine, metabolic, and anthropometric features distinguish obese women with polycystic ovary syndrome (PCOS) who resume ovulation in response to calorie restriction and weight loss from those who do not. Fifteen obese (body mass index 39 [+ or -] 7 kg/[m.sup.2]) hyperandrogenemic oligoovulatory patients undertook a very low calorie diet (VLCD), wherein each lost [greater than or equal to] 10% of body weight over a mean of 6.25 mo. Body fat distribution was quantitated by magnetic resonance imaging. Hormones were measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals before intervention and after 7 days of VLCD. Responders were defined a priori as individuals exhibiting two or more ovulatory cycles in the course of intervention, as corroborated by serum progesterone concentrations [greater than or equal to] 18 nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex hormone-binding globulin (SHBG) concentration but were otherwise indistinguishable from nonresponders. Body weight, the size of body fat depots, and plasma insulin levels declined to a similar extent in responders and nonresponders. Also, SHBG increased, and the free testosterone index decreased comparably. However, responders exhibited a significant decline of circulating estradiol concentrations (from 191 [+ or -] 82 to 158 [+ or -] 77 pmol/l, means [+ or -] SD, P = 0.037) and a concurrent increase in LH secretion (from 104 = [+ or -] 42 to 140 [+ or -] 5 U*[1.sup.-1]*[day.sup.-1], P = 0.006) in response to 7 days of VLCD, whereas neither parameter changed significantly in nonresponders. We infer that evidence of retention of estradiol-dependent negative feedback on LH secretion may forecast follicle maturation and ovulation in obese patients with PCOS under dietary restriction. fertility; ovarian cycle; sex hormones; body fat distribution; gonadotropins