Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS

Abstract

. Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS. Am J Physiol Endocrinol Metab 282: E865-E872, 2002. First published December 11, 2001 10.1152/ajpendo.00458.2001We hypothesized that short-term calorie restriction would blunt luteinizing hormone (LH) hypersecretion in obese women with polycystic ovary syndrome (PCOS) and thereby ameliorate the anovulatory endocrine milieu. To test this hypothesis, 15 obese patients with PCOS and nine age-and body mass index-matched healthy women underwent 24-h blood sampling to quantitate plasma LH, leptin, and insulin levels. PCOS subjects were prescribed a very low caloric liquid diet (4.2 MJ/day) for 7 days and were then resampled. Basal and pulsatile LH secretion was threefold higher in PCOS subjects, but plasma insulin and leptin levels were not different in the calorie-replete state. Contrary to expectation, calorie restriction enhanced basal and pulsatile LH secretion even further. As expected, plasma glucose, insulin, and leptin concentrations decreased by 18, 75, and 50%, respectively. Serum total testosterone concentration fell by 23%, whereas serum estrone, estradiol, sex hormone-binding globulin (SHBG), and androstenedione concentrations remained unchanged. Enhanced LH secretion in the presence of normal metabolic and hormonal adaptations to calorie restriction points to anomalous feedback control of pituitary LH release in PCOS.leptin; insulin; dietary intervention; feedback regulation SPONTANEOUS PULSATILE LUTEINIZING HORMONE (LH) and exogenous gonadotropin-releasing hormone (GnRH)-stimulated LH release are increased (the former as a result of augmented LH pulse frequency and amplitude), whereas follicle-stimulating hormone (FSH) secretion appears normal or reduced in patients with polycystic ovary syndrome (PCOS) compared with normal women studied in the follicular phase of the menstrual cycle (2,7,23,46,57,58). The pathogenesis of LH hypersecretion in PCOS has not been elucidated but could include intrinsic defects in the hypothalamic control of GnRH pulse generation, accentuated pituitary responsiveness to GnRH stimulation, and/or altered hormonal feedback regulation of GnRH release or LH bioactivity (7,19,23,57). Whatever the mechanism, the deleterious effects of LH hypersecretion on fertility are indisputable (for review see Ref. 21). Transgenic mice overexpressing LH are anovulatory and hyperandrogenic and exhibit polycystic ovaries (27,36). Although a coexistent ovarian defect may contribute to anovulation in PCOS, it is conceivable that restoration of normal pulsatile LH secretion in obese PCOS patients would establish ovulatory cycles.Weight loss is often accompanied by resumption of ovulation in obese women with PCOS (33). The mechanism underlying this response remains unclear. One consideration is that calorie restriction and/or the concomitant reduction of plasma insulin and/or leptin concentrations may be responsible. A negative energy balance dampens pulsatile LH secretion in various mammalian sp...

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