Faculty Bibliography

OBJECTIVE: To determine whether leptin and LH secretion in normal women is related to changes in metabolic rate. SETTING: Academic medical center. PATIENT(S) AND DESIGN: Ten young women with normal weight and menses were studied during the early follicular phase. Leptin and LH levels were sampled every 15 minutes over a 24-hour period. Metabolic rate was frequently sampled using indirect calorimetry. Luteinizing hormone pulsatility was analyzed using a Cluster Program analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Leptin, LH, and metabolic rate levels. RESULT(S): All subjects demonstrated a diurnal leptin curve. Luteinizing hormone pulses were increased in amplitude and slower after the leptin peak. The average (+/-SE) number of LH pulses per 6 hours slowed from 4.30 +/- 0.42 to 3.00 +/- 0.42 pulses after the leptin peak, whereas pulse amplitude increased from 1.64 +/- 0.26 to 2.51 +/- 0.42 mIU/mL after the leptin peak. The LH interpulse interval increased from 85.1 +/- 3.64 minutes to 108.8 +/- 10.26 minutes after the leptin peak. Metabolic rate began to drop approximately 4-6 hours before leptin levels peaked, going from 1.66 +/- 0.24 to 1.15 +/- 0.04 kcal/min after the leptin peak. CONCLUSION(S): There is a significant association between the timing of the leptin peak, the nightly slowing of LH pulses, and the fall in metabolic rate, suggesting a metabolic cycle in normal individuals

Caloric restriction caused by undernutrition or over-exercise is increasingly common and has significant health consequences such as hypothalamic amenorrhea, infertility, attainment of low peak bone mass, and bone loss leading to fracture. In these patients, the pathophysiology of amenorrhea and bone loss is multifactorial, involving hormones that integrate the nutritional state with the hypothalamic-pituitary-ovarian axis, including leptin and possibly ghrelin. The pathophysiology of bone loss includes nutritional deficiencies, possibly estrogen deficiency, and direct and indirect effects of leptin on bone. Identifying patients at risk for low bone mineral density and fracture is important, as is screening with dual energy radiograph absorptiometry. Treatment has focused on oral contraceptive use, yet improved bone mineral density is marked by nutritional recovery and anovulation reversal. Therefore, resolving the nutrition deficiency should be the cornerstone of treatment. Cognitive-behavioral therapy aims for weight recovery, which can lead to reversal of amenorrhea and improvement in other associated metabolic abnormalities. During treatment, estradiol levels can be followed to assess hypothalamic-pituitary-ovarian recovery because estradiol secretion may increase well before ovulation occurs. In patients failing the above interventions, hormone replacement should be considered, but bone mineral density should be followed because patients may continue to lose bone despite treatment with oral contraceptives if nutrition is not improved