Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man

To test the validity of venous sampling rates that are generally used to characterize pulsatile LH release in man (e.g. sampling every 15-20 min), we characterized apparent LH pulse frequency in blood withdrawn variously at 20- or 4- min intervals in 19 men, at 2-min intervals in 14 men, and at 1-min intervals in 6 men. In an effort to minimize detection bias, significant LH pulses were evaluated objectively using a computerized pulse-detection algorithm, which tended to maximize recognition of true-positive LH pulses, and minimize falsepositive and false-negative pulses. Under these conditions, intensified rates of venous sampling at 4-, 2-, and 1-min intervals exposed approximately 3.6, 4.9, and 13.7-fold more LH pulses, respectively, than could be discerned at a 20-min sampling frequency. In addition, more rapid rates of venous sampling disclosed a previously unobserved pattern of LH pulses, in which higher frequency, lower amplitude LH pulsations were interposed among low frequency, high amplitude LH peaks. Quantitatively, LH pulses unmasked by intensified rates of venous sampling exhibited significantly lower pulse amplitudes, expressed either as a fractional (%) or absolute (mlU/ml) increment, than pulses identified at 20-min intervals. In conclusion, we demonstrated that intensified rates of venous sampling unmask a significant number of otherwise unrecognized LH pulses in the circulation of normal men. Moreover, because generally employed sampling rates overlooked these more rapid physiological fluctuations in LH concentrations, patterns of both high and low frequency LH pulsations must now be characterized in various states of health and disease using more rapid sampling paradigms.