Random and Non‐Random Coincidence Between Luteinizing Hormone Peaks and Follicle‐Stimulating Hormone, Alpha Subunit, Prolactin and Gonadotropin‐Releasing Hormone ulsations

We have examined the co‐pulsatility of luteinizing hormone (LH) and prolactin, LH and follicle‐stimulating hormone (FSH), and LH and α subunit in normal men. We tested whether the degree of physiologically observed co‐pulsatility (peak coincidence) significantly exceeded expected random concordance between independently pulsating hormone series. To this end, computer simulations were used to create synthetic endocrine time series pulsating randomly and independently at known frequencies. Resultant predictions of the mean, variance and probability distribution of the number of randomly coincident peaks permitted us to test the null hypothesis that physiologically observed hormone co‐pulsatility was due to chance peak associations alone. Physiological observations were made in 33 normal men and in six ovariectomized ewes subjected to combined hypothalamo‐pituitary and jugular venous catheterization. The following salient results were obtained: 1) random peak coincidence rates between independently pulsating hormone series were substantial at high pulse frequencies, but such random rates were significantly exceeded in the case of gonadotropin‐releasing hormone and LH peaks (P< 0.0001); 2) random coincidence was further increased when coincidence was defined as peak maxima occurring not only simultaneously but also within some defined time window (e.g. ±10 min, as commonly done in the literature); 3) significant co‐pulsatility could be demonstrated for simultaneous LH and FSH pulsations in normal men (P< 0.0001); 4) coincidence rates for 10‐min lagged (but not for simultaneous) LH and prolactin pulses were significantly more likely than chance associations; 5) observed coincidence between LH and a subunit pulses significantly exceeded expected (random) peak overlap (P<0.001); and 6) in contrast, hormone peaks in different men were only randomly associated. We conclude that based upon the means, variances and probability distributions calculated here, available reports on peak coincidence between pulsatile neuroendocrine time series must be re‐examined in the light of high rates of random coincidence observed between independently pulsating hormone series.