Methods for Assessing the Linkage Between Pulsatile Hormone Profiles

Abstract

ABSTRACT. Merriam, G.R., Ma, N., Liu, L., Wachter, K.W. and Libre, E. (Reproductive Endocrine Unit, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA). Acta Paediatr Scand [Suppl] 349: 167, 1989. Although the different anterior pituitary hormones are generally considered to be regulated independently, examination of their patterns in blood suggests that pulsatile secretion of several of these hormones may be synchronized. Traditional methods of cross‐correlation analysis may not be adequate for quantifying this linkage. Since some simultaneity may arise by chance, expected rates of random coincidences must also be estimated to determine if apparent concordance rates significantly exceed those due to chance. A method of estimating linkage by counting simultaneous and near‐simultaneous events within temporal‘windows’of varying width is proposed and tested against 11 series of luteinizing hormone (LH) and prolactin measurements from normal men. Rates of concordance in series drawn from different subjects rather than the same subject, or series scrambled in time, do not contain meaningful simultaneous events and so can be used to estimate the rate of random synchrony. By these standards, a clear excess of concordant prolactin and luteinizing hormone (LH) peaks was observed in normal men, suggesting significant physiological synchrony between these pulses of secretion. This method can be applied to a variety of hormonal systems.

Objective assessment of concordance of secretory events in two endocrine time series

“…Other authors have pointed out that a certain degree of spurious concordance between two uncorrelated hormone series occurs by chance alone (6)(7)(8)(9)(10). This chance association has been variously evaluated by computer simulation of data (8,9,23), by mismatching and scrambling the original data (10) and by estimation of approximate probability from all subjects (6,7).…”

“…Various measures have been previously used for the association or temporal relationship between two hormones, such as percent concordance, frac¬ tion of concordance or probability of concordance (6,7,10,25). In some studies, results have been simply expressed as number of coincident peaks (corresponding to "a" in Table 1) (8,9), and the significance assessed for series of given length.…”

“…These new methods (7)(8)(9)(10)26) all have in common the purpose of providing a simple tool for investi¬ gation of endocrine pathophysiology. The present study provides an approach which is simple, intu¬ itive and generally applicable.…”

“…tion of partial cross-correlation coefficients, smoothing and high-pass filtering can be and have been performed (2)(3)(4)(5), at the cost of increased complexity of calculations. Other approaches have been based on calculation of probability levels based on observed frequencies (6,7), on computer simulations (8,9) or on other statistical techniques (10).…”

Temporal coupling among luteinizing hormone, follicle stimulating hormone, β-endorphin and cortisol pulse episodes in vivo

“…This development contrasts with earlier procedures designed to deal with only two (paired) series (e.g. [7][8][9][10][11][12]. Here, we have applied this closed-form methodology for the first time to investigate in vivo triple and quadruple co-pulsatility of LH, FSH, jS-endorphin and cortisol in man.…”