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Department of Internal Medicine and National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville 22908; Medical College of Virginia, Richmond 23249; and Endocrine Section, Veterans Affairs Medical Center, Salem, Virginia 24153
We evaluated an apparent distinction between
follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
dynamics: visually, it appears that the pattern of serum concentrations
of FSH is more irregular than that of LH in younger human females. We
studied healthy humans, with LH and FSH serum samples obtained every 10 min for 24 h. Three groups were studied: 24 young females [8
early follicular (EFol), 8 late follicular (LFol), and 8 midluteal
(MLut)]; 8 postmenopausal females; and 17 males 21-79 yr of
age. To quantify serial irregularity, we utilized approximate entropy
(ApEn), a scale- and model-independent statistic. For young females,
FSH was consistently more irregular than LH per subject: among the younger subjects, ApEn(FSH) 
ApEn(LH) = 0.342 ± 0.270;
ApEn(FSH) > ApEn(LH), P < 0.00001;
ApEn(FSH) > ApEn(LH) for 23 of 24 subjects. For each cycle stage,
pairwise ApEn(FSH) > ApEn(LH): P < 0.005 for both LFol and MLut, P < 0.01 for EFol. Notably, for the postmenopausal women, the
irregularity difference vanished: ApEn(FSH) ApEn(LH) = 0.008 ± 0.205. Males exhibited qualitatively similar results: ApEn(FSH) ApEn(LH) was significantly and negatively correlated with age (r = 0.75,
P = 0.0006). The capability to
quantify (the extent of) differences between FSH and LH release, beyond
the general 1:1 correspondence between primary LH and FSH pulses, suggests a means to assess bihormonal changes as a clinical marker of
altered reproductive status in a variety of settings, e.g., a
perimenopausal milieu. Mechanistically, the erosion of unequal FSH-LH
regularity with age is consistent with a loss of synchrony control
within the integrated hypothalamo-pituitary-gonadal axis.
gonadotropin; approximate entropy; pulsatility; menopause; aging; luteinizing hormone; follicle-stimulating hormone
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