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Emergent Oscillations in Mathematical Model of the Human Menstrual Cycle

  • Natalie L. Rasgon, Lara Pumphrey, Paolo Prolo, Shana Elman, Andre B. Negrao, Julio Licinio and Alan Garfinkel...

Abstract

Background:

The aim of this study was to develop a mathematical model of the hypothalamo-pituitary-gonadal axis that would reflect available data in humans.

Methods:

A model of hormonal relationships at the early follicular and midluteal phases of the human menstrual cycle is proposed.

Findings:

Two distinct temporal patterns of oscillatory behavior have been demonstrated for both pituitary and gonadal steroids in the early follicular phase: first, rapid oscillations in gonadotropin releasing hormone, follicle stimulating hormone, and luteinizing hormone (Q∼1 hour) that were an immediate consequence of the programmed equations. Second, there were slower, undulating, emergent rhythms in luteinizing hormone and follicle stimulating hormone, and also in estrogen, having oscillatory periods of 2–12 hours. There was also a longer-period (Q2–3 days) emergent rhythm in progesterone. In the mid-luteal phase, estrogen and progesterone rhythms were correlated, and all hormones showed an ∼6-hour periodicity.

Conclusion:

To our knowledge, the oscillatory behavior of peripheral sex steroids in the follicular phase has not been previously noted.

Copyright

Corresponding author

Please direct all correspondence to: Natalie L. Rasgon, MD, PhD, Stanford University, Department of Psychiatry and Biobehavioral Sciences, 401 Quarry Road, Room 2360, Palo Alto, CA 94305-5723; Tel: 650-724-6689; E-mail: nrasgon@stanford.edu.

References

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1.Horacek, J, Kuzmiakova, M, Hoschl, C, Andel, M, Bahbonh, R. The relationship between central serotonergic activity and insulin sensitivity in healthy volunteers. Psychoneuroendocrinology. 1999;24:785797.
2.Weber, B, Lewicka, S, Deuschle, M, Colla, M, Heuser, I. Testosterone, androstenedione, and dihydrotestosterone concentrations are elevated in female patients with major depression. Psychoneuroendocrinology 2000;25:765771.
3.Parry, BL, Hauger, R, LeVeau, B, et al. Circadian rhythms of prolactin and thyroid-stimulating hormone during the menstrual cycle and early versus late sleep deprivation in premenstrual dysphoric disorder. Psychiatry Res. 1996;62:147160.
4.Rubinow, DR. Psychiatric disorders of the late luteal phase. Psychopharmacology in practice: clinical and research update 1995. Bethesda, Md: The Foundation for Advanced Education in the Sciences, Inc.; 1995:155183.
5.Haskett, REDiagnostic categorization of psychiatric disturbance in Cushing's syndrome. Am J Psychiatry. 1985;142:911916.
6.Carpenter, WT, Bunney, WE. Adrenal cortical activity in depressive illness. Am J Psychiatry 1971;128:3140.
7.Carroll, BJ, Curtis, GC, Mendels, J. Neuroendocrine regulation in depression. II. Discrimination of depressed from nondepressed patients. Arch Gen Psychiatry 1976;33:10511058.
8.Sachar, EJ, Hellman, L, Fukushima, DK, Gallagher, TF. Cortisol production in depressive illness. A clinical and biochemical clarification. Arch Gen Psychiatry 1970;23:289298.
9.Baischer, W, Koinig, G, Hartmann, B, Huber, J, Langer, G. Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: elevated blood testosterone concentrations compared to normal controls. Psychoneuroendocrinology. 1995;20:553559.
10.Shulman, LH, DeRogatis, L, Spielvogel, R, Miller, JL, Rose, LI. Serum androgens and depression in women with facial hirsutism. J Am Acad Dermatol. 1992;27:178181.
11.O'Donovan, C, Kusumakar, V, Graves, GR, Bird, DC. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry. 2002;63:322330.
12.Rasgon, NL, Altshuler, LL, Gudeman, D, et al. Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report. J Clin Psychiatry. 2000;61:173178.
13.Rasgon, NL, Bauer, M, Glenn, T, Elman, S, Whybrow, PC. Menstrual cycle related mood changes in women with bipolar disorder. Bipolar Disorders. 2003;5:4852.
14.Sturis, J, Polonsky, KS, Mosekilde, E, Cauter, EA. Computer model for mechanisms underlying ultradian oscillation of insulin and glucose. Am J Physiol. 1991;260(Endocrinol Metab 23):E801E809.
15.Parry, BL. Reproductive factors affecting the course of affective illness in women. Psychiatric Clin of North America. 1989;12:207220.
16.Bogumil, RJ, Ferin, M, Rootenberg, J, Speroff, L, Vande Wiele, RL. Mathematical studies of the human menstrual cycle. I. Formulation of a mathematical model. J Clin Endocrinol Metab 1972;35:126.
17.Bogumil, RJ, Ferin, M, Vande Wiele, RL. Mathematical studies of the human menstrual cycle. II. Stimulation performance of a model of the human menstrual cycle. J Clin Endocrinol Metab 1972;35:144.
18.Santen, RJ, Bardin, CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanism. J Clin Invest. 1973;52:26172628
19.Knobil, E. Neuroendocrine Control of the menstrual cycle. Recent Prog Horm Res. 1980;36:5388.
20.Pohl, CR, Knobil, E. The role of the central nervous system in the control of ovarian function in higher primates. Ann Rev Physiol. 1982;44:583.
21.Carr, BR. Disorders of the ovary and female reproductive tract. In: Wilson, JD, Foster, DW, Kronenberg, HM, and Larsen, PR. Williams Textbook of Endocrinology. WB Saunders, 1998:751818.
22.Fink, G. Gonadotropin secretion and its control. In: Knobil, E and Neill, JD, ed. The Physiology of Reproduction. vol.1 New York, NY: Raven; 1988:13491377.
23.Knobil, E, Plan, TM, Wildt, TL, et al. Control of the rhesus monkey menstrual cycle: permissive role of hypothalamic gonadotropin releasing hormone. Science. 1980;207:13711373.
24.Marshall, JC, Dalkin, AC, Haisenleder, DJ, Paul, JS, Ortolano, AG, Kelch, RP. Gonadotropin-releasing hormone pulses: regulators of gonadotropin synthesis and ovulatory cycles. Recent Prog Horm Res. 1991;7:155187.
25.Yen, SSC. The hypothalamic control of pituitary hormone secretion. In: Yen, SSC, ed. Reproductive Endocrinology. Philadelphia, Pa: W.B. Saunders; 1991:65104.
26.Carr, BR. Disorders of the ovary and female reproductive tract. In: Wilson, JD and Foster, DW. Williams, Textbook of Endocrinology. Philadelphia: W.B. Saunders, 1992:733798.
27.Filicori, M, Cognigni, G, Dellai, P, et al. Role of gonadotrophin releasing hormone secretory dynamics in the control of the human menstrual cycle. Hum Reprod. 1993;8(suppl 2):6265.
28.Rossmanith, WG. Ultradian and circadian patterns in luteinizing hormone secretion during reproductive life in women. Hum Reprod. 1993;8:7783.
29.Crowley, WF JrFilicori, M, Spratt, DL, Santoro, NEThe physiology of gonadotropin releasing hormone (GnRH) secretion in men and women. Recent Prog Horm Res. 1985;41:473531.
30.Yen, SSC, Jaffe, RB. Reproductive Endocrinology. 3rd ed. Philadelphia, Pa: W.B. Saunders; 1993.
31.Licinio, J, Negrão, AB, Mantzoros, C, et al. Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci U S A. 1998;95:25412546.
32.Garfinkel, A. A mathematics for physiology. Am J Physiol. 1983;245:R455R466.
33.Iranmanesh, A, Lizarralde, G, Johnson, ML, Veldhuis, JD. Circadian, ultradian and episodic release of beta endorphin in men, and its temporal coupling with cortisol. J Clin Endocrinol Metab. 1989;68:661670.
34.Sollenberger, MJ, Carlsen, EC, et al. Nature of gonadotropin-releasing hormone self-priming of luteinizing hormone secretion during the normal menstrual cycle. Am J Obstet Gynecol. 1990;163:15291534.
35.Garfinkel, A, Spano, ML, Ditto, WL, Weiss, JN. Controlling cardiac chaos. Science. 1992;257:12301235.
36.Babloyantz, A, Destexhe, A. Low-dimensional chaos in an instance of epilepsy. Proc Natl Acad Sci U S A. 1986;83:35133517.
37.Basar, E. Chaos in Brain Function. New York, NY: Springer-Verlag; 1990.
38.Ehlers, CL, Havstad, JW, Garfinkel, A, Kupfer, DJ. Nonlinear analysis of EEG sleep states. Neuropsychopharmacology. 1991;27:95123.
39.Schmidt, GB. Chaos theory and schizophrenia: elementary aspects. Psychopathology. 1991;24:185198.
40.Gottschalk, A, Bauer, MS, Whybrow, PC. Evidence of chaotic mood variation in bipolar disorder. Arch Gen Psychiatry. 1995;52:947959.
41.Hestens, D. A neural network theory of manic-depressive illness. In: Levine, DS, Leven, SJ, eds. Motivation and Goal Direction in Neural Networks. Hillsdale, NJ: Lawrence Erlbaum; 1992.
42.Pezard, L, Nandrino, J-L, Renault, B, et al. Depression as a dynamical disease. Biol Psychiatry. 1996;39:991999.
43.Guckenheimer, J, Holmes, P. Nonlinear Oscillations, Dynamical Systems, and Bifurcations of Vector Fields. New York, NY: Springer-Verlag; 1983:87.
44.Leibenluft, E. Women with bipolar illness: clinical and research issues. Am J Psychiatry. 1996;153:163173.
45.Conrad, CD, Hamilton, JA. Recurrent premenstrual decline in serum lithium concentration: clinical correlates and treatment implications. J Amer Acad Child Psychiatry. 1986;25:852853.
46.Hakim, C, Pichot, P. Prophylactic treatment of manic-depressive psychoses with lithium carbonate. Theoretical and practical value of the study of variations of plasma concentrations. Ann Med Psychol (Paris). 1972;1:238246.
47.Kukopulos, A, Reginaldi, D. Variations of serum lithium concentrations correlated with the phases of manic-depressive psychosis. Agressologie. 1978;19:219222.
48.Chamberlain, S, Hahn, PM, Casson, P, Reid, RL. Effect of menstrual cycle phase and oral contraceptive use on serum lithium levels after a loading dose of lithium in normal women. Am J Psychiatry. 1990;147:907909.

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