Human Reproduction, Vol. 7, No. 10, pp. 1342-1346, 1992
© 1992 European Society of Human Reproduction and Embryology
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Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause
Department of Mathematics, University of Queensland Brisbane, Queensland 4072, Australia 2Department of Physiology, University Medical School Teviot Place, Edinburgh EH8 9AG, UK 3INSERM U-355, Maturation gametique et Fecondation 32, rue des Carnets, 92140 Clamart, France 4Department of Medicine, Royal Victoria Hospital, 687 Pine Avenue West, McGill University Montreal, Quebec H3A 1A1, Canada 5Department of Physiology, University of Texas Health Science Center, University of Texas 7703, Floyd Curl Drive, San Antonio, TX 78284-7756, USA
Correspondence: 1To whom correspondence should be addressed
Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of –0.097 and a second of –0.237. The change occurred when numbers had fallen to the critical figure of 25 000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at 
51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years. The predictions are reassuring insofar as they confirm anecdotal evidence that long-term ovarian function is not substantially comprised by reducing as much as one-half of the mass.
Key words: age/follicle/mathematical model/menopause/ovary
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A. Farrow, M.G.R. Hull, K. Northstone, H. Taylor, W.C.L. Ford, and J. Golding Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception Hum. Reprod., October 1, 2002; 17(10): 2754 - 2761. [Abstract] [Full Text] [PDF]
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E. E. Nilsson and M. K. Skinner Growth and Differentiation Factor-9 Stimulates Progression of Early Primary but Not Primordial Rat Ovarian Follicle Development Biol Reprod, September 1, 2002; 67(3): 1018 - 1024. [Abstract] [Full Text] [PDF]
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T. El-Toukhy, Y. Khalaf, R. Hart, A. Taylor, and P. Braude Young age does not protect against the adverse effects of reduced ovarian reserve--an eight year study Hum. Reprod., June 1, 2002; 17(6): 1519 - 1524. [Abstract] [Full Text] [PDF]
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R. D. Schramm, A. M. Paprocki, and B. D. Bavister Features associated with reproductive ageing in female rhesus monkeys Hum. Reprod., June 1, 2002; 17(6): 1597 - 1603. [Abstract] [Full Text] [PDF]
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D. Nikolaou, S. Lavery, C. Turner, R. Margara, and G. Trew Is there a link between an extremely poor response to ovarian hyperstimulation and early ovarian failure? Hum. Reprod., April 1, 2002; 17(4): 1106 - 1111. [Abstract] [Full Text] [PDF]
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K. Oktay, H. C. M. T. Prinsen, W. R. de Vries, H. P. F. Koppeschaar, and M. G. M. de Sain-van der Velden Evidence for Limiting Ovarian Tissue Harvesting for the Purpose of Transplantation to Women Younger than 40 Years of Age J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1907 - 1908. [Full Text] [PDF]
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J.P. de Bruin, M. Dorland, E.R. Spek, G. Posthuma, M. van Haaften, C.W.N. Looman, and E.R. te Velde Ultrastructure of the Resting Ovarian Follicle Pool in Healthy Young Women Biol Reprod, April 1, 2002; 66(4): 1151 - 1160. [Abstract] [Full Text] [PDF]
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D.W. Cramer, R.L. Barbieri, A.R. Fraer, and B.L. Harlow Determinants of early follicular phase gonadotrophin and estradiol concentrations in women of late reproductive age Hum. Reprod., January 1, 2002; 17(1): 221 - 227. [Abstract] [Full Text] [PDF]
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M. Fukuda, K. Fukuda, C. Y. Andersen, and A. G. Byskov Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy Hum. Reprod., December 1, 2001; 16(12): 2501 - 2507. [Abstract] [Full Text] [PDF]
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R. M. Koivunen, L. C. Morin-Papunen, A. Ruokonen, J. S. Tapanainen, and H. K. Martikainen Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin Hum. Reprod., December 1, 2001; 16(12): 2546 - 2551. [Abstract] [Full Text] [PDF]
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 N. Schupf, D. Kapell, B. Nightingale, J. H. Lee, J. Mohlenhoff, S. Bewley, R. Ottman, and R. Mayeux Specificity of the fivefold increase in AD in mothers of adults with Down syndrome Neurology, September 25, 2001; 57(6): 979 - 984. [Abstract] [Full Text] [PDF]
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J.P. de Bruin, H. Bovenhuis, P.A.H. van Noord, P.L. Pearson, J.A.M. van Arendonk, E.R. te Velde, W.W. Kuurman, and M. Dorland The role of genetic factors in age at natural menopause Hum. Reprod., September 1, 2001; 16(9): 2014 - 2018. [Abstract] [Full Text] [PDF]
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 F Al-Azzawi The menopause and its treatment in perspective Postgrad. Med. J., May 1, 2001; 77(907): 292 - 304. [Full Text]
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J. A. Flaws, A. N. Hirshfield, J. A. Hewitt, J. K. Babus, and P. A. Furth Effect of Bcl-2 on the Primordial Follicle Endowment in the Mouse Ovary Biol Reprod, April 1, 2001; 64(4): 1153 - 1159. [Abstract] [Full Text]
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R. Van den Broecke, J. Van der Elst, J. Liu, O. Hovatta, and M. Dhont The female-to-male transsexual patient: a source of human ovarian cortical tissue for experimental use Hum. Reprod., January 1, 2001; 16(1): 145 - 147. [Abstract] [Full Text] [PDF]
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