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Darryl Holman's Research: Reproductive Aging

djholman@u.washington.edu

The work on pregnancy loss inspired me to investigate other aspects of reproductive and ovarian aging. As a postdoctoral fellow at Penn State, working with James Wood, I helped develop a new project aimed at linking changes in ovarian cycles to the process of ovarian follicular depletion. This ongoing project, funded by a 5-year NIA grant, has many different components and aims. It entailed collecting daily urine specimens from 130 women for six months of the year over five years, and assaying the samples for reproductive hormones. One of my contributions to this project is a new model that links stochastic changes in the number of remaining ovarian follicles to age-related changes in ovarian cycle length. The model explains several phenomena over the reproductive life span as a result of the process of ovarian follicular depletion. More information on the BIMORA project can be found here.

I will highlight two predictions of the model that we are testing using the endocrine observations. First, the model predicts that the increased variability in ovarian cycles at later reproductive ages results from a third phase of the menstrual cycle that we have named the inactive phase. This phase is a period of ovarian quiescence resulting from a stochastic absence of growing ovarian follicles. The timing and length of inactive phases reflect the age-specific size of the ovarian follicle pool. Preliminary results have supported the idea of the three-phase menstrual cycle (Holman et al. in press, O'Connor et al. 1998; O'Connor et al. 2001), and I have begun extensive analyses of the endocrine data. The second prediction is that post-menopausal women should occasionally experience follicular development, which can be detected hormonally but may not result in menses. We have recently presented empirical support for this idea (Holman et al. 2002).

The larger significance of the fecundability, pregnancy loss and ovarian aging work is that it provides a framework for understanding reproductive aging and the end of the reproductive life span. I recently present a paper at the Gerontological Society of America (Holman et al. 2001), where I argued that there is an important distinction between reproductive aging, which is dominated by a gradual age-related increase in risk of pregnancy loss, and ovarian aging, which plays an important role in the maintenance of regular menstrual cycles across the reproductive years but does not appear to play a role in reproductive aging per se. Within anthropology, these findings provide fruitful insights into the on-going debate over an evolutionary role for menopause. My colleagues and I have begun to explore these implications (Wood et al. 2001, in press) and I expand on the issues in my book (Holman, forthcoming).

References cited

  • Holman DJ. (forthcoming) Fecundability, Pregnancy Loss, and Reproductive Aging in Women, Cambridge University Press, Cambridge Studies in Biological Anthropology series.
  • Holman DJ, O'Connor KA, Wood JW (in press) Age and female reproductive function: Identifying the most important biological determinants. In Hill A, Mascie-Taylor N, Leridon H, Sauvain-Dugerdil C (eds.) Age: Human Clock and Scale of Social Organization. Oxford: Oxford University Press.
  • Holman DJ, Wood JW, O'Connor KA (2001) Fecundability, Pregnancy Loss, and Female Reproductive Aging. Gerontological Society of America, Chicago, Nov 16.
  • Holman DJ, O'Connor KA, Brindle E, Wood JW, Mansfield PK, Weinstein M (2002a) Ovarian follicular development in postmenopausal women. Human Biology Association, Buffalo, NY. Abstract: American Journal of Human Biology 14(1):33.
  • O'Connor KA, Holman DJ and Wood JW. (1998) Declining fecundity and ovarian aging in natural fertility populations. Maturitas. 30:127-136.
  • O'Connor KA, Holman DJ, Wood JW (2001) Menstrual cycle variability and the perimenopause. The American Journal of Human Biology 13(4):465-78.
  • Wood JW, Holman DJ, O'Connor KA (2001) Did menopause evolve by antagonistic pleiotropy? In M. Schultz (ed.), Homo-unsere Herkunft und Zukunft. Gottingen: Cuvillier Verlag. pp. 483-90.
  • Wood JW, O'Connor KA, Holman DJ, Brindle E, Barsom SH, Grimes MA (2001) The evolution of menopause by antagonistic pleiotrophy. Working Paper 01-04 Center for Studies in Demography & Ecology, University of Washington.



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