Darryl Holman's Research: Reproductive Aging
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
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).
Holman DJ. (forthcoming)
Fecundability, Pregnancy Loss, and Reproductive Aging in Women,
Cambridge University Press, Cambridge Studies in Biological
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.
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
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