Reproductive Ecology and the Endometrium: Physiology, Variation, and New Directions docx

Reproductive Ecology and the Endometrium: Physiology,
Variation, and New Directions
Kathryn B.H. Clancy*
Department of Anthropology, University of Illinois, Urbana-Champaign, Urbana, IL 61801
KEY WORDS reproductive ecology; endometrium; ecology; energetics; inflammation
ABSTRACT Endometrial function is often overlooked
in the study of fertility in reproductive ecology, but it is
crucial to implantation and the support of a successful
pregnancy. Human female reproductive physiology can
handle substantial energy demands that include the pro-
duction of fecund cycles, ovulation, fertilization, placen-
tation, a 9-month gestation, and often several years of
lactation. The particular morphology of the human endo-
metrium as well as our relative copiousness of menstrua-
tion and large neonatal size suggests that endometrial
function has more resources allocated to it than many
other primates. The human endometrium has a particu-
larly invasive kind of hemochorial placentation and
trophoblast that maximizes surface area and maternal–
fetal contact, yet these processes are actually less effi-
cient than the placentation of some of our primate rela-
tives. The human endometrium and its associated proc-
esses appear to prioritize maximizing the transmission
of oxygen and glucose to the fetus over efficiency and
protection of maternal resources. Ovarian function con-
trols many aspects of endometrial function and thus var-
iation in the endometrium is often a reflection of ecologi-
cal factors that impact the ovaries. However, preliminary
evidence and literature from populations of different
reproductive states, ages and pathologies also suggests
that ecological stress plays a role in endometrial varia-

tion, different from or even independent of ovarian func-
tion. Immune stress and psychosocial stress appear to
play some role in the endometrium’s ability to carry a
fetus through the mechanism of inflammation. Thus,
within reproductive ecology we should move towards a
model of women’s fecundity and fertility that includes
many components of ecological stress and their effects
not only on the ovaries, but on processes related to endo-
metrial function. Greater attention on the endometrium
may aid in unraveling several issues in hominoid and
specifically human evolutionary biology: a low implanta-
tion rate, high rates of early pregnancy loss, prenatal
investment in singletons but postnatal support of several
dependent offspring at once, and higher rate of reproduc-
tive and pregnancy-related pathology compared to other
primates, ranging from endometriosis to preeclampsia.
The study of the endometrium may also complicate some
of these issues, as it raises the question of why humans
have a maximally invasive placentation method and yet
slow fetal growth rates. In this review, I will describe en-
dometrial physiology, methods of measurement, varia-
tion, and some of the ecological variables that likely pro-
duce variation and pregnancy losses to demonstrate the
necessity of further study. I propose several basic ave-
nues of study that leave room for testable hypotheses in
the field of reproductive ecology. And finally, I describe
the potential of this work not just in reproductive ecol-
ogy, but in the resolution of broader women’s health
issues. Yrbk Phys Anthropol 52:137–154, 2009.
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The uterus is the site of many physiological processes
related to pregnancy, starting at implantation. It is the
endometrium that is invaded by the trophoblast, and the
endometrium that in part determines the degree of
maternal–fetal contact. Human female reproductive
physiology and behavior have evolved to handle substan-
tial energy demands and determine not only the viability
of conception, but also 9-month gestation and often sev-
eral years of lactation, with babies that are larger and
larger-brained than all other primates (Mace, 2000).
Only humans have such invasive fetal burrowing to
maximize the transfer of glucose and oxygen from
mother to fetus that, in some cases of pathology, the
placenta can breach the uterine wall (Bischof and
Campana, 1996).
The physiology and cyclic changes of the endome-
trium and placentation vary broadly across the prima-
tes (Martin, 2003). Where the strepsirhines have
epitheliochorial placentation and relatively low mater-
nal–fetal contact, haplorhines have hemochorial placen-
tation with a high degree of maternal–fetal contact.
Human hemochorial placentation and endometrial dif-
ferentiation is characterized by the highest degree of
maternal–fetal contact known, where the interhemal
barrier (the cell layers separating maternal and
fetal blood) narrow to a single-cell layer by the third

trimester.
This allocation of resources in humans to the fetus
required a reorganization of endometrial tissue and a
greater allocation of resources to endometrial function.
Although the ovaries control much of the proliferation
and secretary processes of endometrial function through
the menstrual cycle and can thus be constructive in
understanding variation in fecundity, variation in con-
ception rates cannot be explained by ovulation alone
(Lipson and Ellison, 1996; Kosmas et al., 2004; Ulug
et al., 2006). This does not signal that ovarian function
and endometrial function are not linked, but that ovar-
*Correspondence to: Kathryn B. H. Clancy, Department of An-
thropology, University of Illinois, Urbana-Champaign, 607 S. Math-
ews Ave., 187 Davenport Hall, Urbana, IL 61801, USA.
E-mail:
DOI 10.1002/ajpa.21188
Published online in Wiley InterScience
(www.interscience.wiley.com).
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2009 WILEY-LISS, INC.
YEARBOOK OF PHYSICAL ANTHROPOLOGY 52:137–154 (2009)
ian hormone concentrations explain a portion of varia-
tion in endometrial function rather than all of it. More
direct studies of endometrial functioning are necessary
to understand variation in reproductive function within
and between human populations, especially if we are to
understand reproductive processes that occur after ovu-

lation. The lens of reproductive ecology is useful here, as
the factors that produce variation in ovarian function
are likely to exert some effect on the endometrium, indi-
rectly via the ovaries if not also directly. Population var-
iation in lifestyle, ecology, and developmental conditions
produce significant variation in ovarian hormones
(Ellison et al., 1993). As it is a target tissue of the ova-
ries, but a tissue also responsive to inflammation and
possibly insulin, age, energetic factors, and also immu-
nological and psychosocial stress, ecological factors will
be examined as possible sources of variation in endome-
trial functioning.
I will review the physiology of the endometrium from
basic form to changes through the menstrual cycle,
including some comparative review across the primates
to provide the reader with basic information about
endometrial processes and functioning. I will then
describe some of the methods available for measuring
endometrial function, and synthesize the current litera-
ture on endometrial variation and its proximate determi-
nants. This information will help to inform a set of topics
in the context of reproductive ecology that I propose,
which will create the framework for hypotheses for
future testing.
The central question of this review is to what extent
does the endometrium mediate reproductive success due
to its responsiveness to ovarian hormones that are
themselves mediated by ecology, and how much of endo-
metrial function is independent of the ovaries, that is,
impacted directly by ecological factors? Ecology produces

patterns of variation in ovarian function, which in turn
affects endometrial function; this undoubtedly produces
some effect. Inflammatory processes also exert
significant effects on endometrial function (Sebire, 2001;
Modugno et al., 2005; Agic et al., 2006; Puder et al.,
2006). As the endometrium is largely engaged with
processes of implantation and future gestation, energetic
or more broadly ecological conditions may affect the
ovaries and endometrium in different ways. This varia-
tion could not be detected if only ovarian function were
measured.
This review will show how the study of the endome-
trium will not only help answer current questions in
reproductive ecology, but also lead to new questions
about how adult and childhood energetic condition
affect reproductive functioning, and discuss the possi-
bility of more than one ecological pathway to lead to
variation in endometrial function. An understanding of
several important aspects of hominoid and human
reproduction may be impacted by information regard-
ing variation in endometrial function, including a low
conception rate, high rates of early pregnancy loss,
prenatal investment in singletons but postnatal sup-
port of several dependent offspring at once, and higher
rate of reproductive and pregnancy-related pathology
compared to other primates, ranging from endometrio-
sis to preeclampsia. Finally, the inclusion of the endo-
metrium into the study of human reproductive ecology
has implications not only for women’s health but also
opens avenues for future research into nonhuman

primates.
ENDOMETRIAL PHYSIOLOGY
Physiology and hormonal control of the
endometrium
The endometrium lines the corpus (body) of the
uterus. It is one of the fastest-growing tissues in
humans, composed of two layers: the functionalis and
basalis. Although the basalis does not respond to the
hormonal changes of the cycle, the basalis gives rise to
the functionalis (Heller, 1994). The functionalis responds
to hormonal action and proliferates, maintains, differen-
tiates, or sheds its cells based on these signals (Heller,
1994). Not all mammalian endometria behave in this
way: rodent endometria decidualizes only in the pres-
ence of a blastocyst, where human endometria do it as a
matter of course (Finn, 1974).
Epithelial glands and cellular stroma compose the
endometrium, both of which change morphologically
across the menstrual cycle. Where increasingly coiled
glands and vessels, increased gland complexity, and
mitotic division of the stroma characterize the prolifera-
tive (follicular) endometrium, the secretory (luteal) endo-
metrium is characterized by subnuclear vacuoles lined
up along the glands to maximize secretion, and stromal
edema (swelling) at the time of the window of implanta-
tion (Heller, 1994). The spiral arterioles are maximally
coiled after this point (Heller, 1994), and towards the
end of the cycle the entire stroma decidualizes (becomes
a dense cellular matrix to control trophoblast invasion).
If human chorionic gonadotropin (hCG) from an embryo

had not signaled imminent implantation, the endome-
trium would break down and hemorrhage from its differ-
entiated state, which then leads to menstruation (Heller,
1994).
The main hormones that act on the endometrium are
ovarian sex steroids (estradiol and progesterone), insu-
lin, hCG and luteinizing hormone (LH), prolactin, and
oxytocin. Androgens and glucocorticoid receptors are also
found in the endometrium (Jabbour et al., 2006). Cortisol
may have a role in the endometrium, as it is often acti-
vated as an anti-inflammatory response to the inflamma-
tory mechanisms of menstruation and implantation
(McDonald et al., 2006). Cortisol binds to the glucocorti-
coid receptor and has a high affinity for the mineralocor-
ticoid receptor in the endometrium; high cortisol concen-
trations can interfere with mineralocorticoid signals and
can cause disorders (McDonald et al., 2006). Further,
cortisol is an important indicator of HPA activation and
higher cortisol concentrations are correlated with preg-
nancy loss (Nepomnaschy et al., 2006); chronic psychoso-
cial stress is also associated with low birth weight babies
in a sample of low income women (Borders et al., 2007).
HPA activation can increase levels of matrix metallopro-
teinases, which are involved in degrading the extracellu-
lar matrix (ECM) in tissue remodeling (Yang et al.,
2002). This is important to the creation of spiral arteries,
decidualization of the endometrium, implantation, and
early gestation (Curry and Osteen, 2003).
Estradiol promotes the actions of the proliferative
phase of the endometrium, and primes progesterone

receptors for their role in the secretory phase; progester-
one receptors cannot be expressed without first being
primed by estradiol (de Ziegler et al., 1998). Progester-
one, secreted by the corpus luteum, inhibits some of
estradiol’s proliferative effects, and it maintains
the endometrium through the implantation window in
the mid-secretory phase (Brar et al., 1997). Whether the
138 K.B.H. CLANCY
Yearbook of Physical Anthropology
endometrium responds to ovarian hormones in a thresh-
old (some minimum concentration is required for action)
or dose–response model (the amount of action varies by
hormonal concentration) is unclear. In vitro fertilization
studies, where hormone concentrations are several times
the physiological norm, sometimes demonstrate a dose–
response model, where increased estradiol concentra-
tions are associated with a thicker endometrium (Ran-
dall et al., 1989; Milligan et al., 1995; Zhang et al.,
2005); this relationship holds in some normal cycles as
well (Randall et al., 1989; Bakos et al., 1994). Should the
endometrium prove to operate in a threshold model simi-
lar to testosterone and spermatogenesis, endometrial
thickness and function may not be as functionally rele-
vant as previously thought, or other factors could be im-
portant to the production of variation other than ovarian
hormones. And if the endometrium operates in a dose–
response model, then greater inter and intrapopulational
variation may be expected, as has been found in ovarian
hormone concentrations.
Hormone concentrations vary with energy expendi-

ture, nutritional status, and other ecological factors, and
thus ecology indirectly affects endometrial function (for a
review see Ellison, 2001). But the presence of insulin, in-
sulin-like growth factor-1 (IGF-1), and insulin-like
growth factor-1 binding protein (IGF-1 BP) receptors in
endometrial tissue (Strowitzki et al., 1993; Corleta et al.,
2000) suggests that some energetic factors could directly
affect the endometrium, because insulin is involved in
energy storage and release. Insulin receptors are most
present during the secretory phase, where IGF-1 recep-
tors are present throughout the reproductive cycle and
are modulated by IGF-1 BPs (Strowitzki et al., 1993).
Estrogen receptors are necessary for IGF-1 to stimulate
a proliferative response in the follicular phase (Klotz
et al., 2002; Curtis Hewitt et al., 2005) and significant
cross-talk occurs in this process; IGF-1 BP also modu-
lates embryo implantation (Fluhr et al., 2006). Further,
insulin resistance is associated with thick endometria in-
dependent of reproductive pathology (Iatrakis et al.,
2006), and insulin inhibits differentiation in the endome-
trium in vitro (Giudice, 2006). Insulin and related hor-
mones are most active, therefore, around the window of
implantation, but insulin also plays some role in endo-
metrial proliferation and the downregulation of decidual-
izing mechanisms. These receptors and hormones are
downstream mediators of ovarian function on the endo-
metrium (Klotz et al., 2002), and so are not fully persua-
sive evidence of direct ecological effects on the endome-
trium; however, the relationship between inflammatory
processes and insulin suggests, at the least, that

inflammation in the body can disrupt some of these
mechanisms (Pradhan et al., 2001).
hCG and luteinizing hormone (LH) act on the same
receptors; broadly, hCG signals the presence of an
embryo to the endometrium, and LH triggers ovulation.
Endometrial tissue contains HCG/LH receptors and
mRNA (Licht et al., 2003). The expression of hCG/LH
receptors is affected by cycle phase, in that mid-secretory
phase endometria have full expression of their mRNA
but downregulation of full-length hCG/LH receptor
mRNA occurs in the late secretory phase and early preg-
nancy (Licht et al., 2003). Where maternal processes
may protect against late implantation through receptor
downregulation, which would be in a suboptimal endo-
metrial environment for successful pregnancy, fetal proc-
esses appear to promote maintenance of decidualized
endometrial tissue, as hCG both rescues the corpus
luteum and affects prostaglandin synthesis. HCG exhib-
its a dose-dependent inhibition of IGF-1 BP and prolac-
tin (Fluhr et al., 2006), and prolactin affects endometrial
function. Prolactin is present in the window of implanta-
tion and beyond in the secretory phase of the endome-
trium, and it is necessary for embryo implantation
(Fluhr et al., 2006) through the maintenance of secretory
phase estradiol receptors (Basuray et al., 1983; Frasor
and Gibori, 2003).
Finally, although oxytocin is best known for its dual
roles as a major actor in parturition and as the ‘‘bonding
hormone,’’ oxytocin is also present in the nonpregnant
endometrium, most strongly at mid-cycle (Steinwall et

al., 2004). Oxytocin, like its synthetic partner pitocin,
stimulates muscle contractions. Steinwall et al. (2004)
suggest that oxytocin production is upregulated by estra-
diol and downregulated by progesterone, as this is the
pattern seen for oxytocin production in the hypothala-
mus. Locally produced oxytocin in the nonpregnant
endometrium could produce myometrial contractions
that support sperm and egg transport, menstruation,
and implantation (Steinwall et al., 2004).
It is neither the case that only estradiol and progester-
one control the endometrium, nor that promotion of pro-
liferation and decidualization are the only important
actions on endometrial function. Other hormones act to
promote sperm transport and implantation, as well as
allow the possibility of other direct effects on endome-
trial function such as those by insulin; some of these are
regulated by ovarian hormones, but some may be regu-
lated by other factors. This implies endometrial function
is impacted not just by ovarian function but by
several factors acting in concert to maximize chances for
conception.
Menstrual cycle behavior of the endometrium
In addition to the broad proliferative and secretory
shifts that occur in the endometrium across the men-
strual cycle described earlier, the endometrium exhibits
some specific behaviors at the periovulatory phase, the
implantation phase, and the end of the cycle (menses).
The periovulatory and menstrual phases are described
next, and implantation receives its own separate
discussion.

Periovulatory phase. The endometrium responds to ec-
ological and ovarian signals, but it also plays its own
role in fertility. In natural and IVF cycles, the endome-
trium produces periovulatory waves from cervix (the
neck of the uterus that leads to the vagina) to fundus
(the top of the uterus, at the other end of the corpus).
These waves are quite literal; the muscles of the uterus
contract in such a way that the endometrium moves in a
wavelike, directional motion, that varies in frequency,
direction, and intensity at different phases of the cycle
(Bulletti and de Ziegler, 2005). Cervix to fundus waves
predominate over other types of waves in conceptive
cycles (IJland et al., 1997, 1999). IJland et al. (1997
1999) suggest that these ‘‘inward’’ waves encourage
semen to travel towards the egg and increases the chan-
ces of conception. In their examination of spontaneous,
natural cycles, IJland et al. (1997) showed a greater
‘‘outward’’ (fundus to cervix) waves in nulliparous
women in a nonconceptive cycle than parous women in a
nonconceptive cycle or women in a conceptive cycle.
139REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
Tracking IVF patient cycles, significantly greater endo-
metrial wavelike activity (91% vs. 71% of time observed)
and wave frequency (8.29 waves/min vs. 3.99 waves/min)
were observed compared to spontaneous cycles (IJland
et al., 1999); other research teams also document this
(Lesny et al., 1998). Seventy-three percent of these spon-
taneous cycles had a wave direction switch from
‘‘outward’’ to ‘‘inward’’ at the time of ovum pickup (perio-

vulatory period) (IJland et al., 1999). The earlier this
wave direction switch occurred, the lower the chances of
conception; the findings suggest that the persistence of
‘‘outward’’ waves until hCG administration (34 h before
ovum pickup) is a frequent precursor to pregnancy
(IJland et al., 1999). The endometrium may guide
unwanted endometrial debris, pathogens or other sub-
stances out of the uterus until the periovulatory period,
when it switches to encourage sperm transport and pre-
vent embryo expulsion. Therefore, endometrial behavior
factors significantly in conception.
Menstrual phase. Menstruation is a result of tissue
remodeling, and also an inflammatory process. The men-
strual phase may be susceptible to HPA activation
because of the importance of matrix metalloproteinase
action in the breakdown of the decidualized endome-
trium (Yang et al., 2002). The end of the secretory phase
of a nonconceptive cycle is associated with ‘‘secretory
exhaustion,’’ that is, the endometrium has prepared for
conception, and without an embryonic signal to maintain
it, begins to break down (Heller, 1994). The withdrawal
of ovarian steroids stimulates prostaglandin production,
then prostaglandins aid in menstruation and stimulate
contractions to remove endometrial debris and blood
(Sugino et al., 2004); these prostaglandins are differen-
tially transported away from the endometrium at other
phases of the menstrual cycle (Kang et al., 2005). Luteal
phase defects (defined by reduced corpus luteum func-
tion and/or luteal phase shortening) are associated with
energetic constraint (De Souza et al., 1998; Rosetta

et al., 1998; Williams et al., 1999; Warren and Perlroth,
2001; De Souza, 2003) and affect progesterone levels,
which may affect prostaglandin production. Thus, luteal
maintenance of endometrial tissue is costly, and it is
likely impacted by energetic and more broadly ecological
variation (Strassmann, 1996b). The degree of withdrawal
of ovarian steroids, where a higher degree of withdrawal
is derived from having a higher concentration to begin
with, may also prove to be important in future research
on this topic.
Implantation and invasion of the endometrium
Should an embryo successfully implant and produce
sufficient hCG to rescue the corpus luteum, ovarian ste-
roid withdrawal, prostaglandin production, and other
processes associated with menstruation do not occur
(Baird et al., 2003), and the endometrium changes to
prepare for implantation. Progesterone concentrations
increase and are essential to the processes described
next. In addition to corpus luteum rescue (Csapo and
Pulkkinen, 1978; Baird et al., 2003), subepithelial capil-
lary permeability increases to provide greater access to
maternal blood flow (Tabibzadeh and Babaknia, 1995).
Embryo implantation is then a tissue remodeling process
of adhesion and implantation similar to that found in
other processes of the body such as inflammation and tu-
mor invasion (Bischof and Campana, 1996; Bulletti and
de Ziegler, 2005). Implantation—paracrine cell-signaling
and adhesion—is one of the oldest processes in multi-
celled organisms and a critical step in their development
is the ability for cells to communicate and adhere non-

randomly. For embryonic implantation, the embryo
moves to the uterus, orients itself so that the inner cell
mass is facing the endometrial lining, and dissolves its
zona pellucida. The embryo then apposes, adheres, and
invades the endometrial epithelium. At this point, troph-
oblast syncytia (cell-like structure containing many
nuclei) proliferate to invade the ECM of the endome-
trium; the embryo digests its way through the ECM to
implant, which best occurs when the cells are quiescent
(rather than experiencing frequent or intense wavelike
activity) (Beier and Beier-Hellwig, 1998). Finally,
cytotrophoblastic cells migrate within the forged syncy-
tia pathway, leading placental villi formation (Fig. 1)
(Bischof and Campana, 1996).
In preparation for the receptive period or ‘‘implanta-
tion window,’’ the endometrium changes its adhesion
molecule, cytokine, and key endometrial protein expres-
sion (Tabibzadeh and Babaknia, 1995). The cytokines
present during endometrial receptivity are leukemia in-
hibitory factor (LIF) and the interleukins, especially
interleukin-1 (IL-1) (Lindhard et al., 2002). These cyto-
kines coordinate implantation with the embryo under
the influence of sex steroid hormones (Lindhard et al.,
2002). LIF and IL-1 also are present during inflamma-
tory processes generically in the body, suggesting that
implantation and inflammation are evolutionarily linked.
The apical plasma membrane of the surface epithelium
is non-adhesive until it is specifically altered during
receptivity; then, the plasma membrane acquires the
ability to form reflexive gap junctions, or targets where

cells can attach (Tabibzadeh and Babaknia, 1995). On its
surface, the endometrial epithelium forms pinopodes,
which are secretory membrane elements (Tabibzadeh
and Babaknia, 1995; Beier and Beier-Hellwig, 1998), and
are important to adhesion of the embryo during implan-
tation (Norwitz et al., 2001).
While described earlier as important during the perio-
vulatory period, endometrial wave activity also plays a
functional role in the implantation window. In spontane-
ous cycles, a quiescent endometrium in the midluteal
phase and conception are associated. While ‘‘outward’’
waves characterize the early to mid follicular and late
luteal phases, and ‘‘inward’’ waves characterize the peri-
ovulatory period, the implantation window tends to have
the lowest wave activity (IJland et al., 1997). The picture
is a bit more complicated when wavelike activity in dif-
ferent regions of the uterus during an IVF cycle is meas-
ured; there, the uterus tends to have ‘‘inward’’ waves in
the isthmocervical region (neck of the uterus) and ran-
dom or opposing (both ‘‘inward’’ and ‘‘outward’’) waves in
the corpus (IJland et al., 1999). In artificial cycles of
women with mostly female-origin subfertility (78%),
where wave activity has a greater amplitude and higher
frequency than in spontaneous cycles, there is some indi-
cation that the endometrium guides the embryo to the
main body of the uterus and uses ‘‘inward’’ waves close
to the cervix to prevent embryo loss (IJland et al., 1999).
The decidualization of the endometrium, its thickness,
its wave activity, and its synthesis of a suite of cytokines
and hormones together establish a specific, optimal envi-

ronment for conception and implantation. Following ini-
tial invasion, the trophoblast sends additional cells
responsible for further remodeling of the endometrial
environment during the first trimester. These cells
140 K.B.H. CLANCY
Yearbook of Physical Anthropology
promote arterial reorganization to increase access to the
maternal blood supply, suppress immune function, and
signal to the endometrial glands to create the required
combinations of cytokines, nutrients and growth factors
for fetal nourishment through at least 10 weeks (Burton
et al., 2002; Hempstock et al., 2004).
Beneath the implantation site, the once-thick endome-
trium drastically thins to decrease the trophoblast’s sep-
aration from maternal energy (Hempstock et al., 2004).
Initially, the endometrium creates a hypoxic environ-
ment most suitable to early fetal growth (Jauniaux
et al., 2000, 2003a; James et al., 2006). As the first tri-
mester ends, the placenta takes over the nourishment of
the fetus and much of the endometrium’s activity ceases;
however, the endometrial glands continue to communi-
cate with the spaces between placental villi containing
maternal blood, which suggests they could continue to
provide additional nourishment or some other role (Jau-
niaux et al., 2003b).
The endometrium’s ability to provide a suitable
environment for conception, implantation, and early ges-
tation and placentation relates critically to pregnancy
and fertility. Insufficient endovascular invasion can lead
to hypertension, preeclampsia, and inadequate fetal

growth, whereas unrestricted trophoblast invasion can
lead to placenta accreta (when the placenta attaches
itself too deeply to the uterus), hydatidiform moles (mass
on the trophoblast that usually does not contain tropho-
blast cells), and choriocarcinoma (cancer germ cell con-
taining trophoblast cells) (Bischof and Campana, 1996).
Pathological trophoblast invasion is increasingly thought
to be a problem of the immune system and the regula-
tion of inflammatory processes (Norwitz et al., 2001;
Challis et al., 2009). These pathologies are not commonly
found in other animals; literature searches on typical
laboratory animals or nonhuman primates yielded
no results. Next, I review the broad anatomical and
physiological differences in the endometria of primates
to highlight some of the adaptations particular to
humans.
Nonhuman primate endometria
Long follicular phases characterize primate reproduc-
tive cycles and differentiate them from nonprimate ani-
mals; these follicular phases include estradiol priming of
the endometrium and dominant follicle (or follicles in
some cases) development (Barnett and Abbott, 2003).
Most primates give birth to singletons, with exceptions
in strepsirhines and, notably, the callitrichids within pla-
tyrrhines (Harvey et al., 1987). After that, aspects of
uterine and endometrial physiology diverge within the
primates in at least four ways. First, uterine type
diverges: strepsirhines and tarsiers have bicornuate
uteri where the uterus has two ‘‘horns’’ but is fused in
its lower two-thirds leading to one cervix and vagina,

and the rest of the haplorhines have unicornuate uteri
with one body, cervix, and vagina (Gelder, 1969). Second,
the type of arteries formed to support a fetus varies:
strepsirhines and platyrrhines have straight arteries,
where the arteries of the catarrhines have spiral arteries
(Hernandez-Lopez et al., 1998). Third, strepsirhines do
not menstruate visibly but most haplorhines do (all
catarrhines and most platyrrhines), and menstruation
generally increases in copiousness as one moves through
these categories (Hrdy and Whitten, 1987; Strassmann,
1996a,b).
Forms of placentation are the fourth main way endo-
metrial physiology of primates vary: while hemochorial
placentation has been suggested as the ancestral form
for eutherian mammals and for primates (Wildman et
al., 2006), endotheliochorial placentation has also been
suggested to be ancestral in primates (Martin, 2008).
Strepsirhines and haplorhines diverged in their placen-
tation types, where strepsirhines use epitheliochorial
placentation and haplorhines use hemochorial (Martin,
Fig. 1. The process of embryo implantation. 1, Transport; 2, orientation; 3, hatching of the zona pellucida; 4, apposition; 5, adhe-
sion; 6, invasion; 7, syncytialization; 8, villous formation. Please see the section entitled Implantation and Invasion of the Endome-
trium for a more detailed description. Reproduced from Bischoff P, Campana A. 1996. A model for implantation of the human blas-
tocyst and early placentation. Human Reproduction Update 2(3):262–270, by permission of Oxford University Press.
141REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
2008); strepsirhines have less maternal–fetal contact,
with six cell layers dividing them, and haplorhines have
more contact, with only two cell layers; humans lose one
more cell layer by the third trimester of pregnancy

(Abitbol, 1990).
Several points need to be summarized here. First, the
primate ancestral condition was likely invasive placenta-
tion, but strepsirhines evolved less invasive means to
grow fetuses. Second, primates that give birth to multi-
ples have epitheliochorial placentation with the excep-
tion of the callitrichids, and have straight arteries
including the callitrichids. Thus, epitheliochorial placen-
tation is in strepsirhines because it is more efficient for
the carrying of multiple fetuses. Third, menstrual copi-
ousness increases with placentation invasiveness. In
haplorhines, however, placental invasion only increased,
which suggests greater investment in their singletons.
Primates have greater fetal brain growth than other
mammals (Martin, 1996), which may explain the variety
of attempts made to conserve maternal resources,
increase maternal–fetal contact, or otherwise find an
efficient means of negotiating the trade-offs between
current and future reproduction, and reproduction and
survival.
More resources are then allocated to endometrial
growth and function, and to fetal growth, than in other
animals, with particular emphasis on the catarrhines
and hominoids. The endometrium and its associated
reproductive processes have transformed significantly
across the primates, where more derived adaptations
indicate increased secretory mechanisms and increased
maternal–fetal contact. In particular, human endome-
trial processes imply an increased embryonic and fetal
role in directing maternal energy, and an increased need

for maternal–fetal contact alongside the need for protec-
tion from maternal immunological defenses. Martin
(1996) has suggested that mammals have the largest
brains they can in the context of maternal metabolic
resources during gestation and lactation; further, Martin
et al. (2005) demonstrate relationships between basal
metabolic rate (BMR), gestation period, body mass, and
brain mass that suggest a trade-off between BMR and
gestation period in the development of relatively large
brains. Thus, the close maternal–fetal contact found in
the human placenta and endometrium may be a way for
the fetus to take maximal advantage of maternal energy
for brain growth.
Measuring endometrial function
Several methods exist to measure endometrial func-
tion and morphology; these different methods generate
different kinds of data that indicate different aspects of
endometrial functioning. Asking women to record dura-
tion of menstrual bleeding is the least invasive; asking
them to rate their perceived menstrual copiousness is
also possible, and a pencil-and-paper scale has been
recently described (Mansfield et al., 2004). The difficulty
in creating universal agreement across subjects for what
constitutes menstrual copiousness impairs this method,
as well as the difficulty in determining how many days
one menstruates when the beginning and ending of
cycles does not occur at the same time of day, and the
‘‘end’’ of menses can be difficult for a subject to interpret
(for a review see Belsey and Farley, 1987). Further, sub-
jects often have some difficulty recalling menstrual cycle

dates, perhaps in part due to cultural discomfort with
this biological process (Roberts et al., 2002; Andrist
et al., 2004). The MVJ pencil-and-paper scale (Mansfield
et al., 2004) correlated with menstrual blood loss meas-
ured from used sanitary napkins at r 5 0.683 which,
while a strong relationship, may not be sufficient for
testing mechanistic, physiological hypotheses.
Menstrual fluid can be more precisely measured
through a few different methods of collection, from
weighing used sanitary pads collected in sealed plastic
bags (Mansfield et al., 2004), to performing an alkalin-
hematin method to assess blood in used sanitary pads
involving soaking the used pads in solution and using a
photometer to determine heme (Hallberg and Nilsson,
1964; Newton et al., 1977), and to collecting menses in a
menstrual cup (Morrison and Brown, 2008). All these
methods miss the menstrual blood that is lost through
sanitary practices and urination. Both the method of
subject appraisal of menstrual blood loss and menstrual
fluid collection assess the same thing: the amount of en-
dometrial tissue and blood that was left at the end of a
reproductive cycle; variation in this measurement could
indicate the degree of endometrial proliferation, endome-
trial maintenance after proliferation, or both.
The most invasive method of assessing endometrial
function is through an endometrial biopsy, which
requires entry into the endometrium through the cervix
and the collection of a small amount of endometrial tis-
sue; this requires the most significant clinical support
and can be uncomfortable for the participant. This tissue

can be tested for various molecular and biomarkers of
endometrial activation and receptivity including gene
(Riesewijk et al., 2003), pinopode (Nardo et al., 2002),
and integrin expression (Thomas et al., 2003).
Transvaginal ultrasonography, which is ultrasound
using an endovaginal probe, balances useful, quantita-
tive information with comfort and invasiveness for sub-
jects. Abdominal sonography does not yield consistent
enough results in assessment of nonpregnant reproduc-
tive organs in humans (though it is sufficient for smaller
primates), so while transvaginal ultrasound may at first
seem more daunting, it is the more reliable and compa-
rable method, as it is used clinically for diagnostic and
research purposes. Abdominal sonography also tends to
require a full bladder to adequately view reproductive
organs; this can be more time-consuming and uncomfort-
able than transvaginal ultrasound. Transvaginal
ultrasound can be measured multiple times, even daily,
during a menstrual cycle, which allows observation of
changes in endometrial thickness. In one survey of
women, though they anticipated significant discomfort
before experiencing transvaginal ultrasound, they found
it significantly less uncomfortable than mammography
and Pap smears (Kew et al., 2004).
Transvaginal ultrasound makes possible the measure-
ment of endometrial thickness, endometrial pattern, the
functionalis/basalis ratio, and endometrial volume. Endo-
metrial thickness is the double thickness measurement of
the endometrium on the sagittal plane at its widest point.
Endometrial pattern is an assessment of the degree of

echogenicity of the endometrium, which is thought to
reflect the degree of decidualization and receptivity of the
tissue. Endometrial thickness and pattern in particular
are useful assessments of morphology, both because of
their frequency in the literature and the relationships
that have been found between these measurements and
pregnancy success; results are highly reproducible
between sonographers (Epstein and Valentin, 2002).
142 K.B.H. CLANCY
Yearbook of Physical Anthropology
ENDOMETRIAL FUNCTION VARIATION
In a fecund cycle, the endometrium proliferates in the
follicular phase, and then is generally assumed to be
maintained at about the same thickness while it differ-
entiates through the luteal phase (Johnson and Everitt,
1988; Baerwald and Pierson, 2004). This means there
are two main ways endometrial thickness can vary: in
the degree of follicular proliferation, and in the degree of
luteal maintenance. Most endometrial thickness studies
are in assisted reproduction, when it is measured at the
time of hCG injection or ovum pickup, which approxi-
mates midcycle in a natural cycle; this means current
literature only has information on potential variation in
follicular endometrial proliferation. Any variation in the
endometrium through the window of implantation is
thus not assessed, when its functioning is most relevant
to achieving pregnancy. What follows is a review of the
recent literature. Most work was carried out in medical
settings, and thus the populations are categorized
clinically: normo-ovulatory women, women undergoing

assisted reproductive treatment, postmenopausal
women, and women with endometrial pathology.
Normo-ovulatory women
Menstrual bleeding duration was used as a biomarker
for endometrial function in a study that examined ener-
getic correlates to variation in reproductive functioning.
Duration of menstrual bleeding was shorter in the pre-
harvest hunger season than the harvest season in Lese
women (Bentley et al., 1990). Cycle length, but not dura-
tion of menstrual bleeding has been shown to vary with
work-related physical activity in US workers (Sternfeld
et al., 2002). And in a subcohort of women from that
study who had participated in the Michigan Bone Health
Study, recreational physical activity was negatively asso-
ciated with duration of menstrual bleeding (Sternfeld
et al., 2002).
Other studies examined endometrial function using
endometrial thickness as its proxy. Clancy (2007a,b)
used a single luteal endometrial thickness measurement,
and found that mean endometrial thickness did not dif-
fer between urban US and rural agricultural Polish
women sampled, and that endometrial thickness was
dependent on luteal phase day in Polish women but not
US women. Endometrial thickness was positively corre-
lated with C-peptide concentrations (a biomarker for in-
sulin) and negatively correlated with age in the Polish
sample (P 5 0.05 and P 5 0.04, respectively); a negative
trend was found with energy expenditure calculated in
METs (kcal/min) (P 5 0.09) (Clancy et al., in press).
Only one journal article addressed breastfeeding women,

and it found that recently postpartum breastfeeding
women have less endometrial activity as assessed by en-
dometrial pattern than those women who bottle-feed
their infants (Freedman et al., 1976).
The richest data on endometrial function study nor-
mal, spontaneous cycles, using transvaginal ultrasound
to measure endometrial thickness repeatedly throughout
the cycle. These data provide longitudinal information to
determine population variation in endometrial prolifera-
tion and maintenance across the cycle. Cycle-long stud-
ies of endometrial thickness in natural menstrual cycles
exist on populations in economically developed countries
(Canada, Sweden, the UK), and they align their subjects’
data by ovulation day (Randall et al., 1989; Bakos et al.,
1994; Baerwald and Pierson, 2004; Raine-Fenning et al.,
2004). These data are briefly described below and illus-
trated (Table 1 and Fig. 2).
Ovarian development occurs in waves several times
through the menstrual cycle, with waves defined as a
group of follicles growing synchronously; most women
have two or three waves per cycle (Baerwald et al.,
2003). Baerwald and Pierson (2004) measured endome-
trial thickness, area, volume, and pattern in Canadian
women to test their hypothesis that women with differ-
ent follicular wave patterns would exhibit different endo-
metrial dynamics through the menstrual cycle. They
found endometrial thickness increased earlier during the
follicular phase in women with two over three waves,
and within women with two waves increased earlier in
women with major (a dominant follicle was selected) ver-

sus minor (no dominant follicle selection detected)
waves, and no differences were found in these groups
during the luteal phase (Baerwald and Pierson, 2004).
Follicular waves did not appear to impact luteal phase
endometrial thickness, and these groups were pooled for
the following analysis. They described a plateau in endo-
metrial thickness during the luteal phase that lasts until
just before menses, but their data demonstrate noticea-
ble variation: while the first few days after ovulation do
remain constant, there is a visual drop in endometrial
thickness 4 days after ovulation and then a second pla-
teau that lasts until day 12, with statistical analysis of
this variation forthcoming (Clancy et al., in preparation).
Bakos et al. (1994) described changes in the endome-
trium through the menstrual cycle in 16 Swedish women
to demonstrate the usefulness of sonography in sponta-
neous and artificial cycles. They found a positive rela-
tionship between estradiol and endometrial thickness
when the entire follicular phase was analyzed, but not
when analyzing the late follicular phase (Bakos et al.,
1994). Endometrial thickness varied significantly
between women and displayed a similar two-plateau
effect found in the luteal phase of the Canadian sample,
at a slightly higher overall thickness, though the quali-
tative, rather than statistical, quality of this analysis
must be stressed.
In a sample of English women, endometrial thickness
did not appear to change appreciably through the luteal
phase (Raine-Fenning et al., 2004). These subjects were
measured every 4 days, and the lower measurement fre-

quency may account for the lack of variation found. Ran-
dall et al. (1989) measured estradiol and endometrial
thickness in three groups of Scottish women trying to
conceive: women with unexplained infertility, normal
women with male factor infertility, and women with
tubal occlusion. The results from the normal women are
described here. Estradiol and endometrial thickness pos-
itively correlated, and endometrial thickness increased
through the luteal phase; however, luteal measurement
frequency was only every 5 days (Randall et al., 1989).
Aligning cycles at ovulation rather than at the end of
the cycle provides information about endometrial thick-
ness in the follicular phase and early in the luteal phase,
which supplies important evidence about the influence of
estradiol on endometrial thickness. Through the luteal
phase, endometrial thickness appears to vary more sig-
nificantly, but the presentation of the data make quanti-
tative assessment challenging: aligning at ovulation
allows for comparisons around ovulation, but as women
even in the same population experience wide variation
in luteal phase length the decline in endometrial thick-
143REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
ness cannot be adequately assessed this way. Future
work will assess the original data in a way that allows
for better assessment of the late luteal phase, through
the alignment via days before menses, an alignment typ-
ical to the study of population variation in progesterone.
The variation in mean endometrial thickness in these
populations—from 6 to over 13 mm—suggests the

capacity for significant variation in normal, premeno-
pausal ovulatory cycles.
Assisted reproductive treatments
In vitro fertilization (IVF) studies demonstrate rela-
tionships between the endometrium, hormone concentra-
tions, and pregnancy, though the hormonal manipula-
tions of these cycles can make it difficult to apply the
findings to normal, spontaneous cycles. Endometrial
thickness (ET) has been shown to positively correlate
with implantation rate after IVF (Noyes et al., 1995;
Kovacs et al., 2003; Zhang et al., 2005). In controlled
ovarian hyperstimulation cycles where estradiol is often
four times the physiologically normal concentration,
estradiol and endometrial thickness have been positively
correlated, though only 6% of the variation in endome-
trial thickness could be explained by estradiol concentra-
tions (Zhang et al., 2005). Through the exogenous hor-
mones administered that prepare the endometrium for
implantation, in vitro fertilization also affects endome-
trial receptivity and maturation in the luteal phase
(Kolb and Paulson, 1997; Tavaniotou et al., 2001), which
confirms a link between hormone concentrations and en-
dometrial function. However, these data suggest that the
relationship between ovarian hormones and endometrial
function, while certainly crucial, is not a strict dose–
response model, meaning that incremental increases in
hormones do not necessarily correlate to an equal
increase in endometrial function.
Assisted reproductive technologies research is a con-
tradictory array of information: some studies say endo-

metrial thickness bears no relationship to achieving a
successful pregnancy (Bassil, 2001; Dietterich et al.,
2002; Kolibianakis et al., 2004), another says increasing
endometrial thickness decreases chances of pregnancy
success (Weissman et al., 1999), and still other studies
suggest that endometrial thickness is positively associ-
ated with pregnancy success (Oliveira et al., 1993; Noyes
et al., 1995; Kovacs et al., 2003; Zhang et al., 2005). A
table is provided to demonstrate some of the main differ-
ences in methods and results in a representative sample
of the ART literature on endometrial thickness (Table 2).
Three main issues explain these different results: 1) sta-
tistical and grouping factors, 2) assisted reproductive
method used, and 3) calculation of success of the ART
method (i.e., successful implantation, chemical preg-
nancy, gestational sac, fetal heartbeat, ongoing
pregnancy, live birth).
In terms of statistical methods, some articles com-
pared endometrial thickness means between groups of
pregnant and not pregnant women, while others com-
pared pregnancy rates between groups of high and low
endometrial thickness. This was often determined by the
question the authors were asking; for instance, for those
concerned that an artificially-induced thick endometrium
(from hyperstimulation via exogenous hormone adminis-
tration) could reduce pregnancy rates, the method was
to group according to endometrial thickness, usually
above or below 14 mm. Most of the articles that found
that endometrial thickness had a positive relationship
with pregnancy rates grouped subjects by their preg-

nant/nonpregnant state rather than their endometrial
thickness; thus, a threshold endometrial thickness prob-
ably does not exist over or under which pregnancy is
unlikely. Another factor that complicates interpretations
of this literature are the different methods used to
achieve pregnancy; for instance, clomiphene citrate stim-
ulates ovulation but has been found to reduce endome-
trial thickness (Randall and Templeton, 1991), whereas
GnRh agonists are likely to impact endometrial thick-
ness. Comparisons of these results are challenging
because the degree of exogenous stimulation is so differ-
ent. Finally, authors defined a successful outcome as
chemical pregnancy (positive hCG test), clinical preg-
nancy by ultrasound (gestational sac or heartbeat), or
even ongoing pregnancy (pregnancy for at least 20
weeks). Sometimes subjects were in the pregnancy cate-
gory even if they eventually miscarried, so long as they
hit the milestone that study defined as successful
(Richter et al., 2007), and sometimes the authors did not
know the ultimate outcome of all the pregnancies of the
included subjects (Kovacs et al., 2003).
Despite these methodological differences, the ART lit-
erature has a lot to offer reproductive ecologists. Because
TABLE 1. Characteristics of natural cycle endometrial thickness studies from Clancy et al. (in press)
Country Citation Alignment method Average subject age Number of subjects
Canada (Baerwald and Pierson, 2004) USG confirmation of ovulation 28 50
Sweden (Bakos et al., 1994) LH surge 31.7 16
UK (England) (Raine-Fenning et al., 2004) USG confirmation of ovulation 31 27
UK (Scotland) (Randall et al., 1989) LH surge – 6–10 depending on
measurement day

Fig. 2. Results of four studies of natural luteal phase endo-
metrium (Sweden: Bakos et al., 1994; Canada: Baerwald and
Pierson, 2004; England: Raine-Fenning et al., 2004; Scotland:
Randall et al., 1989). Studies were aligned by ovulation day,
with the knowledge that ovulation (as confirmed by ultrasound)
is 24 h after the LH surge. Error bars were omitted. Reproduced
from Clancy KBH, Ellison PT, Jasienska G, Bribiescas RG.
2009. Endometrial thickness is not independent of luteal phase
day in a rural Polish population. Anthropological Science. DOI:
10.1537/ase.090130.
144 K.B.H. CLANCY
Yearbook of Physical Anthropology
endometrial measurements are standard procedure for
most ART, and the subjects have a stake in the outcome
and tend not to miss appointments, many authors have
successfully measured a large volume of cycles retrospec-
tively and prospectively. So even though ART cycles are
exogenously stimulated, relationships between endome-
trial thickness and different calculations of implantation
or pregnancy can still inform our understanding of vari-
ation in endometrial function. Thus, what these articles
together suggest is that a thicker endometrium largely
improves the outcome for ART, but that those that are
very weak or very strong responders to ART (with a
very thin or thick endometrium) may have less success.
Other factors documented in ART research important
to pregnancy are differentiation of the endometrium, en-
dometrial pattern (Coulam et al., 1994; Sharara et al.,
1999), uterine contractility or endometrial waves (IJland
et al., 1996, 1997, 1999), and molecular indicators of re-

ceptivity (Paulson et al., 1990; Lessey et al., 1996; Beier
and Beier-Hellwig, 1998; Lessey, 2000; Lindhard et al.,
2002; Cavagna and Mantese, 2003). This body of
research implies that endometrial thickness, waves, pat-
tern, and receptivity are all relevant to achieving preg-
nancy, at least in stimulated cycles. Endometrial thick-
ness, waves, and pattern are measured with noninvasive
transvaginal ultrasound; molecular indicators of recep-
tivity require a more invasive endometrial biopsy. And
while it is obvious that hormonal concentrations influ-
ence endometrial proliferation and decidualization, these
data do not resolve whether this relationship is one of a
threshold model (where a threshold hormone concentra-
tion produces an effect), a dose–response model (where
increasing hormone concentrations produce increasing
effects), or whether other factors additionally influence
endometrial variation.
Postmenopausal women
While literature on natural and artificial cycles rarely
includes lifestyle or energetic information, other data on
postmenopausal women and other study populations
indicate that endometrial thickness varies with energy
availability in a dose–response model (Shu et al., 1992;
Douchi et al., 1998; Iatrakis et al., 2006). The postmeno-
pausal endometrium is no longer influenced by active
ovaries, and yet it varies with energy status. Research-
ers have found a positive relationship between BMI and
endometrial thickness (Andolf and Aspenberg, 1996;
Douchi et al., 1998), body weight and endometrial thick-
ness (Andolf and Aspenberg, 1996), and obesity and

endometrial thickness (Serin et al., 2003). A positive
relationship between endometrial thickness and energy
TABLE 2. Representative publications on endometrial thickness from the ART literature
ART protocol Finding
Number of
subjects/cycles
Age of subjects
(years)
Number of
embryos
transferred Citation
Long GnRH,
short GnRH,
GnRH antagonist
ET higher in
conception cycles
in women under
35 yrs; age
negatively correlated
with ET
2339 cycles 19-56, mean 33.5 – Amir et al., 2007
Long GnRH No difference in
ET in conception
vs non-conception cycles
153 cycles \38, mean 31.4 3 Bassil, 2001
Long GnRH,
IVF, and ICSI
High and low ET
in nonconception
cycles; not ss

606 subjects \41 3 Lamanna et al., 2008
GnRH ET higher in those
that achieved
pregnancy
independent of age
1294 subjects Mean 33.7 – Richter et al., 2007
GnRH ET and pregnancy
rate positively
associated
897 cycles Mean 35.6,
range 23-44
Mean 2.6 Zhang et al., 2005
Follicular LA
with GnRH,
luteal LA
Women with ET
over/under 14 mm
had similar clinical
pregnancy rates
570 cycles \40, range 21-39 – Dietterich et al., 2002
GnRH, CC Women with ET
[9 mm had higher
implantation, clinical
pregnancy, and ongoing
pregnancy rates
477 subjects,
516 cycles
Mean 35.9 Mean 3.2 Noyes et al., 1995
CC, short GnRH ET higher in those
that achieved

pregnancy
independent of age
1228 cycles Mean 32 in
pregnant, 33.1
in not pregnant
subjects
Mean 2.9 in
pregnant, 2.6
in not pregnant
subjects
Kovacs et al., 2003
CC with IUI No difference in ET in
women with ongoing
pregnancies or
no pregnancies
168 subjects Kolibianakis et al., 2004
GnRH, gonadotropin releasing hormone; IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; ss, statistically signifi-
cant; ET, endometrial thickness; LA, leuprolide acetate; CC, clomiphene citrate; IUI, intrauterine insemination.
145REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
status in postmenopausal women could indicate aromati-
zation of androgens to estrone by adipose tissue, insulin
and IGF-1 action, or both, on the endometrium. Thus,
both an indirect pathway via steroids (estrone action
implicates this indirectly) or a direct pathway (via insu-
lin) are possible.
Endometrial pathology
Obesity and postmenopausal endometrial cancer risk
positively correlate (Shu et al., 1992; Gull et al., 2001;
Kaaks et al., 2002; Lukanova et al., 2006; Setiawan

et al., 2006; Xu et al., 2006). Further, endometrial thick-
ness and BMI are positively correlated in recovering
anorectics (Andolf et al., 1997). These data further sug-
gest relationship between energy status and functioning.
Women who experience multiple spontaneous miscar-
riages have not had their endometrial function explicitly
measured, but several aspects of this population imply
an endometrial origin to pathology. Choriodecidual
inflammatory syndrome is a main cause of early preterm
delivery and second trimester miscarriage (Sebire, 2001),
and this and other inflammatory syndromes are associ-
ated with undiagnosed and untreated gluten intolerance
(Rostami et al., 2001), which over time promotes sys-
temic inflammation. As many endometrial processes are
inflammatory, it may be important in future research to
examine inflammation and immune function in the con-
text of the endometrium, as another important aspect of
ecology.
Ovarian hormones, insulin and inflammation pull out
as the most relevant factors that produce variation in
endometrial function in the literature, with independent
and interrelated actions documented. Ovarian hormones
are often the bearers of ecological information, insulin
can also inform on energy availability, and inflammation
can be produced by immunological or psychosocial stress.
This article focuses on these factors for its remainder.
ENDOMETRIAL FUNCTION AND REPRODUCTIVE
ECOLOGY
Several hypotheses have been suggested in the last
few decades to explain menstruation and endometrial cy-

clicity. These hypotheses fall into three major categories:
menstruation as a cleansing process, energetic explana-
tions of menstruation, and physiological explanations for
menstruation. Early researchers attempted to isolate an
elusive compound they called the ‘‘menotoxin,’’ a toxic
substance secreted in a menstruating woman’s sweat
that could cause harm to male babies and cut flowers
(Macht, 1924; Freeman et al., 1934; Macht and Davis,
1934; Davis, 1974; Reid, 1974; Bryant et al., 1977;
Pickles, 1979). As problematic as that initial work was,
the idea that menstruation cleanses the body persisted,
perhaps because of the strength of widespread cultural
beliefs in this purpose (Montgomery, 1974; Whelan,
1975): later work focused on the elimination of unwanted
embryos (Clarke, 1994) and sperm-borne pathogens
(Profet, 1993). Strassmann (1996a,b) and Finn (1996,
1998) offered alternatives to these ideas, with their
hypotheses of energy economy and terminal differentia-
tion, respectively. Strassmann (1996b) suggested that it
was more costly to maintain the endometrium from cycle
to cycle, and that menstruation evolved to reduce the
energetic costs of fecundity. Finn (1998) argued that
menstruation is a necessary consequence of the terminal
differentiation of endometrial tissue that occurs after es-
tradiol priming and progesterone action (de Ziegler et
al., 1998); the endometrium must start over once the tis-
sue has differentiated beyond a point at which it can
proliferate for the next cycle.
Finn’s hypothesis gains support in the light of the
physiology and comparative primatology of the endome-

trium: the variability in endometrial and placental archi-
tecture, and the particular architecture of human
placentation demonstrate the specialized tissue the endo-
metrium becomes in preparation for implantation.
Decidualization is a process that cannot be reversed, and
so endometrial tissue must be removed if it is to prolifer-
ate again. Further, the endometrium is maximally recep-
tive through an implantation window in the luteal
phase, after which implantation is unlikely regardless of
embryo quality or stage. Strassmann’s hypothesis loses
support because of this, but also from evidence sur-
rounding ecological variation in endometrial function
described in the previous section of this article. Terminal
differentiation and menstruation’s other important pur-
pose allows endometrium to respond to the ovaries and
ecology from cycle to cycle; without this, the endome-
trium could not respond to changing ecological
conditions. Strassmann’s important contribution to
reproductive ecology is attention on energetics and the
endometrium, without which the ecology of the endome-
trium and the primary topics of this review might never
have been explored. Therefore, the following section will
focus on ecology and endometrial function, synthesizing
the existing literature, and describing new directions for
research in reproductive ecology.
While the relationship between ovarian function and
reproductive success is obvious, the mechanisms that
link them are not. Inter and intrapopulation variation in
ovarian steroids has been consistently documented (i.e.,
Ellison and Lager, 1986; Bledsoe et al., 1990; Lager and

Ellison, 1990; Bentley et al., 1998; Jasienska and Elli-
son, 1998; Rosetta et al., 1998; Warren and Perlroth,
2001; Vitzthum et al., 2002; Nu
´
n
˜
ez-de la Mora et al.,
2007). These data demonstrate relationships of energy
expenditure (Ellison and Lager, 1986; Bledsoe et al.,
1990; Rosetta et al., 1998; Warren and Perlroth, 2001),
energy balance (Lager and Ellison, 1990), nutritional
status (Bentley et al., 1998), and developmental condi-
tions (Vitzthum et al., 2002; Nu
´
n
˜
ez-de la Mora et al.,
2007) with ovarian hormones.
Combine the data demonstrating a relationship
between energy and immunity and the endometrium,
energy and ovarian hormones, estradiol concentrations
and rates of pregnancy in ovulatory cycles, and estradiol
and endometrial function, and it becomes clear that
ovarian and endometrial function are important compo-
nents of fertility that must be studied together in repro-
ductive ecology. Because the endometrium is a target
tissue of ovarian steroids, it is the next place to look to
better explain aspects of fecundity and fertility that
remain unclear with ovarian function alone. In particu-
lar, endometrial function plays a role in variation in fe-

cundity and fertility via variation in endometrial thick-
ness and pattern, as well as variation in implantation
rates and early fetal loss. Ecology, ovarian function, and
age are likely the prime determinants of endometrial
and more general reproductive variation, though genetic
variation is as yet largely unstudied and may also prove
important. Because the endometrium has a strong role
in implantation and early gestation, fetal loss is also of
146 K.B.H. CLANCY
Yearbook of Physical Anthropology
interest. By articulating the relationship between ecol-
ogy and reproductive functioning, and fetal loss and en-
dometrial function, I will elucidate the relationships
between lifestyle and fecundity, and more direct endome-
trial effects on fertility, that require more attention in
reproductive ecology.
Ecology and reproductive function
Several ecological factors have been shown to impact
reproductive functioning: psychosocial stress (Sanders
and Bruce, 1999; Fassino et al., 2002; Nepomnaschy et
al., 2004; Allsworth et al., 2007), energetics (i.e., Jasien-
ska and Ellison, 1998; Warren and Perlroth, 2001;
Jasienska et al., 2006; Nu
´
n
˜
ez-de la Mora et al., 2007,
2008), and immunological stress (Rostami et al., 2001;
Almagor et al., 2004; Martinez de la Torre et al., 2007).
Although those with the strongest correlative effect are

energetic, both psychosocial and immunological stresses
are relevant to this discussion for two reasons. First, the
mechanisms of the stress response and the loss of energy
potential inherent in a body going in and out of allosta-
sis are poorly understood and so may end up being more
strongly related in future research with different meth-
odologies, and second, the stress response—particularly
when chronically activated—induces inflammation, a
process tied to the functioning of the endometrium. In a
study of normal women, there was a trend for psychoso-
cial stress to positively associate with menstrual cycle
length (Sanders and Bruce, 1999), as well as a signifi-
cant positive relationship between stress and cycle
length irregularity in a more recent study of newly
incarcerated women (Allsworth et al., 2007). The incar-
ceration study found not only a higher rate of oligome-
norrhea and amenorrhea in this population than the
general population, but that having a parent with drug
or alcohol problems, and having been a victim of child-
hood physical or sexual abuse, were all significant pre-
dictors of menstrual disturbances (Allsworth et al.,
2007). Despite some indications of a relationship
between cycle length and stress, other studies have not
shown a relationship between ovarian function and
stress: psychosocial stress did not impact ovarian hor-
mones in a sample of college-aged women studying for
the MCAT (Ellison et al., 2007). Notably, Nepomnaschy
et al. (2004) examined the effects of daily stress on a
sample of rural Mayan women and found several associ-
ations between cortisol and reproductive hormones that

varied with menstrual phase. In the follicular phase, LH
and FSH were positively correlated with cortisol, and
cortisol was negatively correlated with progesterone
when controlled for age; in the luteal phase cortisol was
positively associated with FSH and positively associated
with LH, estradiol and progesterone at midcycle and
near the menstrual phase (Nepomnaschy et al., 2004).
This demonstrates a subtle, time-dependent interaction
between stress and reproductive function (Nepomnaschy
et al., 2004).
Infertility and pregnancy loss are other areas where
the study of all types of stress are useful. Nepomnaschy
et al. (2006) have documented a relationship between
maternal cortisol concentrations and increased risk of
very early pregnancy loss. Psychosocial stress can be
more common in individuals diagnosed with infertility:
for instance, one study screened potential infertility cou-
ples for psychopathology and then diagnosed their infer-
tility; those subjects for whom no functional explanation
for infertility could be found had the highest degrees of
psychopathology (Fassino et al., 2002). Broader reviews
have found that the effects of stress on infertility may be
overrated, and explain only 5% of the infertile popula-
tion (Wischmann, 2003). However, measurements of allo-
static load, glucocorticoid concentrations and stress sur-
veys do not fully articulate the ways in which stress can
impact the body, and thus continued attention in this
area is warranted.
Recently, McDade and coworkers have studied
immune function as an underexamined aspect of ecology

that may produce variation in life history trade-offs,
health and reproduction, through a relationship between
chronic inflammation (with C-reactive protein as its
proxy) and disease (McDade 2001, 2003; McDade et al.,
2006). An investment in immune function produces
chronic inflammation (McDade et al., 2008), but psycho-
social stress also correlates with inflammation (McDade
et al., 2006). C-reactive protein has also been positively
associated with fetal loss and negative outcomes in
assisted reproductive cycles (Almagor et al., 2004; Bog-
gess et al., 2005; Levin et al., 2007). This may help
explain reproductive variation in those populations
where energetics do not seem sufficient as a sole predic-
tor of ovarian function (Nu
´
n
˜
ez-de la Mora et al., 2007).
Inflammation is therefore another important proxy for
stress, of particular importance to the endometrium.
Energetic variables have been extensively and
convincingly shown to affect ovarian functioning. These
variables include but are not limited to developmental
condition (Nu
´
n
˜
ez-de la Mora et al., 2007, 2008), energy
expenditure (Jasienska and Ellison, 1998; Warren and
Perlroth, 2001; Jasienska et al., 2006), ponderal index

(BMI at birth) (Jasienska et al., 2005), body fat (Ziom-
kiewicz et al., 2008), weight loss (Lager and Ellison,
1990; Panter-Brick et al., 1993), and nutritional status
(Bentley et al., 1998). All of these factors together
produce variation in both ovarian and endometrial
functioning.
Fetal loss
Waiting time to conception is a determinant of fertility.
Factors that cause variation in waiting time to concep-
tion include coital frequency, fecundability, lactational
amenorrhea, and fetal loss (Wood, 1994; pp. 239-278).
Fetal loss is significant to this discussion of the endome-
trium because of the role that implantation or placenta-
tion could play in its frequency. It is estimated that one
third or more of all preimplantation embryos are sponta-
neously aborted (Hertig et al., 1959; Holman and Wood,
2001; Macklon et al., 2002) and a significant percentage
of postimplantation but early gestation embryos (Wilcox
et al., 1988; Macklon et al., 2002). Endometrial function
may affect fetal losses, given that disruption in para-
crine or endocrine control of the endometrium affects im-
plantation (Bischof and Campana, 1996; Bowen and
Hunt, 2000; Curry and Osteen, 2003; Lessey, 2000,
2003). Most of the focus on fetal loss centered on mater-
nal age and genetic abnormalities of the conceptus
(Weinstein et al., 1990; O’Connor et al., 1998; Holman
and Wood, 2001). Holman and Wood (2001) describe a
U-shaped distribution of pregnancy loss with age, with
risk of pregnancy loss at its lowest around age 20, while
ovarian measures of fecundity begin to decline much

later (O’Rourke et al., 1996; O’Connor et al., 1998).
147REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
Recently, other authors have examined hormonal cor-
relates to early fetal loss. Venners et al. (2006) found
results similar to Lipson and Ellison (1996), as estradiol
concentrations were positively associated with preg-
nancy, and they found that low estradiol was associated
with early pregnancy loss. Nepomnaschy et al. (2006)
found that very early pregnancy loss (within 3 weeks of
conception) is associated with elevated cortisol concen-
trations, which they suggest is related to maternal psy-
chosocial stress. Vitzthum et al. (2006) examined follicu-
lar and luteal progesterone concentrations and found
that early pregnancy losses (which they defined as being
within 5 weeks of conception) were associated with
higher follicular progesterone levels, which they suggest
may be of adrenal origin; they also found a lower luteal/
follicular ratio of progesterone in cycles with early preg-
nancy loss though luteal progesterone values were equiv-
alent across groups. These data indicate continued atten-
tion on maternal stress and early pregnancy loss.
The inflammatory pathway to fetal loss is also rele-
vant. Inflammatory processes can interfere with preg-
nancy whether they are activated from psychosocial
stress, physical stress (i.e., high energy expenditure), or
immunological stress. Inflammation of the chorion
(maternal-fetal membrane) and decidua are thought to
be a leading cause of second term miscarriage and pre-
term birth (Sebire, 2001), and inflammation is widely

recognized to be a determinant of fetal loss in the
medical community (Martinez de la Torre et al., 2007).
C-reactive protein, a biomarker for inflammation, is posi-
tively associated with fetal loss and unsuccessful preg-
nancy attempts in assisted reproduction in some studies
(Almagor et al., 2004; Levin et al., 2007) but not others
(Boggess et al., 2005; Robinson et al., 2008). However,
both an exaggerated or absent inflammatory response in
early pregnancy are considered risk factors for fetal loss
(Sacks et al., 2004), which explain the contradictory
results.
Ovarian hormone concentrations in ovulatory cycles
and pregnancy rates correlate, but the direct effect of
this variation is unclear. A functional relationship exists
and has been empirically demonstrated in natural and
artificial cycles (Lipson and Ellison, 1996; Baird et al.,
1997; Unfer et al., 2004; Lukaszuk et al., 2005; Venners
et al., 2006), as ovarian hormones lead both to ovulation
and the production and maintenance of the corpus
luteum; however, several other steps are necessary for
pregnancy to occur, including implantation and placenta-
tion, that are only partially determined by ovarian hor-
mones. For instance, endometrial function impacts preg-
nancy maintenance and loss: Promislow et al. (2007)
have found that menses after early pregnancy loss (less
than 6 weeks) is lighter, but of longer duration than
menses after a nonconception cycle. The authors suggest
that endometrial factors can negative impact pregnancy
(Promislow et al., 2007); it is possible that endometrial
thickness, secretory capabilities or decidualization were

insufficient to support these pregnancies. Other factors
to consider include aspects of ovarian and uterine func-
tion beyond hormonal signaling (Ellison, 2001; Rockwell
et al., 2000, 2003), implantation (Vitzthum et al., 2004),
trophoblast differentiation (Jauniaux et al., 2003b;
James et al., 2006), first trimester fetal nourishment and
placentation (Burton et al., 2002; Hempstock et al.,
2004), and gestation length (Wadhwa et al., 1998; De
Sutter et al., 2006). The effect of endometrial function on
waiting time to conception could lead to different popula-
tional or individual strategies to alleviate ecological
stress, be it energetic, immunological, or psychosocial.
The endometrium may affect chances of pregnancy at
three main points: at conception, implantation, and fetal
nourishment necessary during early placentation. In
assisted reproduction cycles with donated oocytes, con-
ception rates are associated with recipient age, where
spontaneous abortion rates are associated with donor
age (Levran et al., 1991). Thus, regardless of the age of
the egg donor, the age of the uterine environment affects
the chances of fertilization. Other research has sug-
gested that, independent of age-related degradation of
ovarian function, age-related degradation of endometrial
function affects the success of assisted reproductive tech-
nologies (Meldrum, 1993; Amir et al., 2007).
Conception is not the only reproductive stage impacted
by decreased endometrial function: troubles may arise in
the ability of an embryo to attach to the endometrium
and implant, or may affect an embryo’s ability to remain
implanted and receive adequate maternal nourishment.

The endometrium’s secretory glands provide the develop-
ing embryo with nourishment, when the pregnancy is so
early that the embryo cannot receive it from the pla-
centa (Burton et al., 2002; Hempstock et al., 2004; Jau-
niaux et al., 2005).
Questions for reproductive ecology
Once the basic physiology of the endometrium and
some of the factors that tend to affect reproduction are
understood, several issues in reproductive ecology can be
reframed in the context of endometrial function. We
have incomplete answers to the following: Under what
conditions is endometrial function compromised? How
does variation in endometrial physiology impact preg-
nancy success? We know that endometrial thickness and
pattern vary significantly within and between developed
populations, that they vary with energetic status and
reproductive status, and that generally speaking a
thicker, more decidualized endometrium positively
impacts pregnancy rates. We also know that inflamma-
tory processes can negatively impact pregnancy, and
that one mechanism through which this occurs is in the
endometrium.
To return to the central question of this review—To
what extent does the endometrium mediate reproductive
success due to its responsiveness to ovarian hormones,
and how much of endometrial function is independent of
the ovaries?—we can now provide some preliminary
answers. The endometrium is strongly influenced by
ovarian hormones, which are influenced by ecological
factors. However, the study of insulin receptors, inflam-

matory responses in tissue remodeling, and recent work
on Type I and II GnRH receptors modulating embryo im-
plantation and placentation in a paracrine and autocrine
fashion (Wu et al., 2009), also suggest there may be
direct ecological influences on the endometrium. Mecha-
nistic and population-based studies are still necessary to
parse out these interactions and relationships. Thus,
there are four main areas upon which we should focus
our attention in reproductive ecology, to address broader
questions of female fecundity and fertility: population
variation, ecological variation, conception, and compara-
tive primate physiology; further, the method for the first
steps in this program should involve serial endometrial
ultrasounds to measure thickness and echo pattern.
148 K.B.H. CLANCY
Yearbook of Physical Anthropology
Population variation. The majority of the literature
on endometrial function derives from normal and artifi-
cial cycles in women from developed countries. The reach
of this literature needs to be expanded to women with
more variation in lifestyle, socioeconomic status, physical
activity, and immunological health. This will help parse
out what lifestyle variables impact the endometrium
most strongly.
Ecological variation. In female reproductive physiol-
ogy, ovarian hormones are the primary bearers of ecolog-
ical information to the target tissues, and indirect sig-
naling of ecology via ovaries to the endometrium may
mean the endometrium processes this information differ-
ently. There is also evidence to suggest the endometrium

is able to receive ecological information independent of
the ovaries (Corleta et al., 2000; Fluhr et al., 2006; Iatra-
kis et al., 2006). The endometrium is significant post-
conception because of its role in implantation (Paulson
et al., 1990; Lessey et al., 1996; Beier and Beier-Hellwig,
1998) and fetal nourishment during the first trimester
(Burton et al., 2002; Hempstock et al., 2004; Jauniaux
et al., 2005). The endometrium’s role is literally later in
the reproductive process than the ovaries, once the cycle
has already been determined to be ovulatory or not, and
it is important for the remainder of the pregnancy.
Because it’s energetic and time investments are then
greater, it is possible that the endometrium requires a
longer ecological perspective, meaning that it uses more
information from childhood conditions to project future
conditions. Developmental conditions appear to exert a
greater effect on progesterone concentrations (Nu
´
n
˜
ez-de
la Mora et al., 2007) than estradiol concentrations
(Nu
´
n
˜
ez-de la Mora et al., 2008), as progesterone is more
closely related to endometrial maintenance this provides
some additional evidence in favor of childhood ecology’s
impact on adult functioning.

Ecological factors that produce variation in ovarian
function and fertility could produce variation in endome-
trial function through a number of paths: through
inflammatory processes that directly impact the endome-
trium, through energetic processes that modulate ovar-
ian hormone concentrations that then impact endome-
trial variation, and through energetic processes that
directly impact the endometrium through action on insu-
lin receptors. The effects of inflammation, energetics,
and stress could be measured in the context of ovarian
and endometrial function. Then, to better understand
those factors that produce variation, causal modeling
should be employed to parse out the mechanistic rela-
tionships between ecology, age and reproduction. Causal
modeling will make it possible to test hypotheses regard-
ing direct effects of inflammation and energy availability
on the endometrium, as well as their indirect effects via
ovarian hormones. Developmental condition, psychoso-
cial stress, diet composition, obesity, and immune func-
tion are additional ecological factors necessary to future
study in this topic.
Pregnancy rates. Human gestation has evolved to be
protective of fetal growth (Mace, 2000), and thus likely
places a high premium on the mother’s energy status
before pregnancy is possible; this is indicated by not only
variation in fecund cycles, but the presence of fetal loss
as another way for the body to decide against pregnancy
when conditions are unfavorable (Wood, 1994). No stud-
ies exist that examine endometrial function in normal
women trying to conceive, or in those who have experi-

enced fetal loss. The aforementioned areas of research
measure fecundity, but the measurement of fertility and
fetal loss are also crucial to an understanding of endome-
trial function. The wealth of ART literature demon-
strates the importance of this kind of study, but new
work must diverge from their methods in the frequency
of endometrial measurement.
Comparative primate physiology. As described ear-
lier, humans and other primates have very different pla-
centation types and degrees of trophoblast invasion. Eco-
logical variation in endometrial function across the pri-
mates must be examined to determine the utility and
function of this physiological variation. Endometrial
thickness could be measured via abdominal ultrasound
in some captive nonhuman primate species, and
researchers have successfully performed ultrasounds on
marmosets without sedation (Rutherford and Tardif,
2008). This would make it possible to identify whether
there are any patterns or gradations in functioning that
are consistent, whether there exist significant popula-
tional differences, and whether we might expect to see a
similar range of variation in other nonhuman primates
who have very different endometria.
CONCLUSION
Greater attention on the endometrium may unravel
several issues in primate, hominoid, and specifically
human evolutionary biology, and these topics together
warrant further examination. The most relevant issues
for primates are long follicular phases, for hominoids are
a low conception rate and a high metabolic rate, and for

humans are high rates of early pregnancy loss, prenatal
investment in singletons but postnatal support of several
dependent offspring at once, very invasive trophoblast,
copious menstruation, and long gestation but low daily
cost of gestation compared to the daily cost of lactation.
Further, humans have a high rate of reproductive and
pregnancy-related pathology compared to other pri-
mates, ranging from endometriosis to preeclampsia. For
instance, it has been suggested that a long follicular
phase and high endometrial proliferation to prepare for
a maximally-invasive trophoblast may increase opportu-
nities for endometrial and ovarian pathology (Barnett
and Abbott, 2003). Another area of interest includes
trade-offs between efficiency of maternal energy transfer
and maternal energy cost, indicated by our maximally-
invasive trophoblast but not maximally-efficient placen-
tas, relatively long but low daily cost gestations, and
large and large-brained babies. That is, it may be impor-
tant to reduce the daily energy cost of the mother so
that she can care for multiple offspring at once, so she
spreads resource allocation to the fetus out over a
longer gestation in order to still allocate significantly to
it. This would require additional endometrial and pla-
cental specializations to handle a long gestation and
complements Martin’s (1996) maternal energy hypothe-
sis regarding human brain size. Finally, the endome-
trium may serve as another bottleneck in addition to age
and chromosomal abnormalities susceptible to fetal loss,
as part of a system that invests in few, high-quality
offspring.

Ovarian function has been studied extensively in natu-
ral and experimental contexts, yet work that measures
endometrial function focused mostly on patients with
infertility and postmenopausal women. Over six million
people are afflicted with infertility in the United States,
149REPRODUCTIVE ECOLOGY AND THE ENDOMETRIUM
Yearbook of Physical Anthropology
but our current understanding limits our ability to treat
or describe the significant portion of unexplained infer-
tility. Work on natural endometrial variation in normo-
ovulatory women is necessary to build the foundation
upon which the later study of unexplained sources of
conception and implantation pathology will be possible.
In particular, a mechanism that may explain variation
in early pregnancy loss further than possible only with
the study of hormones is variation in endometrial func-
tion. The elements of endometrial variation may not
cause complete infecundity, but a reduction in the qual-
ity and invasiveness of implantation, or the ability of the
endometrium to nourish the fetus in the first trimester
before placentation is complete (Jauniaux et al., 2000;
Burton et al., 2002; Hempstock et al., 2004). Endome-
trial thickness is also positively associated with preg-
nancy success in assisted reproduction (Oliveira et al.,
1993; Noyes et al., 1995; Kovacs et al., 2003; Zhang et
al., 2005). Thus, while the ovaries are the guardians of
conception, the endometrium, controlled in large part by
hormones from the corpus luteum and then placenta,
may be the guardians of pregnancy.
Future work in reproductive ecology and life history

theory should incorporate endometrial function to pro-
vide a more complete picture of reproduction. Fruitful
areas of research include the study of ecology and endo-
metrial physiology, comparative research into the pri-
mate endometrium, and paracrine and endocrine signals
to endometrial tissue. Ultrasonography of the endome-
trium was established by clinicians working to under-
stand the body in the context of understanding and
treating disease, not the wide range of normal variation
in response to ecology. Thus, the opportunity that awaits
us is in using these methods to understand variation
more broadly: reproductive ecologists can promote a
wide range of healthy physiological states as the most
evolutionarily compatible answer to why we humans
vary. The study of human reproductive biology in an eco-
logical and evolutionary context could make it possible
to influence the degree and kind of treatments used on
certain reproductive pathologies: imagine doses of infer-
tility drugs prescribed not only with a patient’s age in
mind, but her body weight, degree of physical activity,
and age at menarche. In others, we may come to an
understanding that what was considered pathological is
reversible, natural variation: for instance, the energy
surplus lifestyle of many western populations may lead
to greater production of endometrial tissue, and thus to
endometriosis, fibroids, or uncomfortable menses. In all
cases, the importance of the endometrium is highlighted
not only as a downstream responder to ovarian function
and ecology, but also as an important tissue in its
own right that influences the outcome of trophoblast

implantation and invasion.
ACKNOWLEDGMENTS
I thank Charles Roseman and three anonymous
reviewers for their very helpful comments on this manu-
script.
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