Review TRENDS in Endocrinology and Metabolism
Focus on Polycystic Ovary Syndrome
Abdominal adiposity and the
polycystic ovary syndrome
Héctor F. Escobar-Morreale1 and José L. San Millán2
1
Department of Endocrinology, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, Carretera de Colmenar km 9’1,
E-28034 Madrid, Spain
2
Department of Molecular Genetics, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, Carretera de Colmenar km 9’1,
E-28034 Madrid, Spain
Abdominal adiposity, overweightness and obesity are
frequently present in patients with polycystic ovary syn-
drome (PCOS). A large body of evidence suggests that
abdominal adiposity and the resulting insulin resistance
contribute to ovarian and, possibly, adrenal hyperandro-
genism. However, androgen excess itself might also con-
tribute to abdominal fat deposition in hyperandrogenic
women. Recent genomic and proteomic analyses of vis-
ceral fat from PCOS patients have detected differences in
gene expression and protein content compared with
those of non-hyperandrogenic women. Here we review
the existing evidence for a vicious circle whereby andro-
gen excess favoring the abdominal deposition of fat
further facilitates androgen secretion by the ovaries
and adrenals in PCOS patients.
Introduction
The polycystic ovary syndrome (PCOS) is a common endo-
crinopathy in premenopausal women [1]; it affects 7% of
this population [2–4]. Over recent decades, the perception of
PCOS as a mostly cosmetic and reproductive disorder has
evolved to the present view of this syndrome as a complex
endocrine and metabolic disorder that is frequently associ-
ated with insulin resistance and obesity, specifically with a
predominantly abdominal distribution of body fat [5].
This review focuses on the recent evidence suggesting
the role of a vicious circle in the pathogenesis of PCOS. This
circle consists of androgen excess favoring the abdominal
deposition of fat in affected women, and of visceral adipose
tissue further facilitating androgen secretion by their
ovaries and adrenal glands.
What is PCOS?
Current definitions
Most of the advances in understanding PCOS over the past
two decades resulted from the application of the research
criteria derived from the National Institute for Child Health
and Human Development (NICHD) 1990 conference [6]:
clinical and/or biochemical hyperandrogenism, menstrual
dysfunction and exclusion of specific etiologies [6] (Table 1).
These criteria were seldom used by researchers from
Commonwealth and Northern European countries because
Corresponding author: Escobar-Morreale, H.F.
(hescobarm.hrc@salud.madrid.org).
Available online 10 August 2007.
www.sciencedirect.com 1043-2760/$ – see front matter ß 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tem.2007.07.003
Vol.18 No.
ovarian morphology was not considered. In 2003, the
European Society of Human Reproduction and Embryol-
ogy (ESHRE) and the American Society for Reproductive
Medicine (ASRM) organized a consensus workshop, and
the resulting definition requires the presence of two of the
three following criteria: clinical and/or biochemical hyper-
androgenism, chronic oligoovulation and polycystic ovar-
ian morphology in ultrasound [7] (Table 1). This definition
adds two new phenotypes to the older NICHD criteria:
hyperandrogenism with polycystic ovarian morphology
and oligoovulation with polycystic ovarian morphology.
However, the definition does not require evidence for
clinical or biochemical hyperandrogenism [7].
The latter has been the matter of intense debate [8,9]
and has been excluded from the 2006 Androgen Excess
Society evidence-based definition [10]. This society con-
siders PCOS as a mainly hyperandrogenic disorder, and
therefore sustains a diagnosis of PCOS only in the presence
of clinical and/or biochemical hyperandrogenism, which
should be accompanied by either oligoovulation and/or
polycystic ovarian morphology [10] (Table 1).
Androgen excess as the central defect in PCOS
Experiments using ovarian theca cells propagated in
long-term culture have been paramount for the demon-
stration that androgen excess is central to the pathogen-
esis of PCOS [11]. These studies demonstrated that
increased androgen biosynthesis and secretion is a stable
phenotype of theca cells from PCOS patients and persists
after three or four passages in culture, thus excluding an
influence of the in vivo paracrine and endocrine milieu
characteristic of PCOS. Furthermore, almost all the
enzymes involved in androgen biosynthesis are overex-
pressed in these theca cells [11]. Therefore, theca cells
from PCOS patients appear to have the intrinsic property
of synthesizing excessive amounts of androgens when
exposed to appropriate stimuli [11], a property with a
probable genetic basis that remains elusive [12].
Abdominal adiposity, obesity and insulin resistance
as common triggers of androgen excess in PCOS
patients
Many PCOS patients are overweight or obese, and the
abdominal distribution of body fat is especially characteristic
 Review TRENDS in Endocrinology and Metabolism Vol.18 No.7 267

Table 1. Diagnostic criteria for polycystic ovary syndrome (PCOS)

Definition (Year) Diagnostic criteria Possible Exclusion criteria Clinical Biochemical Polycystic
phenotypes hyperandrogenism hyperandrogenism ovarian
morphology
(PCOMa)
NICHDb (1990) Requires the 1.Clinical Congenital adrenal Hirsutism 1.Total Not included
simultaneous and/or hyperplasia Alopecia testosterone
presence of: biochemical Androgen-secreting Acne 2.Free
1.Clinical and/or hyperandrogenism tumors testosterone
biochemical + menstrual Cushing’s syndrome 3.Androstenedione
hyperandrogenism dysfunction Hyperprolactinemia 4.DHEAS c
2.Menstrual
dysfunction

ESHRE/ASRMd Requires the 1.Clinical Congenital adrenal Hirsutism 1.Free androgen At least
(2003) presence of at and/or hyperplasia Acne index or free one ovary
least two criteria: biochemical Androgen-secreting Androgenic testosterone showing
1.Clinical and/or hyperandrogenism tumors alopecia? 2.Total either:
biochemical + Ovulatory Cushing’s syndrome testosterone 1.Twelve or
hyperandrogenism dysfunction 3.DHEAS more
2.Ovulatory 2.Clinical follicles
dysfunction and/or (2–9 mm in
3.PCOM biochemical diameter)
hyperandrogenism 2.Ovarian
+ Ovulatory volume >
dysfunction + 10 ml
PCOM
3.Clinical
and/or
biochemical
hyperandrogenism
+ PCOM
4.PCOM +
Ovulatory
dysfunction
Androgen Requires the 1.Clinical Congenital adrenal Hirsutism 1.Free androgen At least
Excess Society presence of and/or Hyperplasia index or free one ovary
(2006) hyperandrogenism, biochemical Androgen-secreting testosterone showing
clinical or hyperandrogenism neoplasms 2.Total either:
biochemical, and + Oligo- Androgenic/anabolic testosterone 1.Twelve or
either: anovulation drug use or abuse 3.DHEAS more
1.Oligo-anovulation 2.Clinical Cushing’s syndrome 4.Androstenedione follicles
2.PCOM and/or Syndromes of severe (2–9 mm in
biochemical insulin resistance diameter)
hyperandrogenism Thyroid dysfunction 2.Ovarian
+ Oligo- Hyperprolactinemia volume >
anovulation + 10 mL
PCOM
3.Clinical
and/or
biochemical
hyperandrogenism
+ PCOM

a
PCOM, Polycystic ovarian morphology.
b
NICHD, National Institute of Child Health and Human Development.
c
DHEAS, dehydroepiandrosterone sulfate.
d
ESHRE/ASRM, European Society of Human Reproduction and Embriology/American Society of Reproductive Medicine.Reproduced with permission from Codner and
Escobar-Morreale [28], copyright 2007, The Endocrine Society.

of these women [5,13]. This association is explained in part
by the occurrence of insulin resistance and compensatory
hyperinsulinism in women with abdominal adiposity, over-
weightness and obesity because systemic hyperinsulinism
plays a major role in the development of the hyperandro-
genism characteristic of the syndrome [14].
Insulin acts synergically with luteinizing hormone (LH)
to stimulate the synthesis of androgens by ovarian theca
cells in vitro. This effect is mediated by the binding of insulin
to its receptor and, although with much lower affinity,
to insulin-like growth factor-I and hybrid receptors in
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the ovary [14]. It also involves the upregulation of type 1
insulin-like growth factor receptors, reduction of insulin-
like growth factor binding protein-1 and activation of the
insulin-like growth factor-I system [15]. Insulin could also
facilitate adrenocorticotropin (ACTH)-stimulated adrenal
androgen secretion in PCOS patients [14].
In addition, increased insulin levels at the ovary can
stimulate the development of antral follicles by increasing
the sensitivity of granulosa cells to follicle-stimulating
hormone (FSH), resulting in increased numbers and
growth of follicular cysts and of ovarian volume in animals
268 Review TRENDS in Endocrinology and Metabolism Vol.18 No.7
and human models [16–18]. Furthermore, excessive
ovarian insulin concentrations facilitate intra-ovarian
hyperandrogenism, which contributes to the arrest of
follicular maturation characteristic of PCOS patients [19].
Therefore, any clinical situation in which insulin
concentrations are increased in the systemic circulation
might trigger the development of PCOS in predisposed
women because insulin amplifies the exaggerated andro-
gen secretion characteristic of these patients. In conceptual
agreement, the prevalence of PCOS has been reported to be
increased in disorders associated with endogenous hyper-
insulinemia; such disorders include insulin-resistant con-
ditions such as obesity [20], gestational [21] and type 2
diabetes mellitus [22,23], syndromes of extreme insulin
resistance resulting from mutations in the insulin receptor
gene [24] or from autoantibodies against the insulin re-
ceptor [25], or even insulinomas [26,27]. Furthermore,
exogenous systemic hyperinsulinism in women with insu-
lin-treated type 1 diabetes mellitus also frequently results
in PCOS [28].
Abdominal adiposity and obesity might also contribute
to ovarian and adrenal hyperandrogenism by mechanisms
independent from insulin resistance; these mechanisms
are detailed below and include low-grade chronic inflam-
mation, secretion of adipokines such as leptin that exert
direct effects on the ovary [29] and local metabolism of sex
steroids and cortisol in visceral fat [13].
The contribution of obesity to the pathogenesis of PCOS
is exemplified by the relatively frequent development of
PCOS in women after a significant weight gain [13] and,
conversely, the resolution of PCOS in morbidly obese
women after the sustained weight loss attained by these
patients after bariatric surgery [30]. However, abdominal
adiposity, obesity and insulin resistance are not universal
in PCOS patients [31], and conversely, almost half of
morbidly obese women do not develop PCOS even in the
presence of marked insulin resistance [30].
To explain these apparent discrepancies, we propose a
unifying hypothesis that explains PCOS as the result of a
primary defect in steroidogenesis that leads to androgen
excess, whose severity is quite variable (Figure 1). In some
patients, such as lean women without any evidence of
visceral adiposity or insulin resistance, the defect is severe
enough to result in PCOS without the participation of any
other factor. In others, a very mild defect in steroidogenesis
is triggered by obesity, abdominal adiposity and insulin
resistance, and the complete PCOS picture only appears
when these factors are present, explaining the reversibility
of PCOS with marked weight loss [30]. Between the two
extremes there is a spectrum in the severity of the defect in
androgen secretion, explaining the heterogeneity of PCOS
in the relative contribution of obesity and insulin resist-
ance in different patients.
Obviously, the most severe PCOS phenotype develops in
women in whom marked obesity or another factor aggra-
vates an already a substantial steroidogenic defect. How-
ever, because some women who exhibit extreme obesity and
insulin resistance do not develop PCOS [30], a requisite
common trait of all PCOS patients is a defect in androgen
secretion, in conceptual agreement with the central role of
androgen excess in the pathogenesis of this syndrome. A
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Figure 1. The polycystic ovary syndrome as the result of the interaction of a
primary abnormality in androgen synthesis, manifesting as androgen excess, with
environmental factors such as abdominal adiposity, obesity and insulin resistance.
At one extreme (*), in some patients the disorder is severe enough to result in
PCOS even in the absence of triggering environmental factors. At the other
extreme (y), a very mild defect in androgen secretion is amplified by the
coexistence of abdominal adiposity, obesity and/or insulin resistance. Between
the two extremes, there is a spectrum in the severity of the primary defect in
androgen secretion, explaining the heterogeneity of PCOS patients with regards to
the presence of obesity and metabolic comorbidities. However, all patients share a
primary defect in androgen secretion.
genetic predisposition possibly underlies both the primary
steroidogenic abnormality and the triggering factors, which
would explain the frequent familial aggregation of PCOS
[12].
Epidemiology of PCOS and obesity
Prevalence of PCOS in overweight and obese women
Although the association of PCOS with obesity is widely
recognized, until very recently the actual frequency of
PCOS in otherwise healthy overweight or obese women
was unknown.
We recently conducted a prospective study by applying
NICHD criteria to all the premenopausal women reporting
to our department for medical treatment of overweightness
and obesity [20]. The prevalence of PCOS in this popu-
lation was 28.3% with a 95% confidence interval of 20.0% to
36.6% [20], a 5-fold increase over the 5.5% prevalence of
PCOS in lean women of the general population of the same
city [3].
Of note, the prevalence of PCOS did not increase with
increasing grades of obesity and was independent of the
presence or absence of the metabolic syndrome [20],
further suggesting that insulin resistance and adipose
tissue are important contributors to the pathogenesis of
PCOS but are not the primary defects in this disorder.
Surprisingly, despite PCOS’s status as possibly the most
common endocrine comorbidity of obesity in premenopau-
sal patients, screening for PCOS is seldom considered in
current guidelines for the management of obesity [32].
Prevalence of obesity in PCOS
The frequencies of weight excess reported in series of
PCOS patients are heavily dependent on the background
and orientation of the clinical practice where these
 Review TRENDS in Endocrinology and Metabolism
patients were recruited, explaining the 30%–75% range of
prevalences reported worldwide [33]. Despite this, it
should be highlighted that the prevalence of weight excess
is usually higher in PCOS series from the United States
than on other continents [33]. A less biased estimation of
the true frequency of weight excess in PCOS patients
might be derived from epidemiological studies addressing
the prevalence of PCOS in the general population. In the
largest of such studies, conducted in the United States,
overweightness was present in 24% and obesity in 42% of
PCOS patients [4]. These prevalences were 10% and 20%,
respectively, in our much smaller study addressing the
prevalence of PCOS in unselected blood donors from
Madrid, Spain [3].
Abdominal adiposity and the hyperandrogenism of
PCOS: cause or consequence?
Abdominal adiposity facilitates hyperandrogenism
Currently, visceral adipose tissue is considered a highly
active metabolic and endocrine organ and not a mere
energy-storage depot [34]. Accumulation of visceral fat leads
to insulin resistance, hyperglycemia, dyslipidemia, hyper-
tension and prothrombotic and proinflammatory states [34]
that are also relatively common in PCOS patients [33].
Adipose tissue exerts many of these influences through
paracrine and endocrine effects mediated by the increased
or reduced secretion of molecules such as leptin, adiponec-
tin, tumor necrosis factor a (TNFa), interleukin 6 (IL-6) and
plasminogen activator inhibitor-1 [34] that have been found
to be altered in women with PCOS [12,35].
Aside from the well-established role of insulin
resistance and hyperinsulinism as facilitating factors for
androgen excess [14], molecules secreted by adipose tissue
might also influence adrenal and ovarian function, and
adipose tissue itself directly intervenes in the metabolism
of steroid hormones. Adipokines such as leptin and cyto-
kines such as TNFa and IL-6 not only are involved in the
pathogenesis of obesity-related insulin resistance [36] but
also influence ovarian and adrenal function directly. The
increased leptin levels characteristic of obesity might con-
tribute to the ovulatory dysfunction of PCOS because
administration of leptin to experimental animals induces
anovulation by direct ovarian effects [37]. In animal
models, TNFa induces changes that closely resemble those
found in PCOS patients; TNFa stimulates proliferation
and steroidogenesis in rat theca cells in vitro [38,39] and
facilitates the effects of insulin and insulin-like growth
factor-I in a dose-dependent and additive manner [39]. In
addition, TNFa is involved in apoptosis and anovulation in
the rat ovary [40]. On the contrary, leptin and TNFa might
have inhibitory effects on bovine ovarian theca cell ster-
oidogenesis [41,42]. Therefore, extrapolation of these
animal data to PCOS patients must be weighed carefully
because the actions of these factors on human ovarian cells
are largely unknown. IL-6 stimulates adrenal function in
human adrenal cells in culture, resulting in increased
secretion of androgens, mineralocorticoids and cortisol
[43]. Finally, visceral adipose tissue expresses several
enzymes involved in the metabolism of steroid hormones;
such enzymes include 3b hydroxysteroid dehydrogenase,
17b hydroxysteroid dehydrogenase, aromatase and type 1
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Vol.18 No.7 269
11b hydroxysteroid dehydrogenase and might contribute
to or modulate hyperandrogenism in PCOS [13].
Androgen excess might determine abdominal
adiposity and differences in omental adipose tissue
Until recently, hyperandrogenism was considered a
consequence of obesity and insulin resistance and not a
contributing factor to these disorders, mostly because
short-term suppression of androgen levels in PCOS
patients, even when extreme measures such as bilateral
oophorectomy [44] or administration of gonadotropin-
releasing hormone-agonists were used [45], did not shown
any significant effects on insulin resistance.
However, long-term administration of testosterone in
female-to-male transsexuals induces abdominal adiposity
and insulin resistance [46]; it is therefore possible that
chronic androgen excess favors insulin resistance by deter-
mining a predominantly abdominal distribution of body fat
in affected women. In conceptual agreement, mounting
evidence suggests that androgen excess during fetal life
and infancy determines the development of abdominal
adiposity and related metabolic comorbidities later in life
[47–49], providing a plausible explanation for the associ-
ation of PCOS with these metabolic abnormalities.
In utero exposure to androgen excess leads to
phenotypic traits of PCOS in non-human primate, ovine
and rodent animal models [47]. Androgenized female rhesus
monkeys present with hyperandrogenemia, increased sec-
retion of androgens in response to recombinant human
chorionic gonadotropin, oligoovulation and polyfollicular
ovaries, and these abnormalities are accompanied by
accumulation of visceral fat, insulin resistance and impaired
insulin secretion, especially in animals exposed to androgen
early during gestation [47].
Therefore, it is possible that a prenatal androgen excess
from an adrenal [50] and/or ovarian [51] source in hyper-
androgenic female human fetuses determines the occur-
rence of abdominal adiposity and insulin resistance in
adulthood [47]. In contrast, a maternal contribution to
fetal androgen excess seems unlikely given the efficient
placental metabolism of androgens, explaining the
absence of virilization in girls whose mothers had extre-
mely high circulating levels of testosterone during preg-
nancy [52].
Chronic exposure to androgen excess since early life
stages might have contributed to the differences in gene
and protein expression we have recently observed in vis-
ceral-fat biopsies obtained during bariatric surgery from
morbidly obese women presenting with or without PCOS.
Genomic analysis of these samples with DNA microarrays
show that the abnormal gene expression in PCOS omental
fat involves several genes encoding certain components of
several biological pathways, suggesting that the involve-
ment of abdominal obesity in the pathogenesis of PCOS is
more ample than previously thought and is not restricted
to the induction of insulin resistance [53]. Our recent yet
still unpublished proteomic analyses of similar omental fat
biopsies confirmed the dysregulation, specific to PCOS, of
proteins involved in lipid and glucose metabolism, oxi-
dative-stress processes and, especially, adipocyte differen-
tiation.
270 Review TRENDS in Endocrinology and Metabolism Vol.18 No.7
The differences in gene expression and protein content
of visceral fat in PCOS patients versus non-hyperandro-
genic controls integrate genetic and environmental influ-
ences, yet they do not differentiate between them [12].
Therefore, these differences might result from an
environmental influence such as chronic exposure to
androgen excess, might be the consequence of genetic
variants directly related to adipose tissue, or might result
from the interaction of androgen exposure and other
environmental factors such as diet and lifestyle with these
genetic variants.
Androgen excess and abdominal obesity constitute a
PCOS ‘vicious circle’
We propose that PCOS and its associated metabolic
comorbidities could be explained by the existence of a
vicious circle whereby a chronic androgen excess of ovarian
and/or adrenal origin starting early in life, or even prena-
tally, results in abdominal adiposity and android obesity in
affected women (Figure 2). Abdominal adiposity favors
further hyperandrogenism through the direct or indirect
(as a result of insulin resistance and hyperinsulinism)
effects of several mediators, including hypoadiponectine-
mia [35,54], local and systemic cytokine excess [36,55,56]
and increased oxidative stress [57,58], among others
(Figure 2). Furthermore, the relative contribution of andro-
gen excess and abdominal adiposity to this vicious circle
could be quite variable between individual patients, con-
tributing to the clinical heterogeneity of PCOS with respect
to its metabolic associations.
PCOS, abdominal adiposity and obesity: clinical
implications
The efficacy of almost all strategies directed toward
amelioration of obesity and insulin resistance in improving
PCOS symptoms and its metabolic comorbidities is widely
recognized. Non-pharmacological treatment should emph-
asize not only weight loss through dietary modification and
Figure 2. Unifying hypothesis explaining the interplay between the polycystic
ovary syndrome and abdominal adiposity as the result of a vicious circle
represented by the black arrows: androgen excess favors the abdominal
deposition of body fat, and visceral fat facilitates androgen excess of ovarian
and/or adrenal origin directly through the effects (broken arrow) of several
autocrine, paracrine and endocrine mediators, or indirectly by the induction of
insulin resistance and hyperinsulinism.
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exercise but also the modification of additional lifestyle
risk factors such as smoking and excessive alcohol con-
sumption [59]. Insulin sensitizers are effective in reducing
insulin resistance and ameliorate hyperandrogenism and
ovulatory dysfunction [60]. Short-term clinical trials with
anti-obesity drugs such as orlistat [61] and sibutramine
[62] have also demonstrated beneficial effects in PCOS
patients.
Furthermore, the efficacy of weight loss is exemplified
by the resolution of the syndrome in response to the
marked and sustained weight loss achieved by morbidly
obese PCOS patients after bariatric surgery [30]. In a
series of 12 morbidly obese women who presented with
PCOS and underwent to bariatric surgery, marked
weight loss was paralleled by decreases in the hirsutism
score, serum androgen levels, resolution of insulin resist-
ance and restoration of regular menstrual cycles and/or
ovulation in all patients, and in fact the diagnosis of
PCOS could not be sustained in any of them after surgery
[30].
By contrast, the possibility that amelioration of
hyperandrogenism might improve the abdominal adiposity
characteristic of PCOS and associated metabolic disorders
has been considered only recently. When administered in
conjunction with a low-calorie diet to overweight and obese
PCOS adults, the pure antiandrogen flutamide decreased
visceral fat and reduced total and low-density lipoprotein
cholesterol concentrations, in addition to improving
hirsutism and hyperandrogenemia [63,64]. This clinical
evidence strongly supports the hypothesis that hyperan-
drogenism contributes directly to abdominal adiposity
even in adults.
In light of the efficacy of amelioration of insulin
resistance on hyperandrogenism and the improvement
in abdominal adiposity in response to flutamide, drug
therapy combining insulin sensitization with antiandro-
gens has been recently advocated [65]. Although small
trials in hyperandrogenic adolescents suggested an addi-
tive beneficial effect of the combination of low-dose fluta-
mide with the insulin sensitizer metformin on clinical and
biochemical hyperandrogenism, insulin resistance and
lipid abnormalities [66], such an additive effect has
not been confirmed in adult PCOS patients according
to a recently published large, randomized, 12-month,
placebo-controlled study [64].
Summary and conclusions
The interplay between abdominal adiposity and
hyperandrogenism in PCOS patients is not limited to
the well-known role of insulin resistance and compensa-
tory hyperinsulinism in facilitating androgen secretion;
mounting evidence indicates that androgen excess is a
major contributor to the predominantly visceral disposi-
tion of body fat in these women. Accordingly, a vicious
circle in which androgen excess determines abdominal
adiposity and visceral fat facilitates further androgen
excess possibly underlies the pathogenesis of PCOS in
most patients. The amelioration of abdominal adiposity,
obesity and androgen excess should therefore all be con-
sidered when approaching the treatment of this common
disorder.
 Review TRENDS in Endocrinology and Metabolism
Acknowledgements
This work was supported by the Spanish Ministry of Health and
Consumer Affairs, Instituto de Salud Carlos III, Fondo de Investigación
Sanitaria (grants PI050341 and REDIMET RD06/0015/0007).
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Endeavour
The quarterly magazine for the history and
philosophy of science.

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Information revolution: William Chambers, the publishing pioneer by A. Fyfe

Does history count? by K. Anderson
Waking up to shell shock: psychiatry in the US military during World War II by H. Pols
Deserts on the sea floor: Edward Forbes and his azoic hypothesis for a lifeless deep ocean by T.R. Anderson and T. Rice
‘Higher, always higher’: technology, the military and aviation medicine during the age of the two world wars by C. Kehrt
Bully for Apatosaurus by P. Brinkman

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Environmentalism out of the Industrial Revolution by C. Macleod

Pandemic in print: the spread of influenza in the Fin de Siècle by J. Mussell
Earthquake theories in the early modern period by F. Willmoth
Science in fiction - attempts to make a science out of literary criticism by J. Adams
The birth of botanical Drosophila by S. Leonelli

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