Cosmetics as endocrine disruptors are they a health risk.docx

Cosmetics as endocrine disruptors: are they a health risk?
Polyxeni Nicolopoulou-Stamati1 & Luc Hens2 & Annie J.
Sasco3
Published online: 29 January 2016
# Springer Science+Business Media New York 2016
Abstract Exposure to chemicals from different sources in
everyday life is widespread; one such source is the wide range
of products listed under the title Bcosmetics^, including the
different types of popular and widely-advertised sunscreens.
Women are encouraged through advertising to buy into the
myth of everlasting youth, and one of the most alarming con-
sequences is in utero exposure to chemicals. The main route of
exposure is the skin, but the main endpoint of exposure is
endocrine disruption. This is due to many substances in cos-
metics and sunscreens that have endocrine active properties
which affect reproductive health but which also have other
endpoints, such as cancer. Reducing the exposure to endocrine
disruptors is framed not only in the context of the reduction of
health risks, but is also significant against the background and
rise of ethical consumerism, and the responsibility of the cos-
metics industry in this respect. Although some plants show
endocrine-disrupting activity, the use of well-selected natural
products might reduce the use of synthetic chemicals.
Instruments dealing with this problem include life-cycle
analysis, eco-design, and green labels; in combination with
the committed use of environmental management systems,
they contribute to Bcorporate social responsibility .̂

Keywords Endocrine active substances . Endocrine
disruptors . Cosmetics . Sunscreens
1 Introduction
Women and men all over the world use large amount of cos-
metic products in pursuit of everlasting youth, ignoring the
probable health risks. The commercial category of Bcosmetic
products^ entails substances or mixtures of substances that are
designed mainly for external use, for instance to improve the
appearance; clean; perfume; and sometimes protect as in the
case of sunscreens [1]. Many cosmetic products such as oils
and lipsticks contain UV filters, even though they are not
marketed under the term Bsunscreens^ or Bsun lotions^.
Cosmetic products contain active substances, preservatives
and also the so-called Bfragrances^ or Bperfumes^, the exact
composition of which remains a secret under the trade secret
standards [2].
Increasing scientific concern exists about the nature and the
safety of the ingredients used by the cosmetics industry re-
garding their endocrine-disrupting effects. Although numer-
ous studies have proved the endocrine-disrupting potential of
many ingredients, such as parabens, phthalates and UV filters,
and also their ability to cause reproductive impairments [3–6],
these substances are still extensively used and characterized as
Bsafe^. The main justification is the fact that manufacturers
keep the concentrations of the suspected chemical substances
low in accordance with the relevant legislation. However, the
possibility of combination effects (synergism, additivity, inhi-
bition) due to the presence of more than one endocrine
* Polyxeni Nicolopoulou-Stamati
[email protected]
1 School of Medicine, Department of Pathology, MSc
BEnvironment

and Health. Capacity Building for Decision Making^, National
and
Kapodistrian University of Athens, 75 Mikras Asias Str,
11527 Athens, Greece
2 Vlaamse Instelling voor Technologisch Onderzoek (VITO),
Boeretang 200, B2400 Mol, Belgium
3 Epidemiology for Cancer Prevention, Team on HIV, Cancer
and
Global Health, Inserm U 897 - Epidemiology and Biostatistics,
Bordeaux Segalen University, 146 rue Leo Saignat, 33076
Bordeaux cedex, France
Rev Endocr Metab Disord (2015) 16:373–383
DOI 10.1007/s11154-016-9329-4
http://crossmark.crossref.org/dialog/?doi=10.1007/s11154-016-
9329-4&domain=pdf
disruptor must be taken into consideration, because
theoretically-safe doses of single chemicals cannot be guaran-
teed harmless in real-world cases of exposure to chemical
mixtures [7]. Moreover, endocrine disruptors often show com-
plex dose-effect relationships, impairing extrapolation [8, 9].
Endocrine disruptors change the normal function of the
endocrine system, causing serious health problems, and
the endpoints of concern include - among others - devel-
opmental effects, reproductive impairments and infertility,
male and female cancers, neurological disorders, and also
effects on the immune system [6, 10–19]. Exposure to
endocrine-disrupting chemicals begins in utero, and expo-
sure at critical developmental stages (embryo, fetus, peri-
natal, juvenile, puberty) is extremely significant in terms

of the severity of the health outcome [14, 20–22]. As
stated in the literature, a broad range of these endocrine
disruptors seems to challenge estrogen receptors, resulting
in the development of various diseases [23]. Moreover, in
ligand-receptor studies, several of these environmental
compounds demonstrated a molecular structure similar to
natural ligands, and that makes their binding to nuclear
receptors possible, inhibiting or activating their response
[24]. These nuclear receptors can serve as targets for en-
vironmental contaminants due to the presence of a hydro-
phobic pocket that acts as a docking site, which these
molecules have a certain affinity for. The majority of
these endocrine-disrupting contaminants are not chemical-
ly related to natural hormones, making the prediction of
their action difficult [23].
The skin is the main route of exposure, through the appli-
cation of body creams, e.g. sunscreens. Absorption of
chemicals is possible, and the health of the skin is one deter-
mining factor in the effectiveness of the skin barrier [25–27].
Furthermore, exposure is possible through inhalation, as in the
case of hairsprays and fragrances that may contain phthalates,
and also through ingestion, as in the case of lipsticks [25, 28].
The current review aims at highlighting the probable im-
pact of cosmetics as endocrine disruptors. For this purpose,
the groups of parabens, phthalates, perfluorinated chemicals,
and UV filters will be addressed, together with the commonly-
appearing ingredients of Bisphenol A, Triclosan, and alumin-
ium salts.
2 Cosmetic ingredients
Cosmetic products contain numerous substances that are not
directly related to their desired effects, but are included mainly
for their stabilization and preservation properties, and also to

enhance the absorption of the product through the skin
[29–33]. Herein, the ingredients appearing on the labels of
cosmetic products will be covered regarding their probable
effects on the endocrine system.
2.1 Parabens
Parabens (p-hydroxybenzoic acid esters) are effective antimi-
crobial agents used extensively in many products, including
cosmetics such as antiperspirants, body creams and sunscreens
[34]. Cosmetic products are the major source of human expo-
sure to these preservatives [35]. Furthermore, a recent study
with young adults found that the urinary concentration in
women was two times greater than that in men [36]. The most
common parabens are propylparaben (chemical formula:
C10H12O3 [37]), methylparaben (chemical formula: C8H8O3
[37]), ethylparaben (chemical formula: C9H10O3 [37]), and
butylparaben (chemical formula: C11H14O3 [37]). Although
parabens are usually on the list of ingredients on the product
packaging, there are products on the market that contain these
agents but do not include them on the list of ingredients [34].
Parabens display endocrine-disrupting activity both in vitro
and in vivo, and they have been associated with impairments
of the reproductive system of male experimental animals [4,
35, 38, 39]. Evidence exists showing that these endocrine-
disrupting chemicals can cause DNA damage and affect the
mitochondrial function [40], and there are concerns regarding
a possible mitochondrial connection between parabens and
male infertility [41]. Parabens have been found intact in hu-
man breast tumours [42], and their ability to increase the pro-
liferation of human breast cancer cells has been confirmed
in vitro [43]. However, current scientific knowledge is insuf-
ficient to demonstrate a clear cancer risk due to the topical
application of cosmetics containing parabens in the underarm
area, and the controversy about the use of parabens and cancer

risk is ongoing [35, 43, 44].
2.2 Phthalates
Phthalates are present in many everyday products due to their
multi-functionality as they can serve variously as plasticizers,
vehicles for fragrances in cosmetic products, lubricants and
solvents [45–47]. The term Bfragrance^ or Bparfum^ is written
on the labels of the majority of cosmetic products, and the
composition of these substances, which may contain
phthalates, is a trade secret and it is dealt accordingly [2].
Cosmetics usually use low molecular phthalates such as
diethyl phthalate (DEP, chemical formula: C12H14O4 [37]),
dimethyl phthalate (DMP, chemical formula: C10H10O4
[37]), and dibutyl phthalate (DBP, chemical formula:
C16H22O4 [37]). Many other phthalates such as the di-(2-
ethylexhyl) phthalate (DEHP, chemical formula: C24H38O4
[37]) can also be detected in the final products, as a result of
a possible migration from the plastic package or due to the
manufacturing processes [48].
Phthalates are known for their endocrine-disrupting poten-
tial, their ability to cause oxidative stress, embryonic develop-
mental problems, reproductive impairments, and
374 Rev Endocr Metab Disord (2015) 16:373–383
neurobehavioral effects in experimental animals [46, 49–53].
Regarding human exposure to phthalates and their metabo-
lites, there is evidence that prenatal and infant exposure, e.g.
through breast milk [54], may be associated with cognitive,
mental and behavioral effects such as lower IQ indices, preg-
nancy loss, hyperactivity, attention problems, problematic so-
cial communication, as well as with negative effects on the

normal development of the reproductive system [46, 47,
54–57]. Furthermore, male infants are likely to be more vul-
nerable to phthalates and their metabolites than female infants
[54–56]. Evidence points to a possible association between
phthalate exposure and low sperm quality, decreased concen-
trations of sex and thyroid hormones, precocious puberty,
obesity, breast cancer, and also effects on adult remembering
condition [5, 46, 58–60]. Moreover, it should be noted that an
in vitro study has revealed the ability of phthalate mixtures to
induce increases in the proliferation of colorectal adenocarci-
noma cells [61].
2.3 Perfluorinated chemicals
Perfluorinated Chemicals (PFCs) are water, grease, stain and
dirt repellents used in a great variety of everyday products,
including cosmetics such as lotions and nail polishes. Two of
the most common PFCs are perfluorooctanoic acid (PFOA,
chemical formula: C8HF15O2 [37]) and perfluorooctane sulfo-
nate (PFOS, chemical formula: C8HF17O3S [37]), the health
risks of which may have been largely underestimated [62].
These ubiquitous chemicals have been detected in human
breast milk samples and also in umbilical cord blood samples
[63]. PFCs in vitro interfere with the function of sex hormone
receptors [64], and can also enter thyroid cells [65]. It has been
shown that the in utero exposure to PFOS is negatively corre-
lated with the birth weight of human female infants [66], and a
possible connection between human sub-fecundity and PFCs
has been suggested [67]. Furthermore, there is increased sci-
entific concern about the effects of PFCs on normal human
thyroid function and on concentrations of thyroid hormones
[63, 68, 69]. There is also evidence that PFOA may have
carcinogenic potential [63, 70].
2.4 Aluminium salts

Aluminium salts are the antiperspirant agents in underarm cos-
metics that are applied onto the skin very frequently, leading to
continuous dermal exposure [71–74]. Aluminium (Al) is a
metalloestrogen [71, 72, 74], and it has neurotoxic potential
[75, 76]. Furthermore, a recent in vitro study demonstrated that
Al can inhibit human acetylcholinesterase, an enzyme partici-
pating in cholinergic neurotransmission [77]. There are con-
cerns that Al may play a role in the neuropathology of
Alzheimer’s disease, and the probable connection between
chronic exposure to Al and Alzheimer’s disease is a matter of
ongoing controversy [76, 78, 79]. There is also evidence of the
ability of Al to cause problems to the osseous system, bone
pain and fatigue [75, 80]. Aluminium has been detected in both
normal breast tissue and malignant lesions [81, 82], and there
are studies that suggest that the long-term use of aluminium-
based cosmetics applied topically near the breasts may be a risk
factor in the etiopathology of breast cancer [71, 74].
2.5 Triclosan
Triclosan (5-Chloro-2-(2,4-dichlorophenoxy)phenol, chemi-
cal formula: C12H7Cl3O2 [37]) is a common antimicrobial
agent that may act as thyroid agonist [83]. It is used in per-
sonal care products, deodorants, toothpastes, hand soaps,
dishwashing detergents, plastics and fabrics and other prod-
ucts [84]. Its ubiquity can be confirmed by its presence in
household dust [85], and also in human plasma and breast
milk samples [86].
In humans, exposure to triclosan has been associated with
earlier breast development [83]. Furthermore, its endocrine-
disrupting activity has been confirmed in vivo in experimental
animals [87, 88] and in vitro in human breast cancer cells [89].
Furthermore, it has been proven that triclosan can affect the

concentration of thyroid hormones in juvenile male rats [90].
Another worrying factor is dioxin formation after
photodegradation of Triclosan in wastewater, freshwater and
also seawater [91, 92] which constitutes a potential hazard to
aquatic life.
2.6 Bisphenol a (BPA)
Bisphenol A (BPA, chemical formula: C15H16O2 [37]) is a
well-known endocrine disruptor used mainly in the plastics
industry, for example in the production of soft plastic toys
[93–95]. In cosmetics, it serves as an antioxidant agent [95].
BPA can migrate from plastic packaging and contaminate the
contents [96, 97], and in Europe, the use of BPA in infant
feeding bottles and cosmetics is forbidden [1, 98].
In vivo studies with experimental animals showed that BPA
may be associated with reproductive impairments, such as
morphological changes and problematic spermatogenesis,
neurological effects, alterations on the normal body weight,
and carcinogenic effects [93, 99–101]. Regarding exposure to
BPA and probable human health outcomes, there is evidence
for serious health impairments that requires more investiga-
tion and confirmation. For instance, there are concerns about
probable association between BPA and male infertility, cancer
of the reproductive system, polycystic ovarian syndrome, di-
abetes, and problematic behaviour in children [94, 96, 100,
101]. It should be mentioned that a study has suggested that
exposure to BPA during gestation tended to affect the behav-
ioural and emotional parameters of female rather than male
children observed in the third year of life [102].
Rev Endocr Metab Disord (2015) 16:373–383 375

2.7 UV filters
Sunscreens and other cosmetics such as makeup products and
lipsticks contain UV filters that either absorb or block solar
UV radiation (respectively, organic chemical absorbers and
inorganic UV filters, i.e. the nanoparticles of the metal oxides
TiO2 and ZnO) [103–105]. In vivo and in vitro studies have
demonstrated the ability of many organic chemical absorbers
to display endocrine-disrupting activity and cause reproduc-
tive impairments, and there is also evidence that the nanopar-
ticles of the metal oxides may display similar activity [6, 106].
2.7.1 Organic UV filters
Common organic chemical absorbers are benzophenone com-
pound oxybenzone (2-hydroxy-4-methoxybenzophenone,
benzophenone-3, chemical formula: C14H12O3 [37]), octyl
methoxycinnamate (ethylhexyl methoxycinnamate,
octinoxate, chemical formula: C18H26O3 [37]), 4-
methylbenzylidene camphor (enzacamene, chemical formula:
C18H22O [37]), and 3-benzylidene camphor (chemical formu-
la: C17H20O [37]). The endocrine-disrupting activity of these
organic filters has been confirmed in vitro in human estrogen
receptor alpha and androgen receptor assays [107].
Oxybenzone is present in human breast milk samples
[108], and maternal exposure has been associated with an
increase in birth weight in boys and a decrease in birth weight
in girls [109], and also with delayed breast development in
girls [83]. Furthermore, it has been confirmed in vivo in fish
that oxybenzone can down-regulate alpha estrogen receptors
and androgen receptors [110], affect egg production and
hatching percentage [111]; it can also cause an increase in
uterine weight in immature rats [112], reductions in weight
in mice offspring and increases in the mortality rates of lactat-
ing dams [113].

Octyl methoxycinnamate is another organic UV filter
which has been confirmed present in human breast milk
[108]. In vivo studies in experimental animals have revealed
probable impacts on the normal function of the hypothalamic-
pituitary-thyroid axis leading to decreases in concentrations of
various hormones [114], reproductive disorders such as delays
in offspring sexual maturation [115], increases in uterine
weight [112], and also neurological disorders [116].
Furthermore, the in vivo ability of 4-methylbenzylidene
camphor to disrupt the endocrine function has been confirmed
in rats, in aquatic organisms [117–119], and also in insects
[120]. Exposure of rats to this sunscreen filter can increase
uterine and thyroid weight [118], delay male puberty and af-
fect sexual behaviour in female offspring [121].
The ability of the UV filter 3-benzylidene camphor to cause
endocrine and reproductive impairments has been demonstrat-
ed in rats [118, 121], in fish [122, 123], and in aquatic mol-
luscs [119]. Exposure in rats affects male puberty, female
sexual behaviour, oestrous cycles and uterine weight [118,
121]. Furthermore, exposure of fish to 3-benzylidene camphor
has been associated with reproductive impairments, feminiza-
tion of male sex characteristics and fertility issues [123].
There are limited data on other organic UV filters regarding
their potential to cause endocrine and reproductive impair-
ments. For instance, there is evidence that exposure of preg-
nant rats to the filter PABA (4-Aminobenzoic acid, chemical
formula: C7H7NO2 [37]) may slightly affect body mass devel-
opment in rat foetuses [124]. Limited evidence may suggest
that other organic UV filters do not act as endocrine
disruptors, but the limited data cannot guarantee safety and
more investigation is needed to identify possible health risks.

2.7.2 Nanoparticles of metal oxides
The nanoparticles of titanium dioxide (TiO2) and zinc oxide
(ZnO) have replaced the large-scale forms that produced a less
aesthetically-acceptable result when applied to the skin [125].
Oxidative stress and their probable transport through the pla-
cental barrier leading to foetal exposure are two health issues
that have been associated with their use [126, 127]. Since
nanoparticles do not belong to a particular homogenous chem-
ical group, the health risk assessment of these cosmetic ingre-
dients may have to be based on case-by-case testing [128].
ZnO nanoparticle aggregates can affect reproduction in fish
[129]. An in vivo study with fish has also demonstrated that
ZnO nanoparticles can more easily bio-accumulate as com-
pared to the large-scale forms [130]. In vivo studies have also
revealed that the exposure of experimental animals to TiO2
nanoparticles can disrupt pregnancy progression [131], affect
reproductive parameters such as sperm characteristics [131,
132], and the genital and cranial nervous systems [133].
3 Discussion
Cosmetics have been used for centuries and not always with
safe ingredients. In antiquity, even though the substances used
in cosmetics were natural and not man-made, such as mercury
and lead, some were toxic [134, 135], and there was under-
standable ignorance of their toxic effects, in contrast with
today. Ancient Greek civilization admired the classic beauty
of the Venus de Milo, and it is obvious that she never used
cosmetics (Fig. 1).
There is ample evidence that correlates exposure to endo-
crine disruptors with impairments of the reproductive system,
metabolic disorders, neurological problems, disturbance of the

hypophysal-thyroid-genital axis, effects on the fetus, cancer,
and other endpoints of endocrine disruption [14, 15, 18,
136–138]. The cosmetic industry uses many barely-
regulated chemical substances in cosmetic products, of which
a significant number are associated with endocrine disruption.
It is recognized that cosmetics constitute a significant part of
our exposure to chemicals. Even though there are efforts,
based on databases of chemical substances used in cosmetic
products, to inform the consumers, such as certain websites
(for instance: Skin Deep – Cosmetics Database: http://www.
ewg.org/skindeep/, and Clean Makeup: http://web.colby.edu/
cleanmakeup/) and the application FoxTox for smartphones
(http://www.edc-free-europe.org/smart-fox-toxfox-app-helps-
consumers-detect-edcs-in-cosmetics/), the information does
not reach all consumers, raising the serious issue of
unintentional exposure and the subsequent ethical questions.
The impact of endocrine disruptors on health is a subject
that requires improved testing and deeper knowledge for the
identification of endocrine-acting chemicals as, certainly, there
are knowledge gaps requiring supporting environments for
creative innovation and disease prevention. Of course, reduc-
ing exposure would alleviate adverse health effects resulting
from the use of cosmetic products. However, current lifestyles
preclude this, and the need for safer chemicals is urgent. As a
result of scientific uncertainty regarding the subject [15, 139],
consensus statements have been published [140]. An issue of
paramount importance is the exposure of pregnant women,
foetuses and embryos to endocrine-disrupting chemicals. The
results of early-life exposure to endocrine disruptors can ap-

pear later in life, as in the case of testicular dysgenesis syn-
drome [141–143]. Other concerns include the possible in-
creased risk of Polycystic Ovary Syndrome development
[142, 144]. The effects on future generations starting even
before their birth need to be thoroughly addressed.
Cosmetic ingredients are emerging pollutants; their envi-
ronmental monitoring is at a very early stage. However, it is
known that they reach the environment in multiple ways, often
through water, posing health risks to marine and freshwater
ecosystems and to humans, e.g. through the contamination of
drinking water sources and the food chain [145–148]. The
environmental metabolic pathways are multiple and complex.
Wastewater treatment plants are unable to remove endocrine
disruptors totally [146], and barely alleviate the problem of
their distribution throughout the environmental compart-
ments, or of the exposure to them, taking into account that
endocrine-disrupting chemicals display non-monotonic dose
responses [9, 149, 150]. Endocrine disruptors end up in natu-
ral ecosystems, for instance through wastewater treatments
plants, water used to rinse the human body, and also landfill
leachate as may occur with the residues inside cosmetic prod-
ucts’ packaging [145, 146, 151]. The organic contaminants
(many of them have confirmed endocrine-disrupting ability),
their metabolites and their degradation compounds have dif-
ferent physicochemical properties that affect their fate, behav-
iour and transport in natural ecosystems. For instance they can
undergo hydrolysis, and photolysis induced by sunlight, as in
the case of Triclosan, of which the photolytic degradation
leads to dioxin formation [3, 91, 92]. Furthermore, their pos-
sible ability to bio-accumulate in the fatty tissues of fish [145],
and the presence of cosmetic ingredients in marine mussels
[152], and the ability of the UV filters to cause coral bleaching
[153] are important factors that reveal an emerging environ-
mental hazard which is incompletely understood.

The health effects of endocrine-disrupting chemicals in
cosmetics and their impact on public health in particular
are currently incompletely understood. Only some of the
chemicals used in the industry have been tested for their
effects on the endocrine system. Human metabolic and en-
vironmental pathways are known to exist, but have only
been partially defined. Information on dose-effect relation-
ships in this context is scant, and the human-wildlife health
nexus is incompletely understood. In spite of these uncer-
tainties, it is well known that a healthy endocrine system is
essential for the reproduction of humans and wildlife.
Moreover, its impairment affects a cascade of related func-
tions. Concern is raised about the high incidence and the
increasing trends of endocrine-related disorders in humans
and wildlife. The combination of these most significant, par-
tially irreversible health effects and the attendant uncertainty
calls for a precautionary approach. In addition, calculating
Fig. 1 Cosmetics that Venus de Milo never used
http://www.ewg.org/skindeep/
http://www.ewg.org/skindeep/
http://web.colby.edu/cleanmakeup/
http://web.colby.edu/cleanmakeup/
http://www.edc-free-europe.org/smart-fox-toxfox-app-helps-
consumers-detect-edcs-in-cosmetics/
http://www.edc-free-europe.org/smart-fox-toxfox-app-helps-
consumers-detect-edcs-in-cosmetics/
the costs of the health effects of endocrine-disrupting
chemicals in cosmetics is not an exact science [154].
Furthermore, the use of alternatives of natural origin should
not be considered totally safe. Many of these substances

have estrogenic activity, and also act as endocrine disruptors
[72, 155–157]. However, the use of natural alternatives
might alleviate the use of synthetic chemicals.
We live in a challenging world in which we have to make
choices. Being prudent and informed is an attitude that so-
ciety is obliged to adopt. Nevertheless, one must not forget
the continuous development of new substances replacing the
old, hopefully with less adverse effects, but without ade-
quate research on their safety. Life-cycle analysis contributes
to eco-design and green labels. Rigorously-applied environ-
mental management systems in the cosmetics industry con-
tribute to its corporate social responsibility. The more gen-
eralized application of these instruments will contribute to
the safer use of cosmetic products. Along with the industry,
public authorities have a pivotal role in precaution. The re-
lease of new cosmetics should be more thoroughly regulat-
ed. We should be less sensitive to marketing-driven strate-
gies, usually organized by powerful lobbying machines.
Furthermore, we should register, combine and evaluate all
the relevant public and environmental evidence concerning
new cosmetics. Awareness-raising campaigns with the active
participation of the health sector might increase our knowl-
edge on a likely underestimated environmental health prob-
lem [10, 158, 159].
4 Conclusions
It is extremely difficult to design studies in societies that will
give a clear indication whether chemicals included in cos-
metics are acting as endocrine disruptors in all exposed human
beings. Even though we have studies addressing the subject
in vitro and in vivo in experimental animals, extrapolation the
results to humans always needs special attention, as it is diffi-
cult to incorporate both the different personal exposure pattern
of each cosmetics user, and also the genetic predisposition of

each individual [160, 161]. Therefore, the study of endocrine-
disrupting activity, especially after the Delaney Clause and the
banning of animal testing [1, 162–164], rests on population-
based data collection, and as such, any relevant information
will take a long time before it reaches the interested party.
Despite the knowledge gaps and the complexity of the issue,
it seems that there is enough evidence that exposure to cos-
metics is a matter of concern, and citizens should be informed.
As cosmetics are a significant part of the body chemical bur-
den [35, 165, 166], there is a strong need for safer industrial
technologies, transparent information for the safe use of the
products, and consumer awareness in the frame of the precau-
tionary principle [8, 167].
Acknowledgments We wish to thank Sotirios Maipas for his
help in
the editing and careful reading of the text, Bart Hens for his
advice, and
Craig Morrison for his contribution to the final editing of the
manuscript.
Compliance with ethical standards
Conflict of interest The authors declare no conflict of interest.
The
manuscript was not supported by any grant or sponsorship.
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y/docs/sccs_s_009.pdf
Copyright of Reviews in Endocrine & Metabolic Disorders is
the property of Springer
Science & Business Media B.V. and its content may not be
copied or emailed to multiple sites
or posted to a listserv without the copyright holder's express
written permission. However,
users may print, download, or email articles for individual use.
Cosmetics as endocrine disruptors: are they a health
risk?AbstractIntroductionCosmetic
ingredientsParabensPhthalatesPerfluorinated
chemicalsAluminium saltsTriclosanBisphenol a (BPA)UV
filtersOrganic UV filtersNanoparticles of metal
oxidesDiscussionConclusionsReferences
EDITORIAL
Correspondence:
Ewa Rajpert-De Meyts
E-mail: [email protected]
doi: 10.1111/andr.12243
Special issue on endocrine
disruption and reproductive health

1
E. Rajpert-De Meyts and
2
D. T. Carrell
1Department of Growth and Reproduction, Copenhagen
University Hospital (Rigshospitalet),
Copenhagen, Denmark, and 2Departments of Surgery (Urology),
Obstetrics and Gynecology, and
Human Genetics, University of Utah School of Medicine, Salt
Lake City, UT, USA
It is our pleasure to introduce to our readers a special thematic
issue of Andrology. This is the third of such publications,
follow-
ing one special issue focused on genetic aspects of male
infertil-
ity (Krausz & Carell, 2014) and another comprising papers on
basic and clinical aspects of testicular germ cell cancer
(Rajpert-
De Meyts et al., 2015).
The current issue is devoted to the timely topic of endocrine
disruption and the role of this mechanism in the pathogenesis of
increasingly widespread reproductive disorders. This is a very
important issue that remains to be hotly debated in scientific

and political circles due to conflicting interests from chemical
and pharmacological industry, agriculture, governmental com-
mittees as well as NGOs and consumer organizations. On the
one hand, many compounds have immensely contributed to
protecting our health (e.g. from pests) and facilitating daily life.
On the other hand, some of the commonly used chemicals
turned out to have unexpected negative effects on other aspects
of our health, with the endocrine system particularly vulnerable.
The debate has been additionally fueled by conflicting data
from
research labs working on different species and often using doses
not reflecting the real exposure. Despite these controversies, the
field has been expanding because of the constant stream of
newly identified endocrine disrupters and novel pathways they
affect. The current status of the field is nicely summarized in
the
editorial opening this issue (Andersson et al., 2016).
The content of this special issue highlights some of the perti-
nent topics in the field of endocrine disruption that are of rele-

vance to andrologists and researchers interested in male
reproduction. However, the issue also contains a few articles
that
deal with female reproduction and neuroendocrinology. Most of
the articles are based on lectures presented at the 8th
Copenhagen Workshop on Endocrine Disrupters, held in May
2015. These meetings have grown to be the preeminent gather-
ing of leading experts in the field that sets a tone for research in
the field.
We are proud that Andrology participates in the dissemination
of data presented at this and other ‘cutting-edge’ meetings. We
have also added a handful of thematically matching papers sub-
mitted to Andrology independently of the meeting. All papers in
this special issue underwent a usual stringent review process
according to the journal’s standard. The issue has been edited
by
a guest associate editor, Anna-Maria Andersson, the main orga-
nizer of the Copenhagen meeting, and the director of the Danish
Center for Endocrine Disrupters (www.cend.dk), founded by the

Danish Ministry of Environment, which also supported the
meeting financially. She was helped by members of the Pro-
gramme Committee, Katrine Bay, Hanne Frederiksen, and Niels
E. Skakkebæk, as well as Kenneth Grigor, who edited the
meeting
comments included in some of the papers. We are grateful for
their contribution, and hope that our readers will find the issue
interesting.
REFERENCES
Andersson AM, Bay K, Frederiksen H & Skakkebaek NE.
(2016) Endocrine
disrupters: we need research, biomonitoring, and action.
Andrology 4,
556–560.
Krausz C & Carell DT. (2014) Advances in understanding the
genetics
underlying male infertility and evolving diagnostic and
treatment
options. Andrology 2, 302–303.
Rajpert-De Meyts E, Daugaard G, Almstrup K, Jørgensen A,
Rørth M,

Jørgensen N, von der Maase H & Skakkebaek NE. (2015)
Increasing
international efforts to understand and conquer testicular germ
cell
cancer. Andrology 3, 1–3.
© 2016 American Society of Andrology and European Academy
of Andrology Andrology, 2016, 4, 555 555
ISSN: 2047-2919 ANDROLOGY
http://www.cend.dk
Copyright of Andrology is the property of Wiley-Blackwell and
its content may not be copied
or emailed to multiple sites or posted to a listserv without the
copyright holder's express
written permission. However, users may print, download, or
email articles for individual use.
ORIGINAL ARTICLE
Reproductive health and endocrine disruption in women
with breast cancer: a pilot study
Ashlesha Patel & Alicia Roston & Almae Uy &
Erika Radeke & Arden Roston & Louis Keith & H. A. Zaren
Received: 26 September 2013 /Accepted: 31 July 2014
/Published online: 15 August 2014

# Springer-Verlag Berlin Heidelberg 2014
Abstract
Purpose The purpose of this study was to assess whether
incorporation of an original reproductive health assessment
and algorithm into breast cancer care helps providers appro-
priately manage patient reproductive health goals and to fol-
low laboratory markers for fertility and correlate these with
menstruation.
Methods This prospective observational pilot study was set in
an urban, public hospital. Newly diagnosed premenopausal
breast cancer patients between 18 and 49 years old were
recruited for this study prior to chemotherapy initiation. As
the intervention, these patients received a reproductive health
assessment and care per the study algorithm at 3-month inter-
vals for 24 months. Blood samples were also collected at the
same time intervals. The main outcome measures were to
assess if the reproductive health management was consistent
with patient goals and to track any follicle-stimulating hor-
mone (FSH) and thyroid-stimulating hormone (TSH) level
changes throughout treatment and post-treatment period.
Results Two patients were pregnant at study initiation. They
received obstetric consultations, opted to continue pregnan-
cies, and postpone treatment; both delivered at term without
complications. One woman desired future childbearing and
received fertility preservation counseling. All women received
family planning consultations and received/continued effec-
tive contraceptive methods. Seventy-three percent used long-
term contraception, 18 % remained abstinent, and 9 % used
condoms. During chemotherapy, FSH rose to menopausal
levels in 82 % of patients and TSH rose significantly in 9 %.
While 82 % of women experienced amenorrhea, 44 % of these
women resumed menstruation after chemotherapy.
Conclusions The assessment and algorithm were useful in
managing patients’ reproductive health needs.

Chemotherapy-induced endocrine disruption impacted repro-
ductive health.
Keywords Breast cancer . Contraception . Fertility .
Reproductive endocrinology . Reproductive health
Introduction
Breast cancer is the most common cancer diagnosed in wom-
en of childbearing age. According to the American Cancer
Society, 288,130 women were newly diagnosed with breast
cancer in 2011 [1]. Approximately one quarter of these wom-
en were within the reproductive age range. As survival rates
for this malignancy continue to improve, quality of life issues
have assumed paramount importance. In pursuit of survival,
reproductive health issues, including fertility conservation and
contraception, are often overlooked. Several studies indicate
that the reproductive health needs of women with cancer are
inadequately assessed by providers [2–5].
The reproductive health challenges in breast cancer survi-
vors include endocrine disruption, iatrogenic infertility, and
A. Patel (*): A. Roston: A. Uy: A. Roston: L. Keith
Division of Family Planning, Department of Obstetrics and
Gynecology, John H. Stroger, Jr. Hospital of Cook County,
1900 W.
Polk St., Room #435, Chicago, IL 60612, USA
e-mail: [email protected]
A. Patel: L. Keith
Department of Obstetrics and Gynecology, Feinberg School of
Medicine, Northwestern University, Chicago, IL 60611, USA
E. Radeke: H. A. Zaren
John H. Stroger Hospital of Cook County Minority-Based

Community Clinical Oncology Program (SHCC MBCCOP),
Chicago, IL 60612, USA
H. A. Zaren
Nancy N. and J.C. Lewis Cancer & Research Pavilion at St.
Joseph’s/
Candler Hospital, Savannah, GA 31405, USA
Support Care Cancer (2015) 23:411–418
DOI 10.1007/s00520-014-2381-2
teratogenicity. These issues are further complicated by
limitations in patient and provider knowledge and preven-
tive management as well as the unreliability of endocrine
markers to assess fertility. A case series from our institu-
tion documented the exclusion of primary elements of
reproductive health care from cancer management [6]. A
subsequent survey further highlighted the disconnection
between patient reproductive interests and management
plans. Approximately half the women surveyed were in-
terested in future childbearing [2]. Of those who had
completed childbearing, many were not utilizing contra-
ception [2] and of those who were, lower efficacy barrier
methods were most often used [7].
We developed a health assessment and algorithm to
incorporate reproductive health into cancer care. We hy-
pothesize that use of this reproductive health assessment
and algorithm would better align reproductive health goals
and management within the context of breast cancer care.
Materials and methods
Study design and patient population

This was an Institutional Review Board-approved, prospec-
tive observational pilot study conducted within the Family
Planning Division and the Minority-Based Community Clin-
ical Oncology Program (SHCC MBCCOP) of John H.
Stroger, Jr. Hospital of Cook County. This study was funded
by the Chicagoland Area Affiliate of Susan G. Komen for the
Cure. Women were eligible for the study if they were within
3 months of their breast cancer diagnosis, were between the
ages of 18 and 49 years at diagnosis, were receiving cancer
care at Stroger Hospital, had not initiated chemotherapy or
radiation therapy, and had evidence of ovarian function.
Pregnant women were eligible. A total of 48 women who
presented to the medical oncology clinic were screened for
study eligibility by SHCC MBCCOP staff. Twenty-nine
women (60 % of total women presenting) were deemed
ineligible: 10 (34 %) for having non-malignant breast tumors,
9 (31 %) for prior initiation of chemotherapy or radiation
therapy, 1 (3 %) was postmenopausal, 2 (7 %) had prior
hysterectomy, 2 (7 %) planned to receive treatment at outside
institutions, and 5 (17 %) were more than 3 months post-
diagnosis. Three (6 % of total women presenting) patients
were not recruited for participation due to physician disinter-
est in the study. Of the remaining 16 (33 % of total women
presenting) eligible patients, 5 (31 %) declined participation.
All participants signed informed consent documents prior to
their inclusion in the study. Participants were recruited from
March 2008 through April 2009 and followed up for
24 months.
Questionnaire
We designed a 30-question reproductive health assessment to
determine perceptions and choices regarding basic sexuality,
contraception, and oncofertility. The types of questions that
were addressed included the following: diagnosis, stage of

disease, age of diagnosis, cancer history, treatment plan, con-
traceptive history and current usage, menses, sexuality, child-
bearing desires, concern for child health during cancer treat-
ment, fertility details, and plans for unintended pregnancy
during treatment. The survey instrument utilized was not
validated; however, it may serve as a base for future patient
assessments among reproductive age women with a diagnosis
of breast cancer. This assessment was administered to study
participants upon enrollment and at 3-month intervals for
24 months.
Algorithm
An algorithm (Fig. 1) was designed and followed to promote
care consistent with each patient’s reproductive health assess-
ment. The algorithm initially stratified subjects into pregnant
and non-pregnant groups. Pregnant women were referred for
obstetrics and gynecology consultations to determine a preg-
nancy plan that was consistent with the patient’s planned
cancer treatment. Women who were not pregnant were re-
ferred for a family planning consultation to discuss contracep-
tion and future childbearing interests. Further stratification
along the algorithm was based on desire for future childbear-
ing. Those who had not completed childbearing were referred
for a reproductive endocrinology consultation to discuss fer-
tility preservation options.
Biochemical markers
Assessments of follicle-stimulating hormone (FSH) and
thyroid-stimulating hormone (TSH) levels were scheduled at
baseline, prior to each chemotherapy cycle and every 3 months
post-treatment. Women who were pregnant at study enroll-
ment did not receive laboratory assessments until postpartum.
Objectives and statistics

Study objectives were to (1) perform periodic reproductive
health assessments and to follow a reproductive health algo-
rithm for each patient, (2) implement reproductive health
management plans in accordance with reproductive health
goals derived from the reproductive health assessment, (3)
follow laboratory markers for fertility status and assess prev-
alence of endocrine disruption, and (4) correlate laboratory
markers with menstruation.
The primary endpoint for objectives 1 and 2 was adoption
of appropriate reproductive health management consistent
412 Support Care Cancer (2015) 23:411–418
with reproductive health goals as stated at baseline. Manage-
ment was considered appropriate if (1) pregnant women were
referred to an obstetrician and were counseled about pregnan-
cy options, (2) women interested in future childbearing were
counseled and provided a referral for fertility preservation
counseling, or (3) women not interested in immediate preg-
nancy, independent of desire for future childbearing, were
provided a referral for family planning to receive contracep-
tion consistent with plans for sexual activity and future
childbearing.
For objectives 3 and 4, FSH level was considered to have
reached the menopausal range at >23.0 mIU/mL. TSH level
below 0.20 and above 4.50 mIU/L was considered abnormal
and an indication of endocrine disruption. Menstruation infor-
mation was collected in the reproductive health assessment.
Women were asked the date of their last menstrual period, if
they were menstruating regularly, and whether they believed
they had stopped menstruating.

Statistical analyses were performed using SAS 9.2. De-
scriptive statistics were used to analyze the study population.
Pearson correlation coefficient was used to evaluate the asso-
ciation between menstruation and laboratory markers; student
t tests were used to evaluate age differences between those
who experienced endocrine disruption and those who did not.
Staff training
Referral lines to appropriate members of the Obstetric and
Gynecologic faculty were developed to operate within the
MBCCOP/medical oncology service.
Results
Demographics
The 11 study patients ranged in age from 23 to 48 years (mean,
39; SD, 7.4). Of these, 27 % (3/11) had no children, 9 % (1/11)
had one child, and 64 % (7/11) had two or more children. The
majority of participants were English-speaking Hispanics,
64 % (7/11); the remaining 36 % (4/11) identified themselves
as Black/African American. Upon enrollment, 27 % (3/11) of
women were single, 64 % (7/11) married, and 9 % (1/11)
divorced. Education level varied: 27 % (3/11) completed
primary school, 9 % (1/11) attended some high school, 46 %
(5/11) graduated from high school, and 18 % (2/11) attended
some college (Table 1).
Fig. 1 Reproductive health algorithm
Support Care Cancer (2015) 23:411–418 413

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P
at
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en
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ru
at
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g
Reproductive health assessment/algorithm navigation
Of the 11 women, two (18 %) were pregnant at the time of
recruitment and nine (82 %) were not. Both pregnant women
had become pregnant after or during cancer staging but prior
to initiation of chemotherapy. Each had an obstetric consulta-
tion and chose to continue their pregnancies. Each delivered at
term without complication. One woman began chemotherapy
in the second trimester; the other began postpartum. After
completion of their pregnancies, these two women passed
over into the “Not Pregnant” cohort of the algorithm.
Of the 11 women in the newly constituted “Not Pregnant”
cohort, 9 % (1/11) had not yet completed childbearing, where-
as 91 % (10/11) had. The one woman interested in future
childbearing received fertility preservation counseling. All
11 women, independent of future childbearing interest, re-
ceived a family planning consultation.
At the time of cancer diagnosis, 18 % (2/11) of women had
already undergone permanent sterilization and 18 % (2/11)
had an intrauterine device (IUD) in place. After receiving

family planning consultations, an additional 37 % (4/11) of
women selected an IUD. Throughout the study period, 73 %
(8/11) of women continued or started long-term contraception,
whereas 18 % (2/11) remained abstinent and 9 % (1/11)
selected condoms. Both women who were pregnant at study
initiation received IUDs after delivery. Of note, the one wom-
an who had not yet completed childbearing selected an IUD
for interim contraception.
By study definition, 100 % of the women received appro-
priate referrals consistent with their initial and continued
reproductive health goals. The two pregnant women were
referred to an obstetrician before delivery and to a family
planning specialist after delivery. The one woman interested
in future childbearing had both a reproductive endocrinology
as well as a family planning referral. The remaining eight
women who had completed childbearing received family
planning consultations.
Reproductive health biomarkers and menstrual findings
Of the nine non-pregnant participants at study initiation, seven
reported cessation of menses at an average of 3.3 months (SD,
1.6) after initiation of chemotherapy. Of the two remaining
women, one continued to menstruate regularly, although she
did not adhere to her chemotherapy regimen. The other indi-
cated irregular bleeding but was not able to assess whether
menstruation had ceased. Of the seven patients who reported
cessation of menstruation, three confirmed resumption at an
average of 12.6 months (SD, 2.9) after the initiation of che-
motherapy. The two pregnant women did not resume men-
struation between delivery and initiation of chemotherapy, and
thus cessation information was not available. One of these
women resumed menstruation 8.9 months after initiation of
chemotherapy.

In total, five women indicated they were menstruating after
chemotherapy, five indicated they were not, and one was
unsure. The mean age of those who reported menstruating
after chemotherapy was 36.8 years (SD, 4.86) which differed
significantly from those who did not report menstruating after
chemotherapy, mean age of 44 years (SD, 3.39) (p=0.0265).
Of the 11 women, 10 were followed up for laboratory
assessments of fertility, examining FSH and TSH. Changes
in FSH and TSH were noteworthy. FSH rose to menopausal
levels during chemotherapy treatment in 90 % (9/10) of study
participants. Forty-four percent (4/9) of these women returned
to premenopausal levels after treatment within the 24-month
time period (Fig. 2). The woman whose FSH levels did not
reach menopausal levels was not adherent to chemotherapy
regimens. Mean age of the five women who had a FSH level
within the premenopausal range at study completion was
35 years (SD, 7.84), whereas the mean age of those whose
FSH levels remained elevated was 44 years (SD, 3.39). This
difference was statistically significant (p=0.0463).
For the nine individuals where FSH levels and menstrua-
tion status was known, four indicated that they were menstru-
ating after chemotherapy. FSH returned to premenopausal
levels after chemotherapy in these four individuals. Similarly,
FSH levels among the five individuals who failed to resume
menstruation after chemotherapy remained within menopaus-
al levels throughout the remainder of the study. For these nine
individuals, FSH levels and menstrual status after treatment
correlated perfectly (p<0.0001).
One of the 10 patients had a mildly elevated level of TSH
(4.56 uIU/mL) at study entry which returned to normal levels
by her next blood draw, 2.8 months after chemotherapy initi-
ation. A second patient experienced a slight drop in TSH

(0.143 uIU/mL) 2.8 months after chemotherapy initiation.
These levels returned to normal at the next blood draw,
10.5 months after chemotherapy initiation. A third patient
experienced a profound and unexpected change in TSH
(137 uIU/mL) 8.4 months after chemotherapy initiation
(Fig. 3).
Discussion
The use of the reproductive health assessment and algorithm
assisted providers to ensure that all study participants received
management consistent with their personal reproductive
health goals.
Inconsistencies between reproductive health desires and
management are problematic. Breast cancer survivors are
advised to defer future childbearing for up to 3 years post-
treatment due to the threat of cancer progression and
teratogenic therapies [8]. Regardless, one study of 114,165
patients showed that 6 % of pregnancies occurred in women
prescribed category D and X medications [9, 10]. In our study,
the two patients who were pregnant at study initiation became
pregnant after their diagnosis of cancer. These pregnancies
were unintended and may have been prevented by earlier
contraceptive counseling on the part of the diagnostic team.
While some physicians may find it difficult to initiate conver-
sations regarding reproductive health following initial diagno-
sis, this is a critical timeframe to prevent unintended pregnan-
cy and/or early infertility.
Contraceptive provision is essential for breast cancer

survivors who may temporarily or permanently wish to
defer childbearing. Unintended pregnancy accounts for
50 % of all pregnancies in the USA [11], and this rate is
higher among women with chronic diseases [12–14].
Women with chronic disease are more likely to terminate
an unintended pregnancy [15, 16] compared to matched
control subjects. However, contraceptive provision to
women with breast cancer is complicated by the fact that
estrogen and progestin are largely contraindicated, thereby
limiting options [17]. Lack of provider knowledge of
appropriate and effective, non-hormonal contraceptives
(copper IUD) may impede patient access.
The fact that most patients had completed childbearing at
study entry may not reflect the general population. With one
Fig. 3 TSH levels by time
relative to chemotherapy
initiation
Fig. 2 FSH levels by time
relative to chemotherapy
initiation. The red square
indicates when menses stopped
for each patient, and the presence
of green circle indicates the time
point at which menses resumed
study reporting that 56 % of young breast cancer survivors
desire future childbearing at the time of their diagnosis [18], it
is imperative that physicians assess patient’s future childbear-

ing plans to ensure referrals for fertility preservation when
appropriate.
Some cancer therapy modalities induce amenorrhea. After
a short period of chemotherapy-induced amenorrhea, 50 % of
women younger than 35 years resume menstruation, whereas
in older women, the risk of amenorrhea is increased due to
reduced follicular reserve [19]. Our results were consistent
with this observation that older age was associated with con-
tinued amenorrhea. The absence of menstruation, however,
does not necessarily indicate lack of ovarian function and
fertility [20]. Additionally, the possibility of spontaneous re-
covery of ovarian function has been observed [20]. Literature
suggests that fertility rates may decrease between 10 to 50 %
post-chemotherapy [21–23].
For patients who undergo chemotherapy, ovarian function
should be reassessed periodically. This reassessment may
serve dual purposes, guiding those who wish to maintain
fertility as well as those who do not. Since menstruation is
not a reliable index of ovarian function, various tests assessing
FSH, inhibin A or B or antimullerian hormone (AMH) levels
and vaginal ultrasonography assessment for number of antral
follicles can be used [20]. Our study demonstrated significant
alterations in FSH levels and menstruation. Although the
sample size was limited, age was associated with endocrine
disruption. Evaluation of a large sample of patients will be
necessary to develop correlations between laboratory and
physical findings and long-term fertility status. Recent litera-
ture indicates the best biochemical indicators of ovarian re-
serve may be serum FSH and AMH levels [24, 25]. The
knowledge of functional ovarian reserve may benefit patients
prior to making important decisions regarding treatment, fer-
tility preservation, and contraception [26]. Additionally, while
pregnancy may be a future goal, contraception, specifically
long-term reversible contraception, should be offered even if

pregnancy is deferred for only 1 year.
An important finding of this study relates to the alteration
in TSH level observed in 3 of the 10 women who completed
the laboratory portion of the study. Alterations in thyroid
function have been noted in women with breast cancer with
a baseline rate of autoimmune thyroid disease 2–3 times that
of the general population [27]. Thyroid function may be
affected by chemotherapy and radiation treatment, particularly
when treatment is localized to the vicinity of the thyroid [28].
At this point, however, the literature does not support guide-
lines regarding screening for thyroid disease in cancer care.
The major strength of this investigation was its ability to
pilot the use of a previously untested algorithm to better guide
assessment of and compliance with reproductive health needs
of patients presenting with breast cancer. The unexpected
detection of a serious abnormality in TSH levels warrants
further investigation in a large sample. Indeed, our small
sample size was a limitation in obtaining a greater apprecia-
tion of laboratory abnormalities in this population. It also
inhibited us from correlating chemotherapy and menstrual
cessation. Both areas need further study. Future studies should
also include investigations of AMH. Additionally, no quality
of life indicators were collected in the survey to gauge whether
reproductive health referrals impacted patient well-being. As
the study was implemented in a safety net institution, partic-
ipants may not be generalizable to the greater population of
women diagnosed with cancer during reproductive age. Final-
ly, because of its pilot nature, this study did not include
controls.
In summary, this study demonstrates that the utilization of
our novel reproductive health assessment and algorithm may
significantly improve reproductive health management within

the context of cancer care. The second finding of the study
demonstrates women with breast cancer undergoing chemo-
therapy experience significant endocrine disruptions affecting
the ovaries and possibly thyroid. Such disruptions may lead to
symptoms that affect quality of life indicators related to repro-
ductive health. Implications of both tenants of this study
remain the important aspects of research within oncology care.
A large-scale, multicenter trial has been developed based on
the findings of this important pilot study.
Acknowledgments The authors would like to thank Vanessa
Barrera
for her contributions of data collection and Kelly Stempinski for
her
contributions of manuscript editing.
Financial disclosures Funding for this research was provided by
The
Chicagoland Affiliate of Susan G. Komen for the Cure, Hillside,
IL,
Grant No. 3010.
Conflict of interest None of the coauthors have a conflict of
interest.
References
1. American Cancer Society. Breast cancer facts & figures
2011–2012.
Atlanta: American Cancer Society, Inc
2. Patel A, Sreedevi M, Malapati R, Sutaria R, Schoenhage MB,
Patel
AR et al (2009) Reproductive health assessment for women with
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3. Duffy CM, Allen SM, Clark MA (2005) Discussions
regarding
reproductive health for young women with breast cancer
undergoing
chemotherapy. J Clin Oncol 23(4):766–73
4. Thewes B, Meiser B, Rickard J, Friedlander M (2003) The
fertility-
and menopause-related information needs of younger women
with a
diagnosis of breast cancer: a qualitative study. Psychooncology
12(5):500–11
5. Peate M, Meiser B, Hickey M, Friedlander M (2009) The
fertility-
related concerns, needs and preferences of younger women with
breast cancer: a systematic review. Breast Cancer Res Treat
116(2):
215–23
6. Patel AA, Mini S, Sutaria RP, Schoenhage MB, Patel AR,
Radeke
EK et al (2008) Reproductive health issues in women with
cancer. J
Oncol Pract 4(2):101–5
7. Steiner MJ, Trussell J, Johnson S (2007) Communicating
contracep-
tive effectiveness: an updated counseling chart. Am J Obstet
Gynecol
197(1):118

8. Helewa M, Levesque P, Provencher D, Lea RH, Rosolowich
V,
Shapiro HM (2002) Breast cancer, pregnancy, and
breastfeeding. J
Obstet Gynaecol Can 24(2):164–80, quiz 81-4
9. Steinkellner A, Chen W, Denison SE (2010) Adherence to
oral
contraception in women on category X medications. Am J Med
123(10):929–34 e1
10. Andrade SE, Raebel MA, Morse AN, Davis RL, Chan KA,
Finkelstein JA et al (2006) Use of prescription medications with
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Pharmacoepidemiol
Drug Saf 15(8):546–54
11. Finer LB, Zolna MR (2011) Unintended pregnancy in the
United
States: incidence and disparities, 2006. Contraception
84(5):478–85
12. St James PJ, Younger MD, Hamilton BD, Waisbren SE
(1993)
Unplanned pregnancies in young women with diabetes. An
analysis
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don't
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