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GASTROENTEROLOGY
Sex hormones & gastrointestinal health
WWW.IHPMAGAZINE.COM JULY/AUGUST 2015
Giving New Life to your Clinic
Creating your online dispensary
001.IHP Cover_noimages.indd 1 2015-06-30 9:53 AM
contents
DEPARTMENTS
FEATURES
JULY/AUGUST 2015 • IHPMAGAZINE.COM 6
9 Publisher’s Letter
10 Editorial Board
12 Bits and BitesIndustry and Research News
22 Product Pro�les
32 Clinic Pro�leZentai Wellness Centre
50 Exit Strategy
20 HealthwaveCreating your online dispensary
28 Naturopathic Medicine Week
36 Giving New Life to your ClinicWith patients in mind
40 Sex Hormones & Gastrointestinal Health
44 Mindfulness-Based Therapies in the Treatment of Functional Gastrointestinal DisordersA Meta-Analysis
47 An exploratory compartive investigation of Food Allergy/ Sensitivity Test in IBSA comparison between various laboratory methods and an elimination diet
�nd us on4432
40
IHP Contents.indd 6 2015-06-30 9:50 AM
JULY/AUGUST 2015 • IHPMAGAZINE.COM 9
publisher’s letter
I would like to begin with some exciting
news. IHP Magazine is pleased to be
media partner with the Ontario
Association of Naturopathic Doctors
(OAND) for their 2015 Convention and
Tradeshow: Maximizing the Power of the
Mind in Total Wellness: Mind/Body Medicine,
Disease Management, and Treatment
Alternatives, taking place on September
25-27 at the Toronto Congress Centre. This
year, the OAND is celebrating its 65th anni-
versary and we are expecting an amazing
event! IHP is honoured to continue to
support the association in promoting natu-
ropathic medicine in Ontario and nation-
wide. We are also excited to announce a
contest, where everyone attending the
convention will have a chance to win a
Clinic Makeover by top Toronto designer
Melissa Davis who is known for her creative
design and reno work produced for various
HGTV shows!
IHP is looking forward to the Integrative
Healthcare Symposium (IHI) to be held at
the Sheraton Parkway Toronto on October
23-24. We are delighted to support the event
that connects practitioners from all over
the country.
We would also like to make sure you
receive not only the latest updates about
scientific news and industry achievements,
but also timely information on the business
side of your practice. For that reason, we
are introducing a new section, which will
talk about the non-scientific part of health-
care. Furniture, prevailing colours and the
overall design of your clinic – it’s all about
the first impression you give to your first-
time patient. On page 36, interior healthcare
designers from Toronto and Barcelona are
sharing a few tips on how you can take your
clinic’s design to new heights!
If you have not done it yet, please
download your IHP App where you
have access to exclusive content
and full-length reference material.
Founder Sanjiv Jagota
Publisher & Editor-in-Chief Olivier Felicio
Managing Editor Inna Levchuk
Art Director Scott Jordan
Junior Designer Kaitlin Yep
Contributors Monique Aucoin, Kieran Cooley, Eric Forget, Heidi Fritz, Naomi Katz, Deborah A. Kennedy, Marie-Jasmine Lalonde-Parsi, Hannah Lemke, Elaine Lewis, Melissa Reynolds, Maria Shapoval, Erin Wiley
IHP Magazine Inc.
President Olivier Felicio
General Manager Melanie Seth
General Customer Care Manager Lucy Holden
Subscription RatesCanada $80 (gst included) for six issues | International $120
Canada Post Canadian Publication Mail Agreement Number 4067800 The pub-lisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the pub-lisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for edito-rial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their af�liates for editorial pur-poses in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such mate-rial. Please direct submissions to the Editor, ihp magazine.
Published by IHP Magazine
CirculationIHP Magazine Inc.1235 Bay St., suite 400; Toronto, Ontario, M5R 3K4Email: [email protected]
Advertising Olivier Felicio(416) 203-7900 x [email protected]
JULY/AUGUST 2015 • Volume 8 Issue 3
Olivier Felicio
Publisher/Editor-in-Chief
IHP PubLetter.indd 9 2015-06-30 12:24 PM
JULY/AUGUST 2015 • IHPMAGAZINE.COM 40
feature
INTRODUCTIONNumerous studies exist highlighting the
impact of hormonal changes during preg-
nancy on various gastrointestinal conditions,
including improvement in irritable bowel
syndrome (IBS) and aggravations in consti-
pation. Epidemiologically there is a variation
in digestive concerns between men and
women, with higher rates of IBS, inflamma-
tory bowel disease (IBD), gallstones affect-
ing women and higher rates of gastric ulcer
and gastric cancers occurring in men.
The sex hormones discussed in this nar-
rative include testosterone, estrogen and
progesterone. Estrogen and progesterone
are secreted predominantly from the
ovaries, though recent studies report local
production and effect of estrogen in other
areas of the body, far removed from the
reproductive system. Estradiol receptor β(ERβ) is found in enteric nerve cells as well
as colonic smooth muscle cells suggesting
estradiol, the more potent type of estrogen,
may regulate intestinal motility. ERβ is linked
to Na+/H+ exchanger protein in membranes
of cells of the proximal colon; where 17β-es-
tradiol (E2) stimulates its upregulation
resulting in changes in water balance, poten-
tially influencing the consistency of stool.
Progesterone may also indirectly contribute
to intestinal motility regulation through cyto-
kine and prostaglandin release. The impact
of testosterone, produced in Leydig cells of
the testes, on intestinal motility is less known
(Wang 2009).
This narrative will explore the impact
that sex hormones have on several gastro-
intestinal conditions as well as examine the
physiological processes underlying these
connections, including impact on the gut
immune system, microbiota and digestive
hormone secretion.
By Maria Shapoval (ND)Peer-reviewed by Erin Wiley (HBHSc, ND), Hannah Lemke (ND, Cand), Naomi Katz (ND, Cand)
HORMONESSEX
GASTROINTESTINAL HEALTH
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JULY/AUGUST 2015 • IHPMAGAZINE.COM 42
feature
GASTRIC ULCERSGastric ulcers are sores or openings in the inner lining of
the stomach which typically produce symptoms of epigas-
tric pain, nausea, frequent bouts of hunger and possible
weight loss. Ulcers are more prevalent in men than women,
and according to an animal study by Machowaska et al
(2004) may be aggravated by testosterone. The adminis-
tration of testosterone significantly reduced blood flow to
the ulcerated area, prevented gastrin release (a peptide
with protective and healing properties), and increased the
release of a pro-inflammatory cytokine, interleukin 1-β. In
the study conducted by Drago (1999) removal of testos-
terone, by way of testectomy, improved healing time of
gastric ulcres. Interestingly, the administration of proges-
terone had the same effects. Manipulating estrogen did
not yield clear results as E2 was reported to have pro-ul-
cerogenic effects in one study (Drago 1999) and protective
effects in another (Smith 2008)
INFLAMMATORY BOWEL DISEASE (IBD)IBD is a chronic inflammatory condition that involves various
parts of the gastrointestinal tract and produces symptoms
of bloody diarrhea, abdominal pain, reduced appetite and
low grade fever. Ulcerative colitis (UC) and Crohn’s disease
are examples of this condition and are more prevalent in
women than men. Dehydroepiandrosterone (DHEA), a
precursor to several sex hormones, has been shown to be
reduced in patients with IBD. This may contribute to the
pathogenesis as DHEA has direct anti-inflammatory prop-
erties. What leads to low DHEA levels and whether its
reduction leads to alternations in testosterone and E2, its
downstream metabolites, is unclear. The administration of
DHEA appears to offer protection as demonstrated in a
pilot study by Andus et al (2003). Twenty participants with
UC and Crohn’s were supplemented with 200mg DHEA
once/day for 56 days. Supplementation resulted in clinically
significant improvement in both groups with 6 of 7 patients
with Crohn’s and 6 of 13 patients with UC achieving remis-
sion and a decrease in blood diarrhea, abdominal pain and
liquid stools. No masculinization effects were observed.
IRRITABLE BOWEL SYNDROME (IBS)IBS is defined as a sensory-motor disorder of the digestive
tract with symptoms of abdominal pain and alternating
bowel habits, ranging from constipation to diarrhea.
Prevalence of IBS varies between 3:1 and 5:1 depending on
the clinical setting, with higher rates in female patients
(Mulak 2014). The hormonal influence is evident as symp-
toms of IBS change throughout the menstrual cycle and
respond to oral contraceptive and hormone replacement
therapies. Their mechanism of influence is believed to be
through changes in gastrointestinal transit time, visceral
hypersensitivity and gut permeability. Estrogen has an
inhibitory effect on colonic contractility resulting in slower
transit time, while progesterone appears to have dual
function, with high dose reducing motility and low dose
administration increasing motility. Fluctuations of proges-
terone throughout the menstrual cycle could play a role in
the alternating constipation and diarrhea symptoms seen
with IBS. Animal studies examining abdominal pain sensi-
tivity report similar dual impact from estradiol with stan-
dard dose causing hypersensitivity and high dose resulting
in anti-nociception.
Maintenance of an intact intestinal barrier is important
in water balance, immune defense, healthy absorption and
other digestive functions. A decrease in intestinal perme-
ability has been reported with estradiol supplementation,
as well as BPA and soy exposure, suggesting a protective
role of estrogen in gut barrier maintenance (Meleine 2014).
While there are several plausible physiological explanations
for the hormonal impact on IBS, the exact mechanism
remains to be defined.
GALLBLADDER DISEASE Gallstones, in particular stones predominantly made of
cholesterol, occur twice as frequently in women than men
and are believed to be promoted by estrogen. Oral con-
traceptives and conjugated estrogen hormone replacement
therapy both result in increased cholesterol gallstone
formation, with similar impact demonstrated in men receiv-
ing estrogen for prostatic cancer therapy (Wang 2009).
E2 promotes lithiasis (stone formation) by upregulating
the expression of ESR1 in the liver. This results in increased
secretion of cholesterol and supersaturation of bile.
Conversely, progesterone has been demonstrated to reduce
gallbladder emptying time resulting in stasis, which can
further promote lithiasis (Tierney 1999). It is interesting
that soy, a phytoestrogen, has been demonstrated to reduce
IHP Hormones.indd 42 2015-06-30 9:24 AM
JULY/AUGUST 2015 • IHPMAGAZINE.COM 43
the cholesterol content of gallstones (Tomotake 2000),
though its effect may be independent of its estrogenic-like
activity.
COLON POLYPSColon polyps are produced from a local overgrowth of
colonic cells and are typically asymptomatic. The frequency
of colonic polyps, also known as adenomas, is higher in
men and their onset is earlier. Amos-Landgraf et al (2014)
examined the role of testosterone and estrogen on the
formation of adenomas in an animal study. The removal
of estrogen, by ovariectomy, did not impact the formation
frequency in female rats, while orchiectomy yielded a
significantly protective effect on adenomas, which was
reversed with testosterone supplementation. As there were
no androgen receptors found in the tumors, testosterone
is thought to have indirect impact on adenomagenesis.
This impact may occur through the modification of gut
microbiota, which has been demonstrated to be different
between men and women and responsive to hormonal
changes (Yurkovetrskiy 2013).
COLORECTAL CANCER (CRC)Estrogen has been linked to not only reproductive cancers,
such as breast and uterine, but also non-reproductive
cancers like colorectal cancer. The connection between
hormones and CRC has been supported by the Women’s
Health Initiative observation study that demonstrated a
30% reduction in CRC incidence in post-menopausal women
receiving hormone replacement therapy (HRT) (Caizza
2015). The protective mechanism of HRT appears to be
dependent on the estrogen-receptor β (ERβ). Studies exam-
ining animals without the ERβ (genetic knock-outs) demon-
strate increased hyperproliferation of colonic cells, loss of
differentiation and reduced apoptosis, all of which predis-
pose to carcinogenesis. Clinically, ERβ can be present in
both healthy and cancerous cells, with advanced cancer
cells demonstrating a reduction and/or complete loss of
ERβ. Additionally, the lack of ERβ within cancer cells (ERβ
negative status) is associated with a poorer prognosis.
Xenoestrogens, which are endocrine disruptors with
estrogen-like effects, have been implicated in colon car-
cinogenesis. Bisphenol A (BPA) has been demonstrated to
have anti-estradiol activity preventing the apoptosis of
colon cancer cells in an in vitro study (Marino 2014). On a
positive note, flavonoids that act on the ERβ, such as quer-
cetin and naringenin have been shown to have an anti-colon
cancer effect, also demonstrated in vitro (Marino 2014).
CONCLUSION While the full extent of the role that sex hormones play in
gastrointestinal health remains to be further explored, their
possible contribution to gastrointestinal pathology presents
a new target for therapeutic interventions. Clinically explor-
ing the connection between sex hormones and gastroin-
testinal health in patient care may yield additional
therapeutic approaches and interventions that may not
have been considered otherwise.
ReferencesAmos-Landgraf JM, Hejimans J, Wielenga MC, Dunkin E, Krentx KJ, Clipson L et al. Sex disparity in colonic adenomagenesis involves promotion by male hormones, not pro-tection by female hormones. Proc Natl Acad Sci USA. 2014 Nov; 111(46): 16514-9Andus T, Klebl F, Rogler G, Bregenzer N, Scholmerich J, Straub RH. Patients with refractory Crohn’s disease or ulcerative colitits respond to dehydroepiandrosterone: a pilot study. Aliment Pharmacol Ther. 2003 Feb; 17(3): 409-14Caiazza F, Ryan EJ, Doherty G, Winter DC, Sheahan K. Estrogen receptors and their implications in colorectal carcinogenesis. Front Oncol 2015 Feb 2; 19Machowska A, Szlachcic A, Pawlik M, Brzozowski T, Konturek SJ, Pawlik WW. The role of female and male sex hromones in the healing process of preexisting ligual and gastric ulcerations. J Physiol Pharmacol 2004 Jul; 55 Supp 2: 91-104Marino M. Xenoestrogens challenge 17Beta-estradiol protective effects in colon cancer. World J Gastrointest Oncol. 2014 May; 6(3): 67-73
Meleine M, Matricon J. Gender-related differences in irritable bowel syndrome: poten-tial mechanisms of sex hormones. World J Gastroenterol. 2014 Jun; 20(22): 6725-43Mulak A, Tache Y, Larauche M. Sex hormones in the modulation of irritable bowel syndrome. World J Gastroenterol. 2014 Mar; 20(10): 2433-48Smith A, Contreras C, Ko KH, Chow J, Dong X, Tuo B, Zhang HH, Chen DB, Dong H. Gender-specific protection of estrogen against gastric acid-induced duodenal injury: stimulation of duodenal mucosal bicarbonate secretion. Endorcrinology. 2008 Sep; 149(9): 4554-66 Tierney S, Nakeeb A, Wong O, Lipsett PA, Sostre S, Pitt HA, Lillemoe KD. Progesterone alters biliary flow dynamics. Ann Surg. 1999 Feb; 229(2): 205-9Wang HH, Liu M, Clegg DJ, Portincasa P, Wang DQ. New insights into the molecu-lar mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta. 2009 Nov; 1791(11): 1037-47Yurkovetskiy L, Burrows M, et al. Gender bias in autoimmunity is influenced by microbiota. Immunity. 2013 Aug; 13(1): 400-12
IHP Hormones.indd 43 2015-06-30 9:24 AM
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