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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


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

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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

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time patient. On page 36, interior healthcare

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sharing a few tips on how you can take your

clinic’s design to new heights!

If you have not done it yet, please

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have access to exclusive content

and full-length reference material.

Founder Sanjiv Jagota

Publisher & Editor-in-Chief Olivier Felicio

Managing Editor Inna Levchuk

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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

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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


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

IHP Hormones.indd 40 2015-06-30 9:24 AM


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



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


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