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Sex hormones & gastrointestinal health

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contents

FEATURES 20

Healthwave

Creating your online dispensary

Naturopathic Medicine Week

Giving New Life to your Clinic With patients in mind

Sex Hormones & Gastrointestinal Health

Mindfulness-Based Therapies in the Treatment of Functional Gastrointestinal Disorders

A Meta-Analysis

An exploratory compartive investigation of Food Allergy/ Sensitivity Test in IBS

A comparison between various laboratory methods and an elimination diet

40 DEPARTMENTS 9 10 12 22 32 50

Publisherâ&#x20AC;&#x2122;s Letter Editorial Board Bits and Bites

Industry and Research News

Product Profiles Clinic Profile

Zentai Wellness Centre

Exit Strategy

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publisher’s letter

would like to begin with some exciting

that connects practitioners from all over

news. IHP Magazine is pleased to be

the country.

media partner with the Ontario

We would also like to make sure you

Association of Naturopathic Doctors

receive not only the latest updates about

(OAND) for their 2015 Convention and

scientific news and industry achievements,

Tradeshow: Maximizing the Power of the

but also timely information on the business

Mind in Total Wellness: Mind/Body Medicine,

side of your practice. For that reason, we

Disease Management, and Treatment

are introducing a new section, which will

Alternatives, taking place on September

talk about the non-scientific part of health-

25-27 at the Toronto Congress Centre. This

care. Furniture, prevailing colours and the

year, the OAND is celebrating its 65th anni-

overall design of your clinic – it’s all about

versary and we are expecting an amazing

the first impression you give to your first-

event! IHP is honoured to continue to

time patient. On page 36, interior healthcare

support the association in promoting natu-

designers from Toronto and Barcelona are

ropathic medicine in Ontario and nation-

sharing a few tips on how you can take your

wide. We are also excited to announce a

clinic’s design to new heights!

contest, where everyone attending the convention will have a chance to win a

If you have not done it yet, please

Clinic Makeover by top Toronto designer

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Melissa Davis who is known for her creative

have access to exclusive content

design and reno work produced for various

and full-length reference material.

HGTV shows! IHP is looking forward to the Integrative Healthcare Symposium (IHI) to be held at the Sheraton Parkway Toronto on October

Olivier Felicio

23-24. We are delighted to support the event

Publisher/Editor-in-Chief

JULY/AUGUST 2015 • Volume 8 Issue 3 Founder Sanjiv Jagota

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Publisher & Editor-in-Chief Olivier Felicio

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feature

SEX

HORMONES GASTROINTESTINAL HEALTH By Maria Shapoval (ND) Peer-reviewed by Erin Wiley (HBHSc, ND), Hannah Lemke (ND, Cand), Naomi Katz (ND, Cand)

INTRODUCTION

as colonic smooth muscle cells suggesting

Numerous studies exist highlighting the

estradiol, the more potent type of estrogen,

impact of hormonal changes during preg-

may regulate intestinal motility. ERβ is linked

nancy on various gastrointestinal conditions,

to Na+/H+ exchanger protein in membranes

including improvement in irritable bowel

of cells of the proximal colon; where 17β-es-

syndrome (IBS) and aggravations in consti-

tradiol (E2) stimulates its upregulation

pation. Epidemiologically there is a variation

resulting in changes in water balance, poten-

in digestive concerns between men and

tially influencing the consistency of stool.

women, with higher rates of IBS, inflamma-

Progesterone may also indirectly contribute

tory bowel disease (IBD), gallstones affect-

to intestinal motility regulation through cyto-

ing women and higher rates of gastric ulcer

kine and prostaglandin release. The impact

and gastric cancers occurring in men.

of testosterone, produced in Leydig cells of

The sex hormones discussed in this narrative include testosterone, estrogen and

the testes, on intestinal motility is less known (Wang 2009).

progesterone. Estrogen and progesterone

This narrative will explore the impact

are secreted predominantly from the

that sex hormones have on several gastro-

ovaries, though recent studies report local

intestinal conditions as well as examine the

production and effect of estrogen in other

physiological processes underlying these

areas of the body, far removed from the

connections, including impact on the gut

reproductive system. Estradiol receptor β

immune system, microbiota and digestive

(ERβ) is found in enteric nerve cells as well

hormone secretion.

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feature

GASTRIC ULCERS

bowel habits, ranging from constipation to diarrhea.

Gastric ulcers are sores or openings in the inner lining of

Prevalence of IBS varies between 3:1 and 5:1 depending on

the stomach which typically produce symptoms of epigas-

the clinical setting, with higher rates in female patients

tric pain, nausea, frequent bouts of hunger and possible

(Mulak 2014). The hormonal influence is evident as symp-

weight loss. Ulcers are more prevalent in men than women,

toms of IBS change throughout the menstrual cycle and

and according to an animal study by Machowaska et al

respond to oral contraceptive and hormone replacement

(2004) may be aggravated by testosterone. The adminis-

therapies. Their mechanism of influence is believed to be

tration of testosterone significantly reduced blood flow to

through changes in gastrointestinal transit time, visceral

the ulcerated area, prevented gastrin release (a peptide

hypersensitivity and gut permeability. Estrogen has an

with protective and healing properties), and increased the

inhibitory effect on colonic contractility resulting in slower

release of a pro-inflammatory cytokine, interleukin 1-β. In

transit time, while progesterone appears to have dual

the study conducted by Drago (1999) removal of testos-

function, with high dose reducing motility and low dose

terone, by way of testectomy, improved healing time of

administration increasing motility. Fluctuations of proges-

gastric ulcres. Interestingly, the administration of proges-

terone throughout the menstrual cycle could play a role in

terone had the same effects. Manipulating estrogen did

the alternating constipation and diarrhea symptoms seen

not yield clear results as E2 was reported to have pro-ul-

with IBS. Animal studies examining abdominal pain sensi-

cerogenic effects in one study (Drago 1999) and protective

tivity report similar dual impact from estradiol with stan-

effects in another (Smith 2008)

dard dose causing hypersensitivity and high dose resulting in anti-nociception.

INFLAMMATORY BOWEL DISEASE (IBD)

Maintenance of an intact intestinal barrier is important

IBD is a chronic inflammatory condition that involves various

in water balance, immune defense, healthy absorption and

parts of the gastrointestinal tract and produces symptoms

other digestive functions. A decrease in intestinal perme-

of bloody diarrhea, abdominal pain, reduced appetite and

ability has been reported with estradiol supplementation,

low grade fever. Ulcerative colitis (UC) and Crohn’s disease

as well as BPA and soy exposure, suggesting a protective

are examples of this condition and are more prevalent in

role of estrogen in gut barrier maintenance (Meleine 2014).

women than men. Dehydroepiandrosterone (DHEA), a

While there are several plausible physiological explanations

precursor to several sex hormones, has been shown to be

for the hormonal impact on IBS, the exact mechanism

reduced in patients with IBD. This may contribute to the

remains to be defined.

pathogenesis as DHEA has direct anti-inflammatory properties. What leads to low DHEA levels and whether its

GALLBLADDER DISEASE

reduction leads to alternations in testosterone and E2, its

Gallstones, in particular stones predominantly made of

downstream metabolites, is unclear. The administration of

cholesterol, occur twice as frequently in women than men

DHEA appears to offer protection as demonstrated in a

and are believed to be promoted by estrogen. Oral con-

pilot study by Andus et al (2003). Twenty participants with

traceptives and conjugated estrogen hormone replacement

UC and Crohn’s were supplemented with 200mg DHEA

therapy both result in increased cholesterol gallstone

once/day for 56 days. Supplementation resulted in clinically

formation, with similar impact demonstrated in men receiv-

significant improvement in both groups with 6 of 7 patients

ing estrogen for prostatic cancer therapy (Wang 2009).

with Crohn’s and 6 of 13 patients with UC achieving remis-

E2 promotes lithiasis (stone formation) by upregulating

sion and a decrease in blood diarrhea, abdominal pain and

the expression of ESR1 in the liver. This results in increased

liquid stools. No masculinization effects were observed.

secretion of cholesterol and supersaturation of bile. Conversely, progesterone has been demonstrated to reduce

IRRITABLE BOWEL SYNDROME (IBS)

gallbladder emptying time resulting in stasis, which can

IBS is defined as a sensory-motor disorder of the digestive

further promote lithiasis (Tierney 1999). It is interesting

tract with symptoms of abdominal pain and alternating

that soy, a phytoestrogen, has been demonstrated to reduce

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the cholesterol content of gallstones (Tomotake 2000),

receiving hormone replacement therapy (HRT) (Caizza

though its effect may be independent of its estrogenic-like

2015). The protective mechanism of HRT appears to be

activity.

dependent on the estrogen-receptor β (ERβ). Studies examining animals without the ERβ (genetic knock-outs) demon-

COLON POLYPS

strate increased hyperproliferation of colonic cells, loss of

Colon polyps are produced from a local overgrowth of

differentiation and reduced apoptosis, all of which predis-

colonic cells and are typically asymptomatic. The frequency

pose to carcinogenesis. Clinically, ERβ can be present in

of colonic polyps, also known as adenomas, is higher in

both healthy and cancerous cells, with advanced cancer

men and their onset is earlier. Amos-Landgraf et al (2014)

cells demonstrating a reduction and/or complete loss of

examined the role of testosterone and estrogen on the

ERβ. Additionally, the lack of ERβ within cancer cells (ERβ

formation of adenomas in an animal study. The removal

negative status) is associated with a poorer prognosis.

of estrogen, by ovariectomy, did not impact the formation

Xenoestrogens, which are endocrine disruptors with

frequency in female rats, while orchiectomy yielded a

estrogen-like effects, have been implicated in colon car-

significantly protective effect on adenomas, which was

cinogenesis. Bisphenol A (BPA) has been demonstrated to

reversed with testosterone supplementation. As there were

have anti-estradiol activity preventing the apoptosis of

no androgen receptors found in the tumors, testosterone

colon cancer cells in an in vitro study (Marino 2014). On a

is thought to have indirect impact on adenomagenesis.

positive note, flavonoids that act on the ERβ, such as quer-

This impact may occur through the modification of gut

cetin and naringenin have been shown to have an anti-colon

microbiota, which has been demonstrated to be different

cancer effect, also demonstrated in vitro (Marino 2014).

between men and women and responsive to hormonal

CONCLUSION

changes (Yurkovetrskiy 2013).

While the full extent of the role that sex hormones play in

COLORECTAL CANCER (CRC)

gastrointestinal health remains to be further explored, their

Estrogen has been linked to not only reproductive cancers,

possible contribution to gastrointestinal pathology presents

such as breast and uterine, but also non-reproductive

a new target for therapeutic interventions. Clinically explor-

cancers like colorectal cancer. The connection between

ing the connection between sex hormones and gastroin-

hormones and CRC has been supported by the Women’s

testinal health in patient care may yield additional

Health Initiative observation study that demonstrated a

therapeutic approaches and interventions that may not

30% reduction in CRC incidence in post-menopausal women

have been considered otherwise.

References

Meleine M, Matricon J. Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones. World J Gastroenterol. 2014 Jun; 20(22): 6725-43 Mulak A, Tache Y, Larauche M. Sex hormones in the modulation of irritable bowel syndrome. World J Gastroenterol. 2014 Mar; 20(10): 2433-48 Smith 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): 205-9 Wang HH, Liu M, Clegg DJ, Portincasa P, Wang DQ. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta. 2009 Nov; 1791(11): 1037-47 Yurkovetskiy L, Burrows M, et al. Gender bias in autoimmunity is influenced by microbiota. Immunity. 2013 Aug; 13(1): 400-12

Amos-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 protection by female hormones. Proc Natl Acad Sci USA. 2014 Nov; 111(46): 16514-9 Andus 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): 409-14 Caiazza F, Ryan EJ, Doherty G, Winter DC, Sheahan K. Estrogen receptors and their implications in colorectal carcinogenesis. Front Oncol 2015 Feb 2; 19 Machowska 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: 91-104 Marino M. Xenoestrogens challenge 17Beta-estradiol protective effects in colon cancer. World J Gastrointest Oncol. 2014 May; 6(3): 67-73

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