Sex and the Celiac: A Focus on Reproductive Health...celiac disease and infertility ② Discuss...

Sex and the Celiac:��A Focus on Reproductive Health

www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2013. All rights reserved.

Featuring: Stephanie M. Moleski, MD

Thomas Jefferson University Hospital Division of Gastroenterology and Hepatology

Philadelphia, PA

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Three lucky webinar participants will win NFCA swag and a copy of the Winter 2013 edition of Allergic Living magazine.

Welcome!

•  Physician at The Jefferson Celiac Center of TJUH

•  Research focus includes clinical research on celiac disease with an emphasis on women’s gastrointestinal health

•  2012 study on celiac disease and reproductive health won the American College of Gastroenterology/Radhika Srinivasan Gender-Based Research Award

Stephanie M. Moleski, MD

www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2013. All rights reserved. 4

Presentation Objectives

①  Provide a summary of recent key research on the link between undiagnosed celiac disease and infertility

②  Discuss research findings about the impact of the gluten-free diet on improved reproductive health

③  Share a patient case study relevant to the webinar’s topic, helping to bridge the gap between research and real-life applicability

④  Address audience’s questions and concerns


Why a special focus on women’s health?

•  Autoimmune diseases are more frequent in women than men

•  At present, celiac disease is diagnosed more often in females

•  A slight increase in the true prevalence •  60% - 70% of diagnosed individuals are women

•  Females have different health seeking behaviors than men

•  Many complications of undiagnosed celiac disease can significantly impact a woman’s health

•  Average age of celiac disease diagnosis is in the 40’s or 50’s – span of reproductive life may be disrupted


Shah, et al

Background on Reproductive Health Complications

Many aspects have been described, including differences seen in:

•  Fertility

•  Miscarriages (spontaneous abortions)

•  Pregnancy outcomes:

•  Pre-term deliveries •  Mode of delivery (caesarian sections vs. vaginal delivery)

•  Age of menarche (first period) and menopause

•  Sexuality and libido


•  Association first described by Morris, et al in 1970

•  Studies are inconsistent in this area:

•  Small sample sizes

•  Underpowered studies can make application of real life importance difficult

•  Ethnic backgrounds of patients, i.e. Caucasian vs. Asian

•  …BUT trend is clear

•  Spring 2012:

•  Investigators at Thomas Jefferson University Hospital Celiac Center aimed to clarify celiac patients’ experiences with fertility and pregnancy outcomes

Morris JS, et al. 1970; Choi, et al. 2011


Background, cont

TJUH 2012 Study: Methods

•  Patients from the Jefferson Celiac Center and NFCA community members completed an anonymous, on-line survey

•  Control patients who did not carry a diagnosis of celiac disease also completed the survey


•  The questionnaire inquired about patients’:

•  Celiac disease diagnosis •  Menstrual history •  Fertility •  Miscarriages •  Pregnancy outcomes


Methods, cont

•  1022 women responded to the survey

•  473 had been diagnosed with celiac disease by a physician

•  Only those patients diagnosed by small bowel biopsy (n=298) were compared to controls who did not carry a diagnosis of celiac disease (n=560)


Methods, cont

TJUH Results: Fertility

P= 0.04 P=0.03

34 35 36 37

38

39

40

41

42

Celiac Controls

41.2%

36.5%

Difficulty Conceiving

17

18

19

20

21

22

23

Celiac Controls

22.4%

19%

Saw fertility specialist


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TJUH Results: Miscarriages •  Miscarriages in celiac disease patients occurred prior to their celiac disease diagnosis in 79 participants (81.4%)

P=0.02

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34

36

38

40

42

44

Celiac Controls

43.3%

36.6%


TJUH Results: Pregnancy Outcomes •  Celiac disease women were more likely to deliver pre-term (< 37 weeks)

• 37 to 42 weeks is considered full-term

P=0.007

0

5

10

15

20

25

Celiac Controls

23.2%

14%

Pre-term Deliveries


•  More pregnancies in women with celiac disease resulted in C-section compared to women without celiac disease

P<0.001

22

23

24

25

26

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Celiac Controls

26.4%

23.8%

C-sections


Pregnancy Outcomes, cont

TJUH Results: Fertile Life Span

47.8

48

48.2

48.4

48.6

48.8

49

49.2

Celiac Controls

48.3 yo

49.2 yo

Average Age Menopause

12.2

12.3

12.4

12.5

12.6

12.7

Celiac Controls

12.7 yo

12.4 yo

Average Age Menarche P = 0.01 P = 0.3


What else do we know?��


Infertility

•  Celiac disease is rarely included as a potential cause of unexplained infertility

•  Infertility is estimated to affect 7.4%-14% of North American females

•  Of this population, unexplained infertility affects 15%

•  Studies suggest that undiagnosed celiac disease may occur in as many as 4%-8% of women with unexplained infertility

Shah, et al


What’s the prevalence of undiagnosed celiac disease among infertile women?

2011 study from Columbia University and the Mayo Clinic:

•  N= 188 infertile women, aged 25-39

•  Screening detected 2.1% prevalence of celiac disease

•  5.9% of these screen-detected women had unexplained infertility

•  The study’s authors state: “it may now be reasonable to screen any patient presenting with unexplained infertility”

19 www.CeliacCentral.org Restoring Health … Reclaiming Lives.

National Foundation for Celiac Awareness 2013. All rights reserved.

Choi, et al

Infertility & Celiac Disease: Why the link?

•  Nutrient deficiencies such as folate, zinc, antioxidants or micronutrients essential for normal functioning of sex hormones

•  Particularly folate, zinc, selenium, and iron deficiencies

•  Blood clots due to hyperhomocysteinaemia, which is caused by malabsorption of vitamin B12 is frequently involved in infertility

•  tTG is expressed in endometrial cells and has been shown to impair placental function

•  tTG binds to the cells of the trophoblast, which are the tissues that surround an embryo and attach it to the uterus

•  DiSimone et al found a threefold increase in the death of trophoblast cells after exposure to anti-tTG

Ozgör B, et al., Dickey W, et al., Di Simone N, et al.


Fertility on a Gluten-Free Diet •  Swedish study found that women with diagnosed celiac disease had normal fertility, but their

fertility had decreased in the 2 years prior to the diagnosis of celiac disease

•  Likely that fertility improves once on gluten-free diet

•  An Italian study found that women with undiagnosed celiac disease who had had trouble conceiving got pregnant as early as 2 months after starting a gluten-free diet

•  Other studies are contradictory, but there is an evident trend that a gluten-free diet as treatment for celiac disease can moderately improve fertility

•  In their 2010 review, Shah et al stated:

•  “Of the studies included [in this review], none have examined whether adopting a gluten-free diet during pregnancy might influence pregnancy outcome.”

Zugna D, et al; Nenna R, et al; Shah, et al


Other Impacts of the Gluten-Free Diet •  2010 review by Shah et al included studies that found:

•  Higher rate of miscarriage in celiac disease patients before diagnosis and treatment did not seem to improve with the gluten-free diet

•  When compared to patients not adhering to the gluten-free diet, adherent patients had reduced incidences of:

•  Secondary amenorrhea (missed periods)

•  Delayed menarche

•  Early menopause

•  Spontaneous abortion



Shah et al

Miscarriages

•  Deficiency of folic acid, an essential vitamin in rapidly proliferating tissues such as embryo

•  Most of the miscarriages in women with celiac disease occurred prior to official diagnosis and initiation of a gluten-free diet

•  Ciacci et al found that a gluten-free diet resulted in:

• A 9-fold reduction in the miscarriage rate

• A reduction in the prevalence of low birth weight babies from 29.4% to 0

•  Still, some other studies find no association

Ciacci C, et .al


Endometriosis •  Endometriosis:

• A common gynecological condition that occurs in approximately 10% of women

• Common among women with infertility

• Meets many of the criteria for an autoimmune disease, with some research suggesting that it can be classified with chronic inflammatory diseases

•  A Swedish study of 11,000 women with diagnosed celiac disease found an increased risk of endometriosis

• The highest risk of a subsequent diagnosis with endometriosis was observed in the first year after their celiac disease diagnosis

• But was unable to differentiate between patients adherent and non-adherent to the gluten-free diet – could this be a reason?

• Other data have found that endometriosis is associated with chronic inflammation


Stephansson, et al

When should women be tested for celiac disease?

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*The standard initial test for celiac disease in most populations is IgA‑tTG


Population Indications for Celiac Disease Testing*

Women of Childbearing Age Unexplained GI symptoms or weight loss

Anemia

Vitamin deficiencies

Family history of celiac disease

Previous spontaneous abortion

History of unexplained intrauterine growth retardation (IUGR)

Previous low birth weight babies

History of preterm birth

Women with Infertility Unexplained GI symptoms or weight loss

Anemia

Vitamin deficiencies

Autoimmune disorders

Family history of celiac disease

No alternative hormonal or anatomical cause for infertility

Table excerpted from Shah et al 2010 with permission

26 www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2013. All rights reserved.

What is the risk of reproductive health cancer? Background:

•  Significant interest in increased risk of malignancies associated with celiac disease, with a well established increased risk for some GI malignancies

•  Research has identified that celiac disease has an inverse association with breast cancer (leading cause of cancer in females in developed countries)

• Malnutrition and weight loss • …leads to a shorter time of exposure to estrogen

• Estrogen is linked to breast, ovarian and endometrial cancers

Ludvigsson et al

27 www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2013. All rights reserved.

What is the risk of reproductive health cancer? 2011 Study:

• Large Swedish study with 17,852 celiac disease females

• Also included patients with inflammation but no villous atrophy and patients with normal mucosa but positive celiac disease serology

• Compared to the general population, celiac disease females have reduced risk of breast, ovarian and endometrial cancer development one year after diagnosis

• Found negative association between breast cancer and celiac disease and not for the other two patient populations with less mucosal damage

Ludvigsson et al

Male Fertility

•  Yet again, contradictory studies

•  Earlier studies of men with untreated celiac disease:

•  Abnormal hormone levels

•  Low sperm counts

•  Reduced fertility

•  2011 Swedish study:

•  No difference in fertility, both before and after diagnostic biopsy

Zugna D, et al


Libido

•  Italian study found:

•  Untreated celiac disease patients had less intercourse than the control group and fewer were satisfied with their sex lives

•  Why?

•  Untreated celiac disease may cause fatigue and depression or gas and bloating, which effect sexuality

•  Malabsorption of nutrients leads to hormone abnormalities, which effect sexual desire and performance


Ciacci, et al

Kissing •  No scientific data on gluten and kissing

•  Peanut allergy studies have shown that salivary concentration peaked 5 minutes after the meal and became undetectable in most subjects after 1 hour

•  Interventions led to > 80% reduction in the amount of peanut allergen:

•  Brushing teeth, rinsing the mouth, or both

•  Waiting 1 hour

•  Waiting and chewing a gum

Maloney JM, et al


Patient Case •  Medical history:

•  30 year old female presenting for evaluation of a low blood count (anemia) •  Had been trying to conceive for 5 years and had seen a fertility specialist for the past 2 ½ years

•  GI evaluation:

•  Positive celiac serologies •  Upper endoscopy: Pathology consistent with celiac disease (villous blunting) •  DEXA scan showed osteopenia •  Started on a gluten-free diet and nutrition consultation

•  Follow-up visit 6 months after initiation of gluten-free diet:

•  Celiac serologies decreased from >100 at presentation to 40 •  Felt better with less fatigue •  10 months after starting gluten-free diet she is now pregnant and scheduled to deliver in April 2013

This case documents the important relationship between fertility and celiac disease



Conclusion The reproductive health of celiac disease patients is an important aspect of women’s health that needs increased awareness among patients and physicians and continued investigation by researchers.

Where do we go from here?

•  Cost-benefit analysis •  Large, well-designed studies •  Longer-term studies •  Clarify the unknown association between celiac disease and preterm birth


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As we finish…


Questions from the audience?



Save The Date! CeliacCentral.org/Webinars

•  Topic: "Celiac Disease, Gluten Sensitivity and Neuropsychiatric Disease"

•  Date: Tuesday, April 9, 2013

•  Time: 8:30 p.m. Eastern/5:30 p.m. Pacific

•  Speaker: Armin Alaedini, PhD, Assistant Professor, Department of Medicine, Columbia University Medical Center

•  Topic: "Kids Central Special: Planning for Your Child's Gluten-Free Summer Camp"

•  Date: Thursday, March 14, 2013


•  Speaker: Jeffery Lewis, MD, Children’s Center for Digestive HealthCare, LLC, Founder, Camp WeeKanEatit, and Jill Waddell, Director, Camp WeeKanEatit

•  Topic: “Gluten-Free Menu Planning: Budget-Friendly Tips"

•  Date: Wednesday, May 8, 2013


•  Speaker: Kathleen Reale, BeFreeForMe.com

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National Foundation for Celiac Awareness:

• Special education for patients and physicians: CeliacCentral.org/womenshealth

• Sex and The Celiac – 2011 video: YouTube.com/user/NFCAceliaccentral

• Follow-up from January webinar: Q&A with Tricia Thompson, MS, RD

• February: “Cook for Your Love” with brand new gluten-free recipes from Thai Kitchen. Watch our homepage at CeliacCentral.org for the full info, including how to enter that month’s gluten-free giveaway!

•  Stay in touch! Facebook.com/NFCeliacAwareness

•  Join NFCA’s Inspire community discussion board: Inspire.com/groups/celiac-central


Resources

15th Annual International Celiac Disease Symposium:

•  www.ICDS2013.org

Thank you!

Questions? Comments? Feedback?

Kristin Voorhees: [email protected]

Dr. Stephanie Moleski and The Jefferson Celiac Center:

http://www.jeffersonhospital.org/departments-and-services/celiac-center



References & Suggested Reading • Morris JS, Adjukiewicz AB, Read AE. Coeliac infertility: an indication for dietary gluten restriction. Lancet 1970:i:213.

• Riddle MS, Murray JA, Porter CK. The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol. 2012 Aug;107(8):1248-55

•  Shah S, Leffler D. Celiac disease: an underappreciated issue in women’s health. Womens Health (Lond Engl). 2010 Sep;6(5):753-66.

•  Ludvigsson JF, Montgomery SM and Ekbom A. Celiac disease and risk of adverse fetal outcome: a population-based cohort study. Gastroenterol 2005; 129: 454-463.

• Tata LJ, Card TR, Logan RF. Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study. Gastroenterol 2005; 128: 849-855.

• Martinelli P, Troncone R, Paparo F. Coeliac disease and unfavourable outcome of pregnancy. Gut 2000; 46: 332-335.

• Greco L, Veneziano A, Di Donato L. Undiagnosed coeliac disease does not appear to be associated with unfavourable outcome of pregnancy.Gut 2004; 53: 149-151.

• Meloni GF, Dessole S, Vargiu N, et al. The prevalence of coeliac disease in infertility. Hum Reprod 1999; 14: 2759-2761.

• Collin P, Vilska S, Heinonen PK, et al. Infertility and coeliac disease. Gut 1996; 39:3 82-384.

•  Jackson JE, Rosen M, McLean T, et al. Prevalence of celiac disease in a cohort of women with unexplained infertility. Fertil Steril 2008; 89: 1002-1004.

• Kumar A, Meena M, Begum N, et al. Latent celiac disease in reproductive performance of women. Fertil Steril 2011; 95: 922-927.

• Ozgör B, Selimoğlu MA. Coeliac disease and reproductive disorders. Scand J Gastroenterol. 2010 Apr;45(4):395-402

• Nenna R, Mennini M, Petrarca L, Bonamico M. Immediate effect on fertility of a gluten-free diet in women with untreated coeliac disease. Gut. 2011 Jul;60(7):1023-4. doi: 10.1136/gut.2010.232892.

• Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, Patton S, McNulty H. Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery. Scand J Gastroenterol. 2008;43(6):682-8.

• Di Simone N, Silano M, Castellani R, Di Nicuolo F, D'Alessio MC, Franceschi F, Tritarelli A, Leone AM, Tersigni C, Gasbarrini G, Silveri NG, Caruso A, Gasbarrini A. Anti-tissue transglutaminase antibodies from celiac patients are responsible for trophoblast damage via apoptosis in vitro. Am J Gastroenterol. 2010 Oct;105(10):2254-61

• Zugna D, Richiardi L, Akre O, Stephansson O, Ludvigsson JF. A nationwide population-based study to determine whether coeliac disease is associated with infertility. Gut. 2010 Nov;59(11):1471-5.

• Ciacci C, Cirillo M, Auriemma G, et al. Celiac disease and pregnancy outcome. Am J Gastroenterol1996; 91:718–722.

• Ciacci C, De Rosa A, de Michele G, Savino G, Squillante A, Iovino P, Sabbatini F, Mazzacca G. Sexual behaviour in untreated and treated coeliac patients. Eur J Gastroenterol Hepatol. 1998 Aug;10(8):649-51.

• Zugna D, Richiardi L, Akre O, Stephansson O, Ludvigsson JF. Celiac disease is not a risk factor for infertility in men. Fertil Steril. 2011 Apr;95(5):1709-13.

• Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH. Increased prevalence of celiac disease in patients with unexplained infertility in the United States. J Reprod Med. 2011 May-Jun;56(5-6):199-203.

• Maloney JM, Chapman MD, Sicherer SH. Peanut allergen exposure through saliva: assessment and interventions to reduce exposure. J Allergy Clin Immunol. 2006 Sep;118(3):719-24

•  Ludvigsson JF, West J, Ekbom A and Stephansson O. Reduced risk of breast, endometrial and ovarian cancer in women with celiac disease. Int J Cancer, 2012 Aug 1;131(3):E244-50

•  Stephansson O, Falconer H and Ludvigsson JF. Risk of endometriosis in 11,000 women with celiac disease. Human Reproduction, 26(10): 2896-2901.


Sex and the Celiac: A Focus on Reproductive Health...celiac disease and infertility ② Discuss...

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Transcript of Sex and the Celiac: A Focus on Reproductive Health...celiac disease and infertility ② Discuss...