Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Efficacy of a new nutraceutical formulation: L-tryptophan, probiotics, charcoal, chamomile, mint, and licorice (COLONIR®) in the improvement of gastrointestinal symptoms in subjects with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. METHODS: An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with two doses of nutraceuticals/day during meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. RESULTS: After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. CONCLUSIONS: These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies.

EUS-guided tissue acquisition in chronic pancreatitis: Differential diagnosis between pancreatic cancer and pseudotumoral masses using EUS-FNA or core biopsy.

Background and Objective: EUS-FNA sensitivity for malignancy in parenchymal masses of patients with concurrent chronic pancreatitis (CP) has been reported to be unsatisfactory. The aim of the present study was to directly compare the diagnostic accuracy of EUS-FNA and EUS-fine-needle biopsy (FNB) in differentiating between inflammatory masses and malignancies in the setting of CP. Methods: We performed a retrospective analysis of prospective, multicentric databases of all patients with pancreatic masses and clinico-radiological-endosonographic features of CP who underwent EUS-FNA or FNB. Results: Among 1124 patients with CP, 210 patients (60% males, mean age: 62.7 years) with CP and pancreatic masses met the inclusion criteria and were enrolled. In the FNA group (110 patients), a correct diagnosis was obtained in all but 18 cases (diagnostic accuracy 83.6%, sensitivity 69.5%, specificity 100%, positive predictive value [PPV] 100%, and negative predictive value [NPV] 73.9%); by contrast, among 100 patients undergoing FNB, a correct diagnosis was obtained in all but seven cases (diagnostic accuracy 93%, sensitivity 86.8%, specificity 100%, PPV 100%, and NPV 87%) (P = 0.03, 0.03, 1, 1, and 0.07, respectively). At binary logistic regression, focal pancreatitis (odds of event occurrence [OR]: 4.9; P < 0.001), higher Ca19-9 (OR: 2.3;P= 0.02), and FNB (OR: 2.5; P < 0.01) were the only independent factors associated with a correct diagnosis. Conclusion: EUS-FNB is effective in the differential diagnosis between pseudotumoral masses and solid neoplasms in CP, showing higher diagnostic accuracy and sensitivity than EUS-FNA. EUS-FNB should be considered the preferred diagnostic technique for diagnosing cancer in the setting of CP.

FRAX Score Can Be Used to Avoid Superfluous DXA Scans in Detecting Osteoporosis in Celiac Disease: Accuracy of the FRAX Score in Celiac Patients.

The Fracture Risk Assessment (FRAX) tool has been developed to estimate patients' 10-yr probability of fracture, thus establishing which patients should undergo dual-energy X-ray Absorptiometry (DXA) scan. This study aimed to evaluate if the FRAX tool can replace or optimize the use of DXA scan in celiac disease (CD). We prospectively enrolled all CD patients aged over 40 yr diagnosed at our third-level unit. At time of CD diagnosis, all patients underwent FRAX score calculation for risk of major osteoporotic and hip fractures and DXA scan (used as gold standard) to assess the accuracy of the FRAX score. The FRAX score calculation was based on the following 10 variables: age (>40 yr), sex (M/F), body mass index, history of previous fracture (yes/no), parent fractured hip (yes/no), current smoking (yes/no), use of steroids (yes/no), rheumatoid arthritis (yes/no), secondary osteoporosis (yes/no), and alcohol ≥3 units/d (yes/no). DXA assessment was performed within 1 week from FRAX calculation. The FRAX score was dichotomized as normal or pathologic in accordance with the National Osteoporosis Guideline Group. A total of 160 CD patients were enrolled (M/F = 20/140; mean age 48.7 yr). A pathologic FRAX score was evident in 14 out of 160 patients (8.7%), whereas osteoporosis based on DXA scan was found in 10 patients (6%) (κ = 0.6); 3 patients with osteoporosis (1.9%) showed a 10-yr risk of major fracture >10% according to the National Osteoporosis Guideline Group criteria. With regard to diagnostic accuracy, the FRAX score showed sensitivity of 0%, specificity of 91%, positive predictive value of 0%, and negative predictive value of 94%. The prevalence of osteoporosis in adult CD appears to be quite low and only a small proportion of patients would require a DXA investigation. The FRAX score could be an effective tool to avoid useless DXA scans in CD patients in view of its high negative predictive value.

Beneficial effects of gluten free diet in potential coeliac disease in adult population.

BACKGROUND: To date, potential coeliac disease (PCD) occurring in adults remains an almost unexplored condition. AIMS: To explore the prognostic role of Marsh grade in adult PCD patients, and to evaluate the effects of gluten-containing diet (GCD) in asymptomatic PCD patients. METHODS: We retrospectively evaluated all consecutive adult PCD patients followed-up for at least 6 years. Patients were divided into: Group A (patients with Marsh 0 histology) and Group B (Marsh 1 patients). Symptomatic patients were started gluten-free diet (GFD), while asymptomatic subjects were kept on GCD and were followed-up. RESULTS: 56 PCD patients were enrolled (21 in Group A and 35 in Group B). Forty-three patients were symptomatic and started GFD. Of these, none of 15 patients in Group A and 8 of 28 patients in Group B developed immune-mediated disorders (IMD) during follow-up (P=0.03; OR=4.2). The 13 asymptomatic PCD patients were kept on GCD. During the follow-up, 9 patients developed CD-related symptoms, 6 villous atrophy and 8 IMD. At the end, patients kept on GCD were at higher risk of developing IMD than those following a GFD (61% vs 18%, P=0.03, OR=3.3). CONCLUSIONS: Although PCD with normal mucosa seems to be a milder disease, the continuation of GCD places patients at a high risk of developing villous atrophy and IMD compared to commencement of GFD. Adult PCD patients should start GFD even if not symptomatic.

Coeliac disease in the elderly in a tertiary centre.

INTRODUCTION AND AIMS: Coeliac disease (CD) was believed to be a childhood disease while it can affect any age. AIM: to evaluate the prevalence of CD in elderly population, recording the main clinical features of this group respect to young patients. METHODS: We retrospectively analysed the prevalence of CD in an elderly population from 1970 to 2015. We divided patients into three age-groups (group A: 18-34 years; group B: 35-64 years; group C: ≥65 years) and compared them regarding baseline anthropometric and serological variables, clinical features at diagnosis, diagnostic mode, associated autoimmune diseases, and CD-related neoplastic complications. RESULTS: We made 2812 CD diagnoses in adults: 2.5% of them were ≥65 years at diagnosis. When comparing the three groups, we found no differences in sex, haemoglobin, serum iron, albumin, and anti-tissue transglutaminase (anti-tTG) (p = NS) while as expected, we found higher values of cholesterol, glycaemia, and triglycerides in older patients (p < 0.0001). Elderly had a higher risk of being diagnosed with malabsorption symptoms compared to younger patients (OR 2.20, 95%CI 1.3-3.74). No difference in the risk of autoimmune CD-related diseases was seen among groups. Furthermore, we observed 16 neoplastic complications, 13 of them happened in the patients diagnosed with CD aged 35-64 years. The number of CD diagnoses increased over time, particularly in elderly. CONCLUSION: CD diagnosis in elderly population is quite uncommon although not rare. Elderly CD patients have a higher risk of being diagnosed with malabsorption symptoms than younger patients but without increased risk of autoimmune and neoplastic complications.

Gluten-free diet does not influence the occurrence and the Th1/Th17-Th2 nature of immune-mediated diseases in patients with coeliac disease.

INTRODUCTION: Coeliac disease (CD) is the most common Th1-mediated enteropathy, frequently associated with other immune-mediated disorders (IMD). AIMS: To evaluate: (1) the prevalence of IMD at the time of and after CD diagnosis; (2) a possible change in immune response to gluten free diet (GFD); (3) the potential role of GFD in reducing and/or preventing IMD in CD. METHODS: Prospective study including all consecutive adult CD patients who underwent investigations for Th1-Th17/Th2-IMD at the time of CD diagnosis and after a 5-year follow-up period. RESULTS: 1255 CD were enrolled. Of these, 257 patients (20.5%) showed IMD at the time of CD diagnosis, with 58.4% presenting a Th1/Th17-IMD. After a 5-year follow-up period, 682 patients (54.3%) showed new IMD despite GFD. Of these, 57.3% presented a Th1/Th17-IMD and 42.7% a Th2-IMD (p=0.8). When compared the prevalence of each type of IMD before and after CD diagnosis, we did not identify any significant "switch" from Th1/Th17- to Th2-IMD or vice versa. The number of patients with Th1/Th17- and/or Th2-IMD increased during the GFD period (20.5% vs 54.3%; p<0.01; OR 1.9). CONCLUSIONS: The prevalence of IMD at the time of CD diagnosis is high and it seems to increase in the follow-up period despite GFD.

Non-variceal upper gastrointestinal bleeding: Rescue treatment with a modified cyanoacrylate.

AIM: To evaluate the safety and efficacy of a modified cyanoacrylate [N-butyl-2-cyanoacrylate associated with methacryloxysulfolane (NBCA + MS)] to treat non-variceal upper gastrointestinal bleeding (NV-UGIB). METHODS: In our retrospective study we took into account 579 out of 1177 patients receiving endoscopic treatment for NV-UGIB admitted to our institution from 2008 to 2015; the remaining 598 patients were treated with other treatments. Initial hemostasis was not achieved in 45 of 579 patients; early rebleeding occurred in 12 of 579 patients. Thirty-three patients were treated with modified cyanoacrylate: 27 patients had duodenal, gastric or anastomotic ulcers, 3 had post-mucosectomy bleeding, 2 had Dieulafoy's lesions, and 1 had duodenal diverticular bleeding. RESULTS: Of the 45 patients treated endoscopically without initial hemostasis or with early rebleeding, 33 (76.7%) were treated with modified cyanoacrylate glue, 16 (37.2%) underwent surgery, and 3 (7.0%) were treated with selective transarterial embolization. The mean age of patients treated with NBCA + MS (23 males and 10 females) was 74.5 years. Modified cyanoacrylate was used in 24 patients during the first endoscopy and in 9 patients experiencing rebleeding. Overall, hemostasis was achieved in 26 of 33 patients (78.8%): 19 out of 24 (79.2%) during the first endoscopy and in 7 out of 9 (77.8%) among early rebleeders. Two patients (22.2%) not responding to cyanoacrylate treatment were treated with surgery or transarterial embolization. One patient had early rebleeding after treatment with cyanoacrylate. No late rebleeding during the follow-up or complications related to the glue injection were recorded. CONCLUSION: Modified cyanoacrylate solved definitively NV-UGIB after failure of conventional treatment. Some reported life-threatening adverse events with other formulations, advise to use it as last option.

Fluoroquinolone-based protocols for eradication of Helicobacter pylori.

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.

Predictive value of "Marsh 1" type histology in subjects with suspected cealic disease.

INTRODUCTION: The diagnosis of celiac disease (CD) is based on histology in combination with anti-tissue transglutaminase (a-tTG) and anti-endomysial antibodies (EMAs). The increase of intraepithelial lymphocytes defines the Marsh 1 histology that appears not to be specific for CD. AIM: To explore the positive predictive value (PPV) and clinical relevance of Marsh 1 histology in suspected CD. METHODS: We carried out an observational prospective study including all consecutive subjects with a Marsh 1 histology. All patients were tested for a-tTG and EMAs. Diagnosis of potential CD was defined in the presence of Marsh 1 with positive a-tTG and EMAs. Patients were investigated for symptoms, CD familial aggregation, other diseases, and current medication. RESULTS: Sixty-three patients with Marsh 1 were included. Diagnosis of potential CD was made in 23 subjects (36%), so that Marsh 1 histology showed a PPV of 36%. With regard to familial aggregation, patients with potential CD showed a higher frequency of familiarity for CD (60.8% vs. 15.0%; p < 0.01). No significant difference was detected between CD and non-CD in terms of intestinal and extra-intestinal symptoms. We also documented the presence of conditions other than CD in the remaining population: 7 patients (17.5%) with immuno-mediated diseases while 5 patients (12.5%) showed Helicobacter pylori (HP) infection. About medication, 3 patients (7.5%) were on non-steroidal anti-inflammatory drugs, while another 4 (10%) patients were being treated with other drugs. CONCLUSION: The Marsh 1 type histology is not specific for CD and it can also be associated with immuno-mediated disorders, HP infection, and drugs.

Fecal calprotectin in coeliac disease.

We would like to share with the readers the results of our experience in 50 celiac disease (CD) patients, enrolled between September 2012 and April 2013, who were referred to our third-level CD Unit. The fecal calprotectin (FC) concentration of 50 adults with newly diagnosed CD was compared to that of a control group of 50 healthy subjects. FC level was determined by enzyme linked immunosorbent assay with diagnostic cut-off of 75 µg/g. In addition, we tried to correlate the FC level with symptoms, histological severity of CD (Marsh grade) and level of tissue transglutaminase antibodies (aTg) in CD patients. Finally, FC level was increased in five CD patients and in four controls (10% vs 8%, P = NS); mean FC concentration of patients and controls were 57.7 (SD ± 29.1) and 45.1 (SD ± 38.4) respectively. Furthermore, no significant correlation was seen between FC levels and symptoms/Marsh grade/aTg. The five CD patients did not show inflammatory lesions (e.g., ulcers, erosions) at upper endoscopy. The four healthy controls with positive FC were followed-up for further six months; in this observational period they did not show clinical signs of any underlying disease. On these bases, we think that FC is not able to investigate the subclinical inflammatory changes of active CD and FC should be considered a useless tool in the diagnostic work-up of uncomplicated CD but it should be accompanied by aTg when ruling out organic disease in patients with irritable bowel syndrome.

Prevalence of functional dyspepsia and its subgroups in patients with eating disorders.

AIM: To study the prevalence of functional dyspepsia (FD) (Rome III criteria) across eating disorders (ED), obese patients, constitutional thinner and healthy volunteers. METHODS: Twenty patients affected by anorexia nervosa, 6 affected by bulimia nervosa, 10 affected by ED not otherwise specified according to diagnostic and statistical manual of mental disorders, 4th edition, nine constitutional thinner subjects and, thirty-two obese patients were recruited from an outpatients clinic devoted to eating behavior disorders. Twenty-two healthy volunteers matched for age and gender were enrolled as healthy controls. All participants underwent a careful clinical examination. Demographic and anthropometric characteristics were obtained from a structured questionnaires. The presence of FD and, its subgroups, epigastric pain syndrome and postprandial distress syndrome (PDS) were diagnosed according to Rome III criteria. The intensity-frequency score of broader dyspeptic symptoms such as early satiety, epigastric fullness, epigastric pain, epigastric burning, epigastric pressure, belching, nausea and vomiting were studied by a standardized questionnaire (0-6). Analysis of variance and post-hoc Sheffè tests were used for comparisons. RESULTS: 90% of patients affected by anorexia nervosa, 83.3% of patients affected by bulimia nervosa, 90% of patients affected by ED not otherwise specified, 55.6% of constitutionally thin subjects and 18.2% healthy volunteers met the Postprandial Distress Syndrome Criteria (χ(2), P < 0.001). Only one bulimic patient met the epigastric pain syndrome diagnosis. Postprandial fullness intensity-frequency score was significantly higher in anorexia nervosa, bulimia nervosa and ED not otherwise specified groups compared to the score calculated in the constitutional thinner group (4.15 ± 2.08 vs 1.44 ± 2.35, P = 0.003; 5.00 ± 2.45 vs 1.44 ± 2.35, P = 0.003; 4.10 ± 2.23 vs 1.44 ± 2.35, P = 0.002, respectively), the obese group (4.15 ± 2.08 vs 0.00 ± 0.00, P < 0.001; 5.00 ± 2.45 vs 0.00 ± 0.00, P < 0.001; 4.10 ± 2.23 vs 0.00 ± 0.00, P < 0.001, respectively) and healthy volunteers (4.15 ± 2.08 vs 0.36 ± 0.79, P < 0.001; 5.00 ± 2.45 vs 0.36 ± 0.79, P < 0.001; 4.10 ± 2.23 vs 0.36 ± 0.79, P < 0.001, respectively). Early satiety intensity-frequency score was prominent in anorectic patients compared to bulimic patients (3.85 ± 2.23 vs 1.17 ± 1.83, P = 0.015), obese patients (3.85 ± 2.23 vs 0.00 ± 0.00, P < 0.001) and healthy volunteers (3.85 ± 2.23 vs 0.05 ± 0.21, P < 0.001). Nausea and epigastric pressure were increased in bulimic and ED not otherwise specified patients. Specifically, nausea intensity-frequency-score was significantly higher in bulimia nervosa and ED not otherwise specified patients compared to anorectic patients (3.17 ± 2.56 vs 0.89 ± 1.66, P = 0.04; 2.70 ± 2.91 vs 0.89 ± 1.66, P = 0.05, respectively), constitutional thinner subjects (3.17 ± 2.56 vs 0.00 ± 0.00, P = 0.004; 2.70 ± 2.91 vs 0.00 ± 0.00, P = 0.005, respectively), obese patients (3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001; 3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001 respectively) and, healthy volunteers (3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.002; 3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.001, respectively). Epigastric pressure intensity-frequency score was significantly higher in bulimic and ED not otherwise specified patients compared to constitutional thin subjects (4.67 ± 2.42 vs 1.22 ± 1.72, P = 0.03; 4.20 ± 2.21 vs 1.22 ± 1.72, P = 0.03, respectively), obese patients (4.67 ± 2.42 vs 0.75 ± 1.32, P = 0.001; 4.20 ± 2.21 vs 0.75 ± 1.32, P < 0.001, respectively) and, healthy volunteers (4.67 ± 2.42 vs 0.67 ± 1.46, P = 0.001; 4.20 ± 2.21 vs 0.67 ± 1.46, P = 0.001, respectively). Vomiting was referred in 100% of bulimia nervosa patients, in 20% of ED not otherwise specified patients, in 15% of anorexia nervosa patients, in 22% of constitutional thinner subjects, and, in 5.6% healthy volunteers (χ(2), P < 0.001). CONCLUSION: PDS is common in eating disorders. Is it mandatory in outpatient gastroenterological clinics to investigate eating disorders in patients with PDS?

In vitro gliadin challenge: diagnostic accuracy and utility for the difficult diagnosis of celiac disease.

OBJECTIVES: Diagnosis of celiac disease is difficult when treatment with gluten-free diet (GFD) is started before diagnosis and/or when the results of tests are inconsistent. The objective of this study was to evaluate the in vitro gliadin challenge. METHODS: The study cohort included patients without celiac disease (negative controls, n=57), patients with celiac disease (positive controls, n=166 untreated and n=55 on GFD), and patients with difficult diagnosis (n=59). All patients underwent endoscopy for collection of duodenal samples, which served for the diagnosis of celiac disease and for the in vitro evaluation of the gliadin-induced mucosal expression of seven inflammatory markers: PY99, ICAM-1 (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and transglutaminase 2 IgA. Diagnostic work-up for celiac disease included the search of specific serum antibodies. Patients of the difficult diagnosis group were asked to stop GFD for repeated search of these antibodies under untreated conditions. The area under the receptor-operated curve (ROC) was used for statistical analyses on accuracy. RESULTS: HLA-DR had the highest accuracy for celiac disease diagnosis in analyses on negative controls and positive controls also excluding patients on GFD (area under ROC=0.99). Accuracy of test did not increase combining data of HLA-DR with data of other markers. Findings were similar in the 39 patients of the difficult diagnosis group undergoing the search celiac disease-specific antibodies under untreated conditions. CONCLUSIONS: The in vitro response of mucosal HLA-DR to gliadin is an accurate tool for the diagnosis of celiac disease also in patients with difficult diagnosis.

From menarche to menopause: the fertile life span of celiac women.

OBJECTIVE: We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. METHODS: The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. RESULTS: Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). CONCLUSIONS: Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.