Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.     

Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans

Abstract  Our aims were to measure the gastric volume response in excess of ingested meal volume (i.e. gastric accommodation), contribution of swallowed air to this excess, day-to-day variability of gastric volumes measured by MRI and their relationship to volumes measured by single-photon-emission computed tomography (SPECT). In 20 healthy volunteers, fasting and postprandial gastric volumes were measured after technetium^99m-pertechnetate labeling of the gastric mucosa by SPECT and separately by MRI, using 3D gradient echo and 2D half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences. Ten of these subjects had a second MRI exam to assess intra-individual variation. Thereafter, another 10 subjects had two MRI studies during which they ingested the nutrient in 30 or 150 mL aliquots. During MRI, the postprandial gastric volume change exceeded the ingested meal volume by 106 ± 12 mL (Mean ± SEM). The HASTE and gradient echo sequences distinguished air from fluid under fasting and postprandial conditions respectively. This postprandial excess mainly comprised air (61 ± 5 mL), which was not significantly different when ingested as 30 or 150 mL aliquots. Fasting and postprandial gastric volumes measured by MRI were generally reproducible within subjects. During SPECT, postprandial volumes increased by 158 ± 18 mL; gastric volumes measured by SPECT were higher than MRI. MRI measures gastric volumes with acceptable performance characteristics; the postprandial excess primarily consists of air, which is not affected by the mode of ingestion. Gastric volumes are technique specific and differ between MRI and SPECT.     

Comparison of breath testing with fructose and high fructose corn syrups in health and IBS

Abstract  Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) prepared either in water or as HFCS, administered in double-blind randomized order on 2 days in 20 healthy subjects and 30 patients with IBS. Gastrointestinal symptoms were recorded on 100-mm Visual Analogue Scales. Breath hydrogen excretion was more frequently abnormal ( P  < 0.01) after fructose (68%) than HFCS (26%) in controls and patients. Fructose intolerance (i.e. abnormal breath test and symptoms) was more prevalent after fructose than HFCS in healthy subjects (25% vs 0%, P  = 0.002) and patients (40% vs 7%, P  = 0.062). Scores for several symptoms (e.g. bloating r  = 0.35) were correlated ( P  ≤ 0.01) to peak breath hydrogen excretion after fructose but not HFCS; in the fructose group, this association did not differ between healthy subjects and patients. Symptoms were not significantly different after fructose compared to HFCS. Fructose intolerance is more prevalent with fructose alone than with HFCS in health and in IBS. The prevalence of fructose intolerance is not significantly different between health and IBS. Current methods for identifying fructose intolerance should be modified to more closely reproduce fructose ingestion in daily life.     

Lower gastrointestinal functions

Abstract  The human colon serves to absorb water and electrolytes, store intraluminal contents until elimination is socially convenient, and salvage nutrients by bacterial metabolism of carbohydrates that have not been absorbed in the small intestine. The anorectum is responsible for fecal continence and defecation. This article is a broad perspective of the current status and a personal perspective of future challenges in understanding lower gastrointestinal functions in health and disease in humans.     

Effects of an osmotically active agent on colonic transit

It is unknown if sorbitol, a widely used laxative agent, accelerates colonic transit, and if these effects are modified by concomitant meal ingestion. Colonic transit was assessed by (111)In scintigraphy in 40 healthy subjects. After a 24-h scan, subjects received sorbitol (30 mL of 70% solution) or dextrose (30 mL of 70% solution), administered with or without a meal. Colonic transit, breath hydrogen excretion, and symptom scores were recorded for 4 h thereafter. VAS scores for flatulence, but not other symptoms increased (P = 0.004) by 13.1 +/- 6.3 mm (mean +/- SEM) on a 100 mm scale after sorbitol alone or sorbitol with a meal (by 18.9 +/- 7.2 mm), but not after dextrose. After adjusting for GC(24), sorbitol accelerated (P < 0.001) colonic transit (GC(28) = 3.0 +/- 0.3) compared with dextrose (GC(28) = 2.2 +/- 0.2), regardless of meal ingestion. Breath hydrogen excretion was correlated with the change in colonic transit (r = 0.52, P < 0.01) and with flatulence (r = 0.45, P = 0.003) after sugar ingestion. In healthy subjects, sorbitol accelerated colonic transit and increased flatulence but not other symptoms within 4 h, regardless of meal intake.     

Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects

Abstract  Alpha-2 adrenergic receptors tonically inhibit colonic motility and the α₂-adrenergic antagonist yohimbine, given intravenously, increased colonic tone in humans. However, the effect of yohimbine on colonic transit in humans is unknown. In this study, 30 healthy volunteers were randomized to yohimbine 16.2 mg p.o. t.i.d. or identical placebo for 7 days. We evaluated gastric emptying, small intestinal, and colonic transit by scinitigraphy, bowel habits, haemodynamics and plasma catecholamines. As cytochrome P450 enzymes metabolize yohimbine, P450 genotypes ( CYP2D6 and CYP3A4 ) were determined in 25 of 30 subjects who consented to genetic studies. The relationship between drug metabolizer status predicted by CYP2D6 and CYP3A4 and effects of yohmibine were assessed. Compared to placebo, yohimbine increased ( P  ≤ 0.02) diastolic blood pressure, plasma noradrenaline concentrations and maximum tolerated volume during the satiation test [yohimbine (1241 ± 88, mean ± SEM) vs placebo (1015 ± 87), P  = 0.054]. However, yohimbine did not affect gastrointestinal transit. Based on CYP2D6 and CYP3A4 alleles, seven and 18 subjects were, respectively, extensive (EM) and poor (PM) metabolizers of yohimbine. Compared to EM, PM of yohimbine had a greater increase in plasma noradrenaline ( P  = 0.1 for PM vs EM), lower maximum tolerated volumes (1120 ± 95 vs 1484 + 131 mL, P  = 0.02), and faster colonic transit (i.e. GC₂₄ was 3.0 ± 0.4 vs 2.1 ± 0.5, P  = 0.1). These data suggest that CYP2D6 and CYP3A4 genotypes which determine the metabolism of yohimbine may influence its sympathetic and gastrointestinal effects.     

Pelvic floor: anatomy and function

The pelvic floor is a dome-shaped striated muscular sheet that encloses the bladder, uterus, and rectum, and, together with the anal sphincters, has an important role in regulating storage and evacuation of urine and stool. This article reviews the anatomy, nerve supply, pharmacology, and functions of the anal sphincters and the pelvic floor. The internal and external anal sphincters are primarily responsible for maintaining faecal continence at rest and when continence is threatened, respectively. Defecation is a somato-visceral reflex regulated by dual nerve supply (i.e. somatic and autonomic) to the anorectum. The net effects of sympathetic and cholinergic stimulation are to increase and reduce anal resting pressure, respectively. Faecal incontinence and functional defecatory disorders may result from structural changes and/or functional disturbances in the mechanisms of faecal continence and defecation.     

Effect of tolterodine on gastrointestinal transit and bowel habits in healthy subjects

Abstract  Clinical trials and observations suggest that constipation is an uncommon side effect of treating overactive bladder with the muscarinic receptor antagonist tolterodine. Because muscarinic antagonism inhibits gastrointestinal motor activity, we evaluated the effects of tolterodine on bowel habits, gastrointestinal and colonic transit in healthy subjects. In this double-blind study, 36 healthy subjects were randomized to tolterodine extended release (ER, 4 mg daily) or placebo for 6 days. Gastric emptying (GE), small bowel and colonic transit were assessed on days 4–6 by scintigraphy. Bowel habits were recorded by diaries. Tolterodine did not significantly affect half-time for GE (GE t _half) [116 ± 6 min (mean ± SEM) for placebo vs 126 ± 7 min for tolterodine], small bowel transit measured by colonic filling at 6 h (45 ± 6% for placebo vs 36 ± 6% for tolterodine) or the geometric center of colonic transit at 24 h (2.9 ± 0.2 for placebo vs 2.6 ± 0.3 for tolterodine). Subjects who received tolterodine had slightly fewer bowel movements (i.e. 1.34 ± 0.1 stools per day for placebo vs 1.0 ± 0.1 for tolterodine; P  = 0.02 for treatment effect). Tolterodine did not significantly affect stool consistency or ease of defecation. At the therapeutic dose used to treat overactive bladder, tolterodine did not significantly affect gastrointestinal or colonic transit and had minor effects on bowel habits in healthy subjects. Further studies are necessary to elucidate whether these observations are explained by tolterodine effects at muscarinic receptors which stimulate and inhibit gastrointestinal motility.