Menopause Live (16 August, 2010) from IMS 

Up to one-third of the population suffer from irritable bowel syndrome (IBS), which has a female predominance with a female-to-male ratio of 2–2.5 : 1 in those who seek health care. The female predominance is less apparent in the general population, suggesting that women with IBS are more likely to seek health care for their symptoms. IBS is characterized by recurrent abdominal pain or discomfort associated with a change in bowel habits. Adeyemo and colleagues [1] now report on a systematic review and meta-analysis of the literature to evaluate gender differences in individual IBS symptoms and the role of menstrual cycle, menopausal status and hormone supplementation in these symptoms. Of the 599 studies identified by the defined search strategy, only 39 studies were included in the systematic review. In the general population, women were more likely to report abdominal pain and pain-related diagnostic symptoms of IBS but, in the IBS patient population, the prevalence of the pain-related symptoms did not differ between men and women. Women with IBS demonstrated a considerably higher risk for constipation-related symptoms, including abdominal distension, bloating, infrequent stools and hard stools, than men with IBS. Men with IBS were significantly more likely to report the diarrhea-related symptoms, of loose/watery stools and increased stool frequency, than women with IBS. Abstracting the data concerning the effect of menstrual cycles on IBS symptoms showed that 40–60% reported increased gastrointestinal symptoms at the time of menses compared with other phases. The symptoms for which most studies showed a significant effect on the menstrual cycle were (in descending order): loose stools, bloating, abdominal pain, stool frequency and other changes in bowel habit. In general, increased diarrhea was more often reported by women at the time of menses than increased constipation. Although the effects of the menstrual cycle on symptoms were similar in healthy women and IBS women, symptom severity was greater in women with IBS. The few studies which investigated possible differences between premenopausal and postmenopausal women did not demonstrate menopause-specific characteristics. Furthermore, one study addressed the effect of postmenopausal hormone therapy on the incidence of IBS [2]. Women who used hormone replacement therapy were more likely to develop IBS than women who did not. Postmenopausal healthy women who were given estradiol or progesterone therapy alone for 7 days were more likely to have looser stools and greater ease of passage than those on placebo [3].

Comment
It is well known that the prevalence and expression of IBS are linked to gender, pointing at a possible role of female sex hormones in gut physiology [4]. It is believed that gender is among the main components that determine gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and gut function. Additional factors may play a role, including gender-related differences in the neuroendocrine and autonomic nervous system and in stress reactivity, which are related to bowel function and pain. Pregnancy is a good example for sex hormone-induced alterations in this respect [5]: the gallbladder enlarges and empties sluggishly in response to meals during pregnancy, the small bowel transit is slowed, and the resting pressure of the lower esophageal sphincter is reduced. As a result, heartburn, bloating, nausea and vomiting are common complaints during pregnancy. All these effects are reversed by delivery; motility reverts toward normal in the postpartum period.

The basic feature of IBS is disturbed gut motility. Motility is the end result of smooth muscle contraction, which is long known to be affected by sex hormones. Estrogen and progesterone decrease the resting gut muscle tone and counteract cholinergic stimuli, similar to the response in the arterial wall. Our group demonstrated years ago that estradiol markedly reduced the force developed by the rat ileum in response to carbachol [6]. 

To conclude, it seems that, while vasodilatation (vessel wall muscle relaxation) is a beneficial effect of estrogen, the impairment in gut motility may be considered an adverse event, especially in women who suffer from the bothersome symptoms of IBS. However, the consequences of postmenopausal hormone therapy in IBS have not been properly investigated so far.

Amos Pines
Department of Medicine ‘T’, Ichilov Hospital, Tel-Aviv, Israel

References
1. Adeyemo MA, Spiegel BM, Chang L. Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? Aliment Pharmacol Ther 2010 Jul 22. Epub ahead of print.
http://www.ncbi.nlm.nih.gov/pubmed/20662786
2. Ruigomez A, Garcia Rodriguez LA, Johansson S, Wallander MA. Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Maturitas 2003;44:133–40.
http://www.ncbi.nlm.nih.gov/pubmed/12590009
3. Gonenne J, Esfandyari T, Camilleri M, et al. Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Neurogastroenterol Motil 2006;18:911–18.
http://www.ncbi.nlm.nih.gov/pubmed/16961694
4. Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology 2002;123:1686-701.
http://www.ncbi.nlm.nih.gov/pubmed/12404243
5. Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin North Am 1992;21:751-76.
http://www.ncbi.nlm.nih.gov/pubmed/1478733
6. Pines A, Eckstein N, Dotan I, et al. Effect of estradiol on rat ileum. Gen Pharmacol 1998;31:735-6.
http://www.ncbi.nlm.nih.gov/pubmed/9809470