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Expert Critique
FROM THE ASCO Reading Room
It is well known that changing hormonal status over the female monthly and life cycles can affect the incidence and severity of irritable bowel syndrome (IBS) in women. Menses, pregnancy, perimenopause, and menopause can all exacerbate or mitigate symptoms, with some symptoms associated with high-estrogen phases.
But what about exogenous sex steroids in the form of systemic contraceptives, hormone-replacement therapy (HRT), and testosterone-replacement therapy (TRT) for men -- not to mention gonadal hormone inhibition with drugs like leuprolide (Lupron)?
The answer is that not much is known about the impact, but in an era of widespread hormone therapy, "I think we need to look into this issue," , of Beth Israel Deaconess Medical Center in Boston, said in an interview.
It has been shown that pharmacological suppression of ovarian hormones can reduce abdominal pain, and in a, a study lead by Stefano Palomba, MD, of Azienda Ospedaliera Arcispedale Santa Maria Nuova in Reggio Emilia, Italy, et al stressed the need to address sex hormones in the modulation of visceral pain in gastrointestinal disorders.
In addition, further back, a small by , et al, randomized 28 women with moderate to severe functional bowel disease to leuprolide (depot) or placebo for 12 weeks. Symptoms improved so significantly that all patients were allowed to continue on non-depot leuprolide for an additional 40 weeks, with all receiving estrogen replacement and 89% completed 52 weeks of treatment. Continued use of leuprolide at the maximum therapeutic dosage produced even more striking changes, with significant improvements in abdominal pain and distention, early satiety, anorexia, nausea, and vomiting.
In terms of exogenous HRT, by Ana Ruigómez, MD, PhD, and colleagues suggested that this may act in a similar fashion as endogenous ovarian hormones. The study looked at the risk of an IBS diagnosis in two 40,000-plus cohorts of women ages 50 to 69 in a large U.K. health database. The results showed an incidence rate per 1,000 person-years of 1.7 in HRT never-users (age-matched controls) versus 3.8 in HRT ever-users, with both current and past users at increased risk of IBS.
Although the study did not evaluate IBS incidence by type, the authors wrote: "The results suggest that HRT use is associated with an increased risk of IBS similar to the one observed among younger premenopausal women with endogenous estrogenic activity."
Wolf said the finding is interesting in this age group because IBS generally decreases with age so that the incidence in women usually approaches that of men as they get older. In addition, some women diagnosed with IBS also have undiagnosed endometriosis.
Research on the impact of oral contraceptives in women with IBS has not found much of note, Wolf noted, but an exception appears to emerge with oral contraceptives containing drospirenone. A large reported an association between this synthetic progestin, which has anti-mineral corticoid activity and may irritate and cause bleeding in the GI tract.
In the cohort of 939,281 women, who were an average of 29.1 years old and were on oral contraceptives for an average of 247 days, 3,050 incident cases of IBS were diagnosed. The annualized incidence for IBS with drospirenone contraception was 0.77% versus 0.46% with levonorgestrel, yielding a crude hazard ratio of IBS with drospirenone of 1.70 and an adjusted ratio of 1.63.
As for exogenous hormonal effects on either sex, an intriguing of transsexuals receiving cross-hormone administration for sex reassignment also suggested an effect of exogenous gonadal steroids on pain symptoms of functional GI disorders. In this analysis, about a third of the male-to-female patients receiving estrogen and anti-androgen therapy developed chronic pain, including visceral, breast, and musculoskeletal pain as well as headaches. Conversely, about half of the female-to-male subjects given testosterone reported a significant improvement in relief of chronic pain.
But findings on natural androgens in men with IBS are conflicting: A reported that men with IBS were more than twice as likely to have organic or psychogenic erectile dysfunction than were men without IBS, suggesting a possible testosterone deficit. Yet, according to of the University of Michigan in Ann Arbor, one study reported that testosterone levels were actually higher in IBS patients than in controls. "This was a small study, however, with different ages in the patient and control groups," he told Ñý¼§Ö±²¥. "And another study, also small, showed no disparity in testosterone level between men with and without IBS."
Regarding a potential impact of TRT for androgen deficiency on men who also suffer from IBS, testosterone is known to exert positive effects on muscle, increase tolerance to pain, and speed up bowel transit time, so hypothetically TRT could possibly ease pain and IBS-constipation or exacerbate IBS-diarrhea, said of Stanford University in Palo Alto, Calif. "The package insert on testosterone lists diarrhea as a possible side effect." Another side effect listed is stomach cramps. Eisenberg said that he himself, however, has observed no impact on GI symptoms in his urology patients.
Similarly, Wolf said she has not seen any effect of TRT in her GI patients: "I have a number of inflammatory bowel patients on testosterone therapy, and it does not cause an increase in diarrhea," she said.
A few , however, of IBS improvement after TRT can be found online.
The bottom line, said Chey, is that data are lacking on how administering male hormones might affect IBS in men for better or worse: "While I've certainly seen men starting on TRT who report they feel better and their sexual function is better, I can't recall seeing a patient who said his IBS symptoms resolved or even improved."
Further analysis, therefore, is needed to clarify the association between exogenous hormones and IBS, he added.