Triptorelin improves intestinal symptoms among patients with colorectal endometriosis

Abstract

⁎ Corresponding author. Department of Obstetrics and Gynecology, San Martino Hospital, Largo R. Benzi 1, 16132 Genoa, Italy. Tel./fax: +39 10 511 525. E-mail address: dr@simoneferrero.com (S. Ferrero). Little attention has been given to the role of hormonal therapies in treating symptoms caused by bowel endometriosis [1]. The aim of the present open-label prospective study was to evaluate the effects of GnRH analogues (GnRH-a) on pain and intestinal symptoms among patients with colorectal endometriosis. Multidetector computerized tomographyenteroclysis (MDCT-e)was used to determine the presence and severity of colorectal endometriosis [2]. Inclusion criteria for the study were reproductive age, pain and gastrointestinal symptoms suggestive of bowel endometriosis (persisting for at least 12 months), and colorectal nodules infiltrating at least the muscularis propria of the bowel. Exclusion criteria were stenosis of the bowel lumen greater than 60% and presence of endometriotic nodules located on the cecum or the ileum. Study participants received depot intramuscular injections of the 3-month formulation of triptorelin (11.25 mg; Decapeptyl, Ipsen Pharma, Milan, Italy) and oral tibolone (2.5 mg daily; Livial, Organon, Rome, Italy) for 12 months. Patients were allowed to take nonsteroidal anti-inflammatory drugs for the treatment of pain (550 mg naproxen sodium tablet; Synflex Forte 550, Recordati Industria Chimica e Farmaceutica, Milan, Italy) and lactulose (dose of 10 g per 15 mL; Laevolac, Roche, Milan, Italy) for the treatment of constipation. Presence and intensity of symptoms were evaluated before starting the treatment andafter 6 and12 months of treatment. At completion, the overall degree of patient satisfactionwith the treatmentwas determined by responses given to the following question: “Taking into consideration the variations in pain symptoms, overall well-being, and quality of life, as well as any adverse effects experienced, howwould you define the level of satisfaction with your treatment?” [3]. Patients were also asked whether their intestinal symptoms changed during treatment. The local Institutional Review Board approved the study protocol. Patients were informed that surgery is the standard treatment for symptomatic bowel endometriosis [1,4] and the potential benefits and complications of surgery were explained in detail. All study subjects wished to avoid or postpone surgery and requested amedical therapy. Patients were also told that hormonal therapies are not expected to be definitely curative of endometriosis [5]. Study participants provided written informed consent. Variations in grading of symptoms between baseline and follow-up were compared using the paired t test and the signed rank test according to data distribution. Eighteen women were included in the study, with a mean age of 36.1±4.7 years. The larger endometriotic bowel nodule was located on the sigmoid in9women,on the rectosigmoid junction in5women, and on the rectum in 4 women. The mean estimated size of the larger colorectal nodulewas2.2±0.6 cmand themeanestimatedstenosisof the bowel lumenwas42.0%±9.7%.At the 12-monthassessment of the effects of therapy on the symptoms, 13 (72.2%) women were very satisfied or satisfied, 2 (11.1%) were uncertain, and 3 (16.7%) were dissatisfied. Intestinal symptomswere unchanged during treatment in 7 (38.9%) women, while 11 patients (61.1%) reported some improvements in intestinal function. Table 1 shows that patients with symptoms mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) reported improvements in intestinal symptoms significantly more frequently than those with symptoms mimicking constipationpredominant irritable bowel syndrome (IBS-C; 100.0% vs 14.3,P=0.003). The severity of dysmenorrhea, nonmenstrual pelvic pain, deep dyspareunia, anddyscheziawasmeasuredusing a 10-cmvisual analogue scale (VAS). The treatment significantly decreased the intensity of pain symptoms (Table 2). The severity of the intestinal symptoms was measured using a symptom analogue scale questionnaire (1 indicated the absence of the symptom; 10 indicated the highest severity of the symptom). IBS-D, intestinal cramping, abdominal bloating, and passage of mucus improved during treatment; no significant change was observed in IBS-C and feeling of incomplete evacuation (Table 2). The number of naproxen sodium tablets used by patients decreased during treatment; the number of lactulose doses used by patients did not change during treatment (Table 2). Fifteen women (83.3%) reported at least 1 adverse effect (hot flushes, n=6; vaginal bleeding, n=6; sweating episodes, n=3; vaginal dryness and superficial dyspareunia, n=2; nervousness and irritability, n=2; loss of libido, n=2; weight gain, n=2; sleeplessness, n=1; difficulty in concentrating, n=1; fatigue, n=1). At the completion of the study, 7 patients (38.9%) continued the treatment with triptorelin and tibolone; 50.0% of the patients with IBS-D continued the treatment with triptorelin versus 14.3% of the patients with IBS-C (P=0.282).