Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology

Table 1 Inflammatory bowel disease and menstrual abnormalities

Ref.	Participants (groups)	Main findings of the study	Study conclusions
Weber et al[11], 1995	662 women, who had undergone surgery for IBD: 360 CD; 251 UC; 47 of indeterminate type. 4–unknown	(1) Menstrual abnormalities were reported by 58% of women; (2) Symptomatic vaginal discharge, reported by 40%, was more likely to occur in CD than in UC; (3) Infertility was reported by 25% of women; and (4) 117 (18%) had undergone hysterectomy, 52 (44%) at 35 yr or under	(1) Menstrual abnormalities were commonly reported including oligomenorrhea, menstrual periods longer than 3 mo apart, polymenorrhagia, menstrual periods more frequently than every 3 wk, menorrhagia, periods lasting longer than 7 d; metrorrhagia, bleeding between periods; dysmenorrhea, painful periods requiring treatment and irregular menses; and (2) More hysterectomies were performed in women with inflammatory bowel disease, frequent menstrual abnormalities, chronic abdominal and pelvic pain, and in those undergoing of various abdominal operations
Lim et al[18], 2013	47 women with IBD: 13 CD; 27 UC; 7 intestinal Bechter disease. 44 women in the control group	(1) IBD group had significantly more frequent gastrointestinal symptoms, such as nausea (30% vs 7%), flatulence (53% vs 22%), and abdominal pain compared to controls; (2) The IBD group experienced more frequent systemic premenstrual symptoms (79% vs 50%), more severe abdominal pain, and lower mean general condition scores during the menstrual period; and (3) Patients with IBD experienced more frequent premenstrual gastrointestinal symptoms than controls, but their symptoms of IBD did not change significantly during the menstrual cycle	IBD patients were more likely to report PMS and GI symptoms than healthy women, without exacerbating disease-specific symptoms
Saha et al[12], 2013	54 women with CD; 66 women in the control group	(1) The prevalence of dysmenorrhea was 40% in cases and 46% in controls; (2) Pain scores were significantly higher in subjects with dysmenorrhea compared to those without between cases and controls; and (3) In women without dysmenorrhea, more controls used pain relievers for menstrual pain	(1) Dysmenorrhea in women with CD was associated with increased use of pain medications for menstrual pain, but not with higher NSAID use; and (2) Prevalence of dysmenorrhea is lower in the CD group than in controls
Saha et al[13], 2014	121 women with IBD: 61 CD; 48 UC; 12 indeterminant type	(1) 25% of subjects experienced a change in the cycle interval in the year before the diagnosis of IBD and 21% experienced a change in the duration of flow; and (2) Among women with dysmenorrhea, 40% experienced a change in the intensity of menstrual pain and 31% experienced a change in its duration	(1) Changes in menstrual function occur frequently in the year before IBD diagnosis; (2) Screening for menstrual irregularities should be considered in women with newly diagnosed IBD; and (3) Cycles typically become more regular over time
Lahat et al[15], 2020	139 patients with IBD: 100 CD; 39 UC. 258 in the control group	(1) Smoking status was found to be associated with various symptoms during menses in patients with IBD, including a higher level of irritability, nausea, lower back pain, and nervousness; (2) During the premenstrual period, patients receiving biologic treatment reported significantly higher levels of irritability, swelling of the legs, and fatigue; (3) There was no difference in the frequency of pain between patients with CD and UC; and (4) Patients with IBD experience more frequent systemic symptoms during menses than controls	(1) Patients with IBD experience various symptoms during menses significantly more frequently than healthy women; and (2) Smoking, biologic treatment, and previous abdominal operations are risk factors for increased symptomatic burden
Shirwaikar Thomas et al[17], 2020	75 women with IBD: 59 CD; 16 UC	(1) Patients with lower menstrual distress scores had a higher quality of life; and (2) There were no statistically significant differences in MDQ in patients on biologic or conventional therapies; and (3) No statistically significant correlation between MDQ and endoscopic score	The severity of menstrual symptoms is associated with a poorer quality of life among women with IBD. However, this may not reflect the true severity of the disease

IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; MDQ: Mayo dysphagia questionnaire.

Table 2 Anti-tumor necrosis factor and gynecology in animal studies

Ref.	Title	Animal	Main findings
Kaplan and Türk[9], 2020	Adalimumab Increases Follicle Reserve and Follicle Development in Rat Ovary: The Effect of Adalimumab on Ovarian Reserve	Rats	(1) Ovarian follicle count and AMH level were significantly higher in the groups given adalimumab; and (2) Fibrosis decreased proportionally to the dose of adalimumab
Beyazit et al[8], 2019	Adalimumab mitigates ovarian ischemia–reperfusion injury in rats by regulating oxidative stress, apoptosis, and resolution of inflammation	Rats	(1) Total oxidant status of the tissue, the oxidative stress index, and the values of nitric oxide were significantly decreased, and the total antioxidant status of the tissue was found to increase in the group receiving adalimumab; (2) Inflammation, vascular congestion, and hemorrhagia were significantly lower in adalimumab-treated group; and (3) Adalimumab treatment significantly decreased the apoptotic index
Kaplan et al[10], 2022	The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study	Rats	After adalimumab treatment, the average size of the endometriotic implant decreased compared to the control group
Falconer et al[33], 2006	Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon	Baboon	Significant reductions in total surface area, estimated total volume of endometriotic lesions, and both number and surface area of red lesions were observed after infliximab treatment, but not after placebo treatment

TNF: Tumor necrosis factor.

Table 3 Anti-tumor necrosis factor and gynecology: Case reports

Ref.	Disease	Findings
Bes and Soy[6], 2012	Ankylosing spondylitis	Menorrhagia associated with the use of adalimumab
Scheinfeld[5], 2008	Psoriatic arthritis, psoriasis vulgaris	Menorrhagia and severe abdominal pain associated with the use of adalimumab
Katsanos et al[7], 2010	Crohn‘s disease	Menorrhagia associated with the use of adalimumab