Reproductive and sexual health concerns in gastrointestinal illness: a narrative review

Introduction

Gastrointestinal (GI) disorders can have a widespread impact on quality of life, including reproductive and sexual functioning, across all stages of the lifespan. Despite their importance in disease-related quality of life and overall wellbeing, these topics are rarely addressed in GI appointments (1-3) and patients desire more information and guidance (4). Providers often feel they cannot meet these needs due to inadequate knowledge, time, and resources (2,5,6) and some report embarrassment or discomfort with the topics (1,3). Neglecting reproductive and sexual health in GI visits increases the likelihood of patients being misinformed and struggling without access to effective treatments.

This narrative review of the literature on GI illnesses and reproductive and sexual function is organized using a developmental timeline and biopsychosocial lens. The biopsychosocial model illuminates the multifactorial and dynamic nature of reproductive and sexual health concerns in the context of GI disorders, and how patient experience is shaped by reciprocal interactions of biomedical, psychological, sociocultural, and interpersonal factors (7). We discuss relationships between GI symptoms and reproductive and sexual concerns broadly, and address disease- and sex-specific considerations when relevant. This review is primarily focused on GI illnesses with intestinal presentations, i.e., inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), that have the highest incidence during the reproductive years (8-11). Other disorders (e.g., diseases of the liver and pancreas) are beyond this scope (12-14). The purpose of this review is to provide a resource for providers and to outline suggestions of strategies to address these concerns. We present this article in accordance with the Narrative Review reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-38/rc).

Methods

We searched PubMed and Google Scholar up to September 21, 2023, using key terms in Table 1. We evaluated in-text references of relevant publications and completed additional searches as appropriate.

The female reproductive lifespan

In those with female reproductive organs¹, the reproductive lifespan refers to the time period spanning menarche, the first menstrual period, and menopause, the cessation of menses for 12 months (15,16). Each of these life stage transitions is associated with significant biological and social change that can affect GI health.

The menstrual cycle

In women with and without diagnosed GI illnesses, phases of the menstrual cycle are associated with changes in GI functioning (17-20). Between one third (20) and three quarters (18) of healthy women experience cyclical changes to their GI functioning, with symptoms including abdominal pain and diarrhea most prominent premenstrually during the luteal phase and during the menses. Research suggests that women with IBS and some with IBD experience similar, though more severe, cyclical fluctuations in GI symptoms (21,22). Although these patterns are commonly reported by patients, a definitive understanding of the underlying mechanisms is still being established.

Biopsychosocial factors

Biomedical factors

(I) Hormones

The menstrual cycle is regulated by hormonal feedback loops along the hypothalamic-pituitary-ovarian axis and consists of three phases: follicular, ovulatory, and luteal (23,24). Regular ovulation and menstruation occur due to the release of gonadotropin-releasing hormone from the hypothalamus, which triggers production of luteinizing and follicle-stimulating hormones in the anterior pituitary, which act on the ovaries to produce estrogen and progesterone. The presence of sex hormone receptors in the intestines is one link (20,25) between menstrual cycle-related changes to GI motility, visceral sensitivity, and the gut microbiome.

The exact relationships between sex hormones and cyclic GI symptoms are poorly understood. This research has been outlined in detail in reviews by Bharadwaj and colleagues, but comprehensive understanding remains elusive as the findings and quality of evidence in human research are mixed (26,27). Although animal studies establish that estrogen and progesterone slow GI motility (28), findings in humans are contradictory, with some studies demonstrating reduced gut motility during the luteal phase when estrogen and progesterone levels are high, and other studies showing no change. Similarly, ovarian sex hormones have been implicated in nociceptive processing and visceral sensitivity (29,30) and the gut microbiome, though there is no conclusive evidence that this accounts for cyclic GI symptomatology. In line with these inconclusive findings, there is also mixed evidence regarding the benefits of hormonal oral contraceptive pills (OCPs) on GI symptom management, with some research indicating that OCPs reduce cyclic GI symptoms and may even prevent flares in IBD, and other studies finding that OCPs offer no such benefits and may even cause harm by increasing the already high risk of blood clots in IBD (19,26,31).

(II) GI illness type

IBD is associated with ongoing menstrual cycle abnormalities, including delayed menarche, abnormal bleeding, oligomenorrhea, and secondary amenorrhea (32,33). There is some evidence that menstrual cycle changes precede IBD diagnosis and then stabilize and become more regular over time (33).

There may be some key differences between ulcerative colitis (UC) and Crohn’s disease (CD) with respect to cyclic exacerbation of GI symptoms. For example, in a prospective diary study of women with both IBD types and healthy controls, Parlak et al. (22) found that women with UC, CD in remission, and healthy controls all had cyclic variation in GI symptoms. However, women with active CD reported no such cyclic pattern, suggesting that active disease and inflammation overpowered whatever mechanisms contributed to the cyclic patterns in healthy patients. Other researchers have observed differences in type of symptoms during the menstrual cycle; for example, in a retrospective study, Bernstein et al. (17) found that women with CD reported more diarrhea premenstrually than women with UC and healthy controls. The overlap between premenstrual somatic symptoms, dysmenorrhea, and IBD can be challenging to tease apart, but it is of utmost clinical importance to distinguish any cyclic GI symptoms from a true disease flare, and menstrual symptom diaries can be helpful in this case (26).

In both retrospective and prospective studies, women with IBS consistently report worse menstrual-cycle related GI symptoms, such as abdominal pain, bloating, and diarrhea, than healthy controls (26). Given that IBS is a disorder of gut-brain interaction, this distinction may be explained in part by the effects of ovarian hormones on visceral sensitivity and pain perception, key drivers of IBS symptomatology (34). Further supporting this notion is the finding that rectal sensitivity increases during the menses for women with IBS, but does not change for healthy controls (35). Research reviews do not identify any particular pattern with respect to timing of specific symptoms during the cycle.

Psychosocial factors

(I) Anxiety, depression, and premenstrual syndromes (PMS)

Mood and anxiety disorders are prevalent in GI populations (36,37). During the menstrual cycle, women with and without GI diagnoses report a number of cyclic intestinal and non-intestinal symptoms including diffuse somatic concerns (fatigue, headaches) and changes to thinking, mood, and generalized pain. For the majority of women, these issues do not interfere with quality of life (38), but others experience more severe presentations. Up to 30% of women experience PMS, characterized by moderate physical and psychological changes, and between 3–8% of women may be diagnosed with premenstrual dysphoric disorder (PMDD), a mood disorder characterized by recurrent luteal phase mood disturbance and lability, interpersonal difficulties, irritability, and anxiety (39). The prevalence of these disorders in GI populations is not known.

Overall, for women with and without GI diagnoses, anxiety and mood symptoms during the menstrual cycle are correlated with increased variety and severity of GI symptoms. For example, in a sample of women without GI diagnoses, symptoms of anxiety and depression premenstrually and during the menses were associated with increased reporting of GI symptoms (18). Another study of women with and without disorders of gut-brain interaction found that level of health anxiety predicted GI symptom severity during the menstrual cycle (40). This same study found that menstrual cycle phase had no impact on GI symptom severity, suggesting that health-specific anxiety plays a key role in GI symptom presentation beyond hormonal influence.

(II) Cognitive styles and coping

Beyond specific psychiatric diagnoses, certain cognitive styles and behavioral response patterns affect the presentation and experience of both GI and menstrual-cycle related symptoms (41). For example, hypervigilance to internal sensations, rumination, and catastrophizing all contribute to higher levels of emotional disturbance and pain severity and interference during the menstrual cycle and in GI clinical populations (41-45).

Menarche

Biomedical factors

GI illness type

(I) IBD

Adolescents with IBD are more likely to experience delayed menarche and may continue to experience menstrual irregularities like secondary amenorrhea (46-49). Two primary explanatory mechanisms have been identified: malnutrition and inflammation. Low body weight and nutritional deficits are common in adolescents with IBD, particularly with active disease, and research has found that disease activity and remission status predict pubertal development, with active disease causing more significant changes to weight and menstrual patterns (50). Furthermore, increased levels of pro-inflammatory cytokines in IBD can interfere with growth hormone signaling, which can explain why delayed puberty may be observed even in the setting of adequate nutrition and weight gain (46,51,52).

(II) IBS

This review yielded no information connecting IBS to the timing of menarche. The relationship between IBS and pubertal development is poorly understood and under researched. Only one study has evaluated diagnosis of IBS before and after menarche, and contrary to the authors’ hypothesis that diagnosis would increase after menarche, prevalence of IBS was higher in younger children than in adolescents (53). Another study investigating IBS symptom severity in adolescent girls and boys found that sex and developmental stage predicted pain levels (girls further along in development reported more severe pain) but not stool type or frequency. The same study found that regardless of developmental stage, girls reported more somatic symptoms and constipation (54).

Menopause

Biomedical factors

GI illness type

(I) IBD

Research on the relationship between IBD and timing of menopause is inconclusive, with some studies suggesting a link between IBD and early menopause, and other studies finding no connection (55,56). The impact of hormonal changes, namely, declining estrogen levels, on IBD disease activity, is also unclear with limited research available. One retrospective study found no change in IBD symptom severity pre- and post-menopause and identified a protective role of hormone replacement therapy (HRT) in preventing flares (57). Other studies have linked postmenopausal HRT to higher risk of development of UC, though not CD (58).

(II) IBS

Similarly, the impact of menopause on IBS is unclear. Some studies suggest menopause has no impact on IBS symptoms (59,60), whereas others suggest increased symptom severity postmenopause (61). Interestingly, one study found that although postmenopausal women reported more severe overall IBS symptoms than premenopausal women, they did not differ in specific symptoms such as pain and bloating (62). Given that no significant differences were found comparing age-matched men, the authors concluded that these findings were related to hormonal changes and could not be attributed to age alone. The finding that overall symptom burden and quality of life, but not individual symptoms, were worse postmenopause also highlights the strong contribution of psychosocial aspects of IBS including illness perceptions and psychological factors.

Treatment of menstrual-related GI concerns

Biomedical

Biomedical treatments for cyclic GI symptoms are an area of ongoing investigation. As discussed above, there is likely a role for hormonal management (e.g., OCPs and HRT) of GI symptoms, though there are no clear guidelines. Outside the menstrual context, central nervous system neuromodulators are effective in reducing GI pain in functional disorders, and the Rome Foundation has issued recommendations for their use (63). The role of neuromodulators in IBD treatment is less clear. Some studies suggest antidepressants may improve GI symptoms, mood, and functional outcomes in IBD, but more high-quality clinical trials are needed (64,65).

Psychosocial

No research is available on psychological and behavioral interventions specifically for menstrual-related GI symptoms. However, outside the menstrual context, cognitive-behavioral and mindfulness-based therapies that promote awareness and address unhelpful thinking and coping responses, as well as biofeedback and hypnosis, which address somatization, hypervigilance, and pain processing, have been shown to reduce anxiety overall, reduce GI symptom severity in IBS, and prolong remission and support adjustment in IBD (66). Similar approaches have shown promise in reducing menstrual-related mood and anxiety symptoms (67-69). Further research is necessary to determine which of these approaches are most helpful during different phases of the menstrual cycle. Clinicians may benefit from an eclectic approach, tailoring evidence-based treatments based on an individualized biopsychosocial conceptualization of each patient.

Fertility

Infertility refers to the impaired capacity to reproduce or the failure to become pregnant after 12 months of trying (70). More specifically, epidemiologists split infertility into fecundity (the biological capacity to reproduce), fecundability (the probability of conception, based on exposure to semen each reproductive cycle), and fertility (the production of live offspring) (71,72). There is limited research on fertility concerns among patients with IBS, and it is further hindered by poor quality (e.g., claiming to establish a connection between IBS and fertility difficulties while exclusively citing research on IBD). Thus, the following section is focused exclusively on IBD.

A number of large scale population-based surveys (73-75) show that rates of infertility among female and male IBD patients are comparable to the national prevalence of 7–12% (76,77). At the same time, individuals with IBD have fewer children than the general population (4,78,79). A number of biological and psychosocial factors have been implicated in this discrepancy.

Biomedical factors

IBD type and activity

The impact of IBD on reproductive function is dependent on disease type, activity, and treatment, and overall, reproductive function is preserved for the majority of those with inactive or quiescent IBD and no prior surgery (80). Reviews indicate that compared to the general population, infertility rates are higher for women with CD, but not UC (81). There is some evidence that ovarian function may be affected by CD, as studies have found that anti-Mullerian hormone (AMH) levels, which serve as a proxy for ovarian reserve, decline more rapidly after age 30 years in women with CD (82-84). With respect to disease type and activity, theoretically, active IBD, particularly CD, can reduce fecundity by causing pelvic inflammation and adhesions (4,73,81,85). Although IBD activity at time of conception is known to affect pregnancy outcome, there is less high-quality research on the effect of disease activity on fecundity.

Medications and surgery

Surgical treatment of IBD may affect fecundity and fertility in women by causing adhesions and scarring of the fallopian tubes (85,86). Research on the effect of localized bowel surgery is limited compared to studies of the impact of total colectomy with ileal pouch anal anastomosis (IPAA). In surgery-naive women with UC, fertility rates are similar to those in the general population (73-75,81), but meta-analyses demonstrate a significant impact of IPAA, raising the prevalence of infertility to 26–63% (87-89). As minimally invasive surgical approaches have become more common, the reproductive consequences of IPAA have been mitigated (90-92). Other reviewers have highlighted the poor quality of the evidence connecting surgery history and infertility (93,94). Finally, the observed impact of surgery on fertility may also relate to other, non-biological factors, such as delaying surgery until after completing one’s family (78).

IBD medications affect fertility differently by sex, with no impact on women from common medications and reversible effects for men. For men, sulfasalazine and methotrexate can cause changes to sperm count, motility, and morphology, leading to temporary sterility in some cases (55,56,95). The effects of several newer medications, including vedolizumab and ustekinumab, are unknown. Given potential teratogenic effects, drugs including methotrexate and JAK inhibitors are contraindicated in women trying to conceive and their impact on female fertility cannot be determined (55).

Psychosocial factors

Given that biomedical factors account for limited cases of subfecundity and fertility, psychosocial factors help explain reduced rates of reproduction amongst people with IBD.

Beliefs and knowledge

Reduced fertility in IBD may be related to reduced fecundability, or less frequent sexual activity, due to body image concerns, reduced sexual interest, and pelvic pain. These factors are commonly mentioned in the literature [e.g., (96-98)], but their actual contribution to infertility has not been explored in depth. A systematic review by Tavernier et al. (81) identified “voluntary childlessness”, or the choice not to reproduce, as the most consistent non-biological explanation for subfertility. This appears to be driven by inadequate knowledge about pregnancy in IBD (99-102) and fears of disease flares, medication side-effects, passing IBD onto offspring, and being unable to provide adequate childcare (103-106). Although this may be framed as “voluntary” or being childfree “by choice”, these labels may be problematic given that patient fears are often mismatched with the true level of risk involved. When patients receive adequate preconception counseling, they are more likely to have positive beliefs about pregnancy and rates of infertility may decrease (80,99,100,107).

Demographic factors

In addition to IBD-related fears and misinformation, demographic factors also contribute to voluntary childlessness. For example, Marri and colleagues [2007] (4) found that family planning decisions were unrelated to IBD itself; rather, they attributed lower rates of reproduction to higher levels of educational achievement, a trend which is observed in the general population as well (108).

Assessment of reproductive health concerns

Reproductive concerns can be assessed by clinical interview and standardized self-report questionnaires. Given that patients commonly report such concerns are rarely addressed, it is imperative that providers initiate and normalize these discussions, even when it may not be obvious that a patient is having a fertility problem or considering family planning. Standardized measures can be useful for both identifying a problem and monitoring potential change over time. Relevant domains may include GI quality of life, IBD-specific knowledge, and fertility-related quality of life. A list of clinical interview questions and fertility and measures can be found in Table 2.

Treatment of reproductive health concerns

IBD fertility care requires a collaborative and interdisciplinary approach. A treatment team may include gastroenterologists, obstetrician-gynecologists and maternal fetal medicine specialists, reproductive endocrinologists, mental health providers, and dietitians.

Biomedical

Women with IBD should be referred to fertility treatment based on the unique aspects of their medical history and parenting intentions. Referral to reproductive endocrinology is recommended for women with IBD who have been unsuccessful in conceiving after 6 months (80); this is a lower threshold than the standard of 12 months for the general population under age 35 years (112). Early referral may also be warranted for women with CD, given the increased chance of diminished ovarian reserve (80).

Assisted respective technologies (ARTs) such as in vitro fertilization (IVF) are overall safe and effective for women with IBD-related fertility problems. Outcome of ARTs may be impacted by several factors including disease duration, type, surgery history, and age, weight, and hormone levels (113). For example, one retrospective study found no differences in IVF pregnancy and live birth outcomes between women with UC or CD and no prior surgery and the general infertility population (114). Additional analysis of the same cohort database found that longer illness duration affected live birth rates for UC but not CD (113). Findings from another series of cohort-based studies suggest that the live birth rate per embryo transfer cycle is reduced for women with UC (115). Further analyses suggested this was due to failure to achieve pregnancy within the first two weeks after embryo transfer; once pregnant, there were no longer any differences in live birth outcomes for women with UC, CD, and healthy controls (116).

The impact of surgery on ART outcome varies in UC versus CD. Although history of IPAA increases chances of infertility and results in use of ARTs at a rate three times higher than those with no prior surgery, all available research suggests that IPAA has no impact on success of IVF for women with UC (113,117). However, prior CD surgery (e.g., ileocecal resection) does appear to affect IVF outcomes; compared to medical management, CD surgical history is associated with a 50–70% reduced likelihood of live birth following IVF (115,118).

Psychosocial

Education and counseling

In women with GI illnesses, pregnancy is possible and safe, although overall, women with IBD (119) and IBS (120-123) have higher rates of pregnancy-related complications and adverse outcomes. In recent years, expert working groups around the globe have issued comprehensive best practices for the management of IBD from the preconception to postpartum period (80,92,124,125).

Education and counseling is an essential component of IBD care for reproductive-age women. Planning pregnancy reduces the risk of complications for both mother and fetus (126), and it is essential for women with IBD to assess disease status, review medications for teratogenic potential, and provide education. Many women with IBD are at risk of unplanned pregnancies, since contraceptive use is lower than in the general population (4) and those who do use contraception use less effective methods (6,127). The Centers for Disease Control and Prevention (CDC) has published guidelines on the safety of specific contraceptive methods for patients with IBD (128). Online and in-person educational interventions can improve patients’ IBD-specific reproductive knowledge (129-131). Given that inadequate knowledge is associated with riskier illness-related behaviors and fear, such interventions could ultimately help promote disease self-management and safe reproductive outcomes, reduce anxiety, and ensure truly informed reproductive decision-making. Patients may be directed to the My IBD Life Parenthood Project website for comprehensive information on IBD and reproductive health published by the American Gastroenterological Association (132).

Psychotherapy

Fertility problems are associated with high rates of emotional distress (133) and psychotherapy can be beneficial for coping support. Although not examined in the GI-fertility patient population, a number of approaches have been effective in reducing the burden of fertility stress and improving quality of life in women, men, and couples in the general population. Empirically-supported treatments include cognitive-behavioral interventions that aim to balance unhelpful thinking, and mindfulness and acceptance-based approaches that promote non-judgmental awareness, self-compassion, and flexible value-aligned behavior (134-139).

Sexual dysfunction (SD)

SD refers to dissatisfaction with or impaired ability to engage in sexual activity. This includes challenges related to desire for sexual activity, difficulty becoming or staying sexually aroused or achieving orgasm, or pain with sexual activity.

Prevalence

Much of the literature on SD in GI patients centers on IBD, which has a high prevalence of SD. In men with IBD, SD rates range from 14–16% versus 7% in healthy controls (140,141). In women with IBD, estimates of SD range from 49–54%, compared to 19–28% in healthy controls (140,141). In a study of newly-diagnosed patients with IBD, rates of SD were dramatic: 97% in women and 39% in men. Considering erectile dysfunction alone, rather than broad SD, 94% of men screened positive (142,143).

Recent literature documenting SD in IBS provides limited data since most studies extrapolate SD based on quality of life, rather than sexual health questionnaires (144). However, in a 2017 study of IBD that used IBS as a control group, 26% of men and 78% of women were shown to have SD (141). Considering erectile dysfunction alone, 55% of men screened positive.

Though research is sparse, a variety of other GI conditions are associated with elevated rates of SD, including celiac disease (3), gastroesophageal reflux disease (GERD) (145), dyspepsia (146), and globus sensation, chest pain, and aerophagia (147). Patients with intestinal stomas have high rates of SD, though the bulk of the research has been conducted in oncology patients, rather than IBD, between which there are key clinical differences (148).

Biopsychosocial factors

In addition to the biomedical and psychosocial domains discussed above, the biopsychosocial model in sexual health typically includes interpersonal factors. When a partner or partners are involved, it is important to consider that each partner has their own unique set of biopsychosocial variables that they bring to the sexual relationship, which interact with those of the identified patient.

Biomedical factors

Pain and fatigue

Pain can manifest in a variety of ways among patients with GI disorders, including pain directly associated with sexual activity or sexual anatomy, and GI-related pain that impacts sexual desire or activity. Problems related to sexual pain include vulvodynia (chronic pain or discomfort of the vulva), dyspareunia (pain associated with vaginal penetrative intercourse), and vaginismus (involuntary contraction of the vaginal muscles making penetration difficult or impossible). These problems are subsumed under the diagnosis of genito-pelvic pain and penetration disorders, a diagnosis only applicable to female patients. At this time, there is no formal diagnosis that refers to pain associated with anal receptive intercourse (termed anodyspareunia or anal dyspareunia), though there is a small body of literature investigating this phenomenon, reviewed by Nercessian et al., 2023 (149).

Pain and discomfort resulting from a GI condition may also impact desire for sexual activity and ability to emotionally and physically progress through the sexual response cycle. This should be carefully considered in GI disorders with prominent pain such as IBS or centrally-mediated abdominal pain syndrome, and with other GI conditions associated with pain or other uncomfortable symptoms including esophageal disorders, chronic nausea and vomiting, or constipation. In a large sample of patients with IBD, 71% experienced pain over their disease course, with pain enduring for over 5 years for half (150).

Fatigue similarly reduces desire for sexual activity and ability to become aroused or reach orgasm. In IBD, fatigue is an extra-intestinal manifestation that occurs in 47% of patients (151). Fatigue is also common in IBS, shown in a 2016 meta-analysis to occur in 54% of patients (152).

General medical factors and medications

A variety of medical factors can negatively impact sexual function, including hypertension (153), diabetes (154), obesity (155), age (156), and neurological events such as stroke or spinal cord injury (157). Menopause may contribute to painful intercourse and reduced desire and arousal (158).

Medications such as psychotropic medications (especially serotonergic antidepressants, prolactin-inducing antipsychotic medications, and mood stabilizers or anticonvulsants) (159) and antihypertensives (beta blockers and diuretics) (160) commonly contribute to SD. The relationship between use of recreational substances and SD can vary by sex and the amount of substance used, frequency of use, and individual response. A 2018 meta-analysis concluded cigarette smoking and alcohol use had dose dependent associations with erectile dysfunction (161). Data on the effects of cannabis on SD are conflicting (161-163).

GI medical and surgical factors

Upper GI medications, such as histamine H2 receptor antagonists and proton pump inhibitors have been associated with SD. In IBD, methotrexate and corticosteroid use may have more direct effects on SD, though data is limited (164). Other medications are more likely to correlate with SD due to indirect effects by contributing to fatigue, changes in body image, or reducing the ability for sexual spontaneity, as is sometimes the case in use of enemas, suppositories or foams. Although few IBD medications are associated with direct effects on sexual functioning, many patients believe they are. In a study by Muller et al. (98), 40% of patients believed that their IBD medications negatively impacted their sexual desire and activity, and 10% sometimes or frequently discontinued medications as a result.

Surgical procedures have a complex relationship to sexual functioning in GI conditions, including both indirect and direct effects. Surgical procedures can directly impact sexual functioning due to risk to muscles and nerves and development of scar tissue, but can also result in improvement in physical health and functioning that may allow renewed interest and comfort with sexual activity. This is evident in women post-IPAA; although there are inherent anatomical risks, the majority of studies show improvements in sexual functioning (165).

Pelvic floor dysfunction

Pelvic floor dysfunction can affect men and women, and contributes to a variety of problems including painful intercourse, erectile difficulties, and reduced sensation and arousal. Screening for incontinence is important as patients may be hesitant to voluntarily disclose this information, and as pelvic floor muscles control bowel, bladder, and sexual function, there may be overlapping etiology and consequences. Pelvic floor dysfunction is common among patients with IBS (166,167) and constipation (168) and should be considered in patients with IBD experiencing any of these described symptoms.

Psychological factors

Depression and anxiety

Depression and anxiety are potential psychological mediators for SD. Depression has a well-documented relationship with SD (169), almost certainly as a driver of SD but likely also as a consequence. Depression is a key variable for SD in patients with GI disorders (141,170). The role of anxiety is less clear, with studies showing that state-anxiety may facilitate, inhibit, or have no effect on arousal (171). The heterogeneity of features of trait anxiety makes this more difficult to measure, as anxiety can manifest as generalized anxiety, social anxiety, as well as in OCD, panic disorder, or phobias. However, in general, trait anxiety is considered to be a risk factor for SD (172).

In addition to clinical anxiety disorders, sexual-specific cognitive constructs, including spectatoring and sexual performance anxiety, are recognized in the field of sexual health as drivers of SD (173,174). Spectatoring, coined by sexual health researchers Masters and Johnson in the 1970s (175), involves judging and analyzing a sexual encounter as it is occurring, as if viewing from a third person perspective versus remaining in-the-moment and focusing on the experience and sensations. Sexual performance anxiety refers to fear and worry related to sexual activity, including thoughts related to body image, ability to achieve an orgasm, or erections or ejaculatory control. Sexual performance anxiety is seen in IBD (176) and ostomies (177), and is likely among a variety of GI patients.

Body image

Though body image expectations tend to be experienced differently between men and women, for both, body image dissatisfaction is associated with SD (178,179). GI-specific body image concerns are varied and include embarrassment related to symptoms, such as belching, flatulence, urgency, or incontinence; self-consciousness of abdominal distention; or changes in weight. In IBD, perianal involvement of CD increases risk of SD (180). To our knowledge, no studies have formally assessed patients with vulvar CD, but these patients should be closely assessed for SD. With both perianal and vulvar involvement, it is likely that both body image factors and pain drive SD.

Research assessing SD in individuals with stomas demonstrates negative impacts following this change in anatomy (148). The visibility of the pouch, along with any sounds and smells, requires adjustment for patients and partners. In addition, surgical procedures that include the removal of the rectum and anus change the appearance of this intimate area of the body and may contribute to body image dissatisfaction and/or the loss of a source of sexual pleasure.

Trauma and posttraumatic stress disorder (PTSD)

Some individuals who experience traumatic events go on to develop PTSD, with symptoms including intrusive memories, avoidance, negative changes in mood or cognition, and changes in arousal or reactivity. There is a strong relationship between PTSD, which may include sexual or non-sexual traumatic events, and SD (181). Research suggests that trauma and SD may be linked due to processing in similar networks (182). In GI populations, a majority of research has looked at a history of trauma, abuse, or early adverse life events, rather than the clinical diagnosis of PTSD. Most well-studied is IBS, where trauma and abuse are known risk factors for development of the condition (183) and are associated with worse symptoms (184). PTSD is now being studied in IBD, with one study showing that 25% of patients report post-traumatic symptoms stemming from their illness experiences (185). The increased risk of trauma history for all GI patients, regardless of the type of traumatic event, also increases risk of SD.

Sociocultural factors

Sexual education and understanding

Sexual education is an important factor in sexual health. Unfortunately, comprehensive understanding of reproductive sexual anatomy and physiology, the sexual response cycle, and accurate information regarding what is “normal” is the exception rather than the rule. Limited sexual education and understanding can lead to embarrassment in discussing these topics and difficulty articulating the problem or attempting to solve it. GI patients benefit from accurate sexual health information and understanding of the variety of biopsychosocial factors that may contribute to their sexual problem.

Cultural and religious beliefs

All cultures have norms regarding sexual activity that can positively and negatively impact sexual health. Related beliefs about gender, sexuality, and relationship roles can impact self-perception, sexuality, and relationship dynamics. For example, individuals raised in religions and cultures with restrictive views on sexuality may continue to be impacted by those beliefs, even when engaging in “acceptable” expressions of sexuality, such as sex within the context of marriage, or when they no longer consciously maintain these beliefs.

Stigma associated with sexual activity impacts various groups disproportionately. One example is the sexual double standard, in which a society enacts differing expectations and judgments about sexual activity based on gender. Sexual and gender minoritized individuals and individuals with sexually transmitted infections are also at increased risk of experiencing stigma, which may contribute to reticence in communicating with healthcare providers about sexual concerns for fear of receiving negative judgment or even substandard care. Healthcare providers can reduce stigma around GI symptoms and sexual activity by normalizing discussion of these topics rather than avoiding them.

Stress

Chronic stress negatively impacts sexual function (186,187). Patients with GI disorders share the same risks as any individual (e.g., work, family, current events), with the addition of the stress of living with a chronic condition. Stress, GI illness, and SD are likely interrelated in many GI patients.

Interpersonal factors

Partner status

People experiencing SD can have a variety of relationship statuses: single, dating, in a relationship, married, or having one or multiple partners. Even patients who deny engaging in partnered sexual activity may have concerns related to their current or future sexual function, and may still be sexually active through masturbation. Partner or relationship status may impact the nature of the sexual concerns that they have in the present moment.

Relationship factors

For patients in relationships, partners play important roles in the patient’s sexual function. Partners may experience their own sexual problems, or not know how to provide support to their partner related to the sexual problem or GI condition. The quality of the overall relationship affects the sexual relationship. For example, if a couple is in conflict or has poor communication, this can have negative consequences on the sexual relationship. Sexual function may not only be determined by their current partnership but by prior experiences with other sexual and romantic partners. Though a current partner may be an excellent teammate in coping with GI and sexual problems, it may be challenging to separate this from difficult experiences from the past.

Assessment of sexual function

Assessment of sexual function is dependent on the treatment setting and skill of the provider. The PLISSIT model is a tool to help healthcare providers discuss and assess sexual health, and provide referrals or recommendations (188). This four-part model begins with “P” for Permission, in which a provider opens the conversation about sexual health rather than expecting the patient to do so, and responds empathically by normalizing and validating. All GI providers are well-positioned to engage in conversations at this level, and can do so without additional training. “LI” stands for Limited Information, or providing basic information about sexual health, for example, about how common sexual concerns are and biopsychosocial factors that might impact sexual health. Some GI providers may feel comfortable at the next level, “SS”, Specific Suggestions, and can provide recommendations or prescribe medication, but for others this may be a signal to refer (“suggest”) the patient for further assessment or treatment. The final stage, “IT” for Intensive Therapy, is reserved for providers with specific training in the assessment and treatment of sexual problems. This may include a sexual medicine physician, a sex therapist, or pelvic floor physical therapist.

Types of assessment

The clinical interview offers an efficient yet personal approach to discussions related to sexual health. Providers can both normalize and provide context for the assessment by highlighting the frequency of sexual problems among GI patients. Next, the provider can ask the patient directly if they have experienced such a problem. If so, the provider can continue with the PLISSIT model by providing Limited Information and making a suggestion, such as providing a referral to an appropriate provider.

Self-report measures are helpful for tracking symptoms over time and in research settings. They may be advantageous in allowing the patient to disclose a concern without saying it aloud, which can be difficult due to the sensitive nature of the topic. Disadvantages include the practical burden of time and personnel to distribute and score these measures. Table 3 includes a list of clinical interview questions and sexual health measures.

Treatment of SD

Treatment of SD falls among two lines: biomedical and psychosocial. Within these categories are a variety of specific settings and modalities, and many patients with SD will require engagement in multidisciplinary treatment.

Biomedical treatments

Optimal treatment of the GI disorder may directly or indirectly improve SD, but for many patients, meeting with a sexual medicine specialist is also appropriate. For men, erectile dysfunction treatment typically consists of phosphodiesterase 5 (PDE-5) inhibitors, but may also include injections, devices, or surgical procedures. Psychotropic medications may be used for their neuromodulating effects, such as the use of selective serotonin reuptake inhibitors (SSRIs) for premature ejaculation. For women with genito-pelvic pain and penetration disorders, lubricants or hormonal treatments may be recommended, but an evaluation by a pelvic floor physical therapist is indicated to evaluate for problems in the muscles of the pelvic floor that may be contributing to pain. Many pelvic floor physical therapists are also experienced in working with GI problems, such as incontinence or constipation, meaning that both sexual and GI symptoms may benefit from this approach. Pelvic floor physical therapists may recommend specific tools, such as vaginal dilators, that can be used in treatment and home practice.

Psychosocial treatments

Sex therapy

Sex therapy is a form of psychotherapy in which improving sexual health is the primary goal. A sex therapist is a mental health professional (e.g., psychologist, clinical social worker, counselor) with additional training and experience; certified sex therapists have received specialized education and clinical training and have been reviewed and certified by a professional body. Sex therapy is unlike treatment with a physical therapist or medical provider in that it does not involve physical exams or in-session exercises; rather, it is a talk-based approach like other forms of psychotherapy. In most cases, patients should be referred to a sex therapist for evaluation and treatment after they have undergone medical evaluation to ensure that any biomedical factors impacting their symptoms can be identified and addressed. Skilled sex therapists are also educated in red flags pointing toward biomedical factors, and will recommend that a patient undergo additional evaluation as appropriate.

Sex therapy varies based on therapeutic orientation [e.g., cognitive-behavioral therapy (CBT) or psychodynamically oriented] but universally includes evaluation of biopsychosocial factors that may be contributing to SD, with particular emphasis on historical and present psychological, sociocultural, and interpersonal factors that contribute to development and maintenance of sexual problems. Treatment is individually tailored but almost always includes psychoeducation regarding sexual anatomy and physiology and sexual norms. Interventions may be aimed at improving body image satisfaction, stigma, psychological factors such as spectatoring or sexual-performance anxiety, or interpersonal factors such as enhancing communication and emotional intimacy with the partner. Treatment typically includes between-session practice, which may include conversations with a partner, practice of exercises (e.g., physical relaxation, sensual, or meditative), or engagement in sexual activity. Sessions are devoted to discussing patient’s experiences with these exercises and discussion of new concepts. Patients can be single or partnered when engaging in sex therapy, and for those with partners, it is common for partners to be involved in treatment.

Although few mental health specialists have training in both GI disease and sexual health, many sex therapists are experienced in working with patients with chronic medical conditions and SD.

Other psychotherapies

Although sexual concerns may be a primary source of distress, referral to a sex therapist is not always the best fit. For example, if relationship difficulties are significant, a referral to a couples therapist is an appropriate initial referral. After working with a couples therapist, the patient and their partner will likely be more successful in engaging with a sex therapist. Similarly, some patients with SD will require mental health treatment for a different problem before engaging in sex therapy. If unsure of the appropriate referral, GI providers are recommended to consult with a known mental health professional, or may refer their patient for an evaluation with a sex therapist, making the patient aware that this will include recommendations for treatment, rather than a guarantee of sex therapy.

Conclusions

This narrative review applied a biopsychosocial lens to two important aspects of quality of life in the GI patient population: reproductive health and sexual function. The purpose of this review was to evaluate and synthesize current research, highlight how interactions between biological and psychosocial factors influence patients’ experiences, and provide recommendations for clinical practice to a variety of practitioners working in gastroenterology.

There are limitations to this review. Although we attempted to provide a comprehensive overview, we could not include all known sexual and reproductive health concerns and biopsychosocial variables in our analysis. For example, immune and microbiome factors were not explored, and gynecologic conditions such as endometriosis, polycystic ovarian syndrome, and cervical cancer, were all beyond the scope of this review, even these contribute to GI symptoms, and there are important GI-specific considerations to note (e.g., cervical cancer screening recommendations in IBD) (195). There is a dearth of research involving gender and sexual minorities in the GI context (196), even though these individuals are at risk for worse medical, reproductive, and sexual health outcomes. Future research should seek to better understand the unique GI-related reproductive and sexual health needs of this population.

Sexual and reproductive concerns are common in GI populations and are related to considerable physical and psychological burden. In spite of efforts to improve education and counseling, many patients still desire more information. Gastroenterologists and other providers can remedy this ongoing problem by being proactive in routinely querying patients’ reproductive and sexual health knowledge and questions, and sharing appropriate resources.

Acknowledgments

Funding: None.

Footnote

We acknowledge that those born with female reproductive anatomy may have other gender identities. In this review, we will use the terminology used in the original research we are reviewing. We recognize that there is a dearth of research on gender diverse individuals in the GI context.

Provenance and Peer Review: This article was commissioned by the Guest Editors (Sara H. Marchese and Tiffany H. Taft) for the series “Social and Emotional Impacts of Chronic Digestive Diseases” published in Translational Gastroenterology and Hepatology. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-38/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-38/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-38/coif). The series “Social and Emotional Impacts of Chronic Digestive Diseases” was commissioned by the editorial office without any funding or sponsorship. A.B. received honoraria by giving a one-hour lecture on sexual dysfunction and GI illness, hosted by the Rome Foundation. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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