Irritable bowel syndrome (IBS) is a gastrointestinal ‘sensory-motor disorder’ characterised by abdominal pain or discomfort associated with a change in bowel habits.
The role of sex hormones in symptoms and physiological imbalances in IBS is being increasingly recognised. This is based on both the female predominance, as well as the correlation between IBS symptoms and hormonal status during menstrual cycle phases, pregnancy or menopause.
The role that sex hormones, in particular estrogens, play in the physiology and pathology of the digestive system are numerous. The below quote summarises this well:
Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa.
The understanding that sex hormones are involved in IBS started with the awareness that symptoms differ between genders.
Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.
Women with IBS, compared to male patients, are more likely to report constipation, bloating, severe abdominal pain, and feeling of incomplete evacuation, while men with IBS more frequently complain of diarrhoea-assocciated symptoms.
Cain et al. reported higher digestive symptoms (pain, distension, bloating, intestinal gas) in postmenopausal women than in men, but the greatest differences in the overall symptom reporting between men and women were associated with somatic symptoms such as joint and muscle pain.
This gender-related difference was most noticeable when postmenopausal women where compared to men. Gender differences were much weaker for psychological and emotional symptoms except for fatigue, sleep disturbances and stress.
Noteworthy, there is a wide spectrum of chronic pain disorders frequently overlapping with IBS namely fibromyalgia, migraine headache, chronic pelvic pain, interstitial cystitis, and chronic fatigue syndrome.
These diseases are also characterised by female predominance with a correlation between their symptoms and hormonal status.
In addition, women with IBS, more frequently show comorbidity with affective or mood symptoms including anxiety and depression as compared to women without IBS. There are also reports indicating that women with IBS exhibit more anxiety and depressive symptoms compared to men with IBS.
What Are The Mechanisms Involved?
The mechanisms being increasingly recognised include:
- Sex differences in stress response of the HPA axis and autonomic nervous system
- Neuro-immune interactions triggered by stress (via the gut-brain axis)
- Estrogen interactions with serotonin (among other neurotransmitters)
- The hormone corticotropin-releasing factor signalling systems
Sex hormones also modulate the gut microbiome
Recently, the gut microbiota has been also recognised as an important element in the bi-directional communication along the brain-gut axis through neural, immune, and endocrine (such as estrogen) pathways.
The above quote ties in to my article on the gut-brain axis which can be read here.
A concept of “microgenderome” related to the potential role of sex hormone modulation of the gut microbiota is also emerging.
The menstrual cycle in women is divided into three phases:
- The follicular (proliferative) phase
- The luteal (secretory) phase
Estrogen levels are increasing during the mid-follicular phase and then drop precipitously after ovulation. This is followed by a secondary rise in estrogen levels during the mid-luteal phase with a decrease before menstruation. The secondary rise in estradiol parallels the rise of serum progesterone and 17-hydroxyprogesterone levels.
Dynamic changes in ovarian hormones during menstrual cycle can modulate gut contractility, transit, secretion, visceral sensitivity, and immune function at multiple target sites, including those located in the periphery and the brain.
Clinical studies indicate that declining or low ovarian hormone levels in women (such as during menses) may contribute to the occurrence or exacerbation of digestive symptoms, including abdominal pain or discomfort, altered bowel habits and bloating that varies across the menstrual cycle phases.
Rectal sensitivity thresholds have been shown to be significantly lower in IBS patients at menses relative to those at other cycle phases indicating that IBS symptoms experience may be modified by ovarian hormone status.
Approximately one third of otherwise asymptomatic women experience GI symptoms at the time of menstruation
A significant connection between IBS and endometriosis has also been reported. Additionally, polycystic ovary syndrome (PCOS), the most common female endocrine disorder affecting up to 10% of reproductive age women characterised by chronic anovulation and hyperandrogenism, is associated with the increased prevalence of IBS. Interestingly, IBS coexisting with PCOS was associated with a higher BMI and percent body fat when compared to PCOS alone.
Premenopausal healthy women taking oral contraceptives (OCs), monophasic or triphasic preparations, report a typical increase in digestive symptoms at menses. However, women with IBS taking OCs, which contain both estrogen and progestin, appeared to have reduced levels of abdominal symptoms compared with IBS women not taking OCs.
The abundant distribution of estrogen receptors (ERs) at all levels of the brain-gut axis, including the central nervous system (CNS), spinal cord, and the enteric nervous system supports the multiplicity of neuronal action.
ERs are spread throughout the brain, including the amygdala, hypothalamus, pituitary, hippocampus, cerebral cortex, mid-brain, and brain stem, providing neuro-anatomical support for potential numerous target sites of estrogen actions on neurocognitive processes.
Estrogens may also contribute to the important sex differences in the stress-related hypothalamic-pituitary-adrenal (HPA) axis response that have been documented in a number of clinical and experimental studies.
The menstrual cycle phases, menopausal status and pregnancy have been shown to affect the HPA axis as well as ANS functions.
Sex Hormones Influence Liver Detoxification
Additionally, the potential role of interaction between gonadal hormones and the cytochrome P450 pathway may be considered
Health liver detoxification is is important in gut health. Read my article on the gut-thyroid-liver axis for more information on how these are connected.
Stress & Gut Inflammation
Although not directly related to the topic of this article, the below quote is from the paper and I felt was worth including as it has quite profound consequences when we consider the importance of improving our relationship with, and our perception of, stress.
Gastrointestinal inflammation seems to be strongly modulated by stress, especially in IBS patients being characterised by enhanced stress responsiveness.
A pivotal interdependence between the composition and stability of the gut microbiota and GI function as well as stress-related behavioral changes indicate a great therapeutic potential of probiotics, prebiotics and antibiotics in IBS. So far, no gender specificity in probiotics efficacy in IBS patients has been reported. Nevertheless, in the light of the microgenderome concept and sex-dependent differences in the immune regulation driven by gut microbiome, gender specificity in microflora manipulation seem to be essential and is expected to be extensively explored in the near future.
As you can see there seems to be a clear relationship between the digestive system and the sex hormones. It may be that we need to consider more than the digestive system when we are supporting someone with IBS. We may need to consider the sex hormones, the stress system, the immune system and so forth.
Thus a comprehensive, whole lifestyle approach is often the best strategy. That’s not to say we don’t start with the basics – but it is important both client and practitioner are on the same page when it comes to the time it may take to improve health when numerous systems are involved.
When considering our stress levels it’s important to think of our life time exposure (and in fact our family history exposure). You may like to read my article on Key Concepts We Teach and What Is Functional Medicine to understand the importance of appreciating this aspect of our health history and family history (referring to the key term Allostatic Load and transgenerational behaviour or/and disease). You can search for these using the search box on in the top right hand corner of the webpage.
Agata Mulak, Yvette Taché, Muriel Larauche (2014) Sex hormones in the modulation of irritable bowel syndrome, World J Gastroenterol; 14; 20(10): 2433-2448