With roughly one quarter of Australian women aged 18-49 using the oral contraceptive pill, and around 6% of postmenopausal women taking hormone replacement therapy (HRT), the question of how oral oestrogen drugs affect the gut and its microbiome, and consequently the risk of autoimmune and inflammatory diseases, is a crucial one to answer.
I’ve written previously about Hormonal contraception and women’s mental health (to summarise, a Danish study found a disturbingly higher risk of becoming depressed after starting to use any form of hormonal contraception).
It’s entirely possible that the effect of oral oestrogens on the gut may be a significant contributor to impaired mental health… but the impact is more wide-ranging, and disturbing.
When taken orally, as in HRT or ‘the Pill’, oestrogens have four critical effects on the gut:
- They affect intestinal barrier function – that is, the ‘leakiness’ of the gut wall. Altered intestinal permeability is associated with the onset of multiple autoimmune and inflammatory diseases including Alzheimer’s disease, cancer, type 1 diabetes and systemic lupus erythermatosus (SLE).
- They alter the balance of sex steroid hormones, increasing endogenous (self-produced) oestrogen by 60%, and decreasing the androgens testosterone and dehydroepiandrosterone sulfate (DHEAS), by 50%. This imbalance has been shown to affect immune function, causing increased inflammation and a higher risk of autoimmune diseases including Crohn’s disease, a type of inflammatory bowel disease.
- They modify the gut microbiome, driving overgrowth of disease-causing organisms and further reducing testosterone levels.
- Through their influence on thrombosis, or blood clotting, they cause microvascular ischaemia (blockages in tiny blood vessels that supply the gut wall with blood – like a stroke, but in the gut rather than the brain). The damage cause by microvascular ischaemia may play a role in the development of inflammatory bowel disease (Crohn’s disease and ulcerative colitis).
Do these effects translate into real-life increases in disease risk? Yes, they do:
- The Nurses Health Studies I and II (large-scale epidemiological, or population-based, studies that have been tracking the health of female US nurses since 1976) found that women who were currently taking oral contraceptives were nearly 3 times more likely to have Crohn’s disease than women who had never taken the Pill (relative risk 2.82, after adjusting for potential confounding factors including BMI, smoking, age at first menstral period, menopause status and number of pregnancies and births). Women who had taken the Pill in the past but were no longer using it had a nearly 40% higher risk of Crohn’s disease.
- The Nurses Health Study also found a 71% higher risk of ulcerative colitis in postmenopausal women who were currently taking HRT, and a 65% higher risk in those who had taken it in the past.
- A Swedish study of over 4000 women who already had Crohn’s disease indicated that being on the combined Pill (i.e. the types that contain both an oestrogen and a progestin) led to worse outcomes – specifically, a greater risk of needing surgery. The higher the dose of hormones in their Pill, and the longer they stayed on it, the greater was their risk. Women who had been on the Pill for more than 3 years had a nearly 70% higher risk of requiring surgery for their Crohn’s disease. The researchers “estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required.”
- A meta-analysis (analysis of multiple studies – 14, in this case, involving over 75 000 women) found that those currently taking oral contraceptives had a 51% higher risk of Crohn’s disease (46% higher after adjusting for smoking) and a 53% higher risk of ulcerative colitis (28% after adjusting for smoking). The relative risk of developing Crohn’s disease increased the longer the women stayed on the Pill, and in those who had stopped taking it, there was no longer a statistically significant relationship between being on the Pill and developing inflammatory bowel disease. Both these findings provide support for the hypothesis that there is a cause and effect relationship between Pill-taking and developing inflammatory bowel disease.
- A 2017 comprehensive literature review found convincing evidence that use of combined oral contraceptives increases the risk of several autoimmune diseases, most of which are more common in women: multiple sclerosis, ulcerative colitis, Crohn’s disease, SLE, and interstitial cystitis. All of these diseases bar ulcerative colitis are known to be more common in females than in males, although not before puberty. For instance, males have a higher incidence of Crohn’s disease before the age of 15, after which there is a female predominance. Multiple sclerosis is more common in women than in men throughout the world. For every male diagnosed with SLE, there are 9 females.
The take-home message is that women who have autoimmune or inflammatory diseases, or are at increased risk of them due to family history, should seriously consider their use of oral contraceptives. Non-hormonal methods of contraception such as condoms and non-hormonal IUDs don’t affect women’s hormone metabolism, gut barrier function or microbiome.
