Does Hormonal Contraception Affect the Gut?

by | Jan 9, 2022 |

The advent of hormonal contraception was a game-changer to countless people all around the world. It expanded opportunities in many areas including education, economics, sexuality and health. Hormonal contraception whilst undoubtedly liberating, doesn’t come without its health challenges. New research pertaining to the gut has identified a possible relationship between estrogen and the gut, which has sparked the question whether estrogen in contraception alters gut function and thus has a knock-on effect on health.

This blog post will outline what hormonal contraception is, the interplay between estrogen and the gut, how contraception may impact the gut microbiome and overall gut health, and, finally, health outcomes that may ensue as a result.

What is hormonal contraception?

Hormonal contraceptives are a type of birth control containing small amounts of estrogen and progesterone, or progesterone only, used to prevent pregnancy. Taken in various forms, such as by mouth, injected under the skin or placed in the uterus, hormonal contraceptives prevent pregnancy by blocking the release of eggs from the ovaries, thinning the lining of the uterus so it’s unlikely a fertilised egg will be implanted, and preventing sperm from reaching the egg by thickening the cervical mucus.

The estrogen-gut axis

Studies have shown there exist pathways between estrogen and the gut collectively referred to as the estrogen-gut axis (10). Although the mechanisms by which the gut and estrogen interact are not entirely clear, research shows that gut microbes play a key role in the regulation of estrogen levels within the body.

The collection of microbes in our body capable of metabolising estrogens is known as the estrobolome. One function of these microbes is to produce an enzyme that in turn produces active, unbound estrogen. This unbound estrogen can then bind to estrogen receptors, modulating estrogen-dependent processes in the body.

When the gut microbiome is healthy, the estrobolome produces just the right amount of this estrogen-activating enzyme to maintain balanced levels of estrogen in the body. However, when dysbiosis occurs (an occurrence which has been linked to the use of hormonal contraceptives) the enzyme activity may be altered, producing either a deficiency or an excess of free estrogen. Altered levels of circulating estrogens in the body may contribute to estrogen-related diseases such as obesity, metabolic syndrome, endometriosis, cardiovascular disease, gut health and cognitive function, to name a few.

Because the gut microbiome has been shown to be influenced by estrogen, and vice versa (10), it seems plausible to wonder what, if any, the effects hormonal contraceptives may have on the gut and their wider implication for health.

Effects of oral contraceptives on the gut

In your body, an intact gut lining acts as a gatekeeper, allowing vital nutrients and substances to pass through while stopping large molecules, toxins and pathogens from entering your bloodstream. Your immune system also plays a role, responding with inflammation if the lining in your gut is compromised. How you feel, your mood, and your general health is affected by the quality of your gut lining. And it’s the trillions of bacteria setting up shop in our gut that carry out tasks to ensure that the gastrointestinal system stays in top condition. When a healthy gut microbiome is perturbed, however, health issues can ensue.

Research has suggested an association between oral contraceptives and intestinal inflammation (3). While the exact mechanism remains unknown, experimental data suggests that estrogen may modulate intestinal immune and barrier function. In connection with this, it’s been postulated that the use of contraceptives containing estrogen may impact gut permeability and certain immune inflammatory responses (1). It’s also thought that the gut microbiome may be disrupted by exogenous hormones (originating from outside the body), creating dysbiosis whereby the gut lining may become compromised; a problem associated with inflammatory conditions.

Progesterone has been found to increase the relative abundance of certain microbes in models of progesterone supplementation, providing insight into the relationship between hormones and the gut microbiota (9). It’s also thought progesterone may play a beneficial role in gut permeability (2), however more research is needed in order to support this hypothesis.

Possible health conditions related to contraception and the gut

As contraception is thought to be associated with intestinal inflammation, it’s not surprising that several studies have shown inflammatory disorders such as Chron’s disease and ulcerative colitis to be linked with the use of hormonal birth control (4, 5). For example, a meta-analysis (6) showed that current use of oral contraceptives is associated with a nearly 50% increase in risk of Chron’s disease and the risk appeared to increase with longer use and diminished when use of the contraception ceased.

High microbial diversity appears to be associated with health and microbiome stability over time (5). A reduction in microbial diversity, possibly through the use of hormonal contraceptives, may therefore not only affect gastrointestinal health, but other conditions which ensue as a result of impaired immune function and gut permeability. Negative long-term physiological outcomes such as obesity, migraine, type 2 diabetes, atopic eczema and other allergic diseases are just a few of the conditions which have been linked to disturbed microbiota (8).

The microbiome may also play a role in the way we think, behave and make decisions, a possible avenue for exploration into the often reported mood changes experienced by some people taking hormonal contraception.

Conclusion

Hormonal contraceptives are considered by many to be one of the major achievements of our times. While the positives are indeed abundant, as with any drug, it’s always important to consider the downsides in order to accurately weigh risks and benefits. Whilst associations have been made between hormonal contraceptives and inflammatory conditions, mechanistic implications are still largely unknown. It’s hoped that with continued research more will be understood about hormonal contraception and disease causation so people can be more empowered to make informed choices about not only their reproductive health, but their general health also.

Brigid xx

 

References

(1) Looijer-van Langen M, Hotte N, Dieleman LA, Albert E, Mulder C, Madsen KL. Estrogen receptor-β signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol. 2011 Apr;300(4):G621-6. doi: 10.1152/ajpgi.00274.2010. Epub 2011 Jan 20. PMID: 21252046.

(2) Zhou, Z., Bian, C., Luo, Z. et al. Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells. Sci Rep 9, 8367 (2019). https://doi.org/10.1038/s41598-019-44448-0

(3) Khalili, Hamed. “Risk of Inflammatory Bowel Disease with Oral Contraceptives and Menopausal Hormone Therapy: Current Evidence and Future Directions.” Drug safety vol. 39,3 (2016): 193-7. doi:10.1007/s40264-015-0372-y

(4) Rhodes JM, Cockel R, Allan RN, Hawker PC, Dawson J, Elias E Br Med J (Clin Res Ed). 1984 Feb 25; 288(6417):595-6.

(5) Bonfils S, Hervoir P, Girodet J, Le Quintrec Y, Bader JP, Gastard J Am J Dig Dis. 1977 May; 22(5):429-36

(6) Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP Am J Gastroenterol. 2008 Sep; 103(9):2394-400.

(7) Michael I McBurney, Cindy Davis, Claire M Fraser, Barbara O Schneeman, Curtis Huttenhower, Kristin Verbeke, Jens Walter, Marie E Latulippe, Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions, The Journal of Nutrition, Volume 149, Issue 11, November 2019, Pages 1882–1895, https://doi.org/10.1093/jn/nxz154

(8) Bull, Matthew J, and Nigel T Plummer. “Part 1: The Human Gut Microbiome in Health and Disease.” Integrative medicine (Encinitas, Calif.) vol. 13,6 (2014): 17-22.

(9) Nuriel-Ohayon M, Neuman H, Ziv O, Belogolovski A, Barsheshet Y, Bloch N, Uzan A, Lahav R, Peretz A, Frishman S, Hod M, Hadar E, Louzoun Y, Avni O, Koren O. Progesterone Increases Bifidobacterium Relative Abundance during Late Pregnancy. Cell Rep. 2019 Apr 16;27(3):730-736.e3. doi: 10.1016/j.celrep.2019.03.075. PMID: 30995472.

(10) Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017 Sep;103:45-53. doi: 10.1016/j.maturitas.2017.06.025. Epub 2017 Jun 23. PMID: 28778332.

DISCLAIMER: This article is for informational purposes only. It is not intended to constitute or be a substitute for professional medical advice, diagnosis, or treatment. 

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