Progesterone and Gut Health

GI disorders and problems with gut health such as IBS, gallbladder / biliary concerns, and gastritis are extremely common concerns. While we treat all of these gut conditions regularly in our clinic, we also have noted an increased incidence of these in patients with PCOS and other hormonal conditions.

We have quite a bit of information on the microbiome and conditions such as PCOS, but...
  • How do specific hormones like progesterone impact the gut?
  • We know that the gut has receptors for both estrogen and progesterone, but what are they for?

To review, progesterone is released in high amounts for 2 weeks out of every month after ovulation has occurred, also known as the luteal phase of the cycle. Outside of the luteal phase, levels of progesterone, are minimalin comparison.

So, what happens to the gut if someone doesn't ovulate, or has low levels of progesterone?

Since this problem is extremely common in PCOS, endometriosis and perimenopause, all conditions where we see an increase in gut symptoms; it's interesting to consider how this important and overlooked hormone affects gut health.

Progesterone and Upper GI Motility and Satiety

When looking at sex hormone profiles, one study on reproductive aged patients found that esophageal-gastric emptying was slower in those with healthy progesterone levels likely resulting in an earlier feeling of fullness or "satiety" after meals.

Another study found that patients had a slower gastric emptying time during the follicular phase of the cycle, when progesterone levels are lower.

In peri or postmenopausal patients, however other studies did not see any impact on esophageal/gastric emptying based on natural levels or in using progesterone as a hormonal treatment.

Progesterone and Overall Gut Motility

Most studies have shown that progesterone decreases GI muscle cell contractions, relaxing the gut and moderating motility.

It's important to consider that progesterone, like many hormones works in concert with other processes of the body.

For healthy motility, the gut needs to move in the right way, at the right time. It's possible that healthy levels of progesterone are involved in this to some degree. 

Two different studies have assessed the impact of menstrual cycle phases on GI transit (how long it takes for a meal to pass through the gut).

GI transit time was significantly longer in the luteal phase where progesterone is dominant, compared to the follicular phase. Another study looked at a breath tests after ingesting lactulose, a way to measure transit time, and found that it was increased in the luteal phase of the cycle. Another study found that In menopausal women, oral micronized progesterone and estrogen plus progesterone also increased large intestinal transit time compared to placebo.

Progesterone and "Leaky Gut" or Intestinal Permeability

Progesterone also may reduce leaky gut, a name for a common problem where the lining of the intestine becomes more "permeable".

Tight junctions that attach cells lining the intestine to each other, are critical in that they prevent contents of the intestine from entering the body without being digested and processed.

When these tight junctions are disrupted by inflammation or other problems in the gut, contents of the intestine can access the immune system underneath the gut resulting in inflammation, food reactions or gastrointestinal symptoms.

A 2019 study on pregnant patients found that progesterone may play an important role in decreasing intestinal permeability by improving tight junctions and reducing systemic  inflammation during pregnancy.

Progesterone and Gallbladder and Biliary Motility

After consuming high fat foods, a hormone known as CCK is released from the small intestines.

Some Effects of CCK
  • Causes the gallbladder to contract in specific rhythms that help release bile.
  • Produces a sense of satiety and has even been found to affect the brain and conditions such as anxiety.

It's known that the biliary system and its function is commonly altered in PCOS. It's also known that gallbladder and biliary problems often occur around pregnancy and perimenopause, times where there are profound changes in levels of progesterone.

The conclusion from a variety of studies is that progesterone can regulate and calm the contraction of the gallbladder when stimulated by CCK. This may be quite relevant in patients who experience biliary or gallbladder colic, dilated biliary ducts or gallbladder "sludge" but more research needs to be completed on specific pathologies to learn more.

According to research, both estrogen and progesterone have been found to increase the fasting volume of bile the gallbladder without changing the residual volume of bile left in the gallbladder after meals.

Progesterone and GERD or Gastroesophageal Reflux

GERD commonly known as reflux occurs when the stomach contents rise up into the esophagus. Symptoms of reflux include burning, pain, acidic sensations in the throat, cough and many more.

This condition often includes altered function/motility of the esophageal and gastric muscles, altered gastric secretions, impaired acid clearance and impaired defense against injury in the area.

In general it seems that progesterone primarily affects the pressure of the lower esophageal sphincter, which is at the top of the stomach and regulates the opening and closing of the entry point to the stomach. Studies have investigated reflux, GERD in different phases of the menstrual cycle and most have found no clinical correlation to reflux symptoms at natural physiologic levels.

There are no human studies on micronized progesterone therapy and reflux.

In pregnancy, extremely high levels of hormones along with increased abdominal pressure could be involved in contributing to reflux, which is very common in this group.

Progesterone does likely have an impact on reflux but likely works concert with multiple other factors. It would be interesting to see more human studies on this topic,  since reflux affects 25% of people!

Progesterone, H Pylori and Stomach Ulcers

Ulcers are a common cause of stomach and gut pain. Ulcers form when the mucous lining of the stomach or duodenum is disrupted.  This break in the protective barrier results in inflammation and pain. Ulcers can be associated with H pylori infection, with taking Ibuprofen or NSAIDS for pain, and are a major source of discomfort and impact on quality of life.

Both progesterone and estrogen are thought to have a protective effect on the development of gastric and duodenal ulcers, by promoting healing of the gut lining and activating the production of mucous and helping to generate cells that line the stomach. 

Not many studies have reviewed the impact of progesterone on H pylori and ulcers but we have a bit of information to look at. An animal study reviewed the incidence and type of gastritis with respect to hormones and H pylori infection.

 In this study, it was found that H pylori infection was able to cause acute gastritis in postmenopausal animals (these animals had no natural estrogen or progesterone). This effect was  prevented with progesterone treatment.

It also found that H pylori caused a specific type of gastritis known as follicular gastritis in both pre and post menopausal animals. This was also prevented by pre-treatment with either estrogen or progesterone.

 It was also found that estradiol induced an inflammatory response in the gut, and maintained the profileration of cells that line the stomach, whereas progesterone was anti-inflammatory and had opposing effects on the cells.

 Like in other tissues, we see here how estrogen and progesterone have both balancing and opposing functions in the body. More research in particular on humans would need to be conducted before drawing firm conclusions based on this research, but it is fascinating!

Autoimmune Inflammatory Bowel Disease

Not much research has been conducted on progesterone and conditions such as Crohn's and Ulcerative Colitis. One study did look at 47 premenopausal women with IBD. No specific cycle-related impact was found on stool frequency, IBD symptoms and need for medication based on the phase of the cycle.

No studies have been completed to my knowledge on providing progesterone therapy in patients with IBD, however, given the systemic impacts of progesterone as an anti-inflammatory compound,  this would be an interesting area to study.

Ultimately, progesterone has a significant effect on multiple tissues in the body and likely works in conjunction with estradiol and multiple other factors in order to regulate physiology in the gut.

If a patient is of reproductive age and does not ovulate, consistently ovulates late, or has low levels of this hormone it is quite possible the function of the gut will be affected.

Gut problems such as IBS, SIBO, gallbladder and biliary disease are common in patients with hormonal concerns like PCOS, and in times of change such as pregnancy, puberty and perimenopause.

It's very likely given the body of research we have on hormones and the gut that progesterone plays an important role in these symptoms.

References for this article

  • Gonenne J, Esfandyari T, Camilleri M, et al. Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Neurogastroenterol Motil. 2006;18(10):911–918.
  • Marzio L. Factors affecting gallbladder motility: drugs. Dig Liver Dis. 2003;35(3):17–19.
  • Everson GT, McKinley C, Lawson M, et al. Gallbladder function in the human female: effect of the ovulatory cycle, pregnancy, and contraceptive steroids. Gastroenterology. 1982;82(4):711–719.
  • Coquoz A, Regli D, Stute P. Impact of progesterone on the gastrointestinal tract: a comprehensive literature review. Climacteric. 2022 Mar 7:1-25.
  • Lim SM, Nam CM, Kim YN, et al. The effect of the menstrual cycle on inflammatory bowel disease: a prospective study. Gut Liver. 2013;7(1):51–57.
  • Alvarez-Sanchez A, Rey E, Achem SR, et al. Does progesterone fluctuation across the menstrual cycle predispose to gastroesophageal reflux? J Gastroenterol. 1999;94(6):1468–1471.
  • Nelson JL, III, Richter JE, Johns DN, et al. Esophageal contraction pressures are not affected by normal menstrual cycles. Gastroenterology. 1984;87:876–871.
  • Clarrett DM, Hachem C. Gastroesophageal reflux disease (GERD). Mo Med. 2018;115(3):214–218.
  • Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, Scott L, Lester R. Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology. 1981 Jun;80(6):1497-500.
  • Zhou Z, Bian C, Luo Z, Guille C, Ogunrinde E, Wu J, Zhao M, Fitting S, Kamen DL, Oates JC, Gilkeson G, Jiang W. Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells. Sci Rep. 2019 Jun 10;9(1):8367.
  • Saqui-Salces M, Neri-Gomez T, Gamboa-Dominguez A, et al. Estrogen and progesterone receptor isoforms expression in the stomach of Mongolian gerbils. World J Gastroenterol. 2008;14(37): 5701–5706
  • Saqui-Salces M, Rocha-Gutierrez BL, Barrios-Pay an JA, et al. Effects of estradiol and progesterone on gastric mucosal response to early Helicobacter pylori infection in female gerbils. Helicobacter. 2006;11(2):123–130.
  • Marugo M, Molinari F, Fazzuoli L, et al. Estradiol and progesterone receptors in normal and pathologic colonic mucosa in humans. J Endocrinol Invest. 1985;8(2):117–119.
  • Wald A, Van Thiel DH, Hoechstetter L, et al. Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology. 1981; 80(6):1497–1500.