Progesterone and irritable bowel syndrome, headaches and irritable bladder

Progesterone plays a role in preventing or ameliorating irritable bowel syndrome by inhibiting the release of histamine. This important clinical insight is illustrated by two studies, the first one published in the International Journal of Immunopathology and Pharmacology. The authors state:

"Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it."

Histamine triggers inflammatory responses, and the authors demonstrated that progesterone inhibits the secretion of histamine from mast cells when they have been stimulated to react:

"Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy."

The link between progesterone and irritable bowel syndrome (IBS) is highlighted in a study published in the journal Gastroenterology. The authors note:

"Intestinal mast cell infiltration may participate to abdominal pain in irritable bowel syndrome (IBS) patients."

They took mediators like histamine produced by mast cells from the colonic mucosa of IBS patients and applied them to rat sensory neurons in vitro and quantified the stimulatory effects. Histamine and tryptase from mast cells clearly fired things up:

"Mediators from IBS patients, but not controls, markedly enhanced the firing of mesenteric nerves and stimulated mobilization of Ca2+ in dorsal root ganglia neurons...Histamine and tryptase were mainly localized to mucosal mast cells. IBS-dependent nerve firing and Ca2+ mobilization were correlated with the area of the colonic lamina propria occupied by mast cells. IBS-dependent excitation of dorsal root ganglia was inhibited by histamine H1 receptor blockade and serine protease inactivation."

As the authors conclude, mast cell products like histamine are a key mechanism in the gut pain, discomfort and hypersensitivity of IBS:

"Mucosal mast cell mediators from IBS patients excite rat nociceptive visceral sensory nerves. These results provide new insights into the mechanism underlying visceral hypersensitivity in IBS."

This is further evidence for how progesterone can ameliorate IBS by inhibiting the release of inflammatory mediators from mast cells.Clinical note: As noted above, this applies to numerous conditions including migraine, interstitial cystitis (painful/irritable bladder), dysmenorrhea and others. Practitioners must be alert to the role of histamine intolerance—a forthcoming post will examine the literature on its diagnosis, treatment, and widespread clinical significance.