Histamine & Hormones: A Vital Connection Explained

This article is a shortlist of quick facts with references. Learn more about histamine intolerance.

Mast cells have oestrogen and progesterone receptors.
Oestrogen and progesterone may regulate mast cell activity.
When oestrogen binds to mast cell receptors, it stimulates the expression of H2 and H3 histamine receptors, and histamine is degranulated, synthesised and released quickly.
Increasing oestrogen levels result in the release of histamine.
In female reproductive tissue, histamine comes from uterine and ovarian epithelial and mast cells, as well as endometrial and myometrial endothelial cells.
Monoamine transporters in endometrial tissue have a high affinity for histamine uptake.
Oestrogen can downregulate the enzyme DAO activity and, therefore, have an influence on histamine levels (raising them).
Histamine behaviour fluctuates with menstrual hormones – LH, FSH, O and P.
Histamine concentrations in the ovaries and uterus mast cells change across the menstrual cycle, with mast cells most active in endometrial tissue during the premenstrual phase after progesterone and oestrogen decrease right before bleeding starts.
Premenopausal (fertile-age) women – correlation between urinary histamine metabolites and oestrogen in blood plasma – high oestrogen = high histamine.
Women are more susceptible to allergy reactions in peak mid-cycle oestrogen levels, not in the menstrual or luteal phases, when oestrogen is significantly lower.
Histamine results in oestradiol synthesis via activating H1 histamine receptors, resulting in higher oestrogen levels.
Histamine stimulates oestrogen production.
Oestrogen causes histamine release by degranulating mast cells in female reproductive tissue
High oestrogen in parts of the menstrual cycle causes histamine release and can influence tissue responsiveness to histamine.
There is an association between oestrogen, histamine, progesterone, and cortisol.
Progesterone inhibits histamine secretion after mast cell binding.
May be clinically relevant in women with low progesterone and elevated oestrogen.
When the HPA axis is activated by stress, mast cells spew their contents of histamine, thus stress = histamine.
In the hypothalamus, H1 and oestrogen receptors are placed together, and oestrogen can influence these hypothalamic H1 histamine receptors.
Histamine can also stimulate cortisol synthesis by adrenal cells, so high histamine means high cortisol.
When histamine-induced cortisol is high, progesterone synthesis may be inhibited due to steroid steal (progesterone and cortisol share the same base steroid).
This mix of oestrogen, progesterone and histamine may explain menstrual-related headaches and period pain, due to the inflammatory and contractile effects of histamine, in histamine-intolerant people.
This may explain why asthma is more severe in fertile-aged women – blood oestrogen and progesterone concentrations correlate with asthma symptoms, with asthma more severe in preovulatory and premenstrual phases.
Those with hormone-related conditions like endometriosis have more allergies overall.
Microbial colonies may impact histamine levels – list of bacteria that produce histamine.

References

Schwelberger HG, Ahrens F, Fogel W, et al. Histamine metabolism. In: Histamine H4 receptor: a novel drug target in immunoregulatory and inflammatory diseases (Ed. Stark H) 2013: Versita, London/UK. [Full Text]
Jones BL, Kearns GL. Histamine: new thoughts about a familiar mediator. Clin Pharm Ther 2011;89(2):189-197. [Abstract]
Kyriakidis DA, Theodorou MC, Tiligada E. Histamine in two component system-mediated bacterial signaling. Front Biosci 2012;17:1108-1119. [Full Text]
Barcik W, Wawrzniak M, Akkis CA, et al. Immune regulation by histamine and histamine-secreting bacteria. Curr Opin Immunol 2017;48:108-113.[Source]
Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr 2007;85(5):1185-1196. [Full Text]
Gene Database. HRH1 histamine receptor H1, HRH2 histamine receptor (Homo sapiens (human)] 2018. Viewed 11 August 2018, [Source]
Reese I, Ballmer-Weber B, Beyer K, et al. German guideline for the management of adverse reactions to ingested histamine. Allergo J Int 2017;26:72-79. [Abstract]
Kovacova-Hanuskova E, Buday T, Gaviakova S, et al. Histamine, histamine intoxication and intolerance. Allergol Immunolpathol (Madr) 2015;43(5):498-506.[Abstract]
Mauro Martin IS, Brachero S, Garicano Vilar E. Histamine intolerance and dietary management: a complete review. Allergol Immunopathol (Madr) 2016;44(50):475-483.[Abstract]
Munoz-Cruz S, Mendoza-Rodriguez Y, Nava-Castro KE, et al. Gender-related effects of sex steroids on histamine release and FceRI expression in rat peritoneal mast cells. J Immunol Res 2015;2015:351829.[Full Text]
Zierau O, Zenglussen AC, Jensen F. Role of female sex hormones, estradiol and progesterone, in mast cell behavior. Frontiers in Immunology 2012;3:doi:10.3389/fimmu.2012.00169.[Abstract]
Graziottin A, Serafini A. Perimenstrual asthma: from pathophysiology to treatment strategies. Multidisc Resp Med 2016;11:30.[Full Text]
Loewendorf AI, Matynia A, Saribekyan H, et al. Roads less travelled: sexual dimorphism and mast cell contributions to migraine pathology. Front Immunol 2016;7:140.[Abstract]
Theoharides TC, Stewart JM. Genitourinary mast cells and survival. Transl Androl Urol 2015;4(5):579-586.[Abstract]
Ridolo E, Incorvaia C, Martignago I, et al. Sex in respiratory and skin allergies. Clin Rev Allergy Immunol 2018 Jan 6.[Abstract]
Noskova V, Bottalico B, Olsson H, et al. Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2. Mol Hum Reprod 2006;12(8):483-489. [Abstract]
Fogel WA. Diamine oxidase (DAO) and female sex hormones. Agents Actions 1986;18(1):44-45.[Abstract]
Sessa A, Desiderio MA, Perin A. Oestrogenic regulation of diamine oxidase activity in rat uterus. Agents Actions 1990;29(3-4):162-166.[Abstract]
Reed BG, Carr BR. The normal menstrual cycle and the control of ovulation. Endotext 2015. Viewed 19 August 2018, [Abstract]
Lee SK, Kim CJ, Kim DJ, et al. Immune cells in the female reproductive tract. Immune News 2015;15(1):16-26.[Full Text]
Clifton VL, Crompton R, Read MA, et al. Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to estrogen concentration during the menstrual cycle. J Endocrinol 2005;186:69-76.[Abstract]
Kirmaz C, Yuksei H, Mete N, et al. Is the menstrual cycle affecting the skin prick test reactivity? Asian Pac J Allerg Imminol 2004;22:197-203.[Abstract]
Haeggstrom A, Ostberg B, Stjerna P, et al. Nasal mucosal swelling and reactivity during a menstrual cycle. Karger ORL 2000;62:39-42.[Abstract]
Bodis J, Tinneberg HR, Schwarz H, et al. The effect of histamine on progesterone and oestradiol secretion of human granulosa cells in serum-free culture. Gynecol Endocrinol 1993;7(4):235-239.[Abstract]
Vasiadi M, Kempuraj D, Boucher W, et al. Progesterone inhibits mast cell secretion. Intern J Immunopathol Pharmacol 2006;19(4):787-794.[Abstract]
Mori H, Matsuda KI, Yamawaki M, et al. Oestrogenic regulation of histamine receptor subtype H1 expression in the ventromedial nucleus of the hypothalamus in female rats. PLoS One 2014;9 5):e96232.[Abstract]
Zayachkivska O, Musiol A. Histamine-cortisol correlations: new link of multifactorial regulation of inflammation. Conference: University Hospital Centre and Grenoble Institute of Neurosciences Grenoble, France. Viewed 11 August 2018, [Source]
Nakamura Y, Ishimaru K, Shibata S, et al. Regulation of plasma histamine levels by the mast cell clock and its modulation by stress. Sci Rep 2017;7:39934.[Abstract]
Zaitsu M, Narita S, Lambert KC, et al. Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx. Mol Immunol 2007;44(8):1977-1985.[Full Text]
Shah S. Hormonal link to autoimmune allergies. ISRN Allergy 2012; 2012: Article ID 910437.[Full Text]