Quick List: How histamine works with oestrogen, progesterone and cortisol

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, and 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 and progesterone, and cortisol.
  • Progesterone inhibits histamine secretion after mast cell binding.
  • Maybe clinically relevant in women with low progesterone and elevated oestrogen
  • When the HPA is activated by stress, mast cells spew their contents of histamine, thus stress = histamine.
  • In the hypothalamus, H1 receptors 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 women
  • May explain why asthma is more severe in fertile-aged women – blood oestrogen and progesterone concentrations correlate with asthma symptoms with asthma more severe is preovulatory and premenstrual phases
  • Those with hormone-related conditions like endometriosis have more allergies overall

References

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Jessica Lloyd - Vulvovaginal Specialist Naturopathic Practitioner, BHSc(N)

Jessica is a degree-qualified naturopath (BHSc) specialising in vulvovaginal health and disease, based in Melbourne, Australia.

Jessica is the owner and lead naturopath of My Vagina, and is a member of the:

  • International Society for the Study of Vulvovaginal Disease (ISSVD)
  • International Society for the Study of Women's Sexual Health (ISSWSH)
  • National Vulvodynia Association (NVA) Australia
  • New Zealand Vulvovaginal Society (ANZVS)
  • Australian Traditional Medicine Society (ATMS)
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