HistHERmine: The Link with Women's Hormones
Wednesday, 31 March 2021
Tis’ the season where we start to talk about histamine - but i’m going to take the opportunity to explain some of the links we see between the effect female sex hormones have on mast cell (MC) behaviour and corresponding release of histamine.
Histamine is a key molecule that we produce, and in the right amounts required to:
On the flip side, too much histamine can wreak havoc. Common symptoms of high histamine:
What are Mast Cells then?
Mast cells (MCs) belong to the innate part of our immune system (present in our barriers : lungs, gut, vagina, urinary tract and sinuses) and are widely known for their role in allergic reactions via their binding to what is called an IgE receptor.
In addition to the very well known mechanism of mast cell activation from “allergens” like pollen there is a lesser known but very important relationship between female sex hormones, estradiol and progesterone, to activate MC.
As well as IgE receptors MCs have receptors for oestrogen, progesterone, and cortisol! The binding of oestrogen to mast cell receptors stimulates the expression of 2 specific histamine receptors: H2 and H3, and induces rapid histamine degranulation, synthesis and release.
H2-receptors are found in the brain, the endocrine glands (i.e. Ovaries, the respiratory and cardiovascular system) and responsible for the stimulation of gastric acid secretion
H3: These are present throughout the nervous system, though most notably in the central nervous system.
Scroll back up to symptoms of high histamine - makes sense now !
Animal data (yeah - sorry) shows that cellular histamine levels in ovarian and uterine mast cells varies across the menstrual cycle, and the activation of mast cells within endometrial tissue is most significant during the premenstrual phase following the decrease in progesterone and oestradiol - BUT this is still more prevalent in oestrogen than progesterone. The same is true of perimenopause when progesterone levels plummet and leaves oestrogen unopposed = activation of mast cells! And can be part of the link to PMS and perimenopause symptoms like flushing, water retention, heavy menstrual flow, menstrual pain, and most especially, migraine headaches as well as playing a part in Endometriosis.
Now what’s interesting about this is that mast cells, when they degranulate, also release heparin, which is a blood thinner! And can contribute to the flooding experienced by many endo suffers.
Overall, this shows that: histamine can stimulate oestrogen production; oestrogen causes mast cell degranulation in female reproductive tissues; AND elevated oestrogen levels during the menstrual cycle induces histamine release .
What about Progesterone? Well, it has an inhibitory effect on histamine secretion following binding to mast cells.
What has stress got to do with it
A lot! The master controller of our hormones (which we will be delving into in great detail on my practitioner masterclass - Navigating the Web of Women's Hormones:The hypothalamic-pituitary-adrenal (HPA) hormonal response to stress results in mast cell degranulation and consequently results in elevated levels of histamine (i.e. stress =histamine). In the hypothalamus, Histamine (H1 this time) receptors and oestrogen receptors sit side by side having a little hangout session, so oestrogen can influence hypothalamic H1 receptor activity (i.e. oestrogen →histamine), while histamine can also stimulate cortisol synthesis by adrenal cells. (i.e. histamine → cortisol).
The impact of chronic stress on the integrity of the intestinal epithelial lining, adversely influencing the histamine-inactivating capacity of intestinal enzyme DAO, is another process potentially contributing to increased levels of circulating histamine.
Aside from triggering mast cells to release histamine, oestrogen can also down-regulate the enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) which removes histamine. This may then explain why symptoms of histamine intolerance are common at the start of the menstrual period and during perimenopause, when oestrogen levels are unopposed by progesterone, and thus presents as an oestrogen dominant picture. Histamine will also stimulate the ovaries to produce more oestrogen via aiding luteinising hormones (LH) production, leading to a vicious cycle of these two compounds.
One final piece of proof to this linkage is Histamine and Pregnancy. Many women see their “allergic” symptoms lessen when pregnant, explained by the fact that the placenta of a pregnant woman increases the production of DAO by as much as 500 times! Remember that DAO is one of the enzymes that helps us break down histamine.
Overall it is clear that there is an interconnection in the body between histamine, oestrogen, progesterone and cortisol - and another great example of the interconnections of the human body.
In health, Tanya