How your immune system affects ovulation and hormone balance

You might be surprised to learn that supporting immune function can do a lot more for your wellbeing than reducing risks of contracting viruses. In fact, optimal immune health is essential for happy hormones too. It has everything do with inflammation. And inflammation is driven by a cluster of inflammatory chemicals that are triggered by our immune response.

Table 1. Inflammatory chemicals and their subtypes

Let’s cover the basics first. Inflammation is characterized by five cardinal symptoms; redness, heat, swelling, pain and loss of function. It can be acute or chronic. Regardless, when an inflammatory event takes place cell-derived substances are released that trigger a series of processes that aim to promote healing. These substances are cytokines, chemokines and eicosanoids; each made up of highly specialized subtypes. It’s super complicated and deserving of its own blog post. However, for the purpose of understanding its importance for hormone health, all you need to know right now is that they play an important role in both physiological and pathological processes in gynaecological wellbeing. So, let’s dive into their role in ovulation specifically.

When things can go wrong

Diagram of follicle maturation and ovulation.

Ovulation starts in the brain. The hypothalamus releases Gonadotropin Releasing Hormone (GnRH), which sets in motion a downward cascade of hormonal stimulus from the pituitary to the ovaries that aim to mature a follicle; at full maturation it ruptures and releases an egg. A.K.A ovulation. Luteinizing Hormone (LH) is responsible for inducing this rupture. So here we have two super important endocrine hormones that start and end ovulation, GnRH and LH. And guess what? The cytokine Interleukin – 1 (IL-1) that is primarily made by the immune cells monocytes and macrophages, decrease both GnRH and LH levels.(1) IL-1 also has the ability to increase prolactin, a hormone that typically is produced to help stimulate lactation and foetal growth.(1) It must remain low in non-pregnant and non-breastfeeding women during the first half of the cycle in order for ovulation to occur. These mechanisms are examples of how an over active immune response with excessive IL-1 production may interfere with ovulation and a regular cycle. If GnRH and LH are low, and prolactin is high, you might want to consider your immune health in this clinical picture and whether there’s a stealth infection that needs addressing.

Inflammatory chemicals that support ovulation

However, you’d be mistaken to think that the effects of inflammatory chemicals are all bad on ovulation and cycle regulation. They often get a bad reputation, but the truth is we need them. It’s when there’s too little or too much that they become problematic.

Many inflammatory chemicals are essential for healthy ovulation to occur. Whilst LH is needed to rupture a follicle and induce ovulation, there are a series of immune cytokines, many of which are produced locally in the ovaries, that are also needed to aid this process. Tumour Necrosis Factor Alpha (TNF-𝛼), Interleukin-6 (IL-6), Interferon-gamma (INF-𝛾) and Interleukin—8 (IL-8) are found in the ovulatory follicle.(2) IL-1β is found in androgen producing theca cells in the ovaries; whilst IL-1β, IL-6, TNF-𝛼 and TNF-β2 are found in oestrogen producing granulosa cells.(3) And TNF-𝛼 is required by the maturing egg too.(1)

Figure 1. Localization of hyaluronan in pre-ovulatory follicles.

What’s more is, it’s been shown in animal studies that in the lead up to ovulation a hyaluronic acid rich extra cellular matrix expands around the maturing egg before rupture. This process recruits inflammatory chemicals Prostaglandin E2 (PG E2) and TNF-𝛼.(4) The cytokine granulocyte macrophage colony stimulating-factor (GM-CSF), (yes it’s quite the mouthful) stimulates stem cells to produce the immune cells granulocytes, monocytes and mast cells. Together they make and release histamine.(5) Histamine is an all-important inflammatory chemical required for vasodilation and vascular permeability ahead of the follicular rupture that gives way to ovulation. Often, when clients report that their skin sensitivities, such as eczema, worsen around ovulation, or that they experience localized pain in the lower abdomen region, I rationalize this in context of the histamine spike that necessitates ovulation. Typically, if there is a pre-existing immuno-compromised condition that results in higher than normal amounts of histamine, such as the case with eczema or rosacea, ovulation can sometimes exacerbate symptoms due to the temporary histamine spike.

As you can see, each inflammatory chemical plays an instrumental role influencing egg maturation and follicular rupture. To say that ovulation is an inflammatory process is an understatement. The event requires a healthy, balanced and active immune system to support the production of these all important inflammatory chemicals that aid and regulate the entire ovulatory process.

It doesn’t end there. The traditional narrative of what happens after ovulation is that the blister pack that is left behind, the corpus luteum, starts producing progesterone. What’s rarely mentioned is that inflammatory cytokines are needed for remodeling the ruptured follicle into the corpus luteum, for angiogenesis (that’s science talk for the development of new blood vessels to this newly produced organ) and for ovarian steroidogenesis (that’s more science talk for sex hormone and enzyme production).

In fact, cytokines IL-1, TNF- 𝛼 and interferons shift the ovulatory follicle from producing oestradiol to progesterone once it’s transformed into the corpus luteum. Suffice to say, compromised cytokine production due to immune complications may lead to luteal phase defects typically driven by insufficient progesterone production. Common symptoms include infertility, painful ovulation, PMS and/or irregular menstruation.

So what next?

If you suspect that your immune system might be affecting ovulation it’s important to discuss this with your doctor first and explore options with your certified alternative healthcare practitioner too. It’s best to work with a trained specialist in this area as you’ll want to run functional tests to investigate your immune health and how this might be interfering with your hormone balance.

Tune in to my next blog post to learn how our immune system interacts with menstruation too.

Kay Ali, Fx Med Hormone Nutritionist.


  1. Machelon, V. Emilie, D 1997. 'Production of ovarian cytokines and their role in ovulation in mammalian ovary', Eur Cytokine Netw 8(2), pp. 137-43

  2. Bukulmez, O. Arici, A. 1997. 'Potențial therapeutic use of cytokines in gynaecology and obstetrics', BioDrugs 8(3) pp. 193-204

  3. Desai, P. 2007. 'Cytokines in Obstetrics and Gynaecology', J Obstet Gynecol India 57(3), pp. 205-9

  4. Salustri, A, Yanagishita, M, Underhill, CB, Laurent, TC, Hascall, VC: Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle. Dev. Biol. 151, 541-551, 1992

  5. Zhao, Y. Rong, H. Chengini, N. 1995. 'Expression and selective cellular localisation of granulocyte-macrophage colony stimulating factor and GM-CSF alpha and beta receptor messenger ribonucleic acid and protein in human ovarian tissue', Biol Reprod 53, p. 923.

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