A new piece of the endo pain puzzle?
If you're living with endometriosis, you know the pain is relentless - and often poorly explained. Researchers are now looking at a surprising suspect: prolactin. Best known for its role in breastfeeding, this hormone actually has many other roles, and may be quietly fuelling the chronic pain that so many with endo experience every day.
Could prolactin be a future treatment target? Let’s break it down.
So, what exactly is prolactin? (1)
Most people know prolactin as the hormone that triggers milk production. But it does far more than that. Prolactin is a hormone primarily released from the pituitary gland of the brain. It is essential for many functions in the body, such as:
- Water and salt balance
- Growth and development
- Immune system regulation
- Formation of new blood vessels (angiogenesis)
What keeps it in check? Dopamine. The more dopamine you have, the less prolactin circulates. However, several factors can temporarily increase prolactin levels, including:
- Estrogen
- Stress
- Exercise
Prolactin isn’t just made in the brain. Immune cells, endometrial cells and even fat cells can produce it too.
The endometriosis and prolactin connection (1, 2, 3, 4)
In endometriosis, prolactin levels are higher than normal. In fact, in a large review, 17 out of 18 studies reported elevated prolactin levels in women with endometriosis versus controls. Interestingly, high levels of prolactin are also associated with autoimmune disease.
Interestingly, two of these studies reported a correlation between prolactin levels and endometriosis stage.
But systemic levels may not tell the full story.
Endometriosis lesion cells may be creating their own prolactin supply locally. There are three potential contributors:
- Lesion stromal cells: In vitro studies show cultured stromal cells can synthesise their own prolactin locally.
- Infiltrating immune cells: Endometriosis lesions are rich in inflammatory immune cells, which can produce prolactin.
- Adipose tissue: Endometriosis lesions contain white adipose tissue, or fat tissue, which also releases prolactin.
This creates a prolactin-rich environment specifically around the lesions,
A female-specific effect on pain.
Prolactin appears to have a uniquely female effect on pain signalling. When prolactin binds to receptors on pain neurones, it can promote the phosphorylation of ion channels involved in pain processing, making your peripheral neurones more likely to send off pain signals to the brain.
This means two things: existing pain feels worse AND things that weren’t painful before, now are.
Animal studies have shown that prolactin can:
- Increase sensitivity to heat and mechanical stimuli
- Induce migraine
The stress loop nobody talks about
Endometriosis is a condition that creates not only physical stress but psychological stress too. Constant doctors appointments, dismissive opinions and lack of solutions is damaging to the mind, and the body.
Repeated stress exposure activates the hypothalamic-pituitary-adrenal (HPA) axis, your body’s stress response system - which runs straight through the pituitary gland, the same place prolactin is primarily released. This creates increased prolactin levels in response to activation of this pathway.
In endometriosis, two processes converge:
- Lesion growth and inflammation
- Chronic stress activation (physical and psychological)
Together, this increases prolactin levels, which can contribute to ongoing pain.
How to support prolactin balance in endometriosis (1, 5, 6, 7)
This research creates potential new treatment targets:
- Dopamine agonists
These drugs bind to dopamine receptors to inhibit prolactin release from the brain’s pituitary gland. There have also been seen to work directly on neurons to reduce pain and on lesions to inhibit growth.
However, more clinical trials are needed before this approach can be validated as effective.
- Vitamin D
Emerging (though preliminary) research suggests that there could be a correlation between low vitamin D levels and higher prolactin levels, adding yet another reason to keep an eye on your D status if you have endo.
The takeaway
Endometriosis is a complex condition that involves inflammation, hormones and neurological aspects. Prolactin offers a connection between these, and connects lesion growth to chronic pain. More research is needed to confirm how these aspects of endometriosis connect, and if prolactin could be a treatment target in the future.
References:
1. Lee, G. J., Porreca, F., & Navratilova, E. (2023). Prolactin and pain of endometriosis. Pharmacology & therapeutics, 247, 108435. https://doi.org/10.1016/j.pharmthera.2023.108435
2. Chen Y, Moutal A, Navratilova E, Kopruszinski C, Yue X, Ikegami M, … Porreca F (2020). The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females. Science Translational Medicine 12
3. Scotland PE, Patil M, Belugin S, Henry MA, Goffin V, Hargreaves KM, & Akopian AN (2011). Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia. The European Journal of Neuroscience 34, 745–754
4. Mason BN, Kallianpur R, Price TJ, Akopian AN, & Dussor GO (2022). Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine. Headache 62, 11–25.
5. Amit Kyal AP, Mukhopadhyay A, & Mukhopadhyay P (2018). Does cabergoline help in decreasing chronic pelvic pain due to endometriosis compared to medroxyprogesterone acetate? A prospective randomized study. Journal of South Asian Federation of Obstetrics and Gynaecology 10, 167–169
6. Gomez R, Abad A, Delgado F, Tamarit S, Simon C, & Pellicer A (2011). Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia. Fertility and Sterility 95(882–888), Article e881
7. Amanzholkyzy, A., Donayeva, A., Kulzhanova, D., Abdelazim, I. A., Abilov, T., Baubekov, Z., & Samaha, I. I. (2023). Relation between vitamin D and adolescents' serum prolactin. Przeglad menopauzalny = Menopause review, 22(4), 202–206. https://doi.org/10.5114/pm.2023.133883