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Effect of the Seasons

Updated: Jan 25, 2023

A number of environmental and biological factors may have an influence over an individual’s risk of developing fibrosis, and the chances of recovering from it. The body is a highly complex system of processes, with a large number of interactions and feedback effects between hormones and cells, and scientific advances in understanding are made regularly. Small alterations in one hormone can have powerful effects on many functions including stress, digestion, fertility and immune system function.

While the science behind the existence of these environmental and biological factors is sound, it’s not yet clear to what extent they impact on fibrotic processes.

The processes and functions of the body are governed by signalling factors the body makes called hormones. Hormones include growth factors and cytokines that signal cells in different parts of the body to start, stop, increase or decrease specific activities.

Recent research indicates that one of the main stress hormones, called cortisol, is significantly increased in winter in both men and women [1], with the effect greater at higher latitudes.

This may have implications for those at risk of arthrofibrosis if they are planning surgery, since increased cortisol increases levels of proteins that make resistant scar tissue and adhesions. Cortisol also increases the risk of infection. This suggests that the seasonal timing of surgery may impact on recovery, with winter being the least-best season and autumn the best season.

Seasonal timing of surgery may impact on recovery, with winter being the least-best season and autumn the best season.

Seasonal changes in hormones have been well studied in animals, and recent research indicates that humans also have significant seasonal alterations in their levels of a range of hormones. For example, the winter increase in the levels of cortisol increases the expression of lysyl oxidase (LOX), an enzyme (protein) that upregulates the production of scar tissue [2] and cross-links collagen in scar tissue. Highly cross-linked collagen is a hallmark of fibrotic tissue [3] and LOX is strongly implicated in fibrosis [2].

LOX increases cell to collagen adhesion via focal adhesion kinase (FAK), thus increasing both scar tissue production, stiffness and adhesions. In addition, LOX upregulates IL-6, a pro-fibrotic and pro- inflammatory cytokine [2].

  1. Tendler, A. et al. Hormone seasonality in medical records suggests circannual endocrine circuits. Proc Natl Acad Sci U S A 118, doi:10.1073/pnas.2003926118 (2021).

  2. Nguyen, X.-X. M. et al. Lysyl Oxidase Directly Contributes to Extracellular Matrix Production and Fibrosis in Systemic Sclerosis. Am J Physiol Lung Cell Mol Physiol, doi:10.1152/ajplung.00173.2020 (2020).

  3. Kalamajski, S., Bihan, D., Bonna, A., Rubin, K. & Farndale, R. W. Fibromodulin interacts with collagen cross-linking sites and activates lysyl oxidase. Journal of Biological Chemistry, doi:10.1074/jbc.M115.693408 (2016).

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4 comentarios

Hi Maria,

Ive had meniscus surgery, followed by knee replacement, manipulation, revision, manipulation, ruptured bakers cyst, revision and now a knee filled with fluid and scar tissue and now, no one offers hope. How did you ever get in touch with Dr. Usher for advice? I’m weary, my leg hardly bends and the pain is incredible. I’m desperately seeking help. Thank you

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Manon Raap
Manon Raap
06 mar 2023
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Dear Unknown member,

I would advice you to post your message and question on the Forum. Dr Usher always answers there, but your message might get a bit lost here under the blog post 'Effect of the Seasons'. We moved Maria's story there as well.

All the best,


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13 ene 2023

Three years ago, in February 2020, I had a knee replacement and developed Arthrofibrosis afterwards.

I am 76 years old and live in Canada. After my operation I was instructed to do strenuous exercises to gain mobility of my knee till I cried. Each time my knee would swell up and get more and more inflamed.

Nobody was able to help me and knew anything about Arthrofibrosis.

So I searched the internet and found Dr. Kayley Usher’s research about Arthrofibrosis: "Pathological mechanisms and therapeutic outlooks for arthrofibrosis”.

Dr. Usher changed my life and I want to give tribute to her and her work and for creating this website!

Learning to understand that my problem was not mechanical and could not…

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Contestando a

Hi Maria,

Thank you for sharing your story with us, it helps us all to learn and find ways to approach our own situations.

And thank you for the lovely feedback, I'm very glad that I was able to help a little 😊

All the best,


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