Protective effect of estrogen?

[Guy2015]

I'm a 32 year old male and Ive found out my estrogen is low 30pmol/L (Male range 45-150pmol/L), my eyes have suddenly got bad and I have been diagnosed with KC.

I've been doing a lot of research on keratoconus and this recent publication in 2015 states that keratoconus is probably caused by the eyes lack of ability to deal with reactive oxygen species:

http://www.hindawi.com/journals/bmri/2015/795738/

"It is commonly accepted that the etiology of KC is multifactorial combining environmental and genetic factors [1, 101–103]. Moreover, it seems that an environmental factor may be essential to act as a trigger of the condition in genetically predisposed individuals. Environmental factors, which have been recognized, are eye rubbing, atopy, and UV exposure, although the relative contribution of all these factors is currently unknown [6]. An excess of any of these environmental factors cause oxidative damage to KC corneas because of the inability of KC corneas to process reactive oxygen species (ROS), which leads to a degradation process leading ultimately to corneal thinning and loss of vision [104] due to a lack of corneal enzymes such as aldehyde dehydrogenase class 3 (ALDH3), catalase, or superoxide dismutase to remove or neutralize the ROS [105]."

The publication goes on to say that "rubbing KC corneas generates elevated levels of matrix metalloproteinases MMP-1 and MMP-13 [123, 124], which are secreted by epithelial and stromal cells, and inflammatory mediators including IL-6 and TNF-α [5, 125]. The release of these factors form part of the process that leads to KC and its progression."

I also found this study that shows that estrogen has a protective effect on corneal collagen degradation:

http://www.molvis.org/molvis/v17/a368/

METHODS:
Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels with or without sex hormones including 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA). Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression and activity of matrix metalloproteinases (MMPs) were evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) inhibitor NF kappa B Inhibitor-alpha (IκB-α) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively.

RESULTS:
17β-Estradiol and progesterone each inhibited interleukin (IL)-1β-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner, whereas testosterone and DHEA had no such effect. MMP expression and activation in corneal fibroblasts exposed to IL-1β were also inhibited by 17β-estradiol and progesterone. These female sex hormones did not affect cell proliferation or viability. Both 17β-estradiol and progesterone inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs extracellular Signal-regulated Kinase (ERK) or c-jun N-terminal kinase (JNK). 17β-Estradiol also inhibited the IL-1β-induced phosphorylation of IκB-α."

So as you can see estradiol (e2) INHIBITED collagen degradation in corneals by BLOCKING MMP expression. Eye rubbing INCREASES MMP expression. I HAD ZERO eye problems when my estrogen was 130 pmol/L (range 45-160).

In stark contrast Ive seen a study where a woman that was pregnant had a worsening of kerataconus but maybe the hypothesis that increased estrogen can worsen KC is only correlative because the increaed immune strain and oxidative stress of pregnancy is the real causation of the worsening of KC and not elevated estrogen - or they could be correct and it is maybe VERY high levels of estrogen that could make it worse, study (molvis.org link above)shows estrogen protected collagen degradation is a dose responce manner (higher the dose, higher the protective effect). It also closes by stating: "In summary, we have shown that the female sex hormones 17β-estradiol and progesterone each inhibit IL-1β–induced collagen degradation by corneal fibroblasts. These hormones also inhibited the expression or activation of MMP-1, MMP-2, MMP-3, and MMP-9, effects that may result from modulation of MAPK and NF-κB signaling pathways. Our results therefore suggest that female sex hormones warrant further investigation as potential drugs for the treatment of corneal diseases. "

Also during teenage years KC can start but that COULD be dues to an immune responce from the body due to NEW levels of sex steroids. Sex steroids stimulate the immune system and flucations can cause an immune responce before the immune system adapts.

Again clmate and dust can cause allergy which obviously stimulates the immune system and maybe cause a worsening of oxidative stress.

Gentics could play a part in the ability for someone to deal with these issues more so than others.

My question is does anyone know or has been told that low estrogen can accelerate kerataconus?

Thank you.

[Anne Klepacz]

Welcome to the forum and thank you for such an interesting first post! That there's a link between hormone levels and KC seems to have been known for a while, so it's maybe surprising how little research there's been in that area. It's surely significant that KC often starts around puberty, and especially for boys. I'm no scientist, but we get a lot of enquiries from parents of newly diagnosed boys in the 11-14 age range. And KC affects more males than females (something like a 60/40 split). But exactly what role hormones play seems to be complicated. For women with KC, high oestrogen levels can cause a spurt in progress of KC. We've certainly had quite a few members whose KC has worsened during and after pregnancy (although some of our women members have found pregnancy had no effect). This study (by one of the inventors of CXL)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095430/
suggests that high levels of oestrogen weaken the collagen network in the cornea.
So maybe, as you suggest, it's a question of the right balance. And that's obviously going to be affected by gender. It's certainly an area where there needs to be much more research. The trouble is, as you quote at the beginning of your post, the causes of KC are multifactorial, so working out what's significant in any individual's KC progression isn't easy. I wonder if any of our health professional members can tell us more.

[CrippsCorner]

Very interesting! Although I didn't understand many of the long words lol... I've always wondered (and my consultant didn't really have an answer) if rubbing your eyes post-CXL is still going to have a negative effect on your corneas. I find when wearing contacts, I unfortunately end up rubbing my eyes a little more.

[CrippsCorner]

18 month bump!

I still haven't found an answer to my query above... can rubbing your eyes after CXL effect your KC? I seem to do it a lot throughout the evening. Maybe something to do with lack of sleep due to having a baby at home I just don't want to feel like I'm undoing good!

[Anne Klepacz]

I don't know what the answer is post CXL. But I used to naively think that post graft I didn't need to worry about rubbing my eyes. Like you, my main eye rubbing time was in the evening when the contact lenses came out. But I eventually got a return of KC at the bottom of both grafts, and I suspect that's due at least in part to the eye rubbing. So I'd say avoid rubbing if you possibly can. After decades, I've finally found that rubbing the bones around the eyes (without touching the eye itself) gives me the relief I need. An alternative suggestion given by one of the consultants at one of the London group meetings was to just touch the eyelid gently. Good luck!