T Nation

COX-2 & Testosterone


Cyclooxygenase-2 regulation of the age-related decline in testosterone biosynthesis.

Wang X, Shen CL, Dyson MT, Eimerl S, Orly J, Hutson JC, Stocco DM.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA. xingjia.wang@ttuhsc.edu

The age-related decline in testosterone biosynthesis in testicular Leydig cells has been well documented, but the mechanisms involved in the decline are not clear. Recent studies have described a cyclooxygenase-2 (COX2)-dependent tonic inhibition of Leydig cell steroidogenesis and expression of the steroidogenic acute regulatory protein (StAR).

The present study was conducted to determine whether COX2 protein increases with age in rat Leydig cells and whether COX2 plays a role in the age-related decline in testosterone biosynthesis. Our results indicate that from 3 months of age to 30 months, COX2 protein in aged rat Leydig cells increased by 346% over that of young Leydig cells, StAR protein decreased to 33%, and blood testosterone concentration and testosterone biosynthesis in Leydig cells decreased to 41 and 33%, respectively. Further experiments demonstrated that overexpressing COX2 in MA-10 mouse Leydig cells inhibited StAR gene expression and steroidogenesis and that the inhibitory effects of COX2 could be reversed by blocking COX2 activity.

Notably, incubation of aged Leydig cells with the COX2 inhibitor NS398 enhanced their testosterone biosynthesis. Blood testosterone concentrations in aged rats fed the COX2 inhibitor DFU, at doses of 5, 10, 15, and 20 mg/kg body weight per day were increased by 15, 23, 56, and 120%, respectively, over the levels in the rats receiving no DFU. The present study suggests a novel mechanism in male aging involving COX2 and a potential application of the mechanism to delay the age-related decline in testosterone biosynthesi


Does this have anything to do with the Cox II medications that have been so controversial lately?


Yes. I contacted the author of the study. They used DFU (a selective COX-2 inhibitor). He noted that any COX-2 (like Celebrex) should work in the same manner.

COX-2 = inflammation. Inflamed Leydig cells = less conversion of cholesterol to testosterone. COX-2 inhibitor reduces inflammation and increases testosterone in a dose dependant manner. Less inflammation = more cholesterol converted to testosterone.

Curcumin & Bee Propolis are alternative COX-2 inhibitors.


Interesting! I've got a number of q's for you:

  1. Will decreasing tissue inflammation in general help or only that dealing with the Leydig cells and Cox 2 receptor sites?
  2. What is Bee Propolis?
  3. Any recommendations on dosage of curcumin and Bee Porpolis??
  4. Can this even be taken orally?

Thx for the cutting edge info.


And also: any idea why the Cox II's have caused so many health problems? Any way around this?


The authors of the study found a relationship between aging and an increase in COX-2. They also observed that testosterone levels fell as age increased. The hypothesis was/is that it was the increase in COX-2 that caused testosterone levels to drop. To test this hypothesis they used a COX-2 inhibitor to block/reduce COX-2 and found that testosterone levels increased in a dose-dependant manner (stronger COX-2 inhibitor dose = more testosterone produced by leydig cells).

I do not know if reducing inflammation in general would be helpful. I do know that many aging-related diseases (heart disease, alzheimer's) are thought to be inflammation related.

Google Bee Propolis - Lots of info out there and I am not an expert.

I have no idea about Curcumin dose or Propolis dose. There have been studies comparing COX-2 inhibitors with Curcumin. It's possible that you could extract dose info from these studies.

Both Curcumin and Bee Propolis are available as oral supplements. I bought Dr's Best Curcumin with Bioperine and Twin Lab's Propolis.

Are COX-2 inhibitors dangerous? My wife takes
Celebrex as part of her rheumatoid arthritis treatment. Her MD thinks that it is the population of COX-2 inhibitor users that is the issue, not the medicine itself. For example, if you have a population of people who are more prone to cardiac events in the first place, how can you really say that it was the medicine that caused the issue.

That said, I would not run out a get a script for Celebrex (unless you need the medicine).


Thx for all the info. Let us know if you think it helped T-levels, etc.


There are probably safer ways to increase endogenous total and free testosterone.

The long-term use of COX-2 inhibitors might turn out like HRT for post-menopausal women. Good for MIs but bad for strokes.

When they do cost-benefit analysis, slight increased risk of heart disease vs less pain and inflammation in Rheumatoid Arthritis is quite different then slight increase risk of heart disease vs slight increase of testosterone levels.

People here seem to enjoy their Alpha Male/Red Kat/ZMA stacks.

We can't say for sure its safer one way or the other, but considering that COX-2 is and inducible enzyme basically found everywhere dealing with a very important process such as inflammation as opposed as what mild increases in testosterone might do.



Well, I was really curious about the possible curcumin connection. They've found many health benefits of it and the idea that it might decrease inflammation and increase T-levels (however slightly) only increased my curiosity further...


I understand,

hell, I even have a bottle of curcumin. I put some on a lot of things, but the reasearch indicates that it does wonderful things, just like polyphenols in fruit or green tea and all the healthy what-have-you's. So in the end, what we get in our curcumin spice is not the same thing concentration wise as what they use in research labs and then there is the oral bioavailability which might be problematic.

Too many cool things coming out of labs, just not all that useful yet!



True: you'd probably have to smoke it or eat a pound of it...