Study Potentially Harmful Effects of Persistently Elevated LH

[CFC]

At first glance, this study on rodents and analysis centered on women may not seem relevant to male bodybuilders. However, bear with me - the findings contained within suggest it may be mechanistically applicable to both male and female populations.

The theory being developed here suggests that persistently elevated LH levels - such as happens in primary hypogonadism as a result of AAS, and as is intentionally recreated by men during PCT with SERMs - may be partially responsible for a decline in cognition, reduction in spinal nerve density, and subsequent onset of Alzheimer's Disease, independently of altered oestrogen levels (which research already suggests to be neuroprotective in AAS-using bodybuilders).

To quote from the study:

Independent of the ability of estrogens to regulate cognitive and neuronal function, increasing data support a role for LH on cognition. In this regard, serum LH levels are higher in Alzheimer’s disease (AD) patients (Short et al. 2001; Butchart et al., 2012), are associated with increased AD pathology in men (Verdile et al. 2008; Verdile et al., 2014) and cognitive dysfunction in older women (Rodrigues et al. 2008). In rodents, pharmacologically lowering LH levels with leuprolide acetate, a GnRHR super-agonist, is as effective as E2 replacement at improving cognitive function in ovariectomized mice (Bryan et al., 2010) as well as in AD models (Casadesus et al., 2006, Palm et al. 2014). Benefits of reducing serum LH levels on cognition have also been shown using the classic GnRHR antagonists such as antide in male and female rats (Ziegler et al. 2010, McConnell et al. 2012) and cetrorelix in rats and mice (Telegdy et al., 2009; Telegdy et al., 2010). Given the different mechanism of action of these drugs, but common end result (i.e. lowering LH levels), this suggests that peripheral LH rather than GnRHR signaling is associated with cognitive benefits.

What we are starting to understand is that hormones like LH/FSH are not merely passive gonadal signalling mechanisms, but instead may be far more important to our general state of health (both physical and mental) than previously appreciated. Thus persistent elevations in their levels due to hypogonadism may be harmful and not helpful, especially in the presence of lowered sex hormone levels.

For any bodybuilder, but especially those who've risked doing blast-cruise or high-dose cycles for long periods, subsequent abnormally low test/E2 levels and elevated LH/FSH may thus be a portent of an increased risk of long-term neurological damage.

Clearly more research is needed before we can begin to draw anything like firm conclusions, but it's yet another indication that the insensible and/or abusive use of AAS may be leading to further unintended long-term harms that nobody is discussing.

Study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718885/

 

[Serotonin101]

Could you argue it would be beneficial for those on Dr prescribed trt with hcg to drop the hcg?

 

[CFC]

That's a great question. Off the top of my head, I guess it depends on a few factors like: (a) whether hCG (as an analogue of LH with other subunits) actually causes a similar neuronal effect as endogenous pituitary LH (we'd assume it should, but it would still need proof*), and (b) the dose of hCG being given - we'd expect low doses (say 125iu ED/250iu EOD or so) that produce a physiologically equipotent effect to normal-range LH with concomitant physiological test/E2 levels, to be safer than LH levels that go well beyond normal, as is the case in higher doses of hCG.

There's also the bigger picture to consider - some people respond very well to elevated hCG + TRT (eg post drug recovery, depression etc); it could be a trade-off worth tolerating in those limited instances, though personally I'd probably still want to err on the side of caution and avoid hCG if I'm also on TRT. The short-term boost isn't likely to be worth the increased dementia risk in the long-run.

*https://www.ncbi.nlm.nih.gov/pubmed/20844010/ (this does suggest hCG is also deleterious)

 

[Artificial Emotion]

I did one cycle where I took hCG to maintain testicular size during the cycle so do you think I would be at increased risk or do you think I didn't use it for long enough to do any damage?

 

[CFC]

Nah, the risk is likely to be about long-term elevations of LH - a month or two is probably ok assuming there's a decent amount of time off after.

Having said that, if a harsh or long cycle causes some mild long-term primary hypogonadism, it's potentially compounding whatever minor harm may have been caused by the hCG on cycle (ie not really allowing 'recovery').