Selectivity of SARMS and pathological left ventricular hypertrophy
A commonly touted line is that SARMs act on skeletal muscle tissue and leave all of your other organs alone (and the heart, in particular). Is this really true? We know that SARMs don't affect blood pressure and RBC and have a small but real effect on blood lipids.
So here's a really important question: do SARMs pathologically hypertrophy the left ventricle of the heart?
Every study I could find on SARMs measures acute proxies of heart health such as lipids, BP and RBC. A few studies used an EKG, but those studies were of short duration. EKG is also not sufficient to detect pathological left ventricle hypertrophy: an echocardiogram is required.
From what I've read, pathalogical ventricle remodeling of the heart is due to:
- i) Cardiomyocyle hypertrophy
- ii) Myocardial fibrosis
- iii) Changes in gene expression
I'm not sure about how ii) happens. If you have information, please share! According to what I've read (e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768197/), myocardial fibrosis is common in steroid users and steroids cause fibrosis in studies (https://academic.oup.com/cardiovascres/article/79/4/652/344504, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560513/). However, I also found this study which says that "testosterone may attenuate cardiac fibrosis.." (http://www.internationaljournalofcardiology.com/article/S0167-5273(14)02221-9/pdf). This is consistent with what I've read about very low-testosterone populations and heart disease: testosterone treatment can be beneficial in highly testosterone deficient men with advanced heart disease, but that's at very physiological levels.
Note that exogenous testosterone and other AAS have been shown to lead to pathological ventricle remodeling, even in the absence of increased blood pressure / RBC. We obviously know that extended periods of hypertension lead to pathological LVH.
Based on this manuscript, SARMs method of tissue selectivity is almost certainly due to the fact SARMs do not act as a substrate for 5-alpha-reductase. So in one sense, we may be able to think of SARMs as like testosterone, but without aromatization and without 5-alpha-reductase. But what I can't figure out is whether or not we would then expect cardiomyocyte hypertrophy from SARMs.
There's some other interesting related results here, such as:
- Heart contains receptors for dihydrotestosterone but not testosterone: Possible role in the sex differential in coronary heart disease -- https://onlinelibrary.wiley.com/doi/pdf/10.1002/ar.1092230410. tl;dr: circulating DHT, not testosterone, is the androgenic hormone that interacts with the cardiovascular tissue of the baboon.
- Testosterone, Dihydrotestosterone, and Incident Cardiovascular Disease and Mortality in the Cardiovascular Health Study -- https://academic.oup.com/jcem/article/99/6/2061/2537684. tl;dr: DHT and calculated free DHT were associated with incident CVD and all-cause mortality, NOT T.
- Anti-Androgenic Therapy with Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction -- http://circ.ahajournals.org/content/circulationaha/early/2015/01/28/CIRCULATIONAHA.114.012066.full.pdf. tl;dr: In vitro study of heart tissue shows that T and DHT both lead to cardiomyocyte hypertrophy, but when finasteride is also given there is no cardiomyocyte hypertrophy.
On one level, it sort of makes sense that an anabolic would hypertrophy the heart, as it's a muscle. And the left ventricle has more androgen receptors than the right ventricle, so we might expect a pathological hypertrophy. But the above studies may indicate that in the heart, DHT is the primary androgen, similar to what we see in the prostate. So in this case, we might expect SARMs to act similar and leave the heart mostly alone.
I would absolutely love everyone's thoughts on this! I think this is a really important topic and given the lack of hard evidence (as far as I know?) on heart health and SARMs, we definitely need to be discussing this as much as we can!
- Please note that pathological left ventricle hypertrophy is different from the usual cardiovascular hypertrophy you would expect to see in strength trained athletes (e.g. 'athlete's heart). See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905938/, https://academic.oup.com/ehjcimaging/article/10/3/350/2396955,
- Cardiomyocyte hypertrophy and changes in gene expression can be seen in vitro with cardiomyocyte and testosterone in e.g. http://circ.ahajournals.org/content/circulationaha/early/2015/01/28/CIRCULATIONAHA.114.012066.full.pdf (see figures). We also see AAS users having a much higher incidence of pathological LVH than non-AAS using strength athletes, etc -- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768225/