Statins, DHEA, and Testosterone … A Mechanism

Copyright 2019, James Michael Howard, Fayetteville, Arkansas, U.S.A.

I suggest the basis of these findings is increased dehydroepiandrosterone (DHEA) availability.  This is derived from reductions in sulfatase activity caused by statin use (Hepatology. 2012 Jun;55(6):1746-53).  I suggest this effect increases DHEA, the active molecule, by reducing DHEAS (sulfate), the inactive molecule.

It is my hypothesis that evolution selected dehydroepiandrosterone (DHEA) because it optimizes replication and transcription of DNA, that is, genes.  Therefore, DHEA levels affect all tissues and all tissues compete for available DHEA, especially the brain.  (I think evolutionary selection of DHEA produced Mammalia.  "Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94: 177-184, http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm  ).  DHEA naturally begins to decline around the ages of twenty to twenty-five, reaching very low levels in old age.  When DHEA is low, or decreasing, genes and tissues are adversely affected according to competition for DHEA resulting in disturbances of gene functions; when DHEA is too low, death occurs.  Statins exert their positive effects by increasing DHEA, especially in pathological conditions and aging.

I suggest Primates evolved from Mammalia because of natural selection for testosterone.  This effect was selected by evolution because of its effect on availability of, and direction of tissue use of, DHEA caused by increased testosterone.  (It is proven, for example, that human male and female testosterone is higher than chimpanzee male and female testosterone.  Estradiol levels are similar between the species.)   Since testosterone reduces available DHEA, it is known that testosterone levels are highest in humans while DHEA is is highest in the great apes.  

It is part of my work that DHEA and testosterone work together to control growth and development, especially in humans (It is my hypothesis that human evolution is driven by increases in testosterone levels. This is identifiable as the ongoing biological secular trend.    Increased testosterone increases androgen receptors which increase intracellular DHEA.  This increased testosterone in Homo is the basis of the characteristics of Homo sapiens. ("Androgens in Human Evolution," Rivista di Biologia / Biology Forum 2001; 94: 345-362.  If your library does not subscribe to "Rivista ... ," you may find this at: http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm where you may also see a chart of testosterone in humans and great apes which directly supports my hypothesis and was reported in the literature 2 years later.)  

Testosterone is known to increase sulfatase activity.  Statins reduce sulfatase activity because statins reduce testosterone levels.  This is why statins cause reductions in male libido.

For further sake of demonstration, I first suggested that low DHEA was involved in the formation of Alzheimer's disease in 1985; the first reports of low DHEA in AD appeared some years later.  Subsequently, I identified the involvement of testosterone in human evolution which produced our large brains.  This indicates to me that both testosterone and DHEA reductions of aging should be involved in appearance of AD; this is supported.  Therefore, depending upon one's loss of either testosterone or DHEA, statins should produce both positive and negative effects on AD.  This has recently been reported: "The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms," (Transl Neurodegener. 2018 Feb 27;7:5. doi: 10.1186/s40035-018-0110-3 ).

If you are still with me, thank you; Statins exert positive effects because they increase dehydroepiandrosterone (DHEA).  This why "low adherence to statin therapy was associated with a greater risk of dying" ( JAMA Cardiol. 2019; doi: 10.1001/jamacardio.2018.4936)

James Michael Howard
Fayetteville, Arkansas, U.S.A.
www.anthropogeny.com