Explanation of Negative Pathology in Older Childhood / Adulthood Caused by Radio- and Chemotherapy of Childhood Cancers: Reduced testosterone and Dehydroepiandrosterone (DHEA) and Why This is Decreasing.
Copyright 2017, James Michael Howard, Fayetteville, Arkansas, U.S.A.
This is a well-known phenomenon which is well explained in these two, new reports: Cancer Medicine Volume 6, Issue 5 May 2017 Pages 1123–1134 AND Ann Pediatr Endocrinol Metab. 2017 Jun;22(2):82-89.
I propose that the basis of subsequent older childhood / negative adult outcomes following childhood treatment with chemotherapy and radiotherapy is reduced dehydroepiandrosterone (DHEA) and testosterone.
It is my hypothesis that mammals evolved because of selection for dehydroepiandrosterone (DHEA). (Hormones in Mammalian Evolution, Rivista di Biologia / Biology Forum 2001; 94: 177-184 ). This is based on my hypothesis that evolution selected DHEA because it optimizes replication and transcription of DNA. DHEA affects expression of genes. Therefore DHEA levels affect all tissues and the life span. DHEA is important to genes producing libido for initiation of conception in order to function in optimal maintenance of pregnancy. Selection pressure within Mammalia for testosterone produced primates and, with exaggeration, humans. I think testosterone increases cellular absorption of DHEA by increasing androgen receptors through which DHEA enters cells. The selection is basically selection for additional cellular DHEA because of testosterone. Estradiol was selected because of the same mechanism, however, testosterone simply is more effective. Testosterone and DHEA act together. (If you, et al., desire more detail of this: DHEA, Estradiol, Testosterone, and the Relevance of Their Ratio The Androgen Receptor and the Secular Trend, at: http://anthropogeny.com/Androgen%20Receptor%20and%20Secular… .) This is a sexual selection, of course, but the side-effects of increased DHEA in mammals and further enhancement of DHEA caused by further, increased sexual selection caused by testosterone caused the big brains of mammals and the enhanced big brains of Homo sapiens.
This combination of androgens also involve all other tissues, including the tissues affected in child cancer survivors with age and maturity.
For sake of brevity I can demonstrate that anthracyclines, for example, adversely affect testosterone levels. (This is mentioned in Chueh, et al., (above) but does not suggest causality.) Also, it is known that radiation reduces DHEA.
I submit the consequential effects on children affected by radio- and chemotherapy result from this reduction of testosterone and DHEA. Once cancer is successfully treated, treatment with testosterone and DHEA may allow normal older child / adult growth and development.
It has been reported that “Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but have also reduced the incidence of serious chronic morbidity in this population.” (Journal of Clinical Oncology 2017: “Temporal trends in chronic disease among survivors of childhood cancer diagnosed across three decades: A report from the Childhood Cancer Survivor Study,” Gibson, et a.) It is also my hypothesis that the biological secular trend, the increase in child size and earlier puberty, is increasing. I think this trend is caused by increasing testosterone within populations. This could add to decreases in negative treatment outcomes in children treated for cancer now than in the past by increasing testosterone levels at puberty subsequent to reductions in testosterone caused by cancer treatment.