INDEX

Breast Cancer DHEA Testosterone 2023

"Down's Syndrome, Trisomy 21, Dehydroepiandrosterone (DHEA), and DNA Methylation: a Possible Explanation," and "Covid-19 is Cause of Current Increased Virulence of RSV and Influenza" are below.

Covid-19 Infection and Subsequent Pathology are Caused by

Low Dehydroepiandrosterone (DHEA)

(New support: Low DHEA in Covid-19)

New research, 2022, regarding DHEA has been published that supports my hypothesis that Covid-19 is caused by low DHEA: “COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity,” ( Endocrine volume 78 2022 Jul 30. doi: 10.1007/s12020-022-03140-6.) “DHEA was an independent indicator of the disease severity with COVID-19.”

It is my hypothesis that Covid-19 infection and subsequent pathology are caused by low levels of dehydroepiandrosterone (DHEA) which are affected by aging, testosterone and cortisol levels, and antagonism of DHEA by cortisol as in stress, all of which reduce effects of DHEA (© Copyright 2020, James Michael Howard, Fayetteville, Arkansas, U.S.A.). It is already known that DHEA provides protection from pathogenic viruses. “In this study it was shown that DHEA protects mice against WNV, SVNI and SFV lethal infection.” (Arch Virol. 1991;120(3-4):263-71. doi: 10.1007/BF01310481.) High testosterone levels affect DHEA levels by decreasing available DHEA by reducing conversion of DHEA sulfate to the active form, DHEA, and low testosterone levels reduce intracellular DHEA; both reduce DHEA. This is why high levels of testosterone in males and high levels of testosterone of blacks compared to whites increase Covid-19 virulence, therefore, drugs such as dexamethasone, which is known to reduce testosterone reduce Covid-19 This is why reduced DHEA and testosterone of aging increases Covid-19 virulence.

Regarding the “cytokine storm” in Covid-19 infection, a case may be made that these cytokines are produced by cells / tissues to stimulate DHEA production. Therefore, the reduction in DHEA caused by Covid-19 would cause numerous tissues to produce cytokines to stimulate DHEA. Individuals who do not recover significantly by eventually producing DHEA experience “long covid.”

This is derived from my explanation of human evolution involving DHEA (mammalian evolution) and human evolution involving DHEA and testosterone. I suggest testosterone directly affects levels of DHEA and testosterone is increasing throughout human history and is ongoing. At this time I think testosterone has increased in human populations sufficiently to adversely affect DHEA levels. I suggest this is why human populations are experiencing increases in obesity, type 2 diabetes, cancer, infections, at this time, including Covid-19. (Note: some consider obesity as the cause of the others; obesity is simply the earliest sign.)

Since I think these androgens and their ratio control all aspects of the human life span, I think they are involved in all aspects of normal ontogeny as well as pathology. I suggest this is why Covid-19 has been connected with many pathologies as well as disturbances in cytokines, including “hypertension, diabetes, obesity, COPD, and CVD.”

As I stated above, I think testosterone is increasing with time within populations; an over abundance of testosterone can reduce the effects of DHEA and this is why pandemics are occurring, such as the HIV and others at this time. This is why Covid-19 is occurring at this time and is directly connected to other pathology. They are both caused by low DHEA.

“Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your library does not subscribe to “Rivista … ,” you may find this at: http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .

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.

New connections of low DHEA and Covid-19, January, 2023: Low DHEA has been found in “burning mouth (BM),” (Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Oct;108(4):537-43. doi: 10.1016/j.tripleo.2009.06.022. PMID: 19778740.). “Glossodynia [burning mouth] is significantly more common in COVID-19 patients and should be considered in the differential diagnoses among the oral complications of this infection.” (Am J Dent 2022;35:9-1. 2022 Feb;35(11) :9-11

I invite you to read my explanation of Down’s Syndrome which includes a direct explanation of the connection of maternal age in the etiology.

Down's Syndrome, Trisomy 21, Dehydroepiandrosterone (DHEA), and DNA Methylation: a Possible Explanation

© Copyright 2020 James Michael Howard, Fayetteville, Arkansas, U.S.A.

The cause of Down's syndrome (DS) may be low levels of maternal dehydroepiandrosterone (DHEA) in utero. This includes DNA associated characteristics as well as the chromosome 21 aneuploidy. ("DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031)." Reprod Biol Endocrinol. 2010; 8: 140.
Published online 2010 Nov 10. doi: 10.1186/1477-7827-8-140 ) DHEA naturally peaks around ages of 20-25 years, declining, thereafter, to very low levels in old age. DS is characteristically found in offspring of women 35-years-old or later. The “DNA associated characteristics” are the basis of my explanation of DS. (This is derived from my explanations of mammalian and human evolution; citations for these are at the end of this treatise.)

I think DHEA is directly involved in all DNA, gene, activity. A ratio of DHEA and DNA is disturbed by increased DNA, extra chromosome 21, in Down’s syndrome, that is, the ratio of DHEA to DNA is reduced. This may be demonstrated by DNA methylation patterns. I first suggested DHEA is involved in DNA methylation in 2015. "I suggest DNA methylation is an evolutionary consequence of reduced levels of dehydroepiandrosterone (DHEA) and is involved in cancer initiation." ("DNA Methylation, DHEA, and Cancer," http://anthropogeny.com/DNAmethDHEAcancer.html ) Again, DHEA naturally begins to decline in women around ages 20-25. reaching very low levels in old age; I suggest it is the low DHEA of women around age 35 that is the cause of Down syndrome. Low DHEA has been reported in Down's syndrome J Neuroendocrinol. 2011 May;23(5):450-5. doi: 10.1111/j.1365-2826.2011.02118.x ).

A study of DNA methylation in DS reported that "Overall, our results indicate that the chorionic villi cells of DS [Down syndrome] fetuses are hypermethylated in all autosomes and suggested that altered DNA methylation may be a recurrent and functionally relevant downstream response to DS in human cells." ( Clin Epigenet 11, 180 (2019). https://doi.org/10.1186/s13148-019-0756-4 ). This means that all of these chromosomes may be affected by the low DHEA to DNA ratio in DS.

I suggest the low ratio of DHEA to DNA is the cause of Down’s syndrome aneuploidy and the resultant characteristics of Down's syndrome. Measurements of, and adjustment thereof, DHEA in pregnant women, or those intending to become pregnant, should be performed on all women. (For sake of support, low DHEA in young women has been determined to reduce pregnancies.)

“Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your library does not subscribe to “Rivista … ,” you may find this at: http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .

“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.

Covid-19 is Cause of Current Increased Virulence

of RSV and Influenza

I suggest the basis of increased virulence of Respiratory Syncytial Virus and influenza at this time is reduction of dehydroepiandrosterone (DHEA) caused by Covid-19. It is my hypothesis that Covid-19 infection and subsequent pathology are caused by low DHEA. Support of low DHEA associated with Covid-19 virulence has recently been reported. It has been determined that DHEA stimulates / increases antibody formation in aged mice: “When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration.” (The Journal of Infectious Diseases No. 4 (Apr., 1993), pp. 830-840 ).

I submit the Covid-19 pandemic has reduced DHEA throughout the world, which has reduced the antibody response to RSV and influenza. I suggest this is the cause of the ongoing increase in RSV and influenza. This may also explain the common increase in Covid-19, influenza, and RSV in the United States at this time. We may have discarded our prophylaxis of Covid-19 infection too early.

Further support and regarding the current increase in Respiratory Syncytial Virus: It has been reported that “High PRL [prolactin] serum level or hyperprolactinemia is associated with different viral infections.” (Mol Cell Biochem 477, 1381–1392 (2022). https://doi.org/10.1007/s11010-022-04381-9 )

Prolactin is a direct and specific stimulant of DHEA; high PRL indicates an immune response to increase DHEA. “there seems to be a correlation between prolactin signalling and severity of infection [RSV]” (“Respiratory syncytial virus (RSV): a scourge from infancy to old age,” BMJ “Thorax” https://doi.org/10.1136/thoraxjnl-2018-212212 )

INCREASE IN AUTISM RATES reported around January 25, 2023. … another case of effects of low dehydroepiandrosterone (DHEA) caused by Covid-19. (© Copyright 2023, James Michael Howard, Fayetteville, Arkansas USA)

It is my hypothesis of 2003 that high maternal testosterone causes Autism by reducing available DHEA for growth and development of the brain. “The Increase in Autism in California (which [was] is also occurring in other areas),” https://anthropogeny.com/increase%20in%20autism.htm . At the time a large increase in autism frequency was being reported in California. It was also considered to be by enhanced diagnoses. I explained that a mother of high testosterone uses available DHEA at the expense the child and that the 2003 autism increase in California was caused by increased maternal testosterone within the population.
I am suggesting here that Covid-19 reduced these mothers’ DHEA which is causing increasing autism at this time.
My identification of high maternal testosterone has recently been supported.
“SARS-CoV-2 infection indicated an increased risk of preterm delivery (p<0·05) and stillbirth (p<0·05), accounted for primarily by first and second trimester SARS-CoV-2 infections.” (“The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study,” (he Lancet Digital Health, ISSN: 2589-7500, Vol: 4, Issue: 2, Page: e95-e104
Publication Year2022 )
“Findings provide support for direct involvement of maternal hyperandrogenemia in ASD [autism spectrum disorder] etiology. Alternatively, findings might reflect shared genetic and/or environmental factors independently affecting maternal androgen homeostasis and fetal neurodevelopment.” (“Associations of Maternal Androgen-Related Conditions With Risk of Autism Spectrum Disorder in Progeny and Mediation by Cardiovascular, Metabolic, and Fertility Factor,” American Journal of Epidemiology, Volume 190, Issue 4, April 2021, Pages 600–61.

A Basis of Breast Cancer Based on Dehydroepiandrosterone (DHEA) and Testosterone; Expanded

Two recent citations regarding connections of "urban," "rural,"neighborhood," and "racial" with breast cancer may support my explanation of female breast cancer. "Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio," (Breast Cancer Res Treat (2023). https://doi.org/10.1007/s10549-023-06883-6) and "Urban–Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence," (J Urban Health (2023). https://doi.org/10.1007/s11524-023-00718-x)

These 2023 reports regarding breast cancer both consider urban / rural / socioeconomic connections, and race with breast cancer. I suggest these may be explained by the ratio of the androgens dehydroepiandrosterone (DHEA) and testosterone, as I suggested in 1994. Rural / urban areas are characterized by testosterone levels: higher in urban areas.

It is my hypothesis of 1994 that increased testosterone increases breast cancer, as well as other cancers, (International Journal of Cancer 2005; 115: 497). This also explains why breast cancer is increasing; it is my hypothesis that women of higher testosterone are increasing in percentage within populations with time. I also suggest the biological "secular trend," the increase in birth weight and earlier puberty in children is caused by increases in women of higher testosterone. The secular trend is occurring in many places in the world.

The causal mechanism involves testosterone's effects on levels of dehydroepiandrosterone (DHEA). That is, high and low testosterone affect availability of DHEA. I think reductions in DHEA result when increased testosterone occurs early in puberty and and this may occur in the lower socioeconomic levels. Increased testosterone has been connected with reduced learning ability, reduced impulse control, sexuality, and increased negative medical outcomes. All of these reduce the ability to obtain gainful employment and participation in societies increasingly dependent upon advanced educational achievement and personal control. This would concentrate this type of individual within these levels. The concentration mechanism is a higher percentage of females of higher testosterone within these populations.

A report comparing rural areas and a large city found that testosterone is higher in the large city (Folia Histochem Cytobiol. 2001;39 Suppl 2:38-9). This is further supported in American Journal of Human Biology. 2006;18(1):123132: "Men in the most urban group had higher testosterone levels than among groups of farmers and men in informal housing rural areas."

“Black mothers had higher androstenedione and testosterone
concentrations than white mothers.” (Cancer Causes Control 2003; 14: 347-
55) "Serum testosterone was modestly, but significantly, greater in the
black than in the white women." (J Clin Endocrinol Metab 1996; 81: 1023-6.

I suggest increased testosterone may be higher in the lower socioeconomic levels. Again: Increased testosterone has been connected with reduced learning ability, reduced impulse control, sexuality, and increased negative medical outcomes. All of these reduce the ability to obtain gainful employment and participation in a society increasingly dependent upon advanced educational achievement and personal control. This would concentrate this type of individual within these levels. The concentration mechanism is a higher percentage of females of higher testosterone within these populations.

I think testosterone can adversely affect available DHEA in two ways. High testosterone can reduce sulfatase activity. This would reduce conversion of the background source of DHEA, DHEA sulfate, to the active form, DHEA. I think testosterone increases intracellular DHEA by increasing androgen receptors, primarily in the brain. Low testosterone would reduce androgen receptors and reduce intracellular DHEA.

At puberty, testosterone increases which increases growth and development of brain and body in preparation for reproduction. Excess high testosterone at puberty can reduce DHEA and increase the initiation of breast cancer. This could cause earlier breast cancer in black women than white. "Among younger women, Black and non-Hispanic Black women have higher rates of breast cancer compared to white and non-Hispanic white women. Among older women, white and non-Hispanic white women have higher rates of breast cancer compared to Black and non-Hispanic Black women." (https://www.komen.org/breast-cancer/risk-factor/race-ethnicity/ ).

Since testosterone increases intracellular DHEA, the higher testosterone of black women may extend this mechanism into older ages, whereas, in older white women, this would result in reduced intracellular DHEA.

Testosterone levels affect DHEA availability.

The mechanism I produced in 1994, is based on exposure of oncogenes. I suggest DHEA levels positively affect cell adhesion. Reduced DHEA would reduce cell adhesion. Reduced cell adhesion would expose cells of tissues to increased individual cellular surface area. This would expose some tissue cells to increased nutrient availability as well as to increased DHEA. In a reduced DHEA situation within the body, I think this exposure of increased cell surface would significantly increase relative levels of DHEA, compared to their normal tissue state. I suggest this would expose cells containing oncogenes to increased viability. Oncogenes could become active.

High testosterone of an earlier age could reduce DHEA which would reduce cell adhesion which would increase possible oncogene activity. High testosterone would be selected by evolution because it would increase the onset of puberty and sexual activity.

Early, high testosterone would result in earlier puberty and result in an earlier, larger subsequent decline of testosterone. It is known that both DHEA and testosterone are reduced by pregnancy. Since testosterone is involved in increasing intracellular DHEA, an earlier, deeper decline in testosterone would also reduce available DHEA and the exposure of oncogenes. In men "A dose-dependent maintenance of mRNA concentration for E-Cad was observed throughout the epididymis of orchidectomized rats after replacement with testosterone." ( Endocrinology, Volume 130, Issue 1, 1 January 1992, Pages 353–363, https://doi.org/10.1210/en.130.1.353 ) DHEA was not mentioned in this report.

DHEA naturally declines with age, reaching very low levels in old age. "Age is the highest risk factor for developing a majority of cancers, with a few exceptions." (https://www.roswellpark.org/cancertalk/202006/does-cancer-risk-increase-age ).

James Michael Howard, Fayetteville, Arkansas, USA

The importance of DHEA and Testosterone to Human evolution. I think mammalian evolution occurred because of selection for DHEA and human evolution because of selection for testosterone because testosterone increases intracellular DHEA primarily in the brain. This caused "gracilization," the increase in brain size at the expense of the body, a hallmark of human evolution. This is seen in the fossil record in Homo erectus in which sexual dimorphism is reduced by increased female size without a decreased male size. The increase in female size is the key evolutionary change. Increased female testosterone directly affected fetal brain growth and development.

("Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your library does not subscribe to "Rivista ... ," you may find this at: http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .)

(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.)