Thrombosis May Be Caused by Low DHEA

Thrombosis May Be Caused by Low DHEA

The biological mechanism may be that loss of blood, that is loss of DHEA, may be the trigger for clotting. The “problem” is the mechanism is triggered by pathological situations characterized by low DHEA.

It is my hypothesis that thrombogenesis results from low levels of dehydroepiandrosterone (DHEA). DHEA naturally begins to decline around age twenty, reaching very low levels in old age. Thrombosis is "markedly higher in elderly than in younger patients," (Arch Intern Med. 2004 Nov 8;164(20):2260-5). Hormone replacement therapy and "estrogen replacement therapy" both reduce DHEA (Metabolism. 2001 Apr;50(4):488-93). Thrombosis is increased by "estrogen plus progestin" hormone therapy (JAMA. 2004 Oct 6;292(13):1573-80). Extended use of oral contraceptives increases risk of thrombosis (Clin Appl Thromb Hemost. 2004 Jul;10(3):259-63).

DHEA is also low in the very young. Also, testosterone may reduce DHEA by increasing DHEAS. DHEAS is the background source of DHEA, from which DHEA is converted. In some circumstances such as the effect of testosterone on DHEAS, this may indicate that DHEA levels are reduced when DHEAS increases. These effects of low DHEA are seen this report: "Pulmonary embolism (PE), deep venous thrombosis (DVT), and the combination were not rare in pediatric patients in the United States from 1979 to 2001. They were more frequent in infants 0 to 1 year of age and in teenagers 15 to 17 years of age than in children 2 to 14 years of age. Pregnancies doubled the rate of DVT in teenage girls." (J Pediatr. 2004 Oct;145(4):563-5). Thrombosis may be increased in infants because of low DHEA. Once puberty occurs, in boys and girls, testosterone increases and reduces DHEA levels and may account for the increase in the teenagers who have reached puberty compared to children "2 to 14 years of age." Pregnancy is a time when maternal DHEA is shared between the mother and the fetus. This would reduce maternal DHEA and increase the risk of thrombosis. It is known that thrombosis is increased in pregnancy and "may be higher in the second and third trimesters." (Am J Obstet Gynecol. 2004 Aug;191(2):412-24). If fetal growth is dependent upon maternal DHEA, then thrombosis should increase with fetal growth from the first through the third trimester and then decline with time postpartum. This has been found: "The deep vein thrombosis event rate during the first trimester was 21.9 percent (95 percent CI 17.4 to 27.3), 33.7 percent (95 percent CI 28.1 to 39.8) during the second trimester, and 47.6 percent (95 percent CI 39.2 to 56.2) for the third trimester. Heterogeneity testing was not significant. Nine studies compared deep vein thrombosis events between the antepartum and puerperium periods, with 65.5 percent (95 percent CI 58.1 to 72.1) arising during pregnancy, and 34.5 percent (95 percent CI 27.9 to 41.9) postpartum (P = .08, not heterogeneous). Using these figures, the estimated relative distribution of 100 deep vein thrombosis events during pregnancy and the puerperium would be 0.23 per day during pregnancy, and 0.82 per day in the postpartum period. During pregnancy and the puerperium, deep vein thrombosis is more likely to arise in the left leg. More than half of all deep vein thromboses during pregnancy occur during the first and second trimesters. Furthermore, during the puerperium, the risk of developing deep vein thrombosis is significantly higher than antepartum." (Obstet Gynecol Surv. 1999 Apr;54(4):265-71).

It is my hypothesis that low DHEA may cause cancer. DHEA is low in the elderly and cancer occurs more often in the elderly. Thrombosis is often found with cancer and increased with metastatic disease (J Thromb Haemost. 2004 Oct;2(10):1760-5). I suggest that once started, cancer is able to use available DHEA for growth at the expense of the host, thereby reducing DHEA overall. Therefore, metastasis may further decrease DHEA levels and further increase thrombosis.

Low DHEA has been connected with increased thrombosis in some form in the past (Acta Chir Scand. 1985;151(6):515-9). Cortisol, which I suggest evolved to counteract DHEA, may participate in thrombosis formation. I suggest that the major cause of thrombosis is low dehydroepiandrosterone.