Danish study that had data altered prior to publication. The original data showed decreasing Autism rate in Danish children after removal of thimerosal from their vaccines
Interesting cohort of Danish and Finnish men. What is interesting is that in both groups, men born earlier in the 20th century were found to have higher testosterone levels. As the year of birth advanced, there were declines in Testosterone, LH, and higher SHBG.
lower levels of SHBG and serum testosterone were found in more recently born men. Preceding generations of men produced higher testosterone levels than men born in more recent generations.
2012 study that shows a slight uptick in sperm count/concentration in Danish men. However, as the conclusion states, on 25% have optimal sperm quality. When you look at the numbers deeper, the current general population sperm count/concentration was lower than that of men of infertile couples from 1940-1943 cohort. Additionally, when the general population sperm count/concentration was lower than that of compared recent fertile men.
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Nembutal Liquid Pentobarbital (trade name: Nembutal) is a drug from the barbiturate class. It was widely used during the 1940s and 1950s as a sleeping pill (i.e. hypnotic) or anti-anxiety drug (i.e. sedative). Unlike modern sleeping pills, Nembutal is highly lethal in overdose. Because it is very reliable and brings about peaceful death, it is one of drugs of choice for assisted suicide. Nembutal is used by euthanasia organizations in the United States (Oregon Death With Dignity Act), Switzerland (Dignitas) and The Netherlands.
Nembutal Liquid Since it was so easy to overdose on Nembutal (whether accidentally or intentionally), it was almost universally taken off the market and replaced by safer sleeping pills. Nembutal was removed from the Australian prescribing schedule in 1998. However, Nembutal remains in use by veterinary surgeons in order to euthanase bigger animals. Many people were successful in obtaining veterinary Nembutal for their suicide. The famous American actress Marilyn Monroe supposedly used Nembutal to end her life.
The brand name "Nembutal" was coined by Dr. John S. Lundy, who started using it in 1930, from the structural formula of the sodium salt-Na (sodium) + ethyl + methyl + butyl + al (common suffix for barbiturates). Nembutal is trademarked and manufactured by the Danish pharmaceutical company Lundbeck
2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
No significant associations have been observed between 2-OH estrone and breast cancer risk
In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
better worded is no consistent, significant associations. There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
No significant associations have been observed with the 2:16α-OH estrone ratio
In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
The risks of estrogen metabolism are not clear cut. Likely never will be due to the complexity of individual metabolism. This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer. Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism. There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.