Hi Dandelion, how's everything? Hope the bleeding has stopped.
I have been reading about cross tolerance and as I suspected it's not just progesterone that has GABAergic modulation properties. Estradiol also interferes with GABA receptors.
This article is interesting because it shows that estradiol can interfere with neurons by altering responses to GABA receptors, but more importantly, this interaction can happen in both ways, negative and positive feedback, dependent on the time of day, am v pm.
It's a very complex subject and it's been studied in mice, which can be genetically modified, but it's a solid evidence that it's not just progesterone that has a modulating effect on GABA A receptors. The evidence is that the authors used Diazepam to manipulate GABA A receptors apparent affinity. ' We use the term apparent affinity to describe the effect of diazepam on GABAARs because the detailed mechanisms of action of diazepam remain elusive, and the traditional mechanism of diazepam increasing “receptor affinity” may not be the only consequence of activation of the benzodiazepine site.'
The bottom line is that you don't need to be focused on progesterone levels, it's more important to keep both estradiol and progesterone in balance, which is a huge task, but I think you can achieve that by slowly tweaking the doses. It's also interesting that you can switch the time when you apply estradiol gel to see if ot makes a difference to irregular bleeding, because it's clear that estradiol can have different activity in the brain depending on the time of day. 'In both kisspeptin neuron populations from OVX mice, the frequency of GABAergic spontaneous postsynaptic currents was increased in the PM; this increase was blunted by estradiol.'
When do you apply the gel?
Hi Uptick thanks for your post.
I thought the bleeding had stopped but it has come back.
I have been reading about cross tolerance and as I suspected it's not just progesterone that has GABAergic modulation properties. Estradiol also interferes with GABA receptors.
Now I am w
orried, more so.
Reading articles just puts the sh1ts up me because a woman nearly died coming off progesterone.
Luckily she did her research and was able to tell doctors about HPA axis etc, and they saved her, I know I still haven't sent those benzo forum links, I've had too much on.
More worries that are non medical, it's like problems are piling up, problems I cannot find a solution to, problems that may negatively affect a lot of innocent people,
no I haven't killed or fought anyone.
It's a very complex subject and it's been studied in mice, which can be genetically modified, but it's a solid evidence that it's not just progesterone that has a modulating effect on GABA A receptors. The evidence is that the authors used Diazepam to manipulate GABA A receptors apparent affinity. ' We use the term apparent affinity to describe the effect of diazepam on GABAARs because the detailed mechanisms of action of diazepam remain elusive, and the traditional mechanism of diazepam increasing “receptor affinity” may not be the only consequence of activation of the benzodiazepine site.'
So, does this basically mean that I am stuffed?
It's hard to keep both estradiol and progesterone in balance, as I don't even know if my body is absorbing progesterone.
Hurduty seemed to imply on the utrogestan aborption thread that it comes in set doses, I am on the max.
I apply my gel between 7pm and 8pm on a night as that is when I bathe/wash.