[simplyPuru]

Lotus, question for you. You seem very knowledgeable and a lot of this stuff is impressive but over my head haha but Ella suggested I ask my question on this thread:

Based on a woman's ovarian cycle should we take estrogen during the times when estrogen is naturally high or low? Same for progesterone... Should we take it after ovulation when progesterone is high or before when it's low?

I've read articles that support both ways and I'm confused. Thanks for any insight!

[Lotus]

Lotus, question for you. You seem very knowledgeable and a lot of this stuff is impressive but over my head haha but Ella suggested I ask my question on this thread:

Based on a woman's ovarian cycle should we take estrogen during the times when estrogen is naturally high or low? Same for progesterone... Should we take it after ovulation when progesterone is high or before when it's low?

I've read articles that support both ways and I'm confused. Thanks for any insight!

Hey there purly,

Why do they make it so confusing?, my guess?, the docs that suggest continuous supplementation (estrogen & progesterone) have a better grip on balancing hormones. Which tends to make sense in an estro-dominate environment we live in.

Age, obesity, health, diet, etc. will be a determining factor on the potential outcome too. Before starting a NBE regime I would make absolutely sure my liver is functioning properly, without this benefit we can't properly filter or metabolize the new load of phytoestrogens and other supplements it will be introduced too.

Now from what I've seen the natural process of hormones produced endogenously (from within) is highest in the morning and midday, with a slight bump in the evening and midnight. And growth hormones naturally produce in REM sleep. So I would supplement between these intervals at the low points, between the release of hormones, no more than 90 minutes after peak level increase. Hormones synthesize approximately 30-40 minutes after binding, so my calculations suggest this cycle should be every 4 hours -10 am, 2 pm, 6 pm, and 10 pm. and, at low dose. Does that mean PM 4x a day, no, imo you spread to a 2 dose min every 8 hrs. Supplement those off times with other NBE supplements.

Which supplements?, omega 3-6-9, FG, anti-androgens, Green Tea or extract, vitamin C (4x daily-lower dosage) , fruits, veggies/greens. Snack on walnuts, dark chocolate 1 serving, no caffeine, cut the sugar and starch, plenty of filtered water 6-8 cups. w/lemon (1/2 in the AM). There's more you could do, but hey one day at a time.

Detox.......

The other option is to supplement E in the first half, GR/vitex in mid cycle and PC in luteal. Of course if on bc them assumably a across the board reduction should follow as to not induce estrogen dominance. That's just my opinion though.

[simplyPuru]

oh wow Lotus! That was a giant fountain of knowledge right there! thanks soooo much for your help! this gives me alot to think about and plan!!! Im still reading and re-reading and taking it in, seeing how to incorporate it. As for the pill times, thanks for listing them out like that, really helpful and I'll be following that for sure!!!

This forum is so wonderful. It helps alot. Some days its like, I will never be big boobed and get discouraged! but then having support from this forum helps a tonnnnn Thank youuuuu!!!

[Lotus]

Ok, but it may not make much sense,

It's like deconstructing a model (call it a airplane model) that someone else built, only you're working in reverse to deconstruct right. Same applies here, you see a study that states 5 alpha reductase is reduced in the liver, now maybe this study was for cancer research or something similar. Let's take one of these studies,

Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family, which are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

AKRs are involved in the development and progression of many cancers, as well as chemotherapeutic drug resistance. AKR1B1 and AKR1B10 are overexpressed in tumors, such as liver, breast, and lung cancer. Several AKRs (AKR1A1, AKR1B10, and AKR1C1-3) are involved in tobacco-carcinogenesis, but they also catalyze the detoxication of nicotine derived nitrosamino ketones. In addition, AKR1C1-3 enzymes play a key role in the regulation of proliferative signaling in hormone dependent cancers.

So what they did in this study was to cut off the androgen synthesis to the receptors using another steroid , Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

In English, I want to find the link to activate AKR1c in the liver to shut off the androgen receptors therefore DHT never gets activated, simple right?.

Cha-Ching, found it.

Regulates access of 5alpha-DHT to the androgen receptor.

Abstract
Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.
http://www.ncbi.nlm.nih.gov/pubmed/17223255

[twinklepose]

Soooo, in layman's terms... what's it all mean?!

[spanky (aka Lola)]

I think it means that "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" neutralizes 5alpha-dihydrotestosterone (DHT). Where you can get "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" is a mystery to me. It is also unclear to me what the total health effects would be.

http://www.ncbi.nlm.nih.gov/pubmed/12810547

file:///C:/Users/Bill/Downloads/30451.pdf

However, it may be that certain SSRIs might provide it. http://en.wikipedia.org/wiki/3-alpha-HSD

Unfortunately, the last thing I would recommend is taking SSRIs, unless your really, really need them.

[twinklepose]

I think it means that "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" neutralizes 5alpha-dihydrotestosterone (DHT). Where you can get "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" is a mystery to me. It is also unclear to me what the total health effects would be.

http://www.ncbi.nlm.nih.gov/pubmed/12810547

file:///C:/Users/Bill/Downloads/30451.pdf

However, it may be that certain SSRIs might provide it. http://en.wikipedia.org/wiki/3-alpha-HSD

Unfortunately, the last thing I would recommend is taking SSRIs, unless your really, really need them.

Had to Google that. As it happens, I do take Paroxetine anyway, for anxiety and depression. Been taking it for years and it's saved my life. The alternative was a living hell.

Sooooo, is that good for NBE then?

[spanky (aka Lola)]

I think it means that "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" neutralizes 5alpha-dihydrotestosterone (DHT). Where you can get "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" is a mystery to me. It is also unclear to me what the total health effects would be.

http://www.ncbi.nlm.nih.gov/pubmed/12810547

file:///C:/Users/Bill/Downloads/30451.pdf

However, it may be that certain SSRIs might provide it. http://en.wikipedia.org/wiki/3-alpha-HSD

Unfortunately, the last thing I would recommend is taking SSRIs, unless your really, really need them.

Had to Google that. As it happens, I do take Paroxetine anyway, for anxiety and depression. Been taking it for years and it's saved my life. The alternative was a living hell.

Sooooo, is that good for NBE then?

It would take a lot more knowledge than I have to answer with any certainty.

[Lotus]

This is a bit over simplified but Hydroxysteroid Dehydrogenases (HSDs) act like a gate-keeper just before steroids (hormones) bind to receptors (synthesis). Furthermore, these "gate-keepers" can flip the switch (a light switch) on/off to allow passage to the cell receptors. So in essence, they can inhibit or promote hormone activity. Finding a new class of HSD's is the next step, Aldo-keto reductases (AKRs) can help us get there.

By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction[/b]. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

[Lotus]

I think it means that "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" neutralizes 5alpha-dihydrotestosterone (DHT). Where you can get "Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR)" is a mystery to me. It is also unclear to me what the total health effects would be.

http://www.ncbi.nlm.nih.gov/pubmed/12810547

file:///C:/Users/Bill/Downloads/30451.pdf

However, it may be that certain SSRIs might provide it. http://en.wikipedia.org/wiki/3-alpha-HSD

Unfortunately, the last thing I would recommend is taking SSRIs, unless your really, really need them.

Had to Google that. As it happens, I do take Paroxetine anyway, for anxiety and depression. Been taking it for years and it's saved my life. The alternative was a living hell.

Sooooo, is that good for NBE then?

I agree spanky, the side effects alone are risky. Antipsychotics up-regulate prolactin, some antidepressants downregulate estrogen. Certain foods up-regulate GABA and dopamine nuerotransmitters. Almonds and walnuts are 2 good examples, plus, many others food choices to choose from too.

Here's an example of how an androgen actually up-regulates GABA.

The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABA (A) receptors.

Abstract
Testosterone modulates seizure susceptibility, but the underlying mechanisms are obscure. Recently, we demonstrated that testosterone affects seizure activity via its conversion to neurosteroids in the brain. Androstanediol (5alpha-androstan-3alpha,17beta-diol) is an endogenous neurosteroid synthesized from testosterone. However, the molecular mechanism underlying the seizure protection activity of androstanediol remains unclear. Here, we show that androstanediol has positive allosteric activity as a GABA(A) receptor modulator. In whole-cell recordings from acutely dissociated hippocampus CA1 pyramidal cells, androstanediol (but not its 3beta-epimer) produced a concentration-dependent enhancement of GABA-activated currents (EC(50) of 5 microM). At 1 microM, androstanediol produced a 50% potentiation of GABA responses. In the absence of GABA, androstanediol has moderate direct effects on GABA(A) receptor-mediated currents at high concentrations. Systemic doses of androstanediol (5-100 mg/kg), but not its 3beta-epimer, caused dose-dependent suppression of behavioral and electrographic seizures in mouse hippocampus kindling, which is a model of temporal lobe epilepsy. The ED(50) value for antiseizure effects of androstanediol was 50 mg/kg, which did not produce sedation/motor toxicity. At high (2x ED(50)) doses, androstanediol produced complete seizure protection that lasted for up to 3 h after injection. The estimated plasma concentrations of androstanediol producing 50% seizure protection in the kindling model (10.6 microM) are within the range of concentrations that modulate GABA(A) receptors. These studies suggest that androstanediol could be a neurosteroid mediator of testosterone actions on neuronal excitability and seizure susceptibility via its activity as a GABA(A) receptor modulator and that androstanediol may play a key role in men with epilepsy, especially during the age-related decline in androgen levels.