04-12-2012, 08:07 AM
(This post was last modified: 04-12-2012, 04:29 PM by LookingForward2NBE.)
With respect to Steady-State vs. flucating daily rhytms of hormones. Estrogen levels during sleep are quite low when compared to peak concentrations which are typically around 6-7am in the morning and then drop to its low level by mid-day and stay at the level. From the morning high to evening low, it's a 300-400% difference. There are flucuations through the day but as a mean of the top and bottom levels it rises quickly to a peak and then falls off. Maintaining a tight, steady-state concentration by dosing on the T1/2 is definitely altering the natural rhythm of a females cycle (even for NBE). I do not believe SS should be a suggested approach - especially for a female. As for a male, it's a relatively new and poorly charter territory.
I guess its up to each individual to decide if they want to:
1. Maintain a constaint steady-state level all day (then taking PM every 4hrs may be the best approach) in which case the common 2x day dosing is inadequate. However, splitting the the RDI amount into 4 doses will cause your Cmax (maximum blood concentration) to drop significantly so that may affect the Therapeutic window. Thereby, having to increase your RDI to get an equivalent or near equivalent Cmax which will lead to a higher total AUC (area under the curve). Leading to higher extent of absorption but not necessary therapeutic effect. The high extent of absorption could lead to increase prevalence of side affects which is typically associated with Total Exposure - amount of product. Just because something is "deactivated" does not means its eliminated, its conjugated into a non-functional component which is then eliminated but even the inactivated compound could still cause toxicity.
2. Dose like a natural response and take a single dose at waking vs. a split dose taken in 2 doses 12hrs apart.
3. Or taking a single dose between 9am-12pm, when your natural level begins to drop to have a higher elevated amount all day but still allowing your system a rest period late afternoon and throughout your sleep period.
4. Or taking a dose in the morning and a dose afternoon as is typically recommended, thereby decreasing the amount of rest to strictly during the sleep period.
The more I consider my personal program and approach, I'll probably start out 1x per day, late in the morning to give myself a "boosting" effect of Estrogen like activity and delaying the drop for 2-3hrs later into the day and potentially, a smaller dose at 5pm so as to get 50% of the dose out by 9 and 75% of it out by 12midnight.
I guess thats also a consideration for some who are poor responders to PM, changing their dosing time and approach could potentially have a significant impact depending on how their individual diurnal cycle is happening. Maybe going from 1 capsule 2x day to 1.5caps once day may lead to better outcomes and the time of the dose from either 6-7am or 10am-12pm or even after 5pm. Or taking 1/2 capsule 4x per day etc.
From the very very little bit of reading I have done male transformation, knocking out Test (by SP or other means) and dramatically increasing Estrogen will absolutely cause testicular shrinkage (due to lack of activity by the leydig cells i believe ie use it or lose it). With respect to Penis atrophy, the lack of nocturnal erections and lack of sex drive experienced by many when transitioning to predominately female based hormones (irregardless of they are synthetic Estrogen's or phytoestrogens). However, probably not an issue either way but I do not even begin to understand or appreciate the pyschological impact that such an individual is going through. As a man ages after 40-50, the penis does atrophy due to the lose of nocturnal erections due lower hormone levels (GH and Test).. slowly but it does. I recall reading somewhere that it can be by as much as 1/2 or more loss in length and rigidity. But that data was pre-Viagara type products. I guess men transitioning to women do also see the changes unless they are not on female hormone replacement therapy or still masturbate or have sex frequently. I guess even within that community, there are different levels of transgenders feminization...
I guess its up to each individual to decide if they want to:
1. Maintain a constaint steady-state level all day (then taking PM every 4hrs may be the best approach) in which case the common 2x day dosing is inadequate. However, splitting the the RDI amount into 4 doses will cause your Cmax (maximum blood concentration) to drop significantly so that may affect the Therapeutic window. Thereby, having to increase your RDI to get an equivalent or near equivalent Cmax which will lead to a higher total AUC (area under the curve). Leading to higher extent of absorption but not necessary therapeutic effect. The high extent of absorption could lead to increase prevalence of side affects which is typically associated with Total Exposure - amount of product. Just because something is "deactivated" does not means its eliminated, its conjugated into a non-functional component which is then eliminated but even the inactivated compound could still cause toxicity.
2. Dose like a natural response and take a single dose at waking vs. a split dose taken in 2 doses 12hrs apart.
3. Or taking a single dose between 9am-12pm, when your natural level begins to drop to have a higher elevated amount all day but still allowing your system a rest period late afternoon and throughout your sleep period.
4. Or taking a dose in the morning and a dose afternoon as is typically recommended, thereby decreasing the amount of rest to strictly during the sleep period.
The more I consider my personal program and approach, I'll probably start out 1x per day, late in the morning to give myself a "boosting" effect of Estrogen like activity and delaying the drop for 2-3hrs later into the day and potentially, a smaller dose at 5pm so as to get 50% of the dose out by 9 and 75% of it out by 12midnight.
I guess thats also a consideration for some who are poor responders to PM, changing their dosing time and approach could potentially have a significant impact depending on how their individual diurnal cycle is happening. Maybe going from 1 capsule 2x day to 1.5caps once day may lead to better outcomes and the time of the dose from either 6-7am or 10am-12pm or even after 5pm. Or taking 1/2 capsule 4x per day etc.
From the very very little bit of reading I have done male transformation, knocking out Test (by SP or other means) and dramatically increasing Estrogen will absolutely cause testicular shrinkage (due to lack of activity by the leydig cells i believe ie use it or lose it). With respect to Penis atrophy, the lack of nocturnal erections and lack of sex drive experienced by many when transitioning to predominately female based hormones (irregardless of they are synthetic Estrogen's or phytoestrogens). However, probably not an issue either way but I do not even begin to understand or appreciate the pyschological impact that such an individual is going through. As a man ages after 40-50, the penis does atrophy due to the lose of nocturnal erections due lower hormone levels (GH and Test).. slowly but it does. I recall reading somewhere that it can be by as much as 1/2 or more loss in length and rigidity. But that data was pre-Viagara type products. I guess men transitioning to women do also see the changes unless they are not on female hormone replacement therapy or still masturbate or have sex frequently. I guess even within that community, there are different levels of transgenders feminization...