No matter which website you visit investigating your future steroid cycle (admit it, you're looking to use steroids in some form), you'll see the same thing, "Injectable Testosterone bro bro bro". Is injectable testosterone really the best delivery method of this hormone? I'm here to tell you while it's not the worst (oral clearly is due to the first pass effect), it's not the best though.
While I won't make this post long (solely because I have about 5 exams to study for), I just want to post some information that I've come across while studying for androgen deficiency in urologic disorders. A study titled, "Androgen deficiency in the etiology and treatment of erectile dysfunction" by Gore, Swerdloff, and Raifer compared testosterone replacement regimens and looked at four criteria for each regimen. These criteria were: "Achieves Serum Testosterone Concentrations in Normal Range", "Produces Normal Circadian Pattern of Serum Testosterone Concentrations", "Produces Normal Pattern of Serum Concentration of Androgen Metabolites", and "Adverse Effects". While all dosage forms of testosterone were able to achieve serum levels within normal range (minus oral testosterone), not all were able to produce BOTH a normal circadian rhythm or a normal metabolite concentration EXCEPT the transdermal gel. It was found that injectable testosterone produced an over abundance of estradiol that corresponds to a much greater risk of adverse side effects. The transdermal product produces a physiologic level of metabolites (DHT, Estradiol, etc), and was also able to maintain a more consistent serum concentration of testosterone as opposed to injectable which peaks, and then declines giving the body a "non-steady" dose of testosterone which is not particularly favorable.
Anyway, compounding pharmacies these days are able to make testosterone transdermal gels in concentrations up to 20%, meaning 200mg/mL. Although I recommend 100mg/mL due to solubility which will relate to better absorption, it is much better than the commercial 10mg/mL products that are out there. I find that when formulating transdermal preparations for testosterone, for maximum efficacy, dissolve it for 20 minutes in 99% ethanol prior to adding it to a base. These higher concentrated preparations means that you can apply as little as one gram to match 10 grams of the commercially available stuff.
Friday, December 7, 2012
Sunday, December 2, 2012
A Quick Musing: Substrates, Enzymes, and Products oh my!
There's a thought that I have been back and forth on for a few months now. Andy and I have even discussed this, but the lack of research on this matter gives us no real answer as to what is happening. This thought in particular involves inhibition of enzymes to alter substrate and product concentrations within the hormonal cascade, particularly in men.
Lets think about this a little more in depth than the typical person. Hopefully, many readers understand that Androstenedione converts to both estrogens and testosterone, and testosterone also enzymatically converts to both estrogens and DHT. So lets look at the aromatase enzyme real quick before I go study therapeutics and think about this...
In most patients clinically, the use of an Aromatase Inhibitor causes a rise in DHT. I am presuming that this is due to an increase in the concentration of substrate for the 5a-reductase enzyme (Testosterone). Is this physiologically possible? Usually there is a saturation of enzymes that causes a halt in the process only allowing you to convert so much of a substrate to a product. However, in this case, I think there is definitely a possibility that blocking aromatase either A. upregulates 5a-reductase or B. increases the substrate (testosterone) to the point of fully saturating the enzymes. If this is something that is already known, then so be it, here's your explanation. Otherwise, we can utilize this information to now make patient specific doses of aromatase enzymes. The thought of, hey go take 0.25mg of Arimidex every other day could be gone for now, again, patient specific dosing schemes based on lab values relating to Testosterone:DHT ratios and what not.
Being that I mentioned Testosterone:DHT ratios, now is a good quick second to mention the importance of Androstenedione:Estradiol ratios in order to maximize hormonal homeostatis, which for steroid users or TRT patients can result in a minimized risk of prostate effects. This means also utilizing labs for DHEA and AI dosing to get men to the perfect levels of everything in order to 1. restore lifestyle and 2. maximize health and minimize risks.
Just some thoughts.
Enjoy and Happy Holidays.
Dan
Lets think about this a little more in depth than the typical person. Hopefully, many readers understand that Androstenedione converts to both estrogens and testosterone, and testosterone also enzymatically converts to both estrogens and DHT. So lets look at the aromatase enzyme real quick before I go study therapeutics and think about this...
In most patients clinically, the use of an Aromatase Inhibitor causes a rise in DHT. I am presuming that this is due to an increase in the concentration of substrate for the 5a-reductase enzyme (Testosterone). Is this physiologically possible? Usually there is a saturation of enzymes that causes a halt in the process only allowing you to convert so much of a substrate to a product. However, in this case, I think there is definitely a possibility that blocking aromatase either A. upregulates 5a-reductase or B. increases the substrate (testosterone) to the point of fully saturating the enzymes. If this is something that is already known, then so be it, here's your explanation. Otherwise, we can utilize this information to now make patient specific doses of aromatase enzymes. The thought of, hey go take 0.25mg of Arimidex every other day could be gone for now, again, patient specific dosing schemes based on lab values relating to Testosterone:DHT ratios and what not.
Being that I mentioned Testosterone:DHT ratios, now is a good quick second to mention the importance of Androstenedione:Estradiol ratios in order to maximize hormonal homeostatis, which for steroid users or TRT patients can result in a minimized risk of prostate effects. This means also utilizing labs for DHEA and AI dosing to get men to the perfect levels of everything in order to 1. restore lifestyle and 2. maximize health and minimize risks.
Just some thoughts.
Enjoy and Happy Holidays.
Dan
Monday, October 8, 2012
Cholestasis Shouldn't Be A Threat
As promised, Dan and I are putting together some of our more recent musings to celebrate (sort of) 5,000 views on this blog. I'd also like to take this opportunity to gloat and thank the RCS for our invitation to the Chemistry World Science Communication Competition awards ceremony in London this past weekend. Dr. Andrea M. McGhee is a venerable chemist and an extremely accommodating hostess, giving us remote live access from the states. Thanks again.
As for where my mind has been regarding TRT, I've been accumulating research on ursodeoxycholic acid (UDCA) coadministration with methyltestosterone as an anti-hepatotoxic agent dosed at 250mg ED. Our goal is of course to prevent chronic cholestasis, which is the primary malady clinicians encounter when administering orally active androgens. While UDCA is a bit pricy, methyltestosterone is dirt cheap and the combination ends up being much less costly than gel preparations while much more convenient than oil suspensions for intramuscular injection.
Fortunately, the therapeutic doses in mind here (2mg ED) are not evidently toxic in chronic administration. It's also generally known that 17-alpha-alkylated androgen-induced heptotoxicity is largely dose-dependent, and elevated serum liver enzymes have been shown to plateau in some patients after a certain bout of long-term use. There really doesn't seem to be any alarming cases of jaundice in patients using relatively low, therapeutic doses of an oral androgen; however, contraindications come into play regarding hepatotoxicity. We also can't forget drastic lifestyle changes that a patient must acquiesce if he is to adopt a methyltestosterone regimen: this would most certainly preclude even light recreational alcohol consumption. Thus, we turn to UDCA and these worries fall by the wayside.
Another often cited route of hepatotoxicity prevention comes from rodent research using various doses and durations of ethinyl-estradiol along with SAM-e; however, SAMe would add significant cost to the patient and at no empirically evident benefit with additional UDCA. Generally, the benefactor observed is in membrane fluidity in hepatocytes attributed to phospholipid synthesis, but the research only really points to its use in reversing existing cholestasis, not preventing a potential threat.
What makes UDCA ideal for us is that it directly combats the accumulation of endogenous bile acids as a result of chronic methyltestosterone administration.
As for where my mind has been regarding TRT, I've been accumulating research on ursodeoxycholic acid (UDCA) coadministration with methyltestosterone as an anti-hepatotoxic agent dosed at 250mg ED. Our goal is of course to prevent chronic cholestasis, which is the primary malady clinicians encounter when administering orally active androgens. While UDCA is a bit pricy, methyltestosterone is dirt cheap and the combination ends up being much less costly than gel preparations while much more convenient than oil suspensions for intramuscular injection.
Fortunately, the therapeutic doses in mind here (2mg ED) are not evidently toxic in chronic administration. It's also generally known that 17-alpha-alkylated androgen-induced heptotoxicity is largely dose-dependent, and elevated serum liver enzymes have been shown to plateau in some patients after a certain bout of long-term use. There really doesn't seem to be any alarming cases of jaundice in patients using relatively low, therapeutic doses of an oral androgen; however, contraindications come into play regarding hepatotoxicity. We also can't forget drastic lifestyle changes that a patient must acquiesce if he is to adopt a methyltestosterone regimen: this would most certainly preclude even light recreational alcohol consumption. Thus, we turn to UDCA and these worries fall by the wayside.
Another often cited route of hepatotoxicity prevention comes from rodent research using various doses and durations of ethinyl-estradiol along with SAM-e; however, SAMe would add significant cost to the patient and at no empirically evident benefit with additional UDCA. Generally, the benefactor observed is in membrane fluidity in hepatocytes attributed to phospholipid synthesis, but the research only really points to its use in reversing existing cholestasis, not preventing a potential threat.
What makes UDCA ideal for us is that it directly combats the accumulation of endogenous bile acids as a result of chronic methyltestosterone administration.
Image source: Harrison's Internal Medicine, 18th edition. The McGraw-Hill Companies.
Cholestasis develops when relatively hydrophobic bile acids block bile flow to the duodenum, and regardless of the exact pathology i.e. whether chronic cholestasis results from impaired phase-I metabolism, glutathione depletion, et cetera, the problem can be prevented by substituting obstructor bile acids with more hydrophilic UDCA. If sourcing the stuff was easier, there is no doubt that the paradigm in TRT would shift favoring methyltestosterone and perhaps even some more interesting oral androgens studied in breadth and depth through the mid-twentieth century.
Monday, August 13, 2012
Further Evidence Favoring GHRH Peptide Administrating in Aging Adults
As part of the ongoing quest to improve quality of life, it's always a beam of hope when someone publishes a study that inadvertently provides us with more pharmacotherapeutic clout. Striking a similar chord as last month's entry on growth hormone releasing hormone peptide administration, Id like to acknowledge the work of Baker et al., who bring us exciting evidence that GHRH peptides are very much worthy of a spot on clinicians' radars.
In short, Baker et al. found that GHRH administration improved cognitive function (most importantly executive function) in both healthy adults and adults with mild cognitive impairment while decreasing body fat percentage by 7.4%. The peptide, tesamorelin, was self-administirred at 1mg/day before bed via subcutaneous injection. Adverse effects were not serious and 137 adults completed the 20-week study. (1)
As a brief refresher, prolonged glucocorticoid elevation gives rise to long-term depression in hippocampal neurons and reversible damage to the neuronal network. Albeit somewhat speculative, I wouldn't assume it bad science to insinuate that IGF-1 plays a direct role in adult neurogenesis for obvious proliferative reasons. It is widely observable in the rat model along with estrogen's effect on NMDA receptor up-regulation. (3) Together, we should observe significant cognitive improvement in aging adult humans in a model that does not contraindicate other therapeutic interventions like huperzine-A or citicholine.
As highlighted above, the parameter I'd like to focus on is a 117% increase in IGF-1, which is most notably related to both exercise and estrogen regarding hippocampal neurogenesis. Glucocorticoids are naturally involved in hippocampal aging at physiological levels and it appears that elevated IGF-1 combats inhibition of neurogenesis, as the executive function improvement posits.
Lupien et al. famously revealed in 1998 that there is a robust positive relationship between cortisol elevation and memory deficits in aging adults, and this is obviously measurable in hippocampal dysfunction. (2) From our perspective, we are continually compiling additional evidence that cortisol reducing steroids e.g. 7-oxygenated-DHEA metabolites along with synthetic GHRH peptides may be far more than just a body composition target for compounding pharmacists. We are targeting a combative pharmaceutical arsenal against both "normal and 'pathological' aging". (2)
Now for contraindications: foremost we have autoimmune pathologies, most frustratingly arthritis. Of course aging subjects could suffer from mild cortisol suppression, but this is swimming against the current of IGF-1 elevation and is treatable even further with over-the-counter joint health products. More seriously, we are dealing with patients at high risk for symptoms associated with BPH and elevated risk of prostate cancer. Inflammation and proliferation signaling together aren't exactly attractive for big pharma and 5-AR inhibitors are out of the question if male subjects are seeking improved libido. Lastly, GHRH peptides (several of them, at least) are notorious prolactin-o-philes (made up word, deal with it). Regarding memory impairment, this directly works against estrogen in potentiated NMDA excitation and long term potentiation; however, it's also easily ameliorated with dopaminergic drugs. It should be noted that while GHRH peptides may raise cortisol, GH also inhibits 11b-HSD1, so the cortisol elevation should not be a discernable contraindication.
Overall, it's always a pleasure for me to see some undeniably positive results in human subjects using these peptides. It's just a bit daunting to watch the drugs pile up in front of an effort to maximize results without causing any trouble.
1. http://www.ncbi.nlm.nih.gov/pubmed/22869065
2. http://www.nature.com/neuro/journal/v1/n1/pdf/nn0598_69.pdf
3. McEwen B (2002): Estrogen actions throughout the brain. Recent Prog Horm Res 57:357-84. McEwen BS, Gould E, Orchinik M, Weiland NG, Woolley CS (1995): Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes. Ciba Found Symp 191: 52-66; discussion 66-73.
Follow @BePatientBehave
In short, Baker et al. found that GHRH administration improved cognitive function (most importantly executive function) in both healthy adults and adults with mild cognitive impairment while decreasing body fat percentage by 7.4%. The peptide, tesamorelin, was self-administirred at 1mg/day before bed via subcutaneous injection. Adverse effects were not serious and 137 adults completed the 20-week study. (1)
As a brief refresher, prolonged glucocorticoid elevation gives rise to long-term depression in hippocampal neurons and reversible damage to the neuronal network. Albeit somewhat speculative, I wouldn't assume it bad science to insinuate that IGF-1 plays a direct role in adult neurogenesis for obvious proliferative reasons. It is widely observable in the rat model along with estrogen's effect on NMDA receptor up-regulation. (3) Together, we should observe significant cognitive improvement in aging adult humans in a model that does not contraindicate other therapeutic interventions like huperzine-A or citicholine.
As highlighted above, the parameter I'd like to focus on is a 117% increase in IGF-1, which is most notably related to both exercise and estrogen regarding hippocampal neurogenesis. Glucocorticoids are naturally involved in hippocampal aging at physiological levels and it appears that elevated IGF-1 combats inhibition of neurogenesis, as the executive function improvement posits.
fFgures from Lupien et al.'s lengthy, thorough examination of cortisol elevation vs. hippocampal volume in aging human subjects. (2)
Lupien et al. famously revealed in 1998 that there is a robust positive relationship between cortisol elevation and memory deficits in aging adults, and this is obviously measurable in hippocampal dysfunction. (2) From our perspective, we are continually compiling additional evidence that cortisol reducing steroids e.g. 7-oxygenated-DHEA metabolites along with synthetic GHRH peptides may be far more than just a body composition target for compounding pharmacists. We are targeting a combative pharmaceutical arsenal against both "normal and 'pathological' aging". (2)
Now for contraindications: foremost we have autoimmune pathologies, most frustratingly arthritis. Of course aging subjects could suffer from mild cortisol suppression, but this is swimming against the current of IGF-1 elevation and is treatable even further with over-the-counter joint health products. More seriously, we are dealing with patients at high risk for symptoms associated with BPH and elevated risk of prostate cancer. Inflammation and proliferation signaling together aren't exactly attractive for big pharma and 5-AR inhibitors are out of the question if male subjects are seeking improved libido. Lastly, GHRH peptides (several of them, at least) are notorious prolactin-o-philes (made up word, deal with it). Regarding memory impairment, this directly works against estrogen in potentiated NMDA excitation and long term potentiation; however, it's also easily ameliorated with dopaminergic drugs. It should be noted that while GHRH peptides may raise cortisol, GH also inhibits 11b-HSD1, so the cortisol elevation should not be a discernable contraindication.
Overall, it's always a pleasure for me to see some undeniably positive results in human subjects using these peptides. It's just a bit daunting to watch the drugs pile up in front of an effort to maximize results without causing any trouble.
1. http://www.ncbi.nlm.nih.gov/pubmed/22869065
2. http://www.nature.com/neuro/journal/v1/n1/pdf/nn0598_69.pdf
3. McEwen B (2002): Estrogen actions throughout the brain. Recent Prog Horm Res 57:357-84. McEwen BS, Gould E, Orchinik M, Weiland NG, Woolley CS (1995): Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes. Ciba Found Symp 191: 52-66; discussion 66-73.
Follow @BePatientBehave
Monday, July 23, 2012
New Horizons for Drug Delivery
It's always a pleasant surprise when my scant science related Twitter followees share something relevant to my own research, and I can say that because it's true with a 100% pleasant surprise rate (1-for-1).
A recent MedChemComm publication (July 3, 2012) boasts significant advancements in peptide drug delivery, which first and foremost open the door for topical insulin delivery. The delivery system provides a 6-fold increase in systemic peptide delivery against aqueous solution. This kind of advancement should give pharmacologists chills, really, as it is pharmacologically analogous to the Panama canal or like a wormhole or something. Considering a patient's comfort and our overarching theme of life improvement through pharmacotherapy, topical peptides are the holy freakin' grail.
Before I share my apparent excitement for what's to come from this method, here's an obligatory explanation of how the researchers did what they did courtesy of Chemistry World:
"The team made their capsule by surrounding insulin molecules with proteins and coating the protein molecules with a hydrophobic surfactant to from protein–surfactant complexes. Then, they added oligo-arginine peptides as protein transduction domains and dispersed the complexes in oil – isopropyl myristate – which is known to have a permeation-enhancing effect. ‘The main function of this new system is to promote protein penetration through the hydrophobic stratum corneum [outermost layer of the skin],’ explains Goto."
http://www.rsc.org/chemistryworld/2012/07/delivering-insulin-skin-cream
In short, protein transduction domains are designed to promote intercellular permeation while the surfactant-protein complexes enhance paracellular movement across the stratum corneum.
Now, Dan and I have recently been dishing about HRT, specifically about DHT and how to induce 5-AR for clinicians/compounding pharmacists to manipulate DHT/T/androstendione in favor (most logically) of male libido. It seems that IGF-1 mediates 5-AR induction most markedly in humans, ergo, we'd love to think that at some point, likely after vaccines and antibiotics make it into protein-surfactant complexes, IGF-1 and other oligopeptides e.g. GHRP-2, hexarilin, CJC-1295 can be administered topically as part of compounding formulas purported to promote quality of life and healthy body composition in aging adults.
Tahara et al. ePub:
http://pubs.rsc.org/en/content/articlelanding/2012/md/c2md20059g
More on PTDs:
http://biotech.niu.edu.tw/files/news/143_f8d6bd92.pdf
A recent MedChemComm publication (July 3, 2012) boasts significant advancements in peptide drug delivery, which first and foremost open the door for topical insulin delivery. The delivery system provides a 6-fold increase in systemic peptide delivery against aqueous solution. This kind of advancement should give pharmacologists chills, really, as it is pharmacologically analogous to the Panama canal or like a wormhole or something. Considering a patient's comfort and our overarching theme of life improvement through pharmacotherapy, topical peptides are the holy freakin' grail.
Before I share my apparent excitement for what's to come from this method, here's an obligatory explanation of how the researchers did what they did courtesy of Chemistry World:
"The team made their capsule by surrounding insulin molecules with proteins and coating the protein molecules with a hydrophobic surfactant to from protein–surfactant complexes. Then, they added oligo-arginine peptides as protein transduction domains and dispersed the complexes in oil – isopropyl myristate – which is known to have a permeation-enhancing effect. ‘The main function of this new system is to promote protein penetration through the hydrophobic stratum corneum [outermost layer of the skin],’ explains Goto."
http://www.rsc.org/chemistryworld/2012/07/delivering-insulin-skin-cream
In short, protein transduction domains are designed to promote intercellular permeation while the surfactant-protein complexes enhance paracellular movement across the stratum corneum.
Now, Dan and I have recently been dishing about HRT, specifically about DHT and how to induce 5-AR for clinicians/compounding pharmacists to manipulate DHT/T/androstendione in favor (most logically) of male libido. It seems that IGF-1 mediates 5-AR induction most markedly in humans, ergo, we'd love to think that at some point, likely after vaccines and antibiotics make it into protein-surfactant complexes, IGF-1 and other oligopeptides e.g. GHRP-2, hexarilin, CJC-1295 can be administered topically as part of compounding formulas purported to promote quality of life and healthy body composition in aging adults.
Tahara et al. ePub:
http://pubs.rsc.org/en/content/articlelanding/2012/md/c2md20059g
More on PTDs:
http://biotech.niu.edu.tw/files/news/143_f8d6bd92.pdf
Thursday, June 21, 2012
Anti-Estrogen Use in Men: LH? GnRH? Testosterone?
In men, it is commonly known that LH has some role within the production of testosterone. Well, this is true, it does. As I sit here, glaring at this hypogonadism writings figuring out what type of topical testosterone treatments are optimal in HRT settings, I realize that many people in the boydbuilding community (the majority of know-it-alls for pharmacotherapy of hormonal treatment) don't fully understand this relationship. Could I be wrong here and may they truly know everything? Sure. But after overhearing a conversation from two older men in my gym the other day, I couldn't help but to internally punch myself at the stupidity of their conversation. And on a side note, I hope that my unprofessionalism and ranting does not push you away from reading this blog post. So without further ramblings, lets move on to some cool stuff, yes?
GnRH, the primary LH signalling hormone of hypothalamus is rarely talked about. However, it's importance in this is significant. It has been implied through some research that suppressed LH secretion due to testosterone is not from a direct negative feedback to the pituitary (where LH is released), but to the hypothalamus as well (by as well, I am saying that negative feedback from testosterone affects both the pituitary and the hypothalamus). This is particularly from the conversion of testosterone to estradiol from the aromatase enzyme, due to estradiol's direct inhibition of the pituitary and the hypothalamus. However, it seems as if DHT is lost in the mix. You don't hear much about DHT, but nevertheless DHT decreases LH pulse frequency and LH pulse frequency is upregulated in patients with decreased androgen receptor sensitivity. What this means is that the androgen receptor has the ability to affect the GnRH pulse frequency. Where does all this even come into play then? You ever wonder why aromatase inhibitors or SERMs cause an increase in LH? Speaking from a in vivo standpoint, it is due to the decrease in negative feedback produced by the increases in estradiol concentrations. The two drugs studied in men to confirm these findings are anastrozole and clomiphene.
All of this seems rather unorganized and confusing, but essentially, in order to maintain a positive hypothalamic and pituitary function in men treated with testosterone, it is particularly wise to utilize an aromatase inhibitor concurrently. Is it possible that "recovery" post testosterone usage would be "easier" with said aromatase inhibitor (or clomiphene?)? Probably.
References:
SJ Winters. Male Hypogonadism Basic, Clinicial, and Therapeutic Principles. Humana Press Inc. Totowa, NJ
http://ergo-log.com/clomiphenehormonetherapy.html
GnRH, the primary LH signalling hormone of hypothalamus is rarely talked about. However, it's importance in this is significant. It has been implied through some research that suppressed LH secretion due to testosterone is not from a direct negative feedback to the pituitary (where LH is released), but to the hypothalamus as well (by as well, I am saying that negative feedback from testosterone affects both the pituitary and the hypothalamus). This is particularly from the conversion of testosterone to estradiol from the aromatase enzyme, due to estradiol's direct inhibition of the pituitary and the hypothalamus. However, it seems as if DHT is lost in the mix. You don't hear much about DHT, but nevertheless DHT decreases LH pulse frequency and LH pulse frequency is upregulated in patients with decreased androgen receptor sensitivity. What this means is that the androgen receptor has the ability to affect the GnRH pulse frequency. Where does all this even come into play then? You ever wonder why aromatase inhibitors or SERMs cause an increase in LH? Speaking from a in vivo standpoint, it is due to the decrease in negative feedback produced by the increases in estradiol concentrations. The two drugs studied in men to confirm these findings are anastrozole and clomiphene.
All of this seems rather unorganized and confusing, but essentially, in order to maintain a positive hypothalamic and pituitary function in men treated with testosterone, it is particularly wise to utilize an aromatase inhibitor concurrently. Is it possible that "recovery" post testosterone usage would be "easier" with said aromatase inhibitor (or clomiphene?)? Probably.
References:
SJ Winters. Male Hypogonadism Basic, Clinicial, and Therapeutic Principles. Humana Press Inc. Totowa, NJ
http://ergo-log.com/clomiphenehormonetherapy.html
Monday, June 4, 2012
Dulling the Double-edged Sword
To any subscribing clinicians, you all must be reminded tortuously and repeatedly of the weight (no pun) type-II diabetes puts on rising healthcare costs. Further, endocrinologists bogged down with insulin, metformin, and testosterone administration are caught in a pharmacotherapeutic catch-22: these drugs oppose each other with respect to endocrine/cardiovascular health in patients being treated for type-II diabetes and low T concurrently. (4, 5)
The key issues:
1) Adipose tissue is an endocrine organ. Obese men therefore suffer a compromised testosterone:estrogen ratio, which may perpetuate poor body composition and cardiovascular health.
2) Total plasma cortisol is positively correlated with markers of metabolic syndrome in obese men, but SHBG and serum androgen is not coupled to similar markers (hyperlipidemia, hyperglycemia, et cetera). (1, 2)
3) Pathogenic effects of omental and mesenteric fat accumulation is negatively correlated with serum androgens (p<0.001). (3)
We burgeoning young pharmacists/pharmacologists are nipping contraindications in the bud with topical formulations that complement each other, providing therapy from multiple angles rather than toiling with a balancing act. The general health approach to hormone replacement therapy would inspire a compounded topical formula including testosterone, theophylline, an 11bHSD1 reductase inhibitor (decreased cortisol), and an aromatase inhibitor.
The key issues are applicable principles to the ideal therapeutic targets, so deductively, we kill 'em all with the aforementioned formula: patients should acquire a balanced T:e2, decreased insulin/cortisol (permissive of each other in visceral lipogenesis), and decreased subcutaneous fat without affected cardiovascular parameters.
These applications, further, are inexpensive and use existing drugs, expediting the trial process, and they are genuinely open to patent protection for novel use. If you recall our previous musings on convenience, thematically appreciative of the patient's wants, you'll see how this type of therapy is inevitably the future of male HRT.
1. http://jcem.endojournals.org/content/92/9/3568.short
2. http://www.ncbi.nlm.nih.gov/pubmed/20354921
3. http://www.sciencedirect.com/science/article/pii/0026049587900631
4. http://www.nature.com/oby/journal/v9/n11/full/oby200190a.html
5. http://atvb.ahajournals.org/content/19/12/2928.full
Follow @BePatientBehave
The key issues:
1) Adipose tissue is an endocrine organ. Obese men therefore suffer a compromised testosterone:estrogen ratio, which may perpetuate poor body composition and cardiovascular health.
2) Total plasma cortisol is positively correlated with markers of metabolic syndrome in obese men, but SHBG and serum androgen is not coupled to similar markers (hyperlipidemia, hyperglycemia, et cetera). (1, 2)
3) Pathogenic effects of omental and mesenteric fat accumulation is negatively correlated with serum androgens (p<0.001). (3)
We burgeoning young pharmacists/pharmacologists are nipping contraindications in the bud with topical formulations that complement each other, providing therapy from multiple angles rather than toiling with a balancing act. The general health approach to hormone replacement therapy would inspire a compounded topical formula including testosterone, theophylline, an 11bHSD1 reductase inhibitor (decreased cortisol), and an aromatase inhibitor.
The key issues are applicable principles to the ideal therapeutic targets, so deductively, we kill 'em all with the aforementioned formula: patients should acquire a balanced T:e2, decreased insulin/cortisol (permissive of each other in visceral lipogenesis), and decreased subcutaneous fat without affected cardiovascular parameters.
These applications, further, are inexpensive and use existing drugs, expediting the trial process, and they are genuinely open to patent protection for novel use. If you recall our previous musings on convenience, thematically appreciative of the patient's wants, you'll see how this type of therapy is inevitably the future of male HRT.
1. http://jcem.endojournals.org/content/92/9/3568.short
2. http://www.ncbi.nlm.nih.gov/pubmed/20354921
3. http://www.sciencedirect.com/science/article/pii/0026049587900631
4. http://www.nature.com/oby/journal/v9/n11/full/oby200190a.html
5. http://atvb.ahajournals.org/content/19/12/2928.full
Follow @BePatientBehave
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