DHT Mediates Cerebral Ischemia (stroke) In Male Mice

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Deleterious effects of dihydrotestosterone on cerebral ischemic injury

Possibly explains why more men are susceptible to stroke.

"In total, 17 inflammatory genes uniformly showed increased expression pattern in DHT-treated brain versus castrated brain..."

This may also relate to hair loss, if DHT increases these inflammatory markers it may cause hair loss as MPB is associated with inflammation.
 

haidut

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Deleterious effects of dihydrotestosterone on cerebral ischemic injury

Possibly explains why more men are susceptible to stroke.

"In total, 17 inflammatory genes uniformly showed increased expression pattern in DHT-treated brain versus castrated brain..."

This may also relate to hair loss, if DHT increases these inflammatory markers it may cause hair loss as MPB is associated with inflammation.

The thread title is incorrect. DHT does NOT mediate ischemic stroke. The stroke was caused by other means (artery occlusion) after 1 week of hormone treatment. The T/DHT doses were absolutely massive and I am not even sure what they show except that T/DHT do have toxicities. The T/DHT doses used were 50mg per mouse over 7 days. That comes down to about 7mg per mouse daily and assuming the 9-10 week mice weigh about 30g it means the dose was ~230mg/kg. That is a massive dose almost unheard of in other animal trials and the HED is about 20mg/kg daily, which means 1,500mg - 2,000mg daily for a human. This is an absurd dose that dwarfs even the most abusive practices by bodybuilders, as even the "bravest" of them would rarely go above 1,500mg T weekly, let alone daily. The T/DHT given to the mice increase T levels 10 fold over intact mice and DHT levels 5 fold. If this happens in a human, the person can actually get a stroke or heart attack due to the polycythemia that androgens are well-known to cause in higher doses.
After seeing studies like this, I can only conclude that either the people who did the study are not in their right minds or the study was purposefully designed to produce negative effects from T/DHT.
"...This study was conducted in accordance with National Institute of Health guidelines, and all protocols were approved by the Animal Care and Use Committee of Oregon Health and Science University. Male rats were castrated with or without subcutaneous hormone replacement under halothane anesthesia 1 week before MCAO, as previously described (Toung et al, 1998). Gonadally intact animals were sham operated under halothane anesthesia 1 week before MCAO. For infarction studies, four groups of sexually mature, age-matched adult (9- to 10-week-old) Wistar rats (Charles River Laboratories, Wilmington, MA, USA) were studied: intact (n = 9), castrated (n = 14), testosterone replaced, castrated males (50 mg/pellet, Innovative Research of America, Sarasota, FL, USA) (n = 14) and 5α-dihydrotestosterone (DHT, 50 mg/pellet, Innovative Research of America, Sarasota, FL, USA) replaced, castrated males (n = 8). Postischemic bcl-2 and bax transcription was examined in separate cohorts of intact, castrated, and DHT-replaced males (n = 6). Microarray analysis and quantitative PCR (qPCR) confirmation was performed only in castrated (n = 3) and DHT-replaced males (n = 4)."
 
OP
BestSinceDAYONE
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The thread title is incorrect. DHT does NOT mediate ischemic stroke. The stroke was caused by other means (artery occlusion) after 1 week of hormone treatment. The T/DHT doses were absolutely massive and I am not even sure what they show except that T/DHT do have toxicities. The T/DHT doses used were 50mg per mouse over 7 days. That comes down to about 7mg per mouse daily and assuming the 9-10 week mice weigh about 30g it means the dose was ~230mg/kg. That is a massive dose almost unheard of in other animal trials and the HED is about 20mg/kg daily, which means 1,500mg - 2,000mg daily for a human. This is an absurd dose that dwarfs even the most abusive practices by bodybuilders, as even the "bravest" of them would rarely go above 1,500mg T weekly, let alone daily. The T/DHT given to the mice increase T levels 10 fold over intact mice and DHT levels 5 fold. If this happens in a human, the person can actually get a stroke or heart attack due to the polycythemia that androgens are well-known to cause in higher doses.
After seeing studies like this, I can only conclude that either the people who did the study are not in their right minds or the study was purposefully designed to produce negative effects from T/DHT.
"...This study was conducted in accordance with National Institute of Health guidelines, and all protocols were approved by the Animal Care and Use Committee of Oregon Health and Science University. Male rats were castrated with or without subcutaneous hormone replacement under halothane anesthesia 1 week before MCAO, as previously described (Toung et al, 1998). Gonadally intact animals were sham operated under halothane anesthesia 1 week before MCAO. For infarction studies, four groups of sexually mature, age-matched adult (9- to 10-week-old) Wistar rats (Charles River Laboratories, Wilmington, MA, USA) were studied: intact (n = 9), castrated (n = 14), testosterone replaced, castrated males (50 mg/pellet, Innovative Research of America, Sarasota, FL, USA) (n = 14) and 5α-dihydrotestosterone (DHT, 50 mg/pellet, Innovative Research of America, Sarasota, FL, USA) replaced, castrated males (n = 8). Postischemic bcl-2 and bax transcription was examined in separate cohorts of intact, castrated, and DHT-replaced males (n = 6). Microarray analysis and quantitative PCR (qPCR) confirmation was performed only in castrated (n = 3) and DHT-replaced males (n = 4)."

Nice, Hey Dude.

This actually shows you that someone actually goes through the study and critically analyzes said information instead of taking it as gospel.

Whenever I post studies on hairloss forums, they don't care to analyze any of their information and prefer to stick to their dogma.

I seriously think that drug finasteride turns a man's brain into a female one, which makes them more susceptible to emotional outbursts, arguments without actual facts and confirmation bias.

For example, Trump takes it.
 

aguilaroja

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The thread title is incorrect. DHT does NOT mediate ischemic stroke. The stroke was caused by other means (artery occlusion) after 1 week of hormone treatment. The T/DHT doses were absolutely massive and I am not even sure what they show except that T/DHT do have toxicities. The T/DHT doses used were 50mg per mouse over 7 days. That comes down to about 7mg per mouse daily
...

As @haidut points out, there are many problems with the study. It is one of a series of studies over years by labs purporting to “explain” the gender differences in occurrence of (ischemic) stroke. Similar (airquote city coming…) “reasoning” is used to explain how estrogen is supposedly “neuroprotective”. BTW, it is almost impossible to discuss estrogen hazards with “neurosteroid” researchers. Many have gotten angry when the question is even raised in person. They seem immune to, you know, data.

Toxic, non-physiologic dosing is possibility for error. The researchers concede that the dosing is steady-state, not diurnal.
“…we utilized a continuous hormone replacement strategy, recognizing that this does not simulate the physiological, diurnal rhythms of androgen production.” There is also no certainty that an implant releases a drug “steadily”. There will be variation over time. It is also very likely that in real human cases, hormone distribution would shift greatly in the short term response to and recovery from major brain injury.

Looking back at the 1998 study by Toung which purports to show the “neuroprotective” effect of estrogen:
Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats
This was the model cited by Cheng & Hurn (here) for testing brain response to hormone treatment following middle cerebral artery occlusion. The subcutaneous 17β-estradiol dose used in one group (100 micrograms) approximates to a human equivalent dose of 6 mg per day, possibly 30 times the dose of pharmacologic estrogen used for human women. So the research protocols seem to use large animal equivalents, perhaps to see a big research effect. After decades of one protocol built on another, the original “rationale” may be lost.

It often requires study beyond the headlines for informed decisions. And recall that the lifetime stroke risk for women is still high, though a bit lower than for men. So gender difference brings lower risk but is not fully informative about protective factors.

Association of Hypertension with Serum Estrogen Level in Postmenopausal Women. - PubMed - NCBI
"In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with systolic and diastolic blood pressure levels… there is association of hypertension with serum estrogen level in postmenopausal women."

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: An Evidence Review for the U.S. Preventive Services Task ... - PubMed - NCBI
“…risk (per 10,000 women over 5.4 to 7.1 years) was statistically significantly increased for gallbladder disease (213 more cases), stroke (79 more cases), and venous thromboembolism (78 more cases). The risk of urinary incontinence (1,261 more cases per 10,000 women) was increased during a followup of 1 year.

Allometric Scaling Calculator
Rat and Mice Weights | Animal Resources Centre
 
OP
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As @haidut points out, there are many problems with the study. It is one of a series of studies over years by labs purporting to “explain” the gender differences in occurrence of (ischemic) stroke. Similar (airquote city coming…) “reasoning” is used to explain how estrogen is supposedly “neuroprotective”. BTW, it is almost impossible to discuss estrogen hazards with “neurosteroid” researchers. Many have gotten angry when the question is even raised in person. They seem immune to, you know, data.

Toxic, non-physiologic dosing is possibility for error. The researchers concede that the dosing is steady-state, not diurnal.
“…we utilized a continuous hormone replacement strategy, recognizing that this does not simulate the physiological, diurnal rhythms of androgen production.” There is also no certainty that an implant releases a drug “steadily”. There will be variation over time. It is also very likely that in real human cases, hormone distribution would shift greatly in the short term response to and recovery from major brain injury.

Looking back at the 1998 study by Toung which purports to show the “neuroprotective” effect of estrogen:
Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats
This was the model cited by Cheng & Hurn (here) for testing brain response to hormone treatment following middle cerebral artery occlusion. The subcutaneous 17β-estradiol dose used in one group (100 micrograms) approximates to a human equivalent dose of 6 mg per day, possibly 30 times the dose of pharmacologic estrogen used for human women. So the research protocols seem to use large animal equivalents, perhaps to see a big research effect. After decades of one protocol built on another, the original “rationale” may be lost.

It often requires study beyond the headlines for informed decisions. And recall that the lifetime stroke risk for women is still high, though a bit lower than for men. So gender difference brings lower risk but is not fully informative about protective factors.

Association of Hypertension with Serum Estrogen Level in Postmenopausal Women. - PubMed - NCBI
"In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with systolic and diastolic blood pressure levels… there is association of hypertension with serum estrogen level in postmenopausal women."

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: An Evidence Review for the U.S. Preventive Services Task ... - PubMed - NCBI
“…risk (per 10,000 women over 5.4 to 7.1 years) was statistically significantly increased for gallbladder disease (213 more cases), stroke (79 more cases), and venous thromboembolism (78 more cases). The risk of urinary incontinence (1,261 more cases per 10,000 women) was increased during a followup of 1 year.

Allometric Scaling Calculator
Rat and Mice Weights | Animal Resources Centre

What about the studies showing the importance of estrogen in muscle growth (since muscle growth is important for longevity I figured this would be important) and the consequences of low estrogen including osteoporosis?
 

aguilaroja

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What about the studies showing the importance of estrogen in muscle growth (since muscle growth is important for longevity I figured this would be important) and the consequences of low estrogen including osteoporosis?
I am a casual reader, and find little basis for estrogen non-stress augmentation of muscle and bone.

Dr. Peat has written extensively about estrogen and osteoporosis, for instance:
Estrogen and Osteoporosis
Estrogen and Osteoporosis
Estrogen and Osteoporosis

In his articles are searched for “growth hormone” and muscle, a similar outlook may be found, for instance:
Heart and hormones
 

aguilaroja

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... assuming the 9-10 week mice weigh about 30g ... That is a massive dose almost unheard of in other animal trials and the HED is about 20mg/kg daily, ...
Excuse the nitpicking and rodent proof-reading, @haidut.

IIRC, the study @VendettaRed911 cites discussed the Wistar rat model rather than a mouse model The weight of a young male rat subject might be closer to 300 grams than 30 grams. By rough calculation, human equivalent dosing might be around 6 mg/kg or well over 400mg daily. This remains a huge T/DHT amount, far beyond safe levels. The researchers’s dosage choices, in this and other series, remain concerning. @haidut’s well-taken points remain.

@haidut’s many edifying threads and posts are appreciated.
 

Arrade

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Nice, Hey Dude.

This actually shows you that someone actually goes through the study and critically analyzes said information instead of taking it as gospel.

Whenever I post studies on hairloss forums, they don't care to analyze any of their information and prefer to stick to their dogma.

I seriously think that drug finasteride turns a man's brain into a female one, which makes them more susceptible to emotional outbursts, arguments without actual facts and confirmation bias.

For example, Trump takes it.
lol I keep saying we WON'T have a nuclear war because of trump's use of fin
 

haidut

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As @haidut points out, there are many problems with the study. It is one of a series of studies over years by labs purporting to “explain” the gender differences in occurrence of (ischemic) stroke. Similar (airquote city coming…) “reasoning” is used to explain how estrogen is supposedly “neuroprotective”. BTW, it is almost impossible to discuss estrogen hazards with “neurosteroid” researchers. Many have gotten angry when the question is even raised in person. They seem immune to, you know, data.

Toxic, non-physiologic dosing is possibility for error. The researchers concede that the dosing is steady-state, not diurnal.
“…we utilized a continuous hormone replacement strategy, recognizing that this does not simulate the physiological, diurnal rhythms of androgen production.” There is also no certainty that an implant releases a drug “steadily”. There will be variation over time. It is also very likely that in real human cases, hormone distribution would shift greatly in the short term response to and recovery from major brain injury.

Looking back at the 1998 study by Toung which purports to show the “neuroprotective” effect of estrogen:
Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats
This was the model cited by Cheng & Hurn (here) for testing brain response to hormone treatment following middle cerebral artery occlusion. The subcutaneous 17β-estradiol dose used in one group (100 micrograms) approximates to a human equivalent dose of 6 mg per day, possibly 30 times the dose of pharmacologic estrogen used for human women. So the research protocols seem to use large animal equivalents, perhaps to see a big research effect. After decades of one protocol built on another, the original “rationale” may be lost.

It often requires study beyond the headlines for informed decisions. And recall that the lifetime stroke risk for women is still high, though a bit lower than for men. So gender difference brings lower risk but is not fully informative about protective factors.

Association of Hypertension with Serum Estrogen Level in Postmenopausal Women. - PubMed - NCBI
"In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with systolic and diastolic blood pressure levels… there is association of hypertension with serum estrogen level in postmenopausal women."

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: An Evidence Review for the U.S. Preventive Services Task ... - PubMed - NCBI
“…risk (per 10,000 women over 5.4 to 7.1 years) was statistically significantly increased for gallbladder disease (213 more cases), stroke (79 more cases), and venous thromboembolism (78 more cases). The risk of urinary incontinence (1,261 more cases per 10,000 women) was increased during a followup of 1 year.

Allometric Scaling Calculator
Rat and Mice Weights | Animal Resources Centre

You are right, my apologies. It's even in the quote I extracted - they used rats and not mice. Coincidentally, I was reading another study in a separate browser window, and it was also with DHT but used mice. So, it polluted my thinking when I was posting :):
As far as estrogen and its "neuroprotection" I will add this recent study to the ones you posted.
Estrogen Causes Epilepsy/seizures; Aromatase Inhibitors Are Viable Treatment
 
Last edited:

haidut

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What about the studies showing the importance of estrogen in muscle growth (since muscle growth is important for longevity I figured this would be important) and the consequences of low estrogen including osteoporosis?

I beg to disagree. In addition to what @aguilaroja posted I will add the study below. I have been aware for a long time about the myth among bodybuilders, doctors, and veterinarians concerning the necessity of estrogen of anabolism. I don't think that myth has much basis in reality, and while there are not that many studies to back up my point, here is at least one that illustrates my point (and Peat's and @aguilaroja's) perfectly. Namely, estrogen is NOT needed for anabolic effects of steroids like testosterone or trenbolone on neither muscle nor bone. In fact, adding an aromatase inhibitor to T therapy resulted in the greatest anabolic effects compared to the other treatment groups. In addition, adding an aromatase inhibitor to the trenbolone group resulted in much bigger fat loss than any other treatment group. As you can see, even the study authors hardly believe their own results and sound almost apologetic in the Discussion section where they keep mentioning the "well-established" role of estrogen in protecting bone and muscle tissue. But, as they used to say in graduate schools back in the first half of the 20th century, even the most convenient theory can get murdered by a gang of brutal facts:): There are other, older studies showing confirming the findings of this study and I will post them when I find some free time as I read them years ago and it will take some digging.
Since the authors were too afraid to propose an explanation for why estrogen appears anabolic in other studies, I will propose one. Estrogen, when administered to healthy people, tends to irritate the adrenals and produce an elevation of DHEA levels and DHEA has been proven to have anabolic effects in bone by conversion into T and DHT. But estrogen by itself is not anabolic, and the simple fact that estrogen powerfully increases prolactin (which is cataboic for both bone and muscle) should give all estrogen-peddlers a pause.

@AretnaP may want to look at this too.

Influence of aromatase inhibition on the bone-protective effects of testosterone. - PubMed - NCBI
"...TE‐ and TREN‐treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co‐administration slightly inhibited the suppression of bone resorption in TE‐treated animals but did not alter TE‐induced suppression of bone formation or the osteogenic effects of this androgen. In TREN‐treated animals, AN co‐administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co‐ administration did not alter androgen‐induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity."

"...By day 21, ORX +TE + AN animals gained more body mass than all other groups, with the exception of SHAMs (p < 0.05), and this difference was maintained throughout the remainder of the study. No differences in femoral or tibial length/mass were present among groups (data not shown)."

"...LABC mass was 45% lower in ORX and ORX þ AN animals compared with SHAMs ( p < 0.001, Supplemental Table S1). Conversely, LABC mass in TE and TREN animals was 38% to 42% greater than SHAMs ( p < 0.001) and >2.5 times larger than ORX animals ( p < 0.001), a result that was not inhibited by AN co‐administration. Retroperitoneal fat mass was 22% to 24% higher in ORX and ORX þ AN animals compared with SHAMs ( p < 0.05, Supplemental Table S1). All androgen treatments prevented the ORX ‐induced increase in retroperitoneal fat mass, with fat mass being 33% lower in ORX + TE ( p < 0.01), 23% lower in ORX + TE + AN ( p < 0.05), 19% lower in ORX + TREN (nonsigni ficant), and 31% lower in ORX + TREN + AN animals ( p < 0.01)."

"...Herein, we report that TE (an aromatizable androgen) and TREN (a nonaromatizable, nonestrogenic T analogue) provide equal and complete protection against ORX‐induced bone loss in skeletally mature adult male rats. In addition, co‐administration of AN (a potent aromatase inhibitor) did not alter these effects, suggesting that the bone maintenance we observed was androgen‐mediated and occurred independent of the aromatase enzyme. Interestingly, we observed similar myotrophic and lipolytic effects from TE and TREN, and aromatase inhibition did not alter these effects. These findings provide evidence that androgens exert direct effects on musculoskeletal and adipose tissue, and that aromatase activity is not essential for these effects."


"...These results are somewhat surprising, given the plethora of direct and indirect evidence supporting the influence of E2 on the adult male skeleton.(5) For example, elevated bone resorption and reduced bone formation occur in adult men undergoing GnRH‐induced sex‐steroid deficiency.(17) In this model, administration of either physiologic T or physiologic E2 prevents the deleterious alterations in bone turnover. However, the effects of administered T appear to be primarily mediated by aromatase, given that elevated bone turnover persists subsequent to co‐administration of a physiologic dose of T plus letrozole (an aromatase inhibitor).(17) Similarly, pharmacologic aromatase inhibition (via vorozole) increased bone resorption and reduced BMD in aged (12‐month) intact male rats,(20) effects that were prevented by E2 administration.(21) Interestingly, our evidence indicates that androgens are also capable of directly regulating bone turnover. This unique finding certainly does not undermine the known effects of E2 on bone maintenance in males, especially considering that older hypogonadal men rarely exhibit estrogen deficiency and under most circumstances have higher circulating E2 concentrations than postmenopausal females. Instead, our results appear to demonstrate that aromatase activity is not essential for bone maintenance in the presence of supraphysiologic androgens, which may explain why higher‐than‐ replacement T enhances BMD in older hypogonadal men."

"...In contrast to the above results, DHT (a nonaromatizable T metabolite) fully prevents ORX‐induced bone loss when administered to young (7‐week‐old) ORX male rodents, although the potential influence of adrenal‐derived E2 was not accounted for in this study.(38) Regardless, neither T nor DHT administration restores bone mass in male androgen receptor‐knockout mice,(15) and ORX worsens bone loss in male ArKO mice,(39) demonstrating the complementary influence of androgens and estrogens in the developing male skeleton. Androgens also influence skeletal muscle and adipose tissue. We observed equal myotrophic effects after TE and TREN administration, which corroborates previous findings from our laboratory(10,16) and from a number of studies in ruminants demonstrating that aromatizable and nonaromatizable androgens produce similar improvements in lean mass.(31) Interestingly, these myotrophic effects were not influenced by AN, which supports the results of a recent clinical trial reporting that aromatase inhibition does not alter T‐mediated myotrophic effects in adult men.(40) We also observed that TE and TREN produced similar reductions in adiposity and that aromatase inhibition did not influence these androgen‐induced lipolytic effects. It is likely that these results were direct androgen‐ mediated effects given that human preadipocytes and mature adipocytes express ARs(41) and that other nonaromatizable androgens inhibit adipogenesis."
 
OP
BestSinceDAYONE
Joined
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Messages
495
I beg to disagree. In addition to what @aguilaroja posted I will add the study below. I have been aware for a long time about the myth among bodybuilders, doctors, and veterinarians concerning the necessity of estrogen of anabolism. I don't think that myth has much basis in reality, and while there are not that many studies to back up my point, here is at least one that illustrates my point (and Peat's and @aguilaroja's) perfectly. Namely, estrogen is NOT needed for anabolic effects of steroids like testosterone or trenbolone on neither muscle nor bone. In fact, adding an aromatase inhibitor to T therapy resulted in the greatest anabolic effects compared to the other treatment groups. In addition, adding an aromatase inhibitor to the trenbolone group resulted in much bigger fat loss than any other treatment group. As you can see, even the study authors hardly believe their own results and sound almost apologetic in the Discussion section where they keep mentioning the "well-established" role of estrogen in protecting bone and muscle tissue. But, as they used to say in graduate schools back in the first half of the 20th century, even the most convenient theory can get murdered by a gang of brutal facts:): There are other, older studies showing confirming the findings of this study and I will post them when I find some free time as I read them years ago and it will take some digging.
Since the authors were too afraid to propose an explanation for why estrogen appears anabolic in other studies, I will propose one. Estrogen, when administered to healthy people, tends to irritate the adrenals and produce an elevation of DHEA levels and DHEA has been proven to have anabolic effects in bone by conversion into T and DHT. But estrogen by itself is not anabolic, and the simple fact that estrogen powerfully increases prolactin (which is cataboic for both bone and muscle) should give all estrogen-peddlers a pause.

@AretnaP may want to look at this too.

Influence of aromatase inhibition on the bone-protective effects of testosterone. - PubMed - NCBI
"...TE‐ and TREN‐treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co‐administration slightly inhibited the suppression of bone resorption in TE‐treated animals but did not alter TE‐induced suppression of bone formation or the osteogenic effects of this androgen. In TREN‐treated animals, AN co‐administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co‐ administration did not alter androgen‐induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity."

"...By day 21, ORX +TE + AN animals gained more body mass than all other groups, with the exception of SHAMs (p < 0.05), and this difference was maintained throughout the remainder of the study. No differences in femoral or tibial length/mass were present among groups (data not shown)."

"...LABC mass was 45% lower in ORX and ORX þ AN animals compared with SHAMs ( p < 0.001, Supplemental Table S1). Conversely, LABC mass in TE and TREN animals was 38% to 42% greater than SHAMs ( p < 0.001) and >2.5 times larger than ORX animals ( p < 0.001), a result that was not inhibited by AN co‐administration. Retroperitoneal fat mass was 22% to 24% higher in ORX and ORX þ AN animals compared with SHAMs ( p < 0.05, Supplemental Table S1). All androgen treatments prevented the ORX ‐induced increase in retroperitoneal fat mass, with fat mass being 33% lower in ORX + TE ( p < 0.01), 23% lower in ORX + TE + AN ( p < 0.05), 19% lower in ORX + TREN (nonsigni ficant), and 31% lower in ORX + TREN + AN animals ( p < 0.01)."

"...Herein, we report that TE (an aromatizable androgen) and TREN (a nonaromatizable, nonestrogenic T analogue) provide equal and complete protection against ORX‐induced bone loss in skeletally mature adult male rats. In addition, co‐administration of AN (a potent aromatase inhibitor) did not alter these effects, suggesting that the bone maintenance we observed was androgen‐mediated and occurred independent of the aromatase enzyme. Interestingly, we observed similar myotrophic and lipolytic effects from TE and TREN, and aromatase inhibition did not alter these effects. These findings provide evidence that androgens exert direct effects on musculoskeletal and adipose tissue, and that aromatase activity is not essential for these effects."


"...These results are somewhat surprising, given the plethora of direct and indirect evidence supporting the influence of E2 on the adult male skeleton.(5) For example, elevated bone resorption and reduced bone formation occur in adult men undergoing GnRH‐induced sex‐steroid deficiency.(17) In this model, administration of either physiologic T or physiologic E2 prevents the deleterious alterations in bone turnover. However, the effects of administered T appear to be primarily mediated by aromatase, given that elevated bone turnover persists subsequent to co‐administration of a physiologic dose of T plus letrozole (an aromatase inhibitor).(17) Similarly, pharmacologic aromatase inhibition (via vorozole) increased bone resorption and reduced BMD in aged (12‐month) intact male rats,(20) effects that were prevented by E2 administration.(21) Interestingly, our evidence indicates that androgens are also capable of directly regulating bone turnover. This unique finding certainly does not undermine the known effects of E2 on bone maintenance in males, especially considering that older hypogonadal men rarely exhibit estrogen deficiency and under most circumstances have higher circulating E2 concentrations than postmenopausal females. Instead, our results appear to demonstrate that aromatase activity is not essential for bone maintenance in the presence of supraphysiologic androgens, which may explain why higher‐than‐ replacement T enhances BMD in older hypogonadal men."

"...In contrast to the above results, DHT (a nonaromatizable T metabolite) fully prevents ORX‐induced bone loss when administered to young (7‐week‐old) ORX male rodents, although the potential influence of adrenal‐derived E2 was not accounted for in this study.(38) Regardless, neither T nor DHT administration restores bone mass in male androgen receptor‐knockout mice,(15) and ORX worsens bone loss in male ArKO mice,(39) demonstrating the complementary influence of androgens and estrogens in the developing male skeleton. Androgens also influence skeletal muscle and adipose tissue. We observed equal myotrophic effects after TE and TREN administration, which corroborates previous findings from our laboratory(10,16) and from a number of studies in ruminants demonstrating that aromatizable and nonaromatizable androgens produce similar improvements in lean mass.(31) Interestingly, these myotrophic effects were not influenced by AN, which supports the results of a recent clinical trial reporting that aromatase inhibition does not alter T‐mediated myotrophic effects in adult men.(40) We also observed that TE and TREN produced similar reductions in adiposity and that aromatase inhibition did not influence these androgen‐induced lipolytic effects. It is likely that these results were direct androgen‐ mediated effects given that human preadipocytes and mature adipocytes express ARs(41) and that other nonaromatizable androgens inhibit adipogenesis."

https://www.nejm.org/doi/full/10.1056/NEJM199707103370204

"In an attempt to arrest his persistent linear growth and stimulate epiphyseal closure, the patient, after giving informed consent, was treated with 250 mg of testosterone enanthate intramuscularly every 10 days for 6 months. There were no clinical, behavioral, hormonal, or metabolic changes, except for a small decrease in the serum concentration of HDL cholesterol (Table 1). His bone age did not change, and moderate bone pain persisted."

Aromatase inhibitors in men: effects and therapeutic options

Think you need to review this one a bit more closely...
 

haidut

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https://www.nejm.org/doi/full/10.1056/NEJM199707103370204

"In an attempt to arrest his persistent linear growth and stimulate epiphyseal closure, the patient, after giving informed consent, was treated with 250 mg of testosterone enanthate intramuscularly every 10 days for 6 months. There were no clinical, behavioral, hormonal, or metabolic changes, except for a small decrease in the serum concentration of HDL cholesterol (Table 1). His bone age did not change, and moderate bone pain persisted."

Aromatase inhibitors in men: effects and therapeutic options

Think you need to review this one a bit more closely...

I am aware of studies like that. The one I posted also quotes similar ones. Like I said, there could be other explanations for the "beneficial" effects of estrogen on bone - i.e. stimulating DHEA synthesis in healthier people. AFAIK, none of these studies have isolated the effects of estrogen from the effects of other steroids.
As far as the persistent bone growth in aromatase deficiency or inhibition - how does that contradict what I said - i.e. estrogen is not needed for bone growth? It actually seems to confirm it, doesn't it? The osteopenia could be from excessive linear growth. Clearly, if your bones keep growing in length and your daily calcium/protein intake is more or less constant, then you can't expect much bone thickness, right? Something's gotta give.
 
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I am aware of studies like that. The one I posted also quotes similar ones. Like I said, there could be other explanations for the "beneficial" effects of estrogen on bone - i.e. stimulating DHEA synthesis in healthier people. AFAIK, none of these studies have isolated the effects of estrogen from the effects of other steroids.
As far as the persistent bone growth in aromatase deficiency or inhibition - how does that contradict what I said - i.e. estrogen is not needed for bone growth? It actually seems to confirm it, doesn't it? The osteopenia could be from excessive linear growth. Clearly, if your bones keep growing in length and your daily calcium/protein intake is more or less constant, then you can't expect much bone thickness, right? Something's gotta give.

How do you explain the excessive joint point that comes with the use of Aromatase Inhibitors such as Anastrozole / Letro etc. Anastrozole is even associated with hair loss

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e21619

So the whole theory:

Estrogen --> Inflammation --> Hair loss

Doesn't really make sense.

lol I keep saying we WON'T have a nuclear war because of trump's use of fin

Finasteride is feminizing and DHT has calming effects on the brain.

More female leaders of countries have engaged in wars than men, look it up.

That being said, his personality is that he cares A LOT about being liked / going with public sentiment (hence the Syria bombings which his supporters hated)
 
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haidut

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How do you explain the excessive joint point that comes with the use of Aromatase Inhibitors such as Anastrozole / Letro etc. Anastrozole is even associated with har

Well, there is a difference between joint pain and actual osteoporosis. So, I would not use the fact that too little estrogen causes joint pain (and only in some people) to say that because if this effect estrogen is required for bone health and preventing osteoporosis. But I think the actual point was whether estrogen can be suppressed and muscle/bone growth still be unaffected. The answer seems to be yes. Some estrogen is (maybe) needed and btw the AI did not suppress it down to zero. But apparently, even with say 75%+ suppression (which is what anastrozole typically achieves) muscle/bone growth is not affected negatively. In fact, linear bone growth is accelerated as per your study. Which means most people can function just fine on a lot less estrogen than they normally carry. Muscle and bone growth are inhibited primarily by cortisol and all anabolic steroids are glucocorticoid antagonists and/or inhibitors of cortisol synthesis.
Structural Requirements For Optimal Anticatabolic (Anabolic) Steroid
 
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