Brain estrogen creation 'critical to maintain full sexual activity or desire in males'

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Cataceous

Super Moderator
A tip of the hat to "PakMan" at PeakT for the reference to this article. The underlying work is on mice, but may have implications for humans.

Summary: Researchers have uncovered specific regions of brain tissue where aromatase is present, that drives male sexual desire. Aromatase converts testosterone into estrogen in the brain, driving male sexual activity.
Source: Northwestern University
The locus of male sexual desire has been uncovered in specific regions of brain tissue where a key gene named aromatase is present, reports a new Northwestern Medicine study in mice.​
The gene regulates sexual behavior in men, and thus can be targeted by drugs to either increase its function for low sexual desire or decrease its function for compulsive sexual desire, scientists said. Aromatase converts testosterone to estrogen in the brain, which drives male sexual activity.​
The study was published Sept. 10 in the journal Endocrinology.
Aromatase’s full function in the adult brain had not previously been known.​
“This is the first key finding to explain how testosterone stimulates sexual desire,” said senior author Dr. Serdar Bulun, chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Medicine.​
When Northwestern scientists knocked out aromatase selectively in the brain, sexual activity in male mice decreased by 50%, despite their having higher levels of blood testosterone levels (compared with control male mice).​
...​

Original article:
 
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Nelson Vergel

Founder, ExcelMale.com
 

DS3

Well-Known Member
A tip of the hat to "PakMan" at PeakT for the reference to this article. The underlying work is on mice, but may have implications for humans.

Summary: Researchers have uncovered specific regions of brain tissue where aromatase is present, that drives male sexual desire. Aromatase converts testosterone into estrogen in the brain, driving male sexual activity.
Source: Northwestern University
The locus of male sexual desire has been uncovered in specific regions of brain tissue where a key gene named aromatase is present, reports a new Northwestern Medicine study in mice.​
The gene regulates sexual behavior in men, and thus can be targeted by drugs to either increase its function for low sexual desire or decrease its function for compulsive sexual desire, scientists said. Aromatase converts testosterone to estrogen in the brain, which drives male sexual activity.​
The study was published Sept. 10 in the journal Endocrinology.
Aromatase’s full function in the adult brain had not previously been known.​
“This is the first key finding to explain how testosterone stimulates sexual desire,” said senior author Dr. Serdar Bulun, chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Medicine.​
When Northwestern scientists knocked out aromatase selectively in the brain, sexual activity in male mice decreased by 50%, despite their having higher levels of blood testosterone levels (compared with control male mice).​
...​

Original article:
I will be curious to see if there is a reference range for suggested libido optimization in further research. Anecdotally, my libido is at its highest when it starts to peak a couple of days before my next (weekly) AI dosage. However, typically the day of my AI dosage my libido has decreased significantly, coupled with a more feminized ‘feeling’. Perhaps there is a level of dimishing returns with estrogen that, once surpassed, begins to express an inverse relationship with libido.

All anecdotal evidence and hypothesis driven. Curious to see what future research brings.
 

Cataceous

Super Moderator
If this article is accurate then anastrozole is relatively safe in this regard due to reduced penetration of the blood-brain barrier:

Another seldom considered aspect of A.I. use is their effect on brain function. While all A.I.’s affect the level of estrogen exposure in the brain, both letrozole and exemestane demonstrate an increased aptitude for crossing the blood-brain barrier, making them capable of adversely affecting neurosteroid balance to a greater degree than anastrozole. Along with enhanced blood-brain permeability, letrozole also suffers from a reduced clearance rate, allowing concentrations within the brain to climb even higher. While exemestane clears more quickly, its permanent deactivation of aromatase makes it equally problematic in this regard, as the body must first produce additional aromatase before proper neurosteroid balance can be restored.
Due to its greater specificity of action (less apt to interfere with non-target tissues), anastrozole has the clear advantage in this area. It does not penetrate the blood brain barrier as readily, making it much less likely to cause side effects such as sexual dysfunction, libido issues, or depression. Letrozole also appears to negatively impact cellular response to estrogen in areas of the brain that help govern mood, leaning, and memory. Lastly, exemestane and letrozole can disrupt steroid production within the adrenal cortex, while anastrozole does not. Many of the side effects associated with neurosteroid imbalance, such as sexual dysfunction, reduced libido, and depression, have been reported in those who use letrozole. Although exemestane appears to be less problematic in these areas, one could postulate that this is largely due to the infrequent dosing patterns employed by those who use the drug, rather than a diminished ability to affect neurosteroid balance.
 

Nelson Vergel

Founder, ExcelMale.com
There is evidence in some studies of this:


"In 2013, Finkelstein et al. looked at the effects of testosterone and estrogen on male sexual function. They found that the administration of testosterone with and without aromatase inhibitors markedly impaired sexual function when aromatization was inhibited.18 In addition, a study by Ramasamy et al. in 2014 showed that libido was increased in men receiving TST when testosterone levels were >300 ng dl-1 and estradiol levels were >5 ng dl-1. Most compelling is the fact that in men with serum testosterone <300 ng dl-1, sexual drive was seen to be markedly higher when estradiol levels were >5 ng dl-1.19 In addition, when patients with low testosterone were treated with letrozole, a potent aromatase inhibitor, libido was decreased, suggesting that complete elimination of estradiol and decreasing the T/E ratio too severely, adversely affects sexual desire in men.20 These studies provide evidence that both estrogen and testosterone are necessary for normal libido in testosterone-deficient men. Clinically, the dependence of libido in hypogonadal men on both testosterone and estrogen indicates that a cautious approach to the use of aromatase inhibitors is warranted and that the T/E ratio has an impact. It might be reasonable that while prescribing TST one should monitor the levels of both testosterone and estrogen and their relationship to each other. "

 

DorianGray

Active Member
Excellent post and references. So could one assume that it may not be just the production of male estrogen as detected in blood tests but aromatase production specifically in the brain that achieves the effect? As in other brain hormones, epigentic factors, aging, etc., could cause loss of production in the brain that other systemic treatment would not affect?
 

Cataceous

Super Moderator
... So could one assume that it may not be just the production of male estrogen as detected in blood tests but aromatase production specifically in the brain that achieves the effect? ...

This work supports the idea. "These data suggest that aromatase is necessary for sexual activity in male mice. Testicular aromatase plays a dominant role in male sexual behavior, but brain aromatase specifically contributes to regulating the initiation and frequency of sexual activity."

In trying to tease out more details the authors found that castrated mice lacking brain aromatase could have sexual behavior "rescued" with a combination of exogenous testosterone and estrogen, but not testosterone alone. Castrated control mice could be "rescued" with exogenous testosterone alone. "Taken together, our findings indicate that a combination of T and E2 is required to rescue appropriate sexual behavior in mice with deficient E2 production in the brain."

... As in other brain hormones, epigentic factors, aging, etc., could cause loss of production in the brain that other systemic treatment would not affect?

This latter part is less certain, as treatment with exogenous estradiol helped the mice regain sexual behavior. As a practical matter, the side effects of sufficient doses of exogenous estradiol could make this treatment impractical in human males.
 

DorianGray

Active Member
Others seemed to be on to this in 2011, but also considered the influence of progesterone in this interesting paper:

 

DS3

Well-Known Member
Interesting review demonstrated that the benefit elevated estrogen provides to cognition is not uniform across neuroanatomical structures, and in fact has been demonstrated to increase certain forms of cognitive function while impairing other forms.

“We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures.”

@Cataceous @Nelson Vergel
 
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DS3

Well-Known Member
“Although Premarin elevated estradiol and estrone levels, there was no association between hormone levels and cognitive functioning after either 2 or 12 months of treatment.”

 

DS3

Well-Known Member
Another study indicating that increases in memory from estrogen are not uniform across brain structures.

Conclusion: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.

 

TorontoTRT

Active Member
I will be curious to see if there is a reference range for suggested libido optimization in further research. Anecdotally, my libido is at its highest when it starts to peak a couple of days before my next (weekly) AI dosage. However, typically the day of my AI dosage my libido has decreased significantly, coupled with a more feminized ‘feeling’. Perhaps there is a level of dimishing returns with estrogen that, once surpassed, begins to express an inverse relationship with libido.

All anecdotal evidence and hypothesis driven. Curious to see what future research brings.
I’ve never felt any feminizing feelings ever and I’ve had estrogen over 75 on through many times. Also no AI ever.
 

JanSz

New Member
Dr. Mariano has said for years that estrogen is responsible for sex drive in males. Wish he would get back on the boards.
Yes, dr. Mariano, where is he posting now?
@wondering

you may recall a fellow who called himself a G-man
on late dr John Crisler board.
That was many years ago, likely over 10 or 15 years.
He was able to figure out just about everything.
Got his penis working overtime.
His problem was that he was not able to finish, no orgasm.
Eventually, he lost his wife, she was not able to put up with so much demand for sex.

That is my problem now. Not 100% like his but close.
At least I get orgasm maybe once a week.
When it comes it is usually very intensive, much more intensive than in my younger days.

Any ideas on how to deal with that?

.
.
 
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josborne3

New Member
Since having a prostatectomy which also required removing my seminal vessel, the intensity of my "dry" orgasms have greatly increased. Seems odd, except when you aren't able to judge your orgasm intensity by how much and how hard you ejaculate, it frees you up to focus on the orgasm.

My urologist told me I might spontaneously pass some urine during an orgasm. He was right. The easy fix is to be sure to pee prior to having sex. Although, the sensation of squirting a few drops of urine isn't unpleasant.

Sex after a prostatectomy is possible . One just has to be more flexible and inventive. I inject tri-mix in order to achieve a erection. However, a orgasm is possible and intense when not fully erect.
 

wondering

Active Member
Yes, dr. Mariano, where is he posting now?
@wondering

you may recall a fellow who called himself a G-man
on late dr John Crisler board.
That was many years ago, likely over 10 or 15 years.
He was able to figure out just about everything.
Got his penis working overtime.
His problem was that he was not able to finish, no orgasm.
Eventually, he lost his wife, she was not able to put up with so much demand for sex.

That is my problem now. Not 100% like his but close.
At least I get orgasm maybe once a week.
When it comes it is usually very intensive, much more intensive than in my younger days.

Any ideas on how to deal with that?

.
.

oh, your issues can be one of a zillion things. Dr. M's site has been inactive for long time -his site is:https://definitivemind.com. But it has bene inactive for some time. he as writing a book, but I haven't seen one pop up on Amazon yet.
 
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