Estradiol in Men: Libido and Brain Function

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Role of estradiol in the brain

The effect of estradiol on libido is seen at various levels of regulation, starting with direct effects in the brain (Figure 1). Areas of the brain that control sexual behavior in mammals are thought to do so via pheromones that induce specific sexual effects on the autonomic nervous system, including changes in mood and sexual arousal. Pheromones produce increased activity in the medial preoptic area/anterior hypothalamus.1 Neurons, the most basic electrical information-transmitting cells in the central nervous system and peripheral nervous system, as well as astrocytes, star-shaped glial cells which fulfill a number of functions in the central nervous system, both convert testosterone to estrogen with aromatase. The preoptic area and anterior hypothalamus contain the highest levels of aromatase and estrogen receptors (ERs) in male rodents.2,3 Similarly, it is well known that selective serotonin reuptake inhibitors diminish libido. Serotonin receptors follow a pattern of distribution similar to that of ERs in the brain.4 However, the interaction of estradiol and serotonin is complex and will subsequently be addressed. Finally, aromatase activity is highest in the brain during development. Thus, not only does estradiol modulate sexual behavior in the adult male, it also appears to organize the early brain to program sexual behavior.3

Estradiol effect at low testosterone levels

To discern the effect of estradiol, it is important to evaluate its effect on libido at both low and normal levels of circulating testosterone. Decreased testosterone is clearly associated with low libido in males.5 In men with diminished testosterone, the administration of exogenous estradiol has been shown to increase libido.6 This finding is supported by rodent studies demonstrating that castrated animals given exogenous estrogen show an increase in sexual activity in a dose- and temporal-dependent manner.7 In addition, in a unique case report of a male patient with aromatase deficiency and hypogonadism, both estrogen and testosterone were required to increase libido, whereas neither hormone could achieve the effect alone suggesting that estrogen plays a necessary role in sexual desire in the setting of low testosterone.8

Similarly, patients with prostate cancer treated with androgen deprivation therapy (ADT) serve as a good model for the influence of estrogen on libido. When castrate levels of androgens were reached (T <50 ng dl-1), uniform adverse effects of hot flashes, erectile dysfunction (ED), and decrease in libido were reported.9 When comparing androgen receptor (AR) blockers versus castration, the former had better outcomes in maintaining sexual activity, presumably by increased testosterone conversion to estrogen.10This evidence, though indirect, does perhaps suggest that elevated estrogen in men with low or absent testosterone can sustain libido. In addition, administering estradiol to men undergoing ADT for prostate cancer could possibly reduce damage to areas of the brain associated with sexual performance. Thus, an overall increase in sexual quality of life could be achieved.6

Role of estradiol in eugonadal men

While estradiol has been shown to have a positive effect on libido at low levels of testosterone, a limited number of studies have looked into the effect of estradiol supplementation in eugonadal men and reported conflicting results. One study with continuous estradiol administration in men who had normal testosterone levels showed decreases in sexual interest, fantasy, masturbation, and erections.11 In contrast, a randomized, double-blind study conducted on 50 men ages between 20 and 40 years demonstrated that sexual activity was unaffected.12
Uncontrolled case reports also have shown conflicting results. A man with aromatase deficiency was noted to have a relevant increase in sexual behavior with estrogen supplementation,13 while other aromatase-deficient men noted no change in their sexual function.14 These natural models, which have the potential to provide some clarity, along with results of the limited trials undertaken, have not provided definitive evidence one-way or the other regarding estradiol's effects on libido in the eugonadal male.


Role of estradiol in hypogonadal men treated with testosterone supplementation therapy

Perhaps, most relevant to the discussion is the use of testosterone supplementation therapy (TST). The goal of TST, regardless of the method used, should be to maintain not only physiologic levels of testosterone, but also its metabolites, including estradiol which optimizes libido.15

In men with secondary hypogonadism (functioning testes and relatively low levels of luteinizing hormone [LH] and testosterone), clomiphene citrate was used to increase testosterone by acting centrally on the ER weakly. Clomiphene citrate administration raised endogenous testosterone while increasing the testosterone to estradiol (T/E) ratio.16 Also, in a later study, clomiphene citrate administered to hypogonadal men produced an increase in libido, energy, and sense of well-being.17

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.

Clearly, the effect of estradiol on male sexual desire is linked to testosterone levels, as there are different outcomes when estrogen is administered at low and normal testosterone levels. Another example of this duality is seen in men with androgen resistance, where unfettered estrogen is able to stimulate subsequent breast development. However, in men with normal androgen receptor activity, estradiol is unable to stimulate breast development.(If you have gyno issues it's not high e2 it's androgen resistance!!)21 This is thought to be due to an imbalance between the inhibitory and stimulatory effect of these hormones.22,23 Whatever the pathophysiology in breast development or libido, these hormones seem to be inextricably linked in the complicated physiology of male sexuality and development.

Finally, the effect of estradiol on mood must be considered. As mood can correlate with sexual interest, it is reasonable to consider these data when discussing the role of estradiol on libido. While cognition, well-being, and depressive symptoms improve in men whose low testosterone levels were corrected,24,25,26higher levels of estrogen also have been associated with less depression in older patients of both sexes.27In addition, estrogen supports serotonin levels and affects the amount of 5-HT receptors in the brain, and depending on receptor subtype, there is sexual inhibition or facilitation.28,29,30 A recent study showed a significant positive correlation between endogenous plasma estradiol levels and cortical 5-HT2A binding in men, with no independent effects on these receptors from testosterone.31 In addition, when serotonin binds to these 5-HT2A receptors in the cortex, limbic system, hypothalamus, and midbrain, sexual desire is inhibited with subsequent induction of refractoriness and sexual satiety.32 The interaction of estrogen with serotonin is complex, with overlapping influences that reaches beyond sexual desire including mood regulation and cognition.33 This fact makes its true impact on sexual desire and behavior difficult to fully elucidate.

Estradiol and erectile function and more - The role of estradiol in male reproductive function
 
Defy Medical TRT clinic doctor
Very interesting guys, it explains a lot why I got so bad libido, depression and other issues from arimidex and that even high levels of testosterone couldn't have an impact on these symptoms because estradiol is so very important for things we are all after
hopefully doctors will stop prescribing AIs to TRT patients, it's not a waste product and makes us hornier, healthier and happier
some folks who are not on TRT and have high e2 should know that they are actually blessed they would feel way worse if they had low e2 in addition to low t
 

Giovanni73

New Member
On 120 mgs a week my total T came back 616 and my E2 50... However, other than soar, itchy nipples, my libido was through the roof. Yesterday I took .25 of Arimidex with 5 mgs of cialis and had a limp noodle... Ugh... What the hell? Maybe the high estrogen works good for me. I am sure it was the arimidex... It made me very embarrassed if you know what I mean... I might just accept high estradiol and learn to embrace it.
 
Very interesting guys, it explains a lot why I got so bad libido, depression and other issues from arimidex and that even high levels of testosterone couldn't have an impact on these symptoms because estradiol is so very important for things we are all after
hopefully doctors will stop prescribing AIs to TRT patients, it's not a waste product and makes us hornier, healthier and happier
some folks who are not on TRT and have high e2 should know that they are actually blessed they would feel way worse if they had low e2 in addition to low t

Id give you my high E for a month and let you see what that's like, too. You won't be glowing about E afterwards.
 
so what is bothering you with high e2 Vince Carter? what are your symptoms? the ones you described in your thread like night sweats and hot flashes for me its symptoms I get after my e2 gets too low and I have them for a while even if e2 gets high on bloodwork I don't know why. any AI in trt protocol for me = e2 gets crashed = limp penis, no libido, night sweats, hot flashes, brain fog, anxiety and feeling like I have 0 testosternoe in my body even if its 1000 total t at least for half a year..
 
Appreciate this article. I have been wondering the same recently as my TRT is very much dialed in, but libido seems to be a dodging target. I’ve noticed that when I let E2 rise a bit by delaying a dose here or there of my very low dose AI (0.07 anastrozole ED), I will have a couple of days of very strong libido, before it goes away again when I take the next dose. That to say I don’t think it’s as simple as targeting 20-30 in sensitive E2 readings; T/E2 ratios seems to matter more. Plan to discuss in my next check-up.
 
On 120 mgs a week my total T came back 616 and my E2 50... However, other than soar, itchy nipples, my libido was through the roof. Yesterday I took .25 of Arimidex with 5 mgs of cialis and had a limp noodle... Ugh... What the hell? Maybe the high estrogen works good for me. I am sure it was the arimidex... It made me very embarrassed if you know what I mean... I might just accept high estradiol and learn to embrace it.

In my experience, there is no worse ED ever (even before I was on TRT at all) than when E2 is too low. No amount of Viagra or Cialis works for me in this scenario.
 
On 120 mgs a week my total T came back 616 and my E2 50... However, other than soar, itchy nipples, my libido was through the roof. Yesterday I took .25 of Arimidex with 5 mgs of cialis and had a limp noodle... Ugh... What the hell? Maybe the high estrogen works good for me. I am sure it was the arimidex... It made me very embarrassed if you know what I mean... I might just accept high estradiol and learn to embrace it.

The normal amount of Cialas for ED with one time use is 10-20mg 20 being the preferred if you truely have ED.
Low dose cialas 5mg is suppose to be taken once or twice everyday with or without sex.
 

Nashtide

Member
In my experience, there is no worse ED ever (even before I was on TRT at all) than when E2 is too low. No amount of Viagra or Cialis works for me in this scenario.
This is an interesting issue. I think we tend to have symptoms then try to match those symptoms to a blood test. I'm 56. Been on TRT for 21/2 years. Never experienced ED while on TRT or before TRT. I've had my E2 all over the place while on TRT and it never caused ED. Been as low as 12 and as high as 40. So, like all hormone related issues, nothing is as simple as we hope it is.
 

Giovanni73

New Member
The normal amount of Cialas for ED with one time use is 10-20mg 20 being the preferred if you truely have ED.
Low dose cialas 5mg is suppose to be taken once or twice everyday with or without sex.
Yes, I am going to take every day, but the damn price is crazy, but I found a reputable place on line (recommended by a member on here) and the price is fantastic. Can you do 10 mgs a day of Cialis? Just doing 5 mgs three times a week shot my erections and libido through the roof.
 
This is an interesting issue. I think we tend to have symptoms then try to match those symptoms to a blood test. I'm 56. Been on TRT for 21/2 years. Never experienced ED while on TRT or before TRT. I've had my E2 all over the place while on TRT and it never caused ED. Been as low as 12 and as high as 40. So, like all hormone related issues, nothing is as simple as we hope it is.
have you ever taken 1mg arimidex every day for a week? that would give ed and low libido to most sex hungry stalion
 
Yes, I am going to take every day, but the damn price is crazy, but I found a reputable place on line (recommended by a member on here) and the price is fantastic. Can you do 10 mgs a day of Cialis? Just doing 5 mgs three times a week shot my erections and libido through the roof.
I would use the values we have been talking about as guide lines. I only use the minimum required. You have to figure out how much that is for you. As you age it will take more and more so use good judgement. There is no dought 5mg of Cialas and 1 mg of Doxazosin together is one powerhouse for stiffies. i could knock a hole thru sheetrock but the side effect of lower back pain and stuffy nose suck. I am currently looking for other options.
 

Giovanni73

New Member
I would use the values we have been talking about as guide lines. I only use the minimum required. You have to figure out how much that is for you. As you age it will take more and more so use good judgement. There is no dought 5mg of Cialas and 1 mg of Doxazosin together is one powerhouse for stiffies. i could knock a hole thru sheetrock but the side effect of lower back pain and stuffy nose suck. I am currently looking for other options.

Do you take 5 mg of Cialis a day? I hear the generic Cialis from India is just a good and a lot cheaper. They use the same active ingredient. Cialis is ridiculous with their prices. Never heard of Doxazosin... I will Look it up. Is it expensive like Cialis?
 

DorianGray

Active Member
In this study here, The role of estradiol in male reproductive function, sub-heading

ASSOCIATION BETWEEN ESTRADIOL AND ERECTILE FUNCTION​

end of second paragraph, it states:

"...A case–control study of male outpatients with ED with venous leakage showed that the only difference between the men with and without ED was an increased estradiol level. The authors concluded that estradiol increases venous vascular permeability via VEGF and has a detrimental effect on erectile function through increased venous leakage..."

It seems to have an opposite effect in men with venous leakage. Am I understanding that correctly?
 

Nelson Vergel

Founder, ExcelMale.com
We discussed that here

 

Nelson Vergel

Founder, ExcelMale.com
"
As noted above, the serum concentration of E-2 plays a dominant role in male sexual health. Low levels of aromatase, which result in extremely low E-2 concentrations, may, nevertheless, be important in male sexual performance without affecting sexual orientation and gender identity (Gomuła, 2006, Gomuła, 2007). In patients with congenital absence of aromatase only the low-dose E-2 substitution results in significant changes in sexual behavior. Estradiol administration leads to increased erotic fantasies, masturbation, or sexual activity (Carani, et al., 1999).

My own research clearly shows that E-2 is required to maintain sexual functions in adult men (Gomuła, 2007). The manifestations thereof have been observed after prolonged hormonal therapy. Androgen deficiency patients had their testosterone levels increased for therapeutic purposes. During the therapy, a parallel increase occurred in serum E-2 concentrations, as the effect of the all-natural aromatase. Some patients had such high E-2 levels that they exceeded the normal physiological range. In order to reduce E-2 concentration, my patients received preparations blocking aromatase activity. As a result of this therapy, men characterized by high concentrations of testosterone (falling in the upper limits of normal), whose E-2 was detected at very low levels, had a total loss of libido. At the same time, those men suffered from erectile dysfunction, which could even lead to the inability to initiate or maintain an erection. Stopping the drug which blocked aromatase resolved the symptoms and resulted in a rapid return of high concentrations of E-2. Some authors report that in the activation of male sexual behavior the brain level conversion of testosterone to estradiol is of major importance and that testosterone's effects are not in themselves so important (Balthazar & Ball, 1998). Testosterone has a significant effect on the smooth muscle in the corpora cavernosa. Androgens may significantly affect the ultrastructure of the corpora cavernosa and these changes are responsible for erectile dysfunction (Traish & Kim, 2005)."

 

Nelson Vergel

Founder, ExcelMale.com
 

MIP1950

Active Member
Do you take 5 mg of Cialis a day? I hear the generic Cialis from India is just a good and a lot cheaper. They use the same active ingredient. Cialis is ridiculous with their prices. Never heard of Doxazosin... I will Look it up. Is it expensive like Cialis?
My primary back in Maryland told me that many of the ED drugs are made in India for brand name companies. Low cost to make = big profits. India has a large presence in drug manufacturing, including testosterone, but you can't get that injectable brand in the US.
 
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