The Top 18 Things You Did Not Know About Estradiol's Role in Men's Health
By Nick Gold
Table of contents
1. Brain aromatase and why it’s not a good idea to reduce its activity
2. Estrogen and its beneficial effects in bodybuilding
3. Estrogen function in men and why inhibiting its production can be detrimental
4. The effects of aromatase inhibition on bone mineral density in older men
5. High estrogen levels and prostate cancer
6. Testosterone’s conversion to estrogen is important to eliminate anxiety and depression
7. Testosterone activity in the brain
8. High estradiol levels are not correlated with erectile dysfunction
9. Estradiol improve endothelial function in healthy men
10. Estradiol and libido, erectile function and reproduction
11. How estradiol works when testosterone levels are low
12. Estradiol and its influence in eugonadal men
13. Analyzing the role of estradiol on hypogonadal men who undertake testosterone replacement therapy
14. Aromatase inhibition can decrease insulin sensitivity
15. The relationship between estrogen and bodybuilding
16. Estradiol and DHT can make you age slower
17. Symptoms of low estradiol in men
18. Estradiol and reproductive function in men
Brain Aromatase and Why It’s Not a Good Idea to Reduce Its Activity
Every man has free and bound testosterone circulating through his bloodstream. The bound testosterone is attached to either sex hormone-binding globulin or albumin.
The free testosterone is available in small quantities in comparison with the bound testosterone. A small portion of it is converted to estrogen using the enzyme called “aromatase”.
Although estrogen is a female sex hormone, it plays an important role in a male’s body too. For example, estradiol, a type of estrogen, is vital for proper sexual functioning and libido in men.
However, too much estrogen can be detrimental, leading to poor sexual functioning, poor erections, accumulation of fat in the abdominal area and male boobs (gynecomastia).
During testosterone replacement therapy (TRT), some men take drugs to inhibit aromatase and prevent it to convert too much testosterone into estrogen.
One of these drugs is anastrozole which inhibits the aromatase enzyme. Although this might sound like a good idea at first, altering the normal production of aromatase can lead to brain inflammation, studies suggest.
The levels of aromatase and estrogen have been measured in injured brains and it has been discovered that the aromatase enzyme increased to protect the damaged neurons and the connections between them.
Evidence concludes that inhibiting the normal levels of aromatase can lead to inflammation in healthy brains and more injury to already damaged brains.
This happens because the aromatase/estrogen expression is moved from neurons to astrocytes which are a different type of brain cells.
Astrocytes act as a cushion for neurons and they are usually more active when brain injury is detected. These cells can help with the healing process, but if they stay active for too long, this can lead to further damage to the brain.
Studies also show that an insufficient amount of brain aromatase can indicate neurodegenerative diseases such as Alzheimer's. Low amounts of aromatase can increase plaque development which damages the brain.
That’s why it is recommended to be careful when taking anastrozole during testosterone replacement therapy as this drug might mess with the normal levels of aromatase and lead to brain complications.
Estrogen and its beneficial effects in bodybuilding
Estrogen, one of the most important female sex hormone, is vital for professional athletes who aim at increasing their muscle mass.
For example, estrogen can increase the anabolic response by modifying the way glucose is processed in muscle tissue.
This hormone can influence the amounts of glucose 6-phosphate dehydrogenase which is directly correlated to muscle growth and repair. In other words, having adequate amounts of estrogen can maximize muscle gains and strength.
In studies performed on rats, estrogen has also been correlated with a whopping 480% increase in methyltrienolone which is an androgen connected to the levator ani muscle.
The production of growth hormone and IGF-1 (insulin-like growth factor) are also influenced by estrogen. This female sex hormone can increase the proliferation of IGF-1 in body tissues and liver which leads to greater muscle gains and protein synthesis.
Estrogen also plays an important role when it comes to serotonin production. Serotonin is known for regulating the sleep/waking cycle.
Bodybuilders who take aromatase inhibitors as drugs might have low levels of estrogen in the body. This can alter the serotonin production and lead to a thing called “steroid fatigue”.
This is usually characterized by a general feeling of tiredness which can interfere with training regimes and prevent the athlete from performing at his peak. Maximizing muscle gains can be difficult in this case.
Some of the drugs which inhibit aromatase and can lead to “steroid fatigue” are anastrozole, letrozole and fadrozole. This happens if they are taken in high quantities, above the prescribed dosage and for long period of times.
Estrogen function in men and why inhibiting its production can be detrimental
The aforementioned aromatase inhibitors are taken orally while Aromasin can be injected. There haven’t been studies assessing the short-term symptoms of these drugs on the physiology of an athlete.
However, although drugs which inhibit aromatase and subsequently reduce estrogen levels are not usually used for a long period of time, they can cause problems when the estrogen drops under the normal range limit.
Estrogen, particularly estradiol, is a powerful hormone which influences multiple body processes in both men and women.
For example, estrogen can be anabolic in certain tissues such as bone and fat. It directly impacts bone density and can influence how much fat the body accumulates, particularly in the abdominal area.
Estrogen can also have a stimulatory role and it influences protein production in the liver. It has a metabolic effect in the endocrine system and influences the binding globulins for vitamin D.
Estrogen is also a neurosteroid influencing neurotransmitters in the brain. This can have an effect on emotions, motivation, and other functions.
Since estrogen is so important in the human body, it is safe to assume that reducing it to dangerously low levels using drugs can have negative consequences on health.
Similarly, having estrogen levels above the normal limit can also be detrimental for a male’s body. The key is to maintain balance when it comes to estrogen levels and make sure that estradiol E2 doesn’t drop below 20pg/mL.
The effects of aromatase inhibition on bone mineral density in older men
A study was conducted at a tertiary care academic center in Boston, MA, measuring the levels of testosterone and estradiol of 69 men over 60 years of age.
The participants had borderline or low testosterone levels and the study included a placebo group.
The purpose of the study was to determine the effect of aromatase inhibition on bone mineral density and bone turnover.
Each participant received 1 mg anastrozole daily or a placebo drug.
At the end of the study, the serum testosterone increased from 319 ± 93 ng/dl at baseline to 524 ± 139 ng/dl in month 3 and dropped slightly after one year.
The estradiol levels also decreased from 15 at baseline to 12 after 3 months and remained there.
The bone mineral density decreased in the anastrozole group in comparison with the placebo group.
Taking aromatase inhibitors reduce the amount of testosterone which is converted to estradiol and because participants had less estradiol in their bloodstream, their bone mineral density also dropped.
This concludes that estradiol is important for bone mineral density, particularly in older men.
High estrogen levels and prostate cancer
Some studies conclude that high levels of estrogen might help develop prostate cancer cells, but men who already have prostate cancer don’t have high levels of estrogen in the bloodstream.
Other studies show that a sharp increase in estrogen levels might lead to prostate cancer, but more information is required to reach a definitive conclusion.
A small part of the free testosterone which circulates through the bloodstream is converted into estrogen. This hormone is required for maintaining proper health and avoiding cardiovascular diseases as well as diabetes type 2.
On the other hand, low testosterone levels have also been associated with an increase in prostate cancer cells.
A significant body of evidence indicates that high estrogen levels might be dangerous for men and affect their prostate only when testosterone levels are too low.
Increasing testosterone levels through TRT (testosterone replacement therapy) will also increase estrogen levels in a natural way, but this doesn't automatically mean that the risk of prostate cancer will be higher.
Approximately 50 years of studies show that testosterone administration alone doesn’t lead to prostate cancer.
Testosterone’s conversion to estrogen is important to eliminate anxiety and depression
It is estimated that approximately 20 million adults in the United States are affected by depression each year.
Many of these people receive antidepressants and anti-anxiety drugs, but this medicine can have different effects on certain people and they don’t come without side effects.
Testosterone plays an important role in reducing anxiety and depression feelings in men, while estrogen and progesterone also act together as a protective mechanism against depression in women.
Women, in particular, are 70 percent more predisposed to depression during their lifetimes, in comparison with men.
However, certain low-testosterone males also develop depression and antidepressants seem to be inefficient for them.
New evidence suggests that the conversion of testosterone to estrogen is necessary to reap the antidepressant effects of testosterone.
Professor Mohamed Kabbaj reached this conclusion during his studies which were promoted by the National Institute of Mental Health.
It has been discovered that there is a link between testosterone conversion to estrogen and depression in animal studies, but this link might be valid in human studies as well.
This might lead to new antidepressants which impact the brain differently and are more efficient for low-testosterone men.
Testosterone influences a plethora of pathways in the brain and it can have multiple side effects. That’s why it is important to develop a drug which acts only on the pathways responsible with anxiety and depression.
Some of the side effects caused by antidepressants include heart problems and these should be avoided. Better drugs are necessary to impact the brain differently and safely treat anxiety and depression feelings.
Dr. Kabbaj discovered that the antidepressant effects of testosterone happen only after this hormone has been converted to estrogen.
The conversion process is regulated by a special enzyme in the brain. Dr. Kabbaj inhibited this enzyme in the hippocampus area of the brain. This area is responsible for mood regulation and has a strong influence on how a person feels.
When this enzyme has been inhibited, the antidepressant effects of testosterone weren’t present. This leads to the conclusion that the conversion of testosterone to estrogen is very important.
Testosterone impacts the MAPK pathway in the brain to produce these positive and beneficial antidepressant effects.
However, this pathway is also implicated in multiple other body processes, including cell growth and cancer. More work is required to find out ways to get the antidepressant effects of testosterone without increasing the risk of cancer.
Testosterone activity in the brain
Tests have been done on rats to discover the behavior of testosterone when it enters the brain. Castrated rats have been injected with estradiol instead of testosterone and the recovery process of intromission and ejaculation worked normally. The estradiol was injected into the hypothalamus.
However, when DHT was injected instead of testosterone (DHT is a powerful androgen which doesn’t convert to estrogen), no recovery process was detected.
This concludes that testosterone converts to estrogen when it is injected into the hypothalamus and facilitates sexual behavior. The aromatase enzyme is present in this part of the brain as well as estrogen receptors.
It has also been discovered that injecting drugs which block the aromatization process of testosterone to estrogen can change the behavioral effects of testosterone and significantly influence sexual function.
This means that testosterone must convert to estrogen to enable proper male sexual behavior.
Further studies show that inhibiting the aromatization process in monkeys can interfere with their sexual behavior. Men who have a congenital deficiency of aromatase also have a low sex drive and they can benefit greatly from small doses of estradiol to improve sexual functioning.
The testosterone’s effects on male sexuality are twofold. This hormone influences libido directly with the help of androgen receptors and indirectly using estrogen receptors. However, more work is necessary to determine the exact differences between these effects.
High estradiol levels are not correlated with erectile dysfunction
Contrary to the popular belief, high estradiol levels are not associated with poor sexual function in males.
A study was conducted on low testosterone centers in the United States, comprising more than 34,000 men. The participants had different ages, some of them being younger than 25 while others being older than 65.
Estradiol levels were measured using electro-chemiluminescence immunoassay and it has been discovered that having too much estradiol in the bloodstream doesn’t lead to poor sex drive and erectile dysfunction.
It has also been discovered that those with low or normal estradiol levels have a higher incidence of poor sex drive and potential erectile dysfunction.
Estradiol improve endothelial function in healthy men
Studies show that estradiol (sometimes written as oestradiol) can improve endothelial function in healthy men.
The endothelium is a very thin membrane which lines up the insides of your blood vessels and heart. It can also be found on lymph vessels.
Its role is to release substances which help relax or constrict the blood vessels, depending on various factors.
The endothelium is also important for controlling platelets, blood clotting and to regulate immune function in men and women.
It is already known that supplementing with estrogen (particularly estradiol) is linked to a reduced incidence of cardiovascular disease in women who are deficient in this hormone.
The purpose of the study is to determine if estrogen can also be beneficial for the endothelial function in healthy men.
The study included 23 men aged 32 years, give or take up to 8 years. They were split into three groups.
One group was given testosterone supplements alone, one group received a combination of testosterone and 10mg of estradiol and the third group received testosterone and 20mg of estradiol.
These participants were measured one month and six months after multiple tests were performed to determine the influence of estradiol on their health.
The study concluded that those who received estradiol supplementation had a better endothelial function. This means that administering estradiol to healthy men can improve their cardiovascular system.
Estradiol and libido, erectile function and reproduction
Estradiol impacts multiple processes in a human body and it can have a strong influence on the brain.
This hormone can directly influence the brain and dictate the sexual behavior of mammals, creating arousal states and moods which are conducive to reproduction.
This is done by the release of pheromones. These substances can increase activity in the area anterior to the hypothalamus.
Neurons play an important role in converting testosterone to estrogen using the aromatase enzyme. There are billions of neurons in the brain and they transmit electrical information 24/7, helping humans function correctly.
Another important brain cell is the astrocyte. These cells help the neurons transfer information from one part of the brain to the other.
They are star-shaped cells which play an important role, particularly when the brain is injured and they also use the aromatase enzyme to convert testosterone to estrogen.
The anterior area of the hypothalamus contains numerous estrogen receptors. These receptors work similarly to selective serotonin reuptake inhibitors which are known for lowering sex drive.
This might indicate that estrogen can significantly influence sexual functioning and behaviors in men.
How estradiol works when testosterone levels are low
Having low testosterone levels can definitely lead to poor sexual functioning and lack of libido.
To determine the efficacy of estradiol in men and what influences it has, it is important to analyze it in people who have normal as well as low testosterone levels.
Studies have been done on men with low testosterone. They received doses of estradiol and reported an increased sexual drive.
These human studies are supported by the ones performed on rats. Castrated rodents were given estrogen and it has been discovered that this increased their sexual activity.
Another important finding consists of patients who had prostate cancer and received androgen deprivation therapy. This type of therapy is known to slow down or completely stop the advancing of prostate cancer since the cancerous cells require testosterone to grow.
When the androgen levels reached a critical point, the patients reported symptoms which are commonly found in people who have a low sex drive and erectile dysfunction such as hot flashes and other adverse effects.
It has also been discovered that androgen receptor blockers are more efficient in maintaining sexual activity in comparison with castration. This might happen as a result of testosterone conversion to estrogen.
It is possible that supplementing with estradiol might make patients who undertake androgen deprivation therapy have increased brain activity in those areas responsible with sexual behavior.
Estradiol and its influence in eugonadal men
Eugonadal means men with healthy testosterone levels.
Estradiol has been proven beneficial for people with low testosterone levels, increasing libido, and sexual desire. However, some studies show that the same positive results don't apply to eugonadal men.
One study was performed on men with healthy testosterone levels. They received estradiol on a regular basis and they reported a decrease in sexual functioning, libido, masturbation, and erections.
On the other hand, another study reported that administering estradiol to 50 men aged between 20 and 40 years didn’t influence their sexual function and libido at all.
More research is required to understand how estradiol affects eugonadal men, but administering this hormone exogenously can be beneficial for people who have testosterone levels, increasing their libido and sexual desire.
Analyzing the role of estradiol on hypogonadal men who undertake testosterone replacement therapy
Testosterone supplementation therapy aims to improve the quality of life of hypogonadal men as well as increase the levels of circulating testosterone in their bloodstream.
This therapy also tries to increase the number of testosterone metabolites such as estradiol which is known for playing a vital role in sexual desire.
In a test performed on men with secondary hypogonadism, clomiphene citrate was used to increase the levels of testosterone by influencing the estrogen receptors directly.
Secondary hypogonadism means that the testicles function correctly, but there is a scarcity of luteinizing hormone produced by the pituitary gland and this translates into low testosterone levels.
The clomiphene citrate managed to increase testosterone levels in men with secondary hypogonadism as well as increasing the conversion of testosterone to estrogen. Other studies show that clomiphene citrate can increase sexual desire and libido.
Another study performed in 2013 looked at the role of testosterone in healthy men and how it can influence sexual behavior.
Some of the study participants received testosterone in combination with aromatase inhibitors, while others received testosterone without aromatase inhibitors.
As a result, the sexual function was impaired when aromatization was inhibited.
Other studies show that sexual desire increased significantly when men received testosterone supplementation therapy and had estradiol levels above 5 ng/dl.
Even when testosterone levels were below 300 ng/dl and the estradiol levels were higher than 5 ng/dl, the sexual desire was increased.
Yet another study looked at the sexual behavior of men who received letrozole which is a powerful aromatase inhibitor. These men had low testosterone levels and after being given letrozole, their estradiol level dropped even lower.
The result was that libido was significantly decreased. This means that both testosterone and estradiol are important in people who have testosterone deficiency to achieve and maintain healthy sexual desire and libido.
Aromatase inhibition can decrease insulin sensitivity
Insulin sensitivity is extremely important when it comes to diseases such as diabetes type 2. Those who have low insulin sensitivity are more predisposed to become diabetic in the future.
Inhibiting the aromatase enzyme through different types of drugs can have a significant influence on insulin sensitivity in both humans and rats.
A study conducted at a clinical research facility tested 17 healthy men with ages between 18 and 50 years.
This was a double-blind, controlled study. Each participant received anastrozole, an aromatase inhibitor, or a placebo drug for 6 weeks.
The study concluded that inhibiting aromatase can lead to poor insulin sensitivity, particularly when it comes to peripheral glucose disposal.
The relationship between estrogen and bodybuilding
It is well known that estrogen gives you a feeling of wellbeing and the lack of it can lead to depression, mood swings, emotional instability, and even depressive thoughts.
Aromatase inhibitors can reduce the amount of estrogen the body produces and it usually makes a person feel lethargic and unhappy.
For example, menopausal women seem to become more emotionally unstable and being haunted by feelings of anxiety and depression.
Studies show that this can also be the case for bodybuilders and top athletes who regularly take aromatase inhibitors to convert less testosterone to estrogen.
Estrogen is vital when it comes to sexual drive and libido as well and it is a well-known fact that inhibitors such as letrozole and anastrozole can negatively impact sex drive.
A study on two groups of men reached the conclusion that estrogen is very important for libido. The first group received testosterone treatment alone while the second group received testosterone and an anti-estrogenic agent.
At the end of the test, the group who received only testosterone treatment had better sexual drive and libido.
Researchers also believe that lowering the estrogen levels too much in healthy men can lead to anxiety feelings, depression and even osteoporosis.
Estradiol and DHT can make you age more slowly
Another study performed in Australia looked at the link between telomere length and the amount of serum estradiol and DHT in men.
Telomeres are sequences of nucleotides at the end of each chromosome. They are used as a biomarker for aging. Having shorter telomeres means that the biological age is higher, regardless of the actual age of the person.
Having longer telomeres correlated with a smaller biological age which basically means that the person is younger than his or her real age.
The study performed in Australia looked at the telomere lengths of men aged 53, give or take approximately 15 years.
The conclusion of the study was that estradiol and DHT correlate with telomere length and a small reduction in estradiol can amount to an approximate age increase of a decade.
Estradiol alone can influence telomere length and that’s why it is important not to reduce it too much using aromatase inhibitors.
Symptoms of low estradiol in men
A study performed in a medical center on several hundred men concluded that lack of estradiol can give certain vasomotor symptoms similar to those menopausal women have.
These symptoms include hot flashes, sweats and flushes.
The study participants were healthy men with ages between 20 and 50 years. They had normal serum testosterone levels and were split into two groups
The first group of men was administered goserelin acetate which stops gonadal steroids. After 4 weeks, they received placebo drugs or different doses of testosterone gels.
The second group of men received a treatment similar to those in the first group, but they also received anastrozole to block the aromatization of testosterone to estrogen.
The study concluded that those who received aromatase inhibitors and had low estradiol levels experienced vasomotor symptoms such as night sweats and hot flashes.
Similarly, those who received high doses of testosterone gel (approx 10 grams daily), as well as aromatase inhibitors, didn't experience the same symptoms.
This means that when high amounts of testosterone are administered, it can suppress the effect of the aromatase inhibitor and leave estrogen levels intact.
Estradiol and reproductive function in men
The sexual function in males is directly influenced by a mix of multiple substances and organs including testosterone, estradiol, estrogen receptors, testes, penis, and brain.
The aromatase enzyme and estrogen receptors have a similar location in the brain and they are important in the development of sexual function early in life.
They also influence sexual behavior in adulthood in combination with other substances called pheromones.
Estrogen influences the mood and libido of a man, enabling him to alter his cognition for a mental state conducive to reproduction.
Spermatogenesis is another important part of male reproduction. The creation of sperm cells relies on estradiol and these cells contain estrogen receptors and the aromatase enzyme.
Men who undertake testosterone supplementation therapy should also be monitored for their estrogen levels. This is because an estradiol level below 5ng/dl can cause a significant drop in sex drive and libido.
The role of estrogen in the male body is unquestionably important. Bodybuilders, professional athletes, and patients who undertake testosterone replacement therapy should be careful when it comes to managing estradiol levels since this hormone can significantly impact their wellbeing, sex drive, and bone density.