Estradiol Estrogen Tests for Men

Estrogen in Men: Myths and Realities of High Estradiol In men, the liver, fat cells, and other cells aromatize testosterone to produce estradiol, which is a hormone that is more prevalent in women than in men. Estradiol is responsible for healthy bone density and cholesterol, but its role in men’s sex drive, body composition, and other variables is a source of great debate. It is crucial to understand that estrogen plays a significant role in male reproductive health, particularly in the processes of sperm production and maturation within the testes. Many men on testosterone replacement therapy (TRT) initially fear high estradiol levels since they fear it causes water retention and gynecomastia. However, it is important to note that fat cells play a significant role in the production of aromatase, which can lead to higher levels of estradiol in the body. Below, we will discuss why most men on TRT do not have to be overly concerned about the estradiol lab ranges that are ill-fitted for men on TRT, as the ranges of LabCorp and Quest were not derived from a dataset of men on TRT who usually have higher total testosterone blood levels. What is Estradiol and Why is it Important for Men's Health? Estradiol is a type of estrogen hormone that plays a crucial role in men’s health. Often referred to as a 'female sex hormone,' estradiol also plays a crucial role in male health. It helps regulate bone density, cognitive function, libido, and mood. However, high levels of estradiol in men can lead to negative effects like decreased muscle mass, increased body fat, and hormonal imbalances. Men’s liver, fat, and other cells aromatize testosterone to produce estradiol, a hormone that is more prevalent in women than in men. Estradiol is responsible for healthy bone density and cholesterol, but its role in men’s sex drive, body composition, and other variables is a source of great debate. Many men on testosterone replacement therapy (TRT) initially fear high levels of estradiol since they fear it causes water retention and gynecomastia. We will talk about why most men on TRT do not need to worry too much about the estradiol lab ranges that do not work well for them because LabCorp and Quest did not get their ranges from a group of men on TRT who usually have higher total testosterone blood levels. High levels of estradiol in men are associated with abdominal obesity and an increased risk of cardiovascular disease. What is High Estradiol?: Predicted Blood Levels in Young and Older Men on TRT Transcript of video below: There needs to be more clarity on the subject since LabCorp and Quest have very narrow, sensitive estradiol test ranges. Those estradiol test ranges were primarily derived from men not on testosterone replacement therapy. Men on TRT tend to have higher testosterone levels than men not on testosterone replacement. So, believe it or not, a paper published many years ago predicts estradiol and DHT levels in men given different doses of testosterone. This study examined what happens to blood levels of testosterone, estradiol, and DHT when injecting different testosterone doses in young and older men. This study was very nicely done at the Boston University School of Medicine by well-known testosterone researchers. Dr. Basin is one of them and has done excellent work for the last 30 years. Video: How to Predict High Estradiol in Men Testosterone is the precursor hormone for estradiol. The aromatization of testosterone in the liver, fat, and other cells, including the testes, results in estradiol, a hormone that is more prevalent in women than men. Nature created it for a reason. It is responsible for healthy bone density and cholesterol, but its role in men's sex drive, body composition, and other variables is a source of great debate. Many anti-aging or men's health clinics prescribe aromatase inhibitors (AIs) to men who start testosterone replacement therapy (TRT). Higher estradiol blood levels in the presence of low testosterone can cause breast tissue growth (gynecomastia) in some men and possibly other issues. Some people speculate that high estradiol levels can also lead to difficulty achieving or maintaining an erection, but no scientific papers have been published on this subject. Since higher testosterone blood levels can result in higher estradiol levels in men, the belief is that using an AI will prevent breast tissue growth and erectile dysfunction by lowering any potential increase in estradiol. However, we have no data on how high is too high when it comes to this hormone in men using testosterone therapy. Emerging data show that low testosterone-to-estradiol ratios may correlate more closely to infertility, gynecomastia, and erectile problems than high estradiol levels alone. The truth about these speculations is starting to emerge, but we still need more data to say what the upper value of the optimal range of estradiol in men is. We have a lot of evidence about the lower side of the optimal range since it has been found that estradiol blood levels below 10–20 pg/mL can increase bone loss in men. A recently published study also nicely demonstrated that low estradiol could be associated with higher fat mass and lower sexual function in men. So, be careful when a clinic wants to put you on an aromatase inhibitor without first justifying its use. Increased Aromatase Activity and the Role of Aromatase Inhibitors in Men Aromatase is an enzyme that converts testosterone to estradiol, a form of estrogen. Germ cells, along with Leydig cells, are significant sources of estrogen production in the testes. In men, aromatase activity is typically low, but certain conditions can increase it, a process known as aromatase overexpression. This can lead to higher levels of estradiol in the body, which can have negative effects like decreased libido and muscle mass in the adult male. However, some studies suggest that moderate increases in estradiol may have cardiovascular benefits. One condition that can increase aromatase activity and therefore estradiol levels is aromatase excess syndrome, a genetic condition that affects both males and females. It’s important for men to maintain healthy levels of both testosterone and estradiol, and understanding the role of the aromatase enzyme, especially in conditions like aromatase excess syndrome, is crucial in managing estradiol levels. Estradiol in Men After Different Testosterone Doses: Study Details This study's findings were published in the Journal of Clinical Endocrinology and Metabolism in 2010. The fantastic thing is that nobody has reviewed it, even though it's probably the most important paper on what happens to estradiol and DHT in men on TRT. The study enrolled 51 young men aged 19 to 35 and 52 older men aged 59 to 75. These men were given a gonadotropin-releasing hormone agonist to shut down their gonadotropins, LH and FSH, testosterone, estradiol, and DHT. So, these were courageous volunteers who were willing to have their hormones wholly shut down. So, why did they do this? They did it because the researcher wanted to start from zero regarding hormones. So, those men were given injections of different doses of testosterone enanthate, 25, 50, 125, 300, and up to 600 milligrams a week for five months. And the researchers measured the testosterone, estradiol, and DHT blood levels. Unfortunately, they used the old estradiol test based on immunoassay. This estradiol test may not be the best for accurate estradiol testing. The use of an ultra-sensitive estradiol test is more accurate since it has no interference from CRP or inflammatory markers Usually, the sensitive estradiol is 20% lower than the estradiol levels measured by the old test. Let's assume that most of these men did not have inflammation. Here are their baseline characteristics. Interestingly, they were even exposed to such high doses of testosterone. So, after a four-week controlled period, they were given a testosterone blocker, the gonadotropin-releasing hormone agonist that shuts down gonadotropins. This drug is used to treat prostate cancer. They were randomized to receive weekly injections of testosterone enanthate for 20 weeks. The researchers found an issue with the higher testosterone dose in older men, with a few more side effects. They stopped a few men from continuing with the 600 milligrams of testosterone weekly. And then the randomization was limited to 25, 50, 125, and 300 milligrams of testosterone injections weekly. I've warned people not to use high testosterone doses, especially older people with comorbidities and heart problems. Increased blood pressure and tachycardia are some of the side effects listed in the study paper. So, what you see here are serum estradiol E2:T ratios. We talk about ratios on ExcelMale.com. Here are the opposite DHT and T ratios from what I typically talk about when dividing T by E2. And the black bars are younger men, and the white bars are older men. So, this is total estradiol, free estradiol, total DHT, and free DHT. And when we talk about free, what does that mean? It is the unbound estradiol and unbound DHT that aren't bound by sex hormone-binding globulin. And those two free estradiol and free DHT tests are rarely tested in clinics. DiscountedLabs.com does provide a free estradiol test for those who are interested. But since there are no studies about free estradiol blood levels in men, it's hard to say what a good free estradiol level is. High Estradiol in Men on TRT Most men on TRT initially fear high estradiol since they fear it causes water retention and gynecomastia. While high estradiol levels in men can cause gynecomastia, in women, similar hormonal imbalances are linked to an increased risk of breast cancer. They feel puffy; they may have more sensitive nipples. I will discuss this in another video because those symptoms are usually not connected to high estradiol per se when men have moderate to high testosterone levels. The most common cause of edema, or the problem of holding onto water weight, is a slowdown in sodium metabolism in the kidneys brought on by testosterone and androgens. Sodium (salt) retention happens in the first few weeks, especially with higher TRT doses in older men. The stimulating effects of testosterone may be to blame for the sensitive nipple issue, which typically does not cause gynecomastia. However, it is important to note that symptoms of high estrogen in men can also include swelling or enlargement of breast tissue, erectile dysfunction, infertility, depression, and delayed puberty. So, as you can tell, total E2, free E estradiol, and DHT increase with increasing testosterone doses, and this increase is much more pronounced in older men. It’s good to mention that these volunteers were not fat men. The increased fat mass has been linked to increased estradiol levels, which are often measured through body mass index (BMI). These are men with a BMI of around 26, which is not a high number. But anyway, we do see an increase. And older men, in white, tend to have a higher estradiol increase. DHT is the same thing. Although the differences were not as noted between young and old, you can tell here the free DHT. When you divide estradiol into testosterone, that’s when you see a decrease. Estradiol increases to a higher degree than testosterone, so the ratio of E2 divided by T decreases. The total DHT to T ratio is the same; it decreases as we increase the testosterone dose, but not as fast as the estradiol. It is essential to mention that 0.3% to 0.4% of testosterone is aromatized into estradiol. That’s a very tiny amount; that’s 0.4%. The conversion of testosterone to DHT by 5 alpha-reductase is around 10%. That’s why you see the scales a little more prominent on the DHT side. What to Know About Estrogen in Men Estrogen is commonly associated with women, but men also have this hormone in their bodies. The testes and adrenal glands are primarily responsible for producing estrogen in a male body. Estradiol is a type of estrogen that plays an important role in maintaining bone health, regulating cholesterol levels, and supporting brain function. Low levels of estradiol in men can contribute to a variety of health issues, such as decreased libido, erectile dysfunction, and osteoporosis. It's important for men to understand their hormonal balance, including their levels of estradiol, and work with a healthcare provider to address any imbalances or concerns related to erectile function and hormone balance. Buy an affordable, ultrasensitive estradiol test:   Understanding Androgens and Estrogens Estradiol is a type of estrogen that is found in both men and women. While it is often associated with female reproductive health, estradiol plays an important role in male health as well. Estrogens influence male reproductive function by maintaining a hormonal balance between estrogens and androgens, which is crucial for male fertility. In fact, it is responsible for regulating bone density, cholesterol levels, and even mood. When there is high estradiol in men, it can lead to a variety of health problems. Understanding the balance between androgens (male hormones) and estrogens (female hormones) is crucial for sexual development and maintaining optimal health for both men and women, especially in relation to the menstrual cycle. Risk Factors of Having High Estradiol in Men Estrogen is often associated with females, but it also plays a crucial role in men's health. High or low levels of estrogen in males can have negative impacts on their overall health. Men who have higher than normal levels of estrogen, also known as estrogen, may experience breast enlargement, erectile dysfunction, infertility, and other issues. On the other hand, men with lower than normal levels of estrogen may experience decreased bone density, muscle mass, and sex drive. It is important for men to maintain balanced estrogen levels through proper diet, exercise, and medical treatment if necessary. However, it is important to note that too much estrogen, also known as high levels of estrogen, can also be harmful to men's health, and it is important for individuals to monitor their estrogen levels and consult with a doctor if they have any concerns. How Men Can Keep Their Estrogen Levels Balanced Estrogen is typically associated with women, but men also have this hormone in their bodies. Estradiol is the most potent form of estrogen in men and plays a crucial role in maintaining bone density, sperm production, and sexual function. However, too much or too little estradiol can cause various health problems. Men can keep their estrogen levels balanced by maintaining a healthy weight, avoiding exposure to environmental toxins, managing stress levels, and getting enough sleep. A balanced diet rich in fiber and phytoestrogens, along with proper monitoring and control through hormone replacement therapy, may also help regulate estrogen levels in men, ensuring healthy sperm production. Normal Estrogen Levels in Men Estrogen is often thought of as a female hormone. However, it's also present in men, just at lower levels. One type of estrogen found in men is estradiol. Normal levels of estradiol in men vary depending on age and other factors. In general, levels range from 10 to 60 pg/mL. If levels are too high or too low, it can lead to health issues such as osteoporosis, sexual dysfunction, and mood changes. Men should discuss their estrogen levels with their healthcare provider to ensure they are within a healthy range for their age and overall health status. This includes monitoring the amount of estrogen in their body, as there are two main types of estrogen in men: estrone and estradiol, and an imbalance of these hormones can have negative effects on their health. Gynecomastia and High Estradiol in Men Gynecomastia is a condition that causes men to develop breast tissue. Studies on male mice, such as αERKO and ArKO models, highlight the effects of estrogen deficiencies on sexual behavior and fertility. One of the underlying causes of gynecomastia is an imbalance of hormones, including estradiol. Estradiol is a form of estrogen that is typically found at higher levels in women. However, men also have small amounts of estradiol in their bodies. When the balance between estradiol and testosterone is disrupted, it can lead to the development of breast tissue in men. Treatment for gynecomastia may involve addressing the hormonal imbalance through medication or surgery, depending on the severity of the condition. You can buy a gynecomastia lab test panel on Discounted Labs. Low Estradiol Can Cause Loss of Libido and Erectile Dysfunction One of the significant impacts of estradiol deficiency in men is the loss of libido. Low levels of estradiol can lead to decreased sex drive, which can cause problems in relationships and affect overall quality of life. However, it's essential to note that there are other factors that can impact libido as well, such as stress, depression, low testosterone levels, and a lack of sexual activity. If you're experiencing a loss of libido, it's important to talk to your doctor to determine the underlying cause and discuss possible treatment options. A Study Helps to Predict Normal Estradiol and DHT Test Levels in Men on TRT Most men on TRT don't have to be so concerned about the LabCorp or Quest estradiol ranges that usually scare people because they're always high. And there is statistical significance in the baseline values of young and older men. DHT increases were higher in older men. In younger men, usually, that's also connected to total testosterone and is also related to higher libido. Older men had lower DHT, which was also linked to their lower testosterone. Sex hormone-binding globulin (SHBG) is also higher in older men. The researchers in this study came up with a model with factors to predict the estradiol and DHT response curves. They provided two equations for young men (estradiol and DHT) and two for older men. Using those equations, you can roughly estimate the predicted estradiol and DHT levels for different testosterone blood levels. These equations enable us to see what is considered a “normal” estradiol level instead of using estradiol lab ranges that are ill-fitted for men on TRT. As previously mentioned, the estradiol ranges of LabCorp and Quest were not derived from a dataset of men on TRT who usually have total testosterone blood levels over 600 ng/dL (many men on TRT have T levels of 1000 ng/dL or more!). The Importance of Preserving Proper Levels of Estradiol in Men Our bodies transform 0.4% of testosterone into estradiol to balance the potentially negative effects of testosterone alone on lipids and other variables. If you have “high” testosterone, your estradiol should be “high.” Treating that estradiol with an aromatase inhibitor may not be needed and can potentially crash your estradiol level. Estradiol has essential roles in men, including the regulation of hormone levels. Estradiol comes in to protect us from higher testosterone and helps improve lipids, HDL, and endothelial function. Women tend to live longer than men because they have more estrogen to protect them against the cardiovascular risks we are all exposed to. So, don't freak out when you see the 60s, even in the 70s, depending on how high your testosterone is. And the only problem we're having in this field is that we still need to do a study that goes after symptomology depending on estradiol blood levels when we control testosterone. We know that estradiol levels under 15 picograms per milliliter cause problems with bone density and even fat gain. Many members of ExcelMale.com say that their penile sensitivity decreases when they have low estradiol. We do not know what high estradiol in men means in relation to estradiol blood levels in relation to testosterone. Can high estradiol in men on TRT with relatively high testosterone blood levels cause issues? Is there a proper and healthy testosterone-to-estradiol ratio?. If somebody is, let's say, at 1,275 ng/dL of testosterone and 64 pg/mL of estradiol, is there any consequence to that? We don't know. And the problem I'm seeing is that most of you guys are assuming too much; you're assuming that because you're holding water or you have sensitive nipples, you have high estradiol. And you start treating with an AI without even testing your blood levels of estradiol, especially using the sensitive assay. That concerns me because once you start treating with an AI, you can crash your estradiol. “Crashed estradiol” has become one of the most significant traffic source keywords for ExcelMale because people are experiencing that more and more. I hope you enjoyed the presentation. Please remember to subscribe to the ExcelMale forum and the ExcelMale YouTube channel, and make sure that you click on that little bell that will tell you when I upload new videos. Thanks a lot, and stay safe. Estrogen Dominance and Hormonal Imbalance Estrogen dominance occurs when there is an imbalance between estrogen and testosterone levels in the body. This hormonal imbalance can lead to a range of symptoms, including weight gain, mood swings, and decreased libido. Men experiencing estrogen dominance may notice an increase in body fat, particularly around the abdomen, and may struggle with emotional changes such as irritability or depression. Additionally, estrogen dominance can negatively impact overall health by contributing to conditions like insulin resistance and cardiovascular issues. Maintaining a proper balance between estrogen and testosterone is crucial for optimal health and well-being. Exposure to Endocrine Disruptors and Environmental Toxins Endocrine disruptors and environmental toxins can significantly impact estrogen levels and overall health. These substances, found in everyday items like plastics, pesticides, and personal care products, can mimic the effects of estrogen in the body, leading to hormonal imbalances. When these toxins enter the body, they can bind to estrogen receptors, disrupting the natural hormonal balance and potentially causing a range of health problems. It’s essential to be aware of these environmental toxins and take steps to minimize exposure, such as choosing organic foods, using natural personal care products, and avoiding plastic containers. Other Non-Reproductive Effects of High Estrogen High estrogen levels can have a range of non-reproductive effects on the body, impacting various aspects of health and well-being. Some of the common non-reproductive effects include: Weight gain and obesity: Elevated estrogen levels can lead to increased body fat, particularly around the abdomen, contributing to obesity. Mood swings and emotional changes: High estrogen can cause mood swings, irritability, and even depression. Fatigue and low energy: Men with high estrogen levels may experience chronic fatigue and a general lack of energy. Insomnia and sleep disturbances: Hormonal imbalances can disrupt sleep patterns, leading to insomnia and poor sleep quality. Skin problems: High estrogen levels can cause skin issues such as acne and rosacea, affecting overall skin health. Maintaining balanced estrogen levels is essential for overall health and well-being, and addressing any hormonal imbalances can help alleviate these symptoms. Foods that Lower Estrogen: Cruciferous Vegetables and Sulforaphane Cruciferous vegetables, such as broccoli, cauliflower, and Brussels sprouts, are known for their ability to help lower estrogen levels in the body. These vegetables contain a compound called sulforaphane, which has been shown to support the detoxification of excess estrogen. Incorporating cruciferous vegetables into your diet can help maintain healthy estrogen levels and support overall hormonal balance. Additionally, these vegetables are rich in fiber and other essential nutrients, making them a valuable addition to a healthy diet. By including more cruciferous vegetables in your meals, you can naturally help regulate estrogen levels and promote better health. Buy an affordable, ultrasensitive estradiol test:   I hope you enjoyed the presentation. Please remember to subscribe to the ExcelMale forum and the ExcelMale YouTube channel, and make sure that you click on that little bell that will tell you when I upload new videos. Thanks a lot, and stay safe. More information about high estradiol in men Citations Understanding Blood Test Results: Estradiol (Male) Aromatase Inhibitors in Men: Mechanisms and Benefits Aromatase Inhibitors: No More, No Less Estrogen in Men: Understanding Its Role and Effects The Role of Estradiol in Male Reproductive Health Effects of Estrogen on Men's Health Estrogen in Men: What You Need to Know Estrogen's Impact on Men's Health: A Scientific Study When to Take Anastrozole with Testosterone Estrogen and Male Health: Research Findings The Role of Estrogen in Men's Health When to Use Aromatase Inhibitor with TRT What Causes High Estradiol Levels in Males?  

Can Testosterone Make You Tired?  Some men start testosterone replacement therapy (TRT) to address low T and testosterone deficiency and find out their baseline fatigue and low energy get worse. Testosterone and Energy Levels Testosterone controls energy levels in men. When testosterone is within normal range, men feel more energetic and motivated. Testosterone supplementation can also help restore energy in men with low testosterone. Low testosterone can cause fatigue, lethargy, and feeling unwell. Testosterone helps regulate the body’s metabolism, which converts food into energy. Studies have shown that testosterone levels are related to energy levels. Men with low testosterone have lower energy levels; men with normal or high testosterone have higher energy levels. Testosterone replacement therapy also helps improve energy in men with low testosterone. By getting testosterone levels back to normal range, many men feel a big boost in overall energy and vitality. Why does TRT cause fatigue? TRT can cause fatigue in some men for the following reasons: Overstimulation of the body: Increased testosterone can overwork the body and cause fatigue and exhaustion. Insomnia: Some men on testosterone therapy may have difficulty sleeping and get fatigue. Hormonal imbalance: Sudden increase in testosterone can cause imbalance with other hormones in the body and cause fatigue and other symptoms. Side effects of the medication: Testosterone medication can cause side effects like acne, fluid retention, and mood changes, which can also cause fatigue. Testosterone injections, which are a common method of TRT, can cause these side effects. As testosterone levels drop, men may feel more fatigue and lower energy levels, which can be worsened by TRT. Note that testosterone therapy can also help improve energy and reduce fatigue in some men but it’s best to discuss the benefits and risks with a healthcare provider before starting treatment. If no improvement in fatigue is seen after 6 weeks of testosterone replacement, other factors beyond hypogonadism may be present. This article will review a few ways to find out what causes TRT fatigue. Low Testosterone Symptoms Low testosterone can cause many testosterone deficiency symptoms, including: Fatigue and lethargy Low sex drive Erectile dysfunction Loss of muscle mass and strength Increased body fat Decreased bone density Mood changes like depression and anxiety Difficulty concentrating and memory problems If you have any of these symptoms, consult a healthcare professional to find out if low testosterone is the cause. A proper diagnosis will help you explore treatment options, including testosterone replacement therapy, to alleviate these symptoms and improve your life. Thyroid Function and Hormonal Imbalance: The thyroid is a butterfly-shaped endocrine gland located in the lower front of the neck. It produces thyroxine or T4, which is converted to triiodothyronine or T3. T4 production is controlled by thyroid-stimulating hormone or TSH, which is produced by the pituitary. Hypothyroidism, or low thyroid hormone production, can cause sexual dysfunction and depression, fatigue, dry skin and hair, weight gain, and increased sensitivity to cold. Blood tests to measure TSH, T4, and T3 are available and widely used. The American Thyroid Association (thyroid.org) has great info on how to find out if you have hypothyroidism that’s causing your fatigue. Testosterone can decrease thyroxin-binding globulin and total T4 serum levels and increase resin uptake of T3 and T4. Free thyroid hormone levels remain the same and there’s no clinical evidence of thyroid dysfunction. Once thyroid hormone levels are normalized, testosterone tends to increase naturally. Check your thyroid hormones here: Choose Your Test | Discounted Labs   Adrenal Function and Chronic Fatigue: The adrenal glands are located in the abdomen above the kidneys and regulate stress in the human body. When the body is in an emergency situation, the adrenal glands release hormones like adrenaline to enable the body to respond. You may have experienced this reaction called the “fight or flight” response if you were in danger, fear, or shock. Adrenal fatigue is the controversial idea that the adrenal glands can get worn out and cause illness if continuously overstimulated. Proponents of the “adrenal fatigue” theory believe that the adrenal glands may be overworked in some individuals and therefore get “fatigued” and unable to produce enough hormones. When your adrenal glands are exhausted, your cortisol levels drop significantly. Cortisol is your natural stress hormone. Low sex drive and infertility are symptoms of adrenal fatigue. Other symptoms include chronic fatigue, low blood pressure and low blood sugar, dizziness, headaches, anxiety or panic attacks, depression, and other equally debilitating problems. Some doctors may prescribe low doses of corticosteroids if your morning cortisol levels (measured by blood, saliva, or urine tests) are low. But be careful with corticosteroids, as they can increase fat mass and decrease bone density if given in doses higher than what the healthy adrenals would produce. Check your adrenal health. DHEA and Testosterone Levels: The adrenal glands also produce dehydroepiandrosterone (DHEA), the most abundant hormone in the bloodstream. The body uses DHEA as the starting material to produce the sex hormones testosterone and estrogen in men. DHEA supplementation can increase DHEA levels, which in turn can support testosterone production. Studies show it only increases testosterone in women. DHEA production decreases in most people after age 40. In people 70 years old, DHEA levels will be 30% lower than what they were at age 25. Low DHEA levels are associated with many degenerative conditions. Some studies are controversial and inconclusive that people with immune deficiencies and fatigue may benefit from supplementation with this hormone. It’s still available over-the-counter in the US. This may change soon, as a new bill was passed by Congress classifying it as a performance-enhancing steroid (no studies show it has such an effect). One study showed that women with normal DHEA levels can convert it into testosterone as their body needs while men don’t benefit the same way. You need a blood test to know if you have low DHEA-S since most of the DHEA converts into this sulfated form. Common doses for women are 5-30 mg a day, while men benefit from 25-100 mg a day (to bring low DHEA-S to normal). NOTE: Do not use DHEA supplements unless your blood levels of DHEA-S are low. If low, start at a low dose and get your DHEA-S tested again after a month. Men who use DHEA supplements may have problems with higher estrogen levels since DHEA can also convert into estradiol. This can cause gynecomastia and water retention. If you start taking DHEA, get your blood levels checked to make sure they are not above normal. There are many claims about DHEA being an anti-aging and anti-cancer cure but none of these claims have been proven with strong data. To make diagnosis easier, we have created this new Fatigue Panel on DiscountedLabs.com at a discount. Click here: Comprehensive Fatigue Panel Sleep Apnea: Sleep apnea is a sleep disorder in which a person stops breathing or breathes shallowly many times during sleep and therefore doesn’t get enough restful sleep; oxygen levels in the blood drop and the brain starves of oxygen. Besides causing daytime fatigue, it can increase blood pressure and cardiovascular risks. Testosterone replacement therapy has been linked to the worsening of sleep apnea or the development of sleep apnea, especially in men who use higher doses of testosterone or who have other risk factors for sleep apnea (high body weight, thick necks, snoring, alcohol consumption, etc.). Upper-airway narrowing doesn’t seem to be caused by testosterone replacement therapy; it suggests that testosterone replacement contributes to sleep-disordered breathing by central mechanisms rather than by anatomical changes in the airway. Tell your doctor if your spouse or partner complains that you snore loudly at night and feel fatigued. The only way to know for sure if you have sleep apnea is to have your doctor refer you to a sleep lab for a sleep study. If you are diagnosed with sleep apnea, a continuous positive airway pressure (CPAP) machine can be prescribed to help open up your airways with a small air pump while you sleep. Some people love it; some hate wearing a mask while being hooked up to a machine at night. I have seen men regain their quality of life after starting CPAP. It’s covered by insurance, Medicare, and most HMOs. A new option for those who hate CPAP machines with mild to moderate apnea is the use of oral appliances. Worn in the mouth like an orthodontic appliance during sleep, oral appliances keep the soft tissue from collapsing and interrupting normal breathing patterns. The purpose of the oral appliance may be to reposition the lower jaw, tongue, soft palate, and hyoid bone into a certain position; to keep the airway open with stabilization of the tongue and jaw; or to provide artificial muscle tone to prevent collapse and resulting airway blockage. The doctors will fit your oral appliance for comfort by using a mold of your mouth to design your unique fit. Fatigue Management with Testosterone Therapy Testosterone therapy can help manage fatigue in men with low testosterone. Testosterone gel is another way to get testosterone therapy to help manage fatigue. Testosterone therapy can bring many health benefits, including improved cardiovascular health, better blood sugar control and reduced risk of osteoporosis and diabetes. But it’s important to understand the benefits and risks of testosterone therapy and to discuss them with your doctor. Some men will experience a big boost in energy and overall well-being; others will find their fatigue persists or even worsens. This variability is why personalized medical advice and regular monitoring are important to tailor the treatment to your needs. Energy Tips In addition to testosterone therapy, there are several lifestyle changes that can help men regain energy and overall health. These are: Regular Exercise: Strength training and cardio exercises can help build muscle and boost energy. Exercise also helps with better sleep and reduces stress, which can further increase energy. Healthy Diet: Eating a balanced diet rich in protein, healthy fats, and complex carbohydrates can give you energy all day. Lean meats, fish, nuts, seeds, and whole grains are good choices. Sleep: Aim for 7-9 hours of sleep per night to help regulate testosterone and energy. Good sleep hygiene practices like a consistent sleep schedule and a restful environment can make a big difference. Stress Management: Meditation, yoga, or deep breathing exercises can help manage stress, which can help increase energy. Chronic stress can lower testosterone so finding ways to cope is important. Hydration: Drinking plenty of water throughout the day is key to maintaining energy and overall health. Dehydration can cause fatigue and decreased physical performance. Natural Testosterone Boosters While testosterone replacement therapy may be needed for some men, there are also natural testosterone boosters that can increase testosterone. These are: Exercise Regularly: Exercise, especially weightlifting and high-intensity interval training, can increase testosterone. Eat a Healthy Diet: A diet rich in protein, healthy fats, and complex carbohydrates can support testosterone. Get Enough Sleep: Sleep is key to testosterone production so aim for 7-9 hours of sleep per night. Reduce Stress: High stress can lower testosterone so find ways to manage stress through meditation or yoga. Get Enough Vitamin D: D: Vitamin D is important for testosterone production, so make sure you get enough through sun exposure, supplements, or fortified foods. Implementing these lifestyle changes can support your body’s natural testosterone production, and if you’re already on testosterone replacement therapy,. Testosterone Therapy Risks and Considerations Testosterone therapy can be good for men with low testosterone, but there are testosterone side effects and considerations to be aware of: Blood Clots and Stroke: Testosterone therapy can increase the risk of blood clots, which can cause stroke or other cardiovascular events. Cholesterol and Cardiovascular Health: Testosterone therapy can affect cholesterol levels, which can increase heart disease risk. Lipid profiles should be monitored regularly. Fertility and Sperm Production: Testosterone therapy can reduce sperm production. Men who want to have children should talk to their doctor. What to Expect from Testosterone Men on testosterone therapy can expect: Increased Energy and Reduced Fatigue: Many men feel more energetic and less fatigued after starting testosterone therapy. More Muscle and Strength: Testosterone therapy can increase muscle mass and strength for better physical performance and overall health. Better Bone Density: Testosterone therapy can increase bone density, reducing the risk of osteoporosis and fractures. Libido and Sexual Function: Many men experience improved libido and sexual function, which can improve their quality of life. Overall Well-Being: Testosterone therapy can improve mood and overall sense of well-being for better quality of life. But you need to have realistic expectations and understand that testosterone therapy is not a magic pill. It may take several months to see the full effects and regular monitoring and adjustments may be needed to get the best results. Testosterone Monitoring Monitoring testosterone levels is crucial to ensure treatment is working and to minimize side effects. This means working with a healthcare professional to track progress and adjust therapy. Why Blood Tests Blood work is needed to monitor testosterone levels and adjust treatment. These tests can: Confirm Diagnosis: Blood tests can confirm low testosterone levels so testosterone therapy is appropriate. Monitor Results: Testing helps to monitor testosterone therapy and ensure testosterone levels are in range. Identify Side Effects: Blood tests can detect side effects like changes in cholesterol or liver function so treatment can be adjusted. Healthy Ranges: Keeping testosterone levels in a healthy range is key to minimizing risk and maximizing benefits. You need to work with a healthcare professional to determine the best testing schedule and to make sure testosterone levels are being monitored regularly. This proactive approach will get the best results and overall health. Get your own testosterone test here. When to See a Doctor for Fatigue If you have persistent or severe fatigue, you need to see a doctor. Fatigue can be a sign of an underlying medical condition like low testosterone, anemia, or diabetes. A healthcare professional can help figure out what’s causing your fatigue and develop a plan to treat it. If you have any of the following, see a doctor: Fatigue that lasts more than 2 weeks Severe fatigue that affects daily activities Fatigue with other symptoms like weight loss, fever, or night sweats Fatigue that doesn’t go away with rest or sleep A healthcare professional can do a physical exam, take a medical history and order diagnostic tests like blood work to figure out what’s causing your fatigue. Knowing the cause is key to developing a treatment plan and overall health and wellness. References Here are the clickable links with their corresponding titles: Can Testosterone Replacement Therapy Cause Insomnia? TRT and Fatigue: Understanding the Connection and How to Overcome It Testosterone Therapy: Effects and What to Expect Experiencing Extreme Tiredness and Fatigue on TRT? Can Testosterone Therapy Make Me Less Tired? Addressing Fatigue with Testosterone Pellets

TRT Side Effects: How to Manage Them What are the Main Side Effects of Testosterone Replacement Therapy (TRT)? Acne/oily skin  Hair loss Increased sex drive Unresolved erectile dysfunction Insomnia Sleep Apnea Testicular atrophy Enhanced assertiveness or reactivity High blood pressure/water retention Gynecomastia (male breast development)   Understanding Testosterone Replacement Therapy (TRT) Testosterone replacement therapy (TRT) is a medical treatment designed to restore normal testosterone levels in men with hypogonadism, a condition where the testicles do not produce enough testosterone. This therapy aims to alleviate symptoms such as low libido, fatigue, and decreased muscle mass, which are commonly associated with low testosterone levels. TRT involves administering testosterone through various methods, including injections, gels, patches, and oral medications. By restoring testosterone levels, TRT helps improve overall quality of life for men suffering from androgen deficiency syndromes. What are the Main Side Effects of Testosterone Replacement Therapy (TRT)? Like all treatments, testosterone therapy is associated with a number of known risks, particularly for men with testosterone deficiency. These risks should be communicated to patients prior to initiation of treatment. A key item is impaired spermatogenesis (sperm production) due to suppression of gonadotropins (LH and FSH). Men considered candidates for TRT should be questioned as to their desire to induce a pregnancy. Since sperm production may be reduced to zero, exogenous T alone should be avoided until fertility is no longer a concern. Treatment with hCG injections or oral clomiphene citrate may be considered in these men, as they do not suppress spermatogenesis. There is some limited data on the use of testosterone plus hCG for improvement of sperm quality and quantity in men. Acne may occur in younger men. Edema can be occasionally observed in middle-aged or older men due to the fluid-retentive properties of testosterone. Erythrocytosis (increased red blood cell count that causes high hematocrit) is infrequently seen with topical and injectable TRT treatments but is routinely observed in men treated parenterally with short-acting injections or implanted pellets. Although there is no evidence to date that T-induced erythrocytosis is associated with adverse events, it seems reasonable to prevent the hematocrit from rising excessively. Men whose hematocrit rises above 54% (or hemoglobin greater than 18 g/dL) should be considered for dose reduction, temporary discontinuation of T therapy, blood donation, or therapeutic phlebotomy. Read this first since it is the most common testosterone side effect: High hematocrit Acne/oily skin  Caused by Dihydrotestosterone (DHT) effect on increased oil production · Accutane– a powerful prescription item - 40 mg/day for one week sometimes stops acne if started at the first sign or as directed by your doctor. Accutane is potentially highly liver toxic and can lower testosterone. Do not use unless as last resort.· Sporanox—Effective for some acne-like eruptions that are caused by fungi. Some doctors also prescribe antibiotics, like tetracycline, for acne with good results.. Minocycline. Shower with Nizoral shampoo. Anti-bacterial soaps: use a scrubbing brush and wash twice a day, especially after sweating during a workout.· UV light or sunlight with moderation.. Zinc/copper supplements or zinc soaps may help some men with acne.. Other options: How to treat and prevent acne Hair loss Caused by DHT effect on hair follicles · Nizoral shampoo—Available by prescription and over-the-counter as a lower-dose product.· Rogaine—Available over the counter· Propecia - Available by prescription. A few males experience decreased erections with finasteride. Do not use. Increased sex drive · A problem? Sex drive is part of quality of life. Testosterone therapy may somewhat improve sexual function in men with low testosterone levels. This is not necessarily a bad side effect. Enjoy it. Unresolved erectile dysfunction · ED Medications: Available by prescription; enables robust erections. If you have sinus congestion or headaches/backaches, take non-drowsy allergy medication and ibuprofen. ED drugs can be combined with alpha-blockers and/or nitric oxide precursor amino acids (arginine or citrulline).· Yohimbine (Yocon) - Available by prescription; increases sex organ sensitivity. Can increase heart rate and blood pressure· Muse—Available by prescription; a pellet is inserted into the urethra to produce an erection. Unpopular· Trimix – Available by prescription from compounding pharmacies. The best and cheapest formula for injection into the penis for lasting erections.· Caverject - Available by prescription. An injection into the penis that produces an erection that can last 1 to 2 hours. Be careful with injecting too much since it can produce dangerously long erections that need to be treated in emergency rooms! Follow instructions from your urologist.· Papaverine—an older injectable medication, less expensive than Caverject.· Wellbutrin—prescription at 300 to 450 mg/day; increases dopamine.· HCG—First dose is 2,000 IU, then 250-500 IU twice or three times a week. No protocol has been proven in controlled studies yet. When Testosterone Replacement Doesn't Lead to Better Erections Insomnia Usually, this is caused by dosages that are too high. Find the least amount that gives you a good result. · Sleeping medications—e.g., Ambien, Sonata, Lunesta, Restoril· Melatonin: 1 to 3 mg before bedtime. If you wake up groggy after 6 hours, your dose should be lower.· Avoid working out too close to bedtime.· Limit caffeine, especially after 3 pm.· You may want to try a sleep formula with tryptophan, melatonin, and magnesium. Nutrients do not work as well as drugs, but they can help some people.Article: How to protect your circadian rhythm Unresolved Fatigue · Have your doctor prescribe a sleep study if you snore and wake up tired even after 7 hours of sleep. Some people may have to wear a C-PAP machine to breathe at night. Visit Home - SleepApnea.org for more information. There are also oral devices for those people who fail CPAP. Fatigue—When Testosterone Is Not Enough Testicular atrophy · HCG– One 2,000-unit injection per week for 2 weeks, followed by maintenance of 350-500 IU twice a week. Decrease testosterone dosage accordingly after starting hCG to reach levels around 500-1200 ng/dL while keeping all other lab work monitored. Watch this video on hCG and men Enhanced assertiveness or reactivity · Make sure you are getting enough sleep.. Count until 10 and be aware of your interaction with others.· Decrease caffeine.· Meditation, mindfulness, yoga; breathe from your belly for a few minutes when overreacting.· The testosterone dosage may be too high.· Ask yourself: Do I need to always be right?. Vent extra energy at the gym, sex, and sharing with your buddies at www.excelmale.com High blood pressure/water retention · Caused by sodium retention in the kidneys. Try to limit salt consumption. Caution is required due to potential water retention issues in patients with chronic kidney disease. . Blood pressure medications - Elevated blood pressure may be transient or not. Try ACE or ARBs since they seem to have fewer sexual dysfunction-related effects. · Magnesium (600 mg/day); vitamin B6 (100 to 200 mg/day); may help reduce water retention. · Water - Drink extra water every day to help flush the kidneys. . Check your estradiol to make sure it is not over 45 pg/ml. Treat if high with a low dose of anastrozole. . Make sure you are doing cardio exercise at least 3 times a week for 30 min. Sweat and lower your salt intake since TRT increases sodium retention in some men. Gynecomastia (male breast development) Caused by high estradiol in the presence of low testosterone. This is rare in men on testosterone replacement. · Arimidex inhibits estrogen production. Available by prescription. 0.25 mg per week. There is no agreement on what the highest E2 level is for men on TRT with high testosterone. Ensure that your estradiol does not go too low (under 20 pg/ml) if you use anastrozole since it is needed for bone, skin, brain, lipids, libido, good lipids and hair health.· Nolvadex (tamoxifen)– Competes with estrogen for receptors. Available by prescription, 10 to 20 mg/day. Use of Nolvadex during a steroid cycle may reduce the net anabolic effect, as it decreases the production of GH and IGF-1. High IGF-1 may be implicated in gynecomastia.. Severe cases may require removal of the breast tissue by surgery.· DHT cream- Some people have obtained great results by rubbing a 10% DHT cream on their nipples. Not available in the US but some people order it online from Germany. Read about medications/foods to avoid if you have gynecomastia.. Those who do know to respond to the above check other reasons. Find out how long it takes testosterone replacement to potentially show benefits For affordable blood tests in most cities in the U.S. : DiscountedLabs.com More information on TRT lab tests. Monitoring and Testing During TRT Regular monitoring and testing are essential during TRT to ensure safe and effective treatment. This includes: Regular blood tests to check testosterone levels, PSA, hematocrit, and liver enzymes Baseline bone density testing (DEXA) and bi-yearly bone density tests Monitoring of prostate health through PSA levels and DREs Regular check-ups with a healthcare provider to discuss any concerns or side effects These tests help in tracking the effectiveness of the therapy and in identifying any potential issues early, ensuring that the treatment remains beneficial and safe. When to Seek Care It is essential to seek medical attention immediately if any of the following occur during TRT: Symptoms of a cardiovascular event, such as chest pain or shortness of breath Severe side effects, such as acne, hair loss, or mood changes Changes in prostate health, such as increased PSA levels or abnormal DRE results Concerns about testosterone levels or overall health By understanding the benefits and risks of TRT, monitoring prostate health, and seeking care when necessary, men with hypogonadism can safely and effectively manage their condition and improve their overall quality of life. Regular communication with healthcare providers and adherence to recommended monitoring protocols are key to successful testosterone replacement therapy. References: [i]   Metzger, DL, et al. Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence. J Clin Endocrinol Metab (1994) 79(2):513-518. [ii] el-Sheikh, MM, et al. The effect of Permixon (saw palmetto) on androgen receptors. J Acta Obstet Gynecol Scand (1988) 67(5):397-399. [iii] Suzuki, K, et al. Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol (1995) 29:65-68. [iv] Gann, PH, et al. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. The Prostate (1995) 26:40-49.   Buy your own on DiscountedLabs.com

Key Highlights Understand the importance of sensitive estradiol testing for hormone therapy and men's health. Learn about the benefits of choosing discounted labs for your estradiol sensitive test. Discover the differences between standard and sensitive estradiol tests, including the testing methodologies involved. Prepare effectively for your estradiol sensitive test by following specific guidelines. Get insights into interpreting and understanding your estradiol test results with the help of healthcare providers. Explore the convenience of ordering your estradiol sensitive test online and what to expect during the process. Introduction Estradiol is an important hormone for both men and women. It affects many parts of our health. It plays a significant role in maintaining bone health, cognitive functions, sex drive, and overall body composition in both genders. It is especially important to understand estradiol in men's health. There are many myths about estradiol in men. This makes it essential to have accurate testing. Choosing a sensitive estradiol test can give clear information about hormonal levels. This allows for quick action if needed. This blog looks at the benefits of discounted labs for these tests. It also helps you know how to order and prepare for a sensitive estradiol test. Understanding Estradiol and Its Importance for Men Estradiol plays an important role in men's health. As the hormone responsible for developing and regulating the male reproductive system, it affects many body functions, including bone strength, sex drive, and mood. Understanding estradiol is crucial because imbalances in levels can lead to issues such as weaker bones, changes in sex drive, and hormone imbalances. That's why it is important to regularly check estradiol levels through tests to identify any potential concerns that may require medical attention. The Role of Estradiol in Male Health Estradiol is very important for men’s health, even though it is mostly known as a hormone for women. In men, estradiol helps keep bones strong, manage sexual desire, and support heart health. It also plays a key role in mood, thinking, and making proteins. Moreover, estradiol helps control the production of testosterone. If the levels of estradiol are not right, it can cause health problems. This shows how important it is to know about and check this hormone in men's health. Common Misconceptions About Estradiol in Men Estradiol is important for men's health, not just a hormone for women. Men can also experience problems with estradiol levels, which can affect their well-being. One common myth is that all types of estrogen are bad for men. In fact, having the right amount is key for good health. Another myth is that high estradiol always causes harm. Both low and high levels can negatively impact men's health. Knowing the truth about these myths can help people make better choices for their health care. Why Opt for a Sensitive Estradiol Test? Find out important hormonal imbalances with a sensitive estradiol test. This test gives specific results that normal tests may overlook. It helps in making accurate health evaluations. Differences Between Standard and Sensitive Estradiol Tests Standard estradiol tests check a wide range of estradiol levels in the blood. This gives a general view of hormone levels. On the other hand, sensitive estradiol tests use advanced methods like liquid chromatography and mass spectrometry, also known as immunoassay estradiol test. These methods help find low levels of estradiol with more accuracy, making it a highly sensitive estradiol test. The LC-MS estradiol test is primarily suggested for situations with very low estrogen levels. The sensitive test is better for people who need careful hormonal analysis. While standard tests can work well in many cases, sensitive tests give more detailed information. This is especially true for those with mild hormone imbalances. Choosing the right test depends on how much detail you need about estradiol levels. Identifying Symptoms of Estradiol Imbalance Estradiol imbalances can show different symptoms. In men, low estradiol levels may cause a lower sex drive and tiredness. High estradiol levels can result in male feminization. Both men and women may have dry skin and hormonal changes. Due to changes in estradiol levels, which birth control pills can also affect, women may experience irregular menstrual cycles or fertility issues. It's important to notice these signs and get estradiol testing to fix any imbalances quickly. Symptoms are key indicators showing the need to check for possible estradiol imbalances. Stay aware of these signs to keep good health. The Benefits of Using Discounted Labs for Buying Your Estradiol Sensitive Test Online Discounted labs provide a cheap way to get your estradiol test without losing quality. They have lab locations all over the country, making it easy for you to access their services. By using discounted labs, you save money while getting accurate test results. This is a great option for people looking for affordable healthcare. These labs give you a wallet-friendly choice without lowering the dependability and accuracy of your test results. Using discounted labs can help you monitor your estradiol levels easily and conveniently. Affordability Without Compromising Quality Discounted labs provide lowest cost estradiol sensitive teststhat are still high quality. These affordable options help you take care of your health without spending too much money. When you choose discounted labs, you get reliable results while saving cash. Being affordable does not mean you lose accuracy or dependability. These labs follow strict quality rules to give you trustworthy results that you can rely on. Caring for your health should not cost a lot, and discounted labs make great testing cheap and easy to get. You can pick affordable options without losing quality in your healthcare experience. Nationwide Lab Locations for Your Convenience Find it easy to access lab locations for your sensitive estradiol test. You can place a simple order online and choose the testing laboratory near you. There is a large network of collection sites to make your testing process smooth and quick. You will enjoy the ease of getting your blood sample taken at a place that works best for you. This saves you time and effort. Whether you’re in a busy city or a small town, you can find the closest lab location for your estradiol test at our nationwide reference lab locations without any trouble. How to Order Your Estradiol Sensitive Test Online To get your Estradiol Sensitive Test online, go to Discounted Labs's Sensitive Estradiol product page. Find the test in the menu and add it to your shopping cart. Next, go to checkout and fill out the information needed. After you place your order, you will get a confirmation email with instructions on how to download your lab request. Then, relax while the lab processes your lab request and gets ready for your test. It’s easy to take control of your health with just a few clicks. Simple Steps to Secure Your Test To get started, go to our website and pick the "Estradiol Sensitive Test" from our list of lab tests. Add the test to your shopping cart. Then, go to the checkout. Fill in the needed details and choose the closest lab location that works for you. After you pay, you will get a lab order to take with you to the lab. Don't worry, the process is easy and helps check your estradiol levels accurately through secure and reliable repeat testing. What to Expect After Placing Your Order When you order the sensitive estradiol test online, you will get a quick confirmation email about your purchase. Usually, the test kit will be sent to your address fast. Once you get it, follow the instructions it comes with to collect your sample. Then, send the sample back as directed for testing. Your results will be processed quickly, and you will receive them safely by email within the set time. You can feel confident that your experience with the sensitive estradiol test is simple and easy. Preparing for Your Estradiol Sensitive Test Prepare well for your Estradiol Sensitive Test by following these simple steps. First, talk to your healthcare provider for any special instructions. It is important to schedule this test during the follicular phase of your menstrual cycle and avoid taking any medication that might alter your estradiol levels during this time, such as birth control pills. Also, let the lab know if you are taking any medication that might change your estradiol levels. Make sure to arrive at the collection site well-hydrated. This will make the blood draw easier. By knowing these steps, you will get correct and trustworthy results from your test. Understanding the luteal phase of your menstrual cycle is also important in interpreting your estradiol levels, as they will naturally fluctuate during this time. Understanding Your Test Results Estradiol test results give important information about the hormone levels in your body, especially for individuals with conditions such as liver disease. This sensitive test provides detailed facts for your healthcare provider. Knowing the levels of estradiol is key because they can show if there are hormone imbalances or other health problems. These levels can also affect things like bone health, sex drive, and your overall well-being. Understanding these results can be complex, so it's important to talk to your healthcare provider. They can help you make sense of your estradiol test results. Conclusion Regularly checking estradiol levels is important for men's health. You can choose a sensitive estradiol test online to learn more about your hormone balance. Discounted labs provide easy and affordable options while still offering good quality. You can easily order your test online and prepare by following simple steps. Knowing your test results is key to spotting any hormone imbalance. Take control of your health today to keep your hormone levels at their best for your overall well-being and energy.   References The role of estradiol in male reproductive function Estradiol in Men- Myths and Realities Role of Estradiol (Estrogen) in Men and Its Management

Historically, when we think of sex hormones in men and women, we identify testosterone as the core regulator of orderly male growth and sexual function. In a similar fashion, we identify estrogens as central to regulating sexual and reproductive function, along with a host of non-reproductive functions in women. 17ß-Estradiol or E2, the principal form of estrogen, is also produced in significant quantities in males. Research over the last two decades has demonstrated that estrogens can play a pivotal role in regulating male sex drive, erectile function, spermatogenesis, and can also be responsible for body fat distribution, bone density, and overall morbidity and mortality. High estradiol, however, is known to cause breast tissue growth (gynecomastia) and water retention in men with low testosterone. Because of this dynamic, regulation of the balance of testosterone and estradiol in men is paramount. Although there is evidence to suggest that lower levels of estradiol (10-20 pg/ml) can increase bone loss, the impact of high levels of estrogen on male reproductive function and other morbid conditions is complex, and it is difficult to discern upper values for the optimal range where deleterious effects begin to occur. The impact of both estrogen deficiency and excess remains controversial. We present here a background of estradiol in men along with studies that highlight the importance of estrogen in male physiology.   Video: Increased Estradiol Improved Sex Drive in Men   Estradiol in Men: Background As early as the 1930s, it was known that the male testis was responsive to estrogen and that exposure to high doses of estrogens causes developmental abnormalities. It was also speculated that the source of estrogen in males was the conversion from testosterone, which at the time was still considered the main “male hormone.” It wasn’t until the 1950s that conversion of testosterone to estrogen became well-documented. In the following decades, it became well-established that males produced significant quantities of estrogens and males of multiple species had quantifiable amounts of circulating estradiol that was synthesized in reproductive and non-reproductive tissues. In females, ovaries are the main source of circulating estrogens and regulate many facets of the female reproductive system. In males, it has been shown that the testes only produce approximately 20% of circulating estrogens, with the remainder being produced in tissues such as adipose, brain, bone, and skin, which convert testosterone to estrogens through the aromatase cytochrome P450. The diffuse pattern of estrogen production in men meant that there was no simple means to produce an estrogen-deficient state in the male comparable to an ovariectomized female. Thus, the role of estradiol and estrogen signaling in the normal male remained elusive due to a shortage of clear endpoints for estrogen action, as well as a lack of a good experimental model to approach the problem. One significant advancement in the field came in the 1970s when it was demonstrated that the testes were the major source of estrogens in men. Biochemical analysis on aromatization of androgens to estrogens and protein labeling studies for localization of estrogen receptors (ER) and the conversion enzyme aromatase in the testis were utilized to further characterize the system. New developments in the ‘80s and ‘90s led to the hypothesis that estrogen and its α-receptor were “essential” for normal fertility. Because of this, the interest in the implications of estrogen signaling in the male reproductive system increased toward the end of the century. Work over the last two decades in genetically modified mouse models, and the discovery of natural mutations in men helped to make major advances in the investigation of estrogen physiology in men. Studies further revealed that estrogens are critical for normal development and function of male reproductive and nonreproductive organs.   Sex Steroids and the Male Libido As mentioned earlier, testosterone has long been identified as the dominant sex hormone in men, and we now know that estradiol, previously thought to be only a female hormone, also plays a critical role in modulating libido, erectile function, and spermatogenesis. The extent of this role, however, is unclear and remains the subject of debate. There is an abundance of estrogen receptors, as well as aromatase in organs important to sexual function such as the brain, penis, and testis. Estradiol, therefore, can affect libido at multiple stages. Studies have indicated that decreased testosterone is associated with low libido in males. In these men, administration of exogenous estradiol can improve libido. It is known that higher testosterone levels in men can prompt higher estradiol levels through conversion of androgens like testosterone to estradiol. In male hypogonadism, a condition in which the body does not produce enough testosterone, testosterone replacement (or supplementation) therapy can improve quality of life. Testosterone therapy is prescribed for millions of men and the numbers are increasing yearly. Currently, testosterone therapy is more often used in patients with non-specific symptoms, such as sexual function and fatigue, when lab levels of testosterone fall below a certain criterion (2 standard deviations below the mean value for health young adults). Although the measure is helpful, it fails to address the physiological changes at certain testosterone levels or potential role of the associated decline in estrogens that may occur in androgen deficiency. Effect of Testosterone and Estradiol on Men's Libido: In an innovative study to address these concerns, one group recruited healthy males to determine the point at which undesirable changes begin to occur with testosterone deficiency, estrogen deficiency or both and whether these changes were androgen-dependent, estrogen-dependent or a combination of the two.(Finkelstein et al. 2013) 2 groups of males (20 to 50 years of age) with normal testosterone levels were given goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive varying amounts of 1% testosterone gel (0g, 1.25g, 2.5g, 5g, or 10g) for 16 weeks. One group also received an aromatase inhibitor to suppress the conversion of testosterone to estradiol. Over the 16-week period, changes in body fat percentage, lean mass, subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were assessed. The findings of this study indicate that when estradiol production was intact, fat accumulation began with mild testosterone deficiency (about 300 to 350 ng per deciliter). Lean mass, thigh-muscle area, and muscle strength, however, were maintained until testosterone levels dropped below 200 ng per deciliter. Sexual desire and erectile function exhibited different patterns in response to changes in serum testosterone reduction. While changes in lean mass, thigh-muscle area, and leg-press strength were associated with variations in testosterone levels, changes in fat measures were associated with changes in estradiol levels. Also, both androgens and estrogens were responsible for the maintenance of libido and erectile function.   Low Estradiol and Fat Gain: Surprising Results This study provides important information regarding the interpretation of testosterone levels in young and middle-aged men. The authors indicate that the increases in intraabdominal fat with aromatase inhibition can foreshadow an increase in cardiovascular disease observed with long-term estrogen deficiency. Lastly, since lean mass, thigh-muscle area, and erectile function were reduced at a dose of testosterone that prompted a mean serum level of approximately 200 ng per deciliter (1.25g per day).   High Estrogen in Men: Studies In the past, there has been some concern with possible side effects of elevated estrogen levels (hyperestrogenism), such as fatigue, gynecomastia, diminished libido, and erectile dysfunction. A large retrospective study conducted at 35 Low T Centers sought to understand if there were predictive factors of patients who were more likely to develop high estradiol levels after testosterone replacement therapy. (Tan, Cook, and Reilly 2015) As part of the study, the researchers also incorporated the use of aromatase inhibitor (AI) such as anastrozole (Arimidex) and selective estrogen receptor modulators (SERM) such as tamoxifen (Nolvadex) to alleviate symptoms of hyperestrogenism. The trend in estradiol levels in the 4 age groups studied (<25, 25 to 44, 45 to 65, and >65 years) was analyzed. Estradiol was lowest in the <25 years age-group with a rise in the 2 middle age groups the gradually tapered in the oldest age group (>65 years). Much of the use of aromatase inhibitors was in the 2 middle age groups, resembling the prevalence of hyperestrogenism. Interestingly, it was determined that patients with lower estradiol (<42.6 pg/ml) had complaints of low libido. The authors also make note that despite the use of AI and SERM in 30% of the treatment population, side effects occurred in <1%. One additional study worth mentioning sought to determine the associations between serum testosterone, estradiol, and libido in men undergoing testosterone supplementation therapy for symptomatic hypogonadism (total testosterone <300 ng/dl and 3 or more symptoms on the Androgen Decline in Aging Male questionnaire [ADAM]). (Ramasamy et al. 2014) As part of the ADAM questionnaire, all men were asked to rate their libido on a 5-point scale. Men were categorized into low (<300 ng/dl) or high (>300 ng/dl) testosterone and low (0.5-5.0 ng/dl) and high (>5.0 ng/dl) estradiol. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), serum testosterone, and sex hormone-binding globulin (SHBG) were analyzed to evaluate factors predicting libido. Men with high serum testosterone and estradiol levels reported greater libido. In total, 60.4% of men with both high serum testosterone and estradiol levels reported a very good to excellent levels of libido on their questionnaire. When analyzing the combined data, only estradiol at serum levels >5 ng/dl was associated with a greater libido. The authors indicate several limitations of the study and despite the lack of proper controls, a small sample size, and absence of score comparison before and after initiation of therapy, the study emphasizes the importance of estradiol in men on testosterone. Another recent study showed that change in estradiol level was the best predictor not only of the change in bone mineral density (BMD) and sexual desire.    Conclusions: In a review of the clinical implications of estrogens for sexual function and testosterone replacement therapy, one group notes that estrogens may contribute to the persistence of sexually stimulated erectile function when serum testosterone is severely depressed. Naturally occurring elevations in estradiol do not appear to be harmful, and the incidence of symptoms of excess estrogens are rare. They also add that the use of aromatase inhibitors is not recommended for long-term use and recommend against the use of aromatase inhibitors in men that experience positive effects from testosterone therapy despite elevated estradiol concentrations. When used, an aromatase inhibitor should be titrated so that estradiol levels remain above 40 pmol/L to preserve bone health. It is important to mention that levels of circulating sex hormones are highly regulated via feedback loop of the hypothalamic-pituitary-gonadal (HPG) axis and on a tissue level with aromatase activity. As levels change, the body compensates. Caution should be taken when testosterone is used pharmacologically. It is difficult to compare the response from patient to patient because of many contributing factors and levels of testosterone alone may not give a clear picture of an individual’s disposition.   References Cooke PS, Nanjappa MK, Ko C, Prins GS, Hess RA. Estrogens in Male Physiology. Physiol Rev. 2017 Jul 1;97(3):995-1043. Finkelstein JS, Yu EW, Burnett-Bowie SA. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Dec 19;369(25):2457. Tan RS, Cook KR, Reilly WG. High estrogen in men after injectable testosterone therapy: the low T experience. Am J Mens Health. 2015 May;9(3):229-34. Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. Elevated serum estradiol is associated with higher libido in men on testosterone supplementation therapy. Eur Urol. 2014 Jun;65(6):1224-5. Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male. 2002 Jun;5(2):98-102. Kacker R, Traish AM, Morgentaler A. Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency. J Sex Med. 2012 Jun;9(6):1681-96. Hess RA. Estrogen in the adult male reproductive tract: a review. Reprod Biol Endocrinol. 2003. Rochira V, Granata AR, Madeo B, Zirilli L, Rossi G, Carani C. Estrogens in males: what have we learned in the last 10 years? Asian J Androl. 2005 Mar;7(1):3-20. Schulster M, Bernie AM, Ramasamy R. The role of estradiol in male reproductive function. Asian J Androl. 2016 May-Jun;18(3):435-40. Blakemore J, Naftolin F. Aromatase: Contributions to Physiology and Disease in Women and Men. Physiology (Bethesda). 2016 Jul;31(4):258-69.

What are the common symptoms of gynecomastia? Common symptoms of gynecomastia include breast swelling and tenderness, nipple discharge, and breast enlargement. It is important to note that gynecomastia may occur on one or both sides of the chest and can affect males of all ages, from infants to older adults. What is Gynecomastia and How to Diagnose it   Gynecomastia is a benign enlargement of the male breast resulting from a growth of the glandular tissue of the breast, known as male breast tissue. It is defined clinically by the presence of a rubbery or firm mass extending concentrically from the nipples. At least 30% of males, including older men, will be affected during their life. Since it causes anxiety, psychosocial discomfort, and fear of breast cancer, early diagnostic evaluation of male breast tissue enlargement is important, and patients usually seek medical attention. Evaluation of gynecomastia must include a detailed medical history, clinical examination, specific blood tests, imaging, and tissue sampling. Individual treatment requirements can range from simple reassurance to medical treatment or even surgery. Men who start experiencing this problem complain of pain and tenderness around the nipple area. Gynecomastia was reported to cause an imbalance between estrogen and androgen action or an increased estrogen to androgen ratio, due to increased estrogen production, decreased androgen production or both, which can lead to a decrease in the level of testosterone compared with the level of estrogen. As men get older, they produce less testosterone. Older men also tend to have more body fat, and this can cause more oestrogen to be produced. These changes in hormone levels can lead to excess breast tissue growth. Androgens include testosterone and DHT. High estradiol in the presence of low testosterone and DHT, growth hormone (IGF-1 is a metabolite), and a genetic predisposition to gynecomastia can increase the size of breast tissue in men. Additionally, the lowered testosterone can cause the breast glands to enlarge and the weight gain means fatty tissue accumulates under the breast, leaving the man with a larger quantity of glandular tissue and more fat in the breast. As fat cells are estrogenic, this additional fat can further disrupt the balance between testosterone and estrogen. Gynecomastia Causes Physiological gynecomastia, also known as physiologic gynecomastia, is common in pubertal boys and appears to be associated with increased hormone levels of insulin-like growth factor-1 (IGF-1) and pubertal growth, but not with a shift in the balance between estrogen and testosterone, a new study suggests. Study authors noted that IGF-1 together with estrogen is essential for the growth of breast tissue, and it appears that the effect of growth hormone on breast growth is mediated through IGF-1. "The stimulatory effect of IGF-1 on breast formation was synergized by estradiol, which was also elevated in boys with physiologic gynecomastia in our study. However, serum testosterone was similarly elevated, leaving the estradiol/testosterone ratio unaltered." Prolactin, another anterior pituitary hormone integral to breast development, is not only secreted by the pituitary gland but may also be produced by normal mammary tissue epithelial cells and breast tumors (14, 15). Testosterone converts into estradiol, DHT, and other metabolites. Men with higher amounts of the enzyme aromatase usually have this problem even at lower doses of testosterone. The growth of this glandular tissue is also influenced by a higher fat percentage, older age, excessive alcohol intake, and the use of certain medications. Gynecomastia rarely occurs in men using testosterone replacement since testosterone to estradiol ratios are improved. Estrogen levels that are too high or are out of balance with testosterone levels can cause liver disease and gynecomastia. In several studies on testosterone replacement, only a very small percentage of people receiving testosterone experience growth of breast tissue. In one HIV-specific study conducted by Dr. Judith Rabkin in New York, she reported that out of 150 men enrolled in the study, two men experienced this adverse reaction. Dihydrotestosterone (DHT) is a natural metabolite of testosterone that has antiestrogen activity and cannot be converted into estradiol at the tissue level. Systemic or locally administered DHT has been successfully prescribed for the treatment of patients with idiopathic and estrogen-induced gynecomastia. Gynecomastia is also seen in men with androgen resistance with low testosterone production and DHT, where unfettered estrogen can stimulate subsequent breast development. However, in men with normal androgen receptor activity, estradiol is unable to stimulate breast development. This is thought to be due to an imbalance between the inhibitory and stimulatory effect of these hormones. Gynecomastia may be caused by abnormal hormone changes, any condition that leads to an increase in the ratio of estrogens/androgens such as liver disease, kidney failure, thyroid disease, and some non-breast tumors. Certain health conditions, like hypogonadism, can either cause or be linked with gynecomastia. Click: Buy gynecomastia blood test panel   Gynecomastia Symptoms Gynecomastia is a condition that causes the breast tissue in males to swell and become larger than usual. The primary symptom of gynecomastia is noticeable breast enlargement in men, which can be unilateral or bilateral. Other symptoms include tenderness or pain around the nipple area, swelling or lumps in the breast tissue, and changes in breast shape or texture. In some cases, one of the gynecomastia symptoms may also be the discharge from the nipples. If you experience any of these symptoms, it's essential to consult with a doctor to determine the underlying cause and explore treatment options. Medications and Products That Can Cause Gynecomastia Some medications have been reported in the medical literature to cause gynecomastia due to decreases in testosterone, increases in estradiol, or both. These include: · Antiandrogens.  · HIV medications.  · Anti-anxiety medications. · Tricyclic antidepressants.  · Glucocorticoid steroids. · Antibiotics. · Ulcer medication such as cimetidine . · Cancer treatment (chemotherapy). · Heart medications such as digitalis and calcium channel blockers. · Anabolic steroids · Soy and flaxseed · Exposure to pesticides and byproducts of plastic processing has also been linked to increased estrogen and decreased sperm count in men. If the cases of gynecomastia are drug-induced, gynecomastia symptoms like decreased tenderness and softening of the glandular tissue will usually be apparent within one month after discontinuation of the drug. However, if the cases of gynecomastia have been present for more than one year, it is unlikely to regress substantially, either spontaneously or with medical therapy, because of the presence of fibrosis. In such circumstances, surgical subcutaneous mastectomy, ultrasound-assisted liposuction, and suction-assisted lipectomy, including gynecomastia surgery options like liposuction, are the best options for cosmetic improvement, as described in several case series. If symptoms persist after two years or past 17 years of age, further evaluation is indicated. During the rapid, proliferative phase, manifested clinically as breast pain and tenderness, medical therapy may be attempted. Most studies of drugs -- including testosterone (in patients without hypogonadism), have been uncontrolled and thus difficult to interpret because gynecomastia may resolve spontaneously. The few randomized, double-blind, placebo-controlled trials generally have been limited by small samples and do not disclose the potential side effects. Gynecomastia Treatments: Although not approved for the treatment of gynecomastia, the selective estrogen-receptor modulator tamoxifen, administered orally at a dose of 20 mg daily for up to 3 months, has been shown to be effective in randomized and nonrandomized trials, resulting in partial regression of gynecomastia symptoms in approximately 80% of patients and complete regression in about 60%. Patients in whom tamoxifen is effective usually experience a decrease in pain and tenderness within one month. In a retrospective analysis of a series of patients with idiopathic gynecomastia, 78% of patients treated with tamoxifen had complete resolution of gynecomastia, as compared with only 40% of patients receiving danazol. In case series describing the use of tamoxifen for this condition in more than 225 patients, adverse events were uncommon but can include body aches, low sex drive, and fatigue. In a double-blind study of 282 men randomized to receive 20 mg of tamoxifen once per day with bicalutamide or bicalutamide alone found that after six months, gynecomastia and breast pain were significantly reduced in men who received tamoxifen (88 versus 96 percent in the control group). The aromatase inhibitor anastrozole was not shown to be more effective than placebo in a randomized, double-blind, placebo-controlled trial in boys with pubertal gynecomastia. Although in an uncontrolled study of 10 patients with pubertal gynecomastia, the selective estrogen-receptor modulator raloxifene was shown to result in more than a 50% decrease in the size of the gynecomastia in the majority of the boys, there are insufficient data to recommend its use at this time. Lowering the testosterone dose had not proven helpful for the two patients in Dr. Rabkin's study. The use of antiestrogens, such as tamoxifen 10 mg twice daily, with lower doses of testosterone have been effective. Some physicians prescribe low dose aromatase inhibitors for men with early-onset gynecomastia. Gynecomastia can become permanent if the condition lasts very long although it may reduce in size when the androgen use is discontinued. In rare cases, surgical correction may be necessary in severe cases. For men who experience enlarged breast size, doctors usually check estradiol levels to determine whether too much testosterone is being converted into estrogen. However, physicians usually forget that other hormone metabolites like DHT and IGF-1 may be involved in the development of gynecomastia, so they do not include these tests in the diagnostics panel. In order to properly diagnose gynecomastia, your healthcare provider will take your past health and medicine history and give you a physical exam. A blood test may also be recommended to check hormone levels. In some cases, a biopsy may be performed to examine the breast tissue for cancer cells, especially if there are any breast abnormalities detected during a mammogram. Warning: Bringing estrogen down to very low levels could cause health problems in men in the long run. Hair/skin quality and health, brain function, bone density, lipids, sexual function, and other important factors may be greatly influenced by estrogen. More information about estradiol and gynecomastia. Bibliography: Braunstein, G. D., M.D. (2007). Gynecomastia. The New England Journal of Medicine, 357(12), 1229-123712 Schulster M, Bernie AM, Ramasamy R. The role of estradiol in male reproductive function. Asian J Androl 2016;18:435-4034

Introduction Most men would not believe that estradiol is a male hormone, as they are unaware of the role that estradiol (E2) plays in the maintenance of men's health. E2 is important for many things, including the quality and quantity of sperm [1,] controlling the GH-IGF-1 axis [3,] bone growth and keeping bones healthy [4,] body composition and glucose metabolism [5,] vasomotor stability [6,] and brain function [8]. Estradiol is a hormone more abundant in women than men that is produced by the aromatization of testosterone in the liver, fat, and other cells [1]. It has been shown to be responsible for healthy bone density [2], but its role in men's sex drive, body composition, and other variables is debated [3]. High estradiol blood levels can cause gynecomastia in the presence of low testosterone [4]. Anastrozole, a blocker of estradiol production, is prescribed to men who start testosterone replacement therapy (TRT) [5]. However, there is no data on how high is too high when it comes to estradiol in men [6].   Table of Contents Introduction The Essential Role of Aromatase in the Production of E2 E2 and the Function of the Male Reproductive System The Effect of E2 on the Growth Hormone-IGF-1 Axis The Effects of E2 on the Development and Health of Bones and Skeletons The Influence of E2 on the Composition of the Body as well as Glucose Metabolism Regulation of Vasomotor Stability by E2 and Its Effects The Role of Nitric Oxide in Vasodilation The Effects of Estrogen on NO Production and Vasodilation The Need for Further Research Potential Side Effects of Testosterone Therapy and the Role of Aromatase Inhibitors A Critical Review of Current Evidence Potential Risks of Overuse of Aromatase Inhibitors The Case for Individualized Treatment Approach Estradiol: Overview and Effects Impact of High Estradiol Levels Low Estradiol: Risks and Treatment Testosterone and Estradiol: A Complex Relationship Estradiol's Role in Physiology Estradiol in Hypogonadism Studies and Findings Estradiol and Chronic Heart Failure Estradiol's Impact on Bone Density Estrogen in Men: Studies Conclusion References: The Essential Role of Aromatase in the Production of E2 Aromatase is an enzyme that converts androstenedione and testosterone into E2 in males [3]. According to the research that has been done, the hormone E2 is critically important in the control of a variety of different elements of male health [6]. E2 and the Function of the Male Reproductive System The modulation of spermatogenesis is one of the key functions that E2 performs in the male reproductive system. Working as a paracrine factor, it does its job in the Sertoli cells of the testis, where it helps germ cells mature and divide [1]. It also changes the hypothalamic-pituitary-gonadal axis, which controls the production of testosterone and the making of sperm [1, 7]. The Effect of E2 on the Growth Hormone-IGF-1 Axis It has been proven that E2 plays a significant role in the regulation of the GH-IGF-1 axis in men [3]. In healthy men, there is a positive correlation between the levels of E2 and the levels of serum IGF-1. It is possible that E2 uses negative feedback to limit GH secretion. The Effects of E2 on the Development and Health of Bones and Skeletons E2 is a crucial hormone for the growth and upkeep of men's bones, as well as their overall skeletal health. It does so by promoting osteoblast differentiation and activity and suppressing osteoclast differentiation and activity [4] [11]. In this way, it exerts an indirect influence on these features. The Influence of E2 on the Composition of the Body as well as Glucose Metabolism E2 has an effect on both the makeup of a man's physique as well as his glucose metabolism. It appears to selectively accelerate the accumulation of body fat in subcutaneous regions while at the same time limiting the accumulation in visceral regions [5]. Additionally, it has been demonstrated that E2 can improve glucose metabolism in hypogonadal men [5]. Regulation of Vasomotor Stability by E2 and Its Effects Additionally, E2 contributes to the regulation of vasomotor stability in males. People think that the production of nitric oxide (NO) plays a role in how ethyl ester affects blood vessels. The Role of Nitric Oxide in Vasodilation Nitric oxide, often known as NO, is an important physiological mediator that plays a role in a wide variety of biological activities, some of which are associated with the cardiovascular system. In the setting of the vascular system, NO plays an important function in vasodilation, controlling blood pressure, preventing blood clots, and stimulating angiogenesis [1, 2, 5]. The Effects of Estrogen on NO Production and Vasodilation It has been demonstrated that estrogens, in general, can have an effect on the generation of NO and, as a result, can mediate vasodilation. They can use both direct and indirect processes to achieve the desired vasodilatory effects. There are direct mechanisms that involve attaching to estrogen receptors on endothelial cells and making more NO. This, in turn, causes the blood vessels to become more dilated. One of the indirect ways that could be at work is by changing the production and release of other vasoactive chemicals, like prostaglandins, which could have an effect on NO production. The Need for Further Research Please be aware that despite the fact that the idea that NO synthesis mediates the vasodilation effects of E2 is reasonable based on the known actions of estrogens and NO, further research is required to determine the particular role that E2 plays in this process. Because of this, to get a better understanding, it would be important to look at the original research papers or more recent studies that focus on the part that E2 plays in changing NO production and vasodilation. Potential Side Effects of Testosterone Therapy and the Role of Aromatase Inhibitors When men undertake testosterone therapy (TTh), their estrogen levels may increase, and this may, in some instances, result in the development of nipple or breast soreness or even gynecomastia (the formation of male breast tissue in males). This can be a clear indicator that aromatase inhibitors should be used to reduce the amount of estrogen in the body. A Critical Review of Current Evidence Even so, there is not enough proof to support the regular use of aromatase inhibitors along with TTH when there are not any signs of estrogen overload. Although testosterone levels returned to normal after therapy with an aromatase inhibitor, the symptoms of low testosterone did not improve, according to the findings of one randomized controlled trial. Potential Risks of Overuse of Aromatase Inhibitors In addition, decreasing estrogen levels below a key threshold may raise the likelihood of developing osteoporotic changes and decrease insulin sensitivity, particularly in people who are receiving TTH. These risks may be increased in people who are already at higher risk for developing osteoporosis. The Case for Individualized Treatment Approach The study did not find any evidence to support the claim that taking TTH with aromatase inhibitors or other medicines would lead to lower levels of estrogen that would be better than taking TTH by itself. On the other hand, it was shown that certain TTH-treated men who had elevated estrogen levels but did not experience any clinical improvements from TTH did respond to actions taken to lower estrogen levels. These efforts included either a reduction in the amount of testosterone or the use of aromatase inhibitors. When this occurs, DXA monitoring is an option that should be examined. Estradiol: Overview and Effects Estradiol is a hormone more abundant in women than men that is produced by the aromatization of testosterone in liver, fat and other cells [1]. It has been shown to be responsible for healthy bone density [2], but its role in men's sex drive, body composition, and other variables is debated [3]. Impact of High Estradiol Levels High estradiol blood levels can cause gynecomastia in the presence of low testosterone [4]. Anastrozole, a blocker of estradiol production, is prescribed to men who start testosterone replacement therapy (TRT) [5]. However, there is no data on how high is too high when it comes to estradiol in men [6]. Low Estradiol: Risks and Treatment Low estradiol can be associated with higher fat mass and lower sexual function in men [7], so it is important to be careful when a clinic wants to put you on this drug without first justifying its use [8]. The most important details are that many clinics may be using the wrong estradiol test [9], and that most men on testosterone replacement therapy (TRT) do not develop gynecomastia even without using anastrozole [10]. Testosterone and Estradiol: A Complex Relationship Some physicians monitor estradiol blood levels after 6-8 weeks of TRT initiation using the sensitive estradiol test to determine if anastrozole use is warranted [11]. After 4-6 weeks on anastrozole, its dose can be adjusted to ensure that estradiol is not under 20 pg/ml [12]. The body of evidence suggests that after aromatase P450 inhibitors biotransform testosterone in the tissues, the ERs (estrogen receptors) in men mediate its effects [13]. Estradiol's Role in Physiology Some of the things that estrogen does are control LH feedback, skeletal homeostasis, lipid metabolism, cardiovascular physiology, brain development, and spermatogenesis [14]. Estradiol in Hypogonadism Estradiol serum concentration in adult males is around 20-30 pg/ml, with a production rate of 45 g/d [15]. Low levels of estradiol are associated with increased fat and decrease in sexual desire and erectile function compared to higher levels [16]. Studies and Findings This study found that estradiol levels of 21.80 pg/ml and > 30.11 pg/ml resulted in greater mortality in men with hypogonadism, suggesting that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism [17]. Estrogens have a fundamental role in the regulation of body fat and sexual function, and this suggests that measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism [18]. Estradiol and Chronic Heart Failure A study examined the relationship between serum concentration of estradiol and mortality in men with chronic heart failure and reduced left ventricular ejection fraction (LVEF) [19]. Results showed that men in the lowest and highest estradiol quintiles had increased mortality, while those in the highest quintile had increased survival rates [19]. Estradiol's Impact on Bone Density Estradiol below 11 pg/ml was associated with increased bone loss [20]. Estrogen deficiency is common in men with chronic HF and is associated with increased morbidity and mortality [21]. Estrogen appears to play an important role in determining bone mineral density in men, but it is unclear if it also affects bone   Estrogen in Men: Studies Estradiol is a hormone more abundant in women than men that is produced by the aromatization of testosterone in liver, fat and other cells [1]. It has been shown to be responsible for healthy bone density [2], but its role in men's sex drive, body composition and other variables is debated [3]. High estradiol blood levels can cause gynecomastia in the presence of low testosterone [4]. Anastrozole, a blocker of estradiol production, is prescribed to men who start testosterone replacement (TRT) [5]. However, there is no data on how high is too high when it comes to estradiol in men [6]. Low estradiol can be associated with higher fat mass and lower sexual function in men [7], so it is important to be careful when a clinic wants to put you on this drug without first justifying its use [8]. The most important details are that many clinics may be using the wrong estradiol test [9], and that most men on testosterone replacement therapy (TRT) do not develop gynecomastia even without using anastrozole [10]. Some physicians monitor estradiol blood levels after 6-8 weeks of TRT initiation using the sensitive estradiol test to determine if anastrozole use is warranted [11]. After 4-6 weeks on anastrozole, its dose can be adjusted to ensure that estradiol is not under 20 pg/ml [12]. The body of evidence suggests that testosterone in men is mediated by the ERs (estrogen receptors) after its biotransformation by the aromatase P450 inhibitors in the tissues [13]. These estrogen-mediated actions include feedback regulation of LH, regulation of skeletal homeostasis, lipid metabolism, cardiovascular physiology, and brain and spermatogenesis [14]. Estradiol serum concentration in adult males is around 20-30 pg/ml, with a production rate of 45 g/d [15]. Low levels of estradiol are associated with increased fat and decrease in sexual desire and erectile function compared to higher levels [16]. This study found that estradiol levels of 21.80 pg/ml and > 30.11 pg/ml resulted in greater mortality in men with hypogonadism, suggesting that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism [17]. Estrogens have a fundamental role in the regulation of body fat and sexual function, and this suggests that measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism [18]. A study examined the relationship between serum concentration of estradiol and mortality in men with chronic heart failure and reduced left ventricular ejection fraction (LVEF) [19]. Results showed that men in the lowest and highest estradiol quintiles had increased mortality, while those in the highest quintile had increased survival rates [19]. Estradiol below 11 pg/ml was associated with increased bone loss [20]. Estrogen deficiency is common in men with chronic HF and is associated with increased morbidity and mortality [21]. Estrogen appears to play an important role in determining bone mineral density in men, but it is unclear if it also affects bone loss in elderly men [22]. Another study assessed longitudinal rates of change in bone mineral density in young and elderly men and related these to circulating total and bioavailable estrogen and testosterone levels [23]. The rate of increase in bone mineral density at the forearm sites in the young men was significantly correlated to serum total and bioavailable estradiol and estrone levels, but not with total or bioavailable testosterone levels [23].  Elderly men with bioavailable estradiol levels below the median had significantly higher rates of bone loss and levels of bone resorption markers than men with bioavailable estradiol levels above 40 pmol/liter [23]. Ranjith Ramasamy and Larry Lipshultz conducted a study of 423 men on TRT and found that those with high testosterone and estradiol levels had significantly greater libido than those with low levels [24]. The results are expected to be presented at the American Urological Association annual meeting in Orlando [24]. Hyperestrogenism is believed to be harmful to male sexuality [25]. A study screening 34,016 men in Low T Centers revealed that 7,215 (20.2%) had high estradiol levels [26]. The age distribution of those with high estradiol levels was as follows: 132/989 (13.3%) were older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years, 2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than 25 years [26]. The correlation coefficient of serum estradiol to age was .53 [26]. Low blood levels of estradiol (E2) are associated with brittle bones in old men, according to a new study [27]. Age-adjusted models showed that E2 and free E2 but not testosterone (T) associated significantly inversely with cortical porosity [28]. Free E2 also associated significantly with trabecular bone volume fraction, but this association did not remain significant after further adjustment [28]. Low serum E2 may reduce cortical bone strength and increase fracture risk in older men [29]. Conclusion The hormone estradiol, also known as E2, has emerged as a key player in a myriad of biological functions in males. It is involved in the regulation of sperm health, the growth hormone-insulin-like growth factor-1 axis, bone health, body composition, glucose metabolism, vasomotor stability, and brain function. The key enzyme aromatase, which facilitates the conversion of androstenedione and testosterone to E2, is integral to these processes. Understanding the role of E2 in male physiology helps shape our approach to health issues like low testosterone and the potential side effects of testosterone therapy. While the use of aromatase inhibitors can sometimes be beneficial in managing the effects of elevated estrogen levels, more evidence is needed before they can be recommended for routine use alongside testosterone therapy. It is also crucial to consider the balance between testosterone and E2 in the male body, as overly suppressing estrogen levels might lead to unintended consequences such as osteoporotic changes and decreased insulin sensitivity. As we deepen our understanding of E2's role in the body, it becomes clear that a nuanced, individualized approach to treatment is needed to balance the benefits and risks. Finally, there are still many open questions about the specific mechanisms through which E2 influences different aspects of male health. For example, the relationship between E2 and nitric oxide in mediating vasodilation remains to be fully elucidated. Therefore, more research is required to continue building a comprehensive understanding of E2's role in men's health. As we continue to learn, our approach to male hormonal health will evolve, bringing about new strategies for maintaining and improving men's health.   Buy the best-priced  gold standard ultrasensitive estradiol test on DiscountedLabs.com.   References:   1 https://www.healthline.com/health/estrogen-in-men 2 https://www.medicalnewstoday.com/articles/estrogen-in-men 3  https://academic.oup.com/ejendo/article/181/1/R23/6654090 4 https://tctmed.com/estrogen-in-men/ 5 https://www.news-medical.net/health/The-Role-of-Estrogen-in-Mene28099s-Health.aspx 6 https://my.clevelandclinic.org/health/body/22353-estrogen 7 https://eje.bioscientifica.com/downloadpdf/journals/eje/181/1/EJE-18-1000.pdf 9 https://www.testosteronewisdom.com/role-of-estradiol-in-men-and-its-management-2/ 10  https://www.news-medical.net/health/What-does-Estradiol-do.aspx 11  https://eje.bioscientifica.com/view/journals/eje/181/1/EJE-18-1000.xml  

Although testosterone frequently overshadows estradiol, a hormone more commonly associated with women, estradiol plays a significant role in men's health. Derived from testosterone through a process known as aromatization, estradiol contributes to various physiological aspects in men. Although it's crucial for maintaining bone density, its role in sexual health, body composition, and other health parameters is subject to ongoing discourse. Here, we delve into the dynamics of estradiol in men, its implications, and the importance of accurate measurement. Understanding Estradiol in Men The hormone estradiol, although present in smaller quantities in men compared to women, is produced through the aromatization of testosterone in liver, fat, and other cells. This conversion is nature’s design, hinting at a purpose behind it. Besides promoting bone health, estradiol’s influence on men's libido, body composition, and other factors is a hot topic among researchers. Excessive levels of estradiol, especially alongside low testosterone levels, could lead to conditions like gynecomastia (enlarged breasts in men). Hormonal Balance: The HPT Axis The Hypothalamic-Pituitary-Testicular (HPT) axis is a hormonal cascade that adjusts testosterone production based on the levels of testosterone and estradiol in the body. When either hormone level goes up too high, the HPT axis responds by decreasing the production of testosterone to keep hormone levels in balance. Aromatase Inhibitors: Boon or Bane? Aromatase inhibitors (AIs) stop the production of estradiol and are often given to people who are getting testosterone replacement therapy (TRT) to help them look younger and stay healthy. While higher estradiol levels could potentially cause gynecomastia and water retention, there's speculation, albeit without scientific backing, linking high estradiol levels to erectile dysfunction. The use of AIs is thought to mitigate these issues by lowering estradiol levels. However, the exact threshold of estradiol levels in men, beyond which it could be detrimental, remains undefined. Unveiling the Optimal Range Recent studies have started to shed light on estradiol's optimal range. For instance, levels below 20 pg/ml have been associated with increased bone loss, higher fat mass, and diminished sexual function in men. It is very important to get a correct reading of estradiol, and it is better to use a sensitive estradiol test (LC/MS assay) instead of the more common ECLIA-based test to avoid getting wrongly high estradiol readings from things like CRP (C-reactive protein). Estradiol’s Diverse Effects: A Closer Look 1. Bone Density: A study showed that estradiol levels below 11 pg/ml were linked to increased bone loss in men, emphasizing estradiol's role in bone health (Source). 2. Libido and Erectile Function: One groundbreaking study revealed that lower estradiol levels were correlated with increased body fat and a decrease in sexual desire and erectile function (Source). 3. Mortality Rate: A study highlighted that men with estradiol levels either below 21.80 pg/ml or above 30.11 pg/ml had a higher mortality rate, indicating a potential sweet spot for estradiol levels (Source). 4. Testosterone Therapy: In men undergoing TRT, elevated estradiol levels were associated with heightened libido, suggesting a nuanced interplay between testosterone and estradiol (Source). Conclusion The journey to demystify estradiol's role in men is ongoing. While its importance in bone health is well acknowledged, the hormone's broader impact on male physiology is gradually being unraveled. Accurate estradiol measurement and a deeper understanding of its optimal range could pave the way for enhanced men's health management, particularly for those undergoing testosterone replacement therapy.     Here is a more detailed discussion on estradiol in men: Click here   How to Get a sensitive estradiol test  

Table of Contents What are Estradiol and Aromatase? When aromatase is unbalanced, estradiol becomes an issue Low estrogen levels in men, not testosterone increases risk of heart disease Androgen deprivation therapy can cause cognitive decline Does estradiol restore cognitive function during ADT? Should high estradiol levels be treated? What are Estradiol and Aromatase? Estradiol is a form of the female hormone estrogen. Although estradiol production is typically considered a female concern, men also need to maintain healthy levels of this hormone for optimal health. Since men lack ovaries (where most estradiol is produced in women), estradiol in men is created by a process that uses an enzyme called aromatase (1) in testicles, liver and fat cells. Aromatase converts a very small portion of testosterone levels into estradiol, and health problems can arise when aromatase levels are too high or too low (1). When aromatase is unbalanced, estradiol becomes an issue As men age, they can experience excess aromatase activity, raising estradiol levels and reducing testosterone to unhealthy levels. Low T levels will adversely impact quality of life by reducing libido, ability to maintain an erection, mood, and muscle mass, among other health factors (2). However, when the body produces too little aromatase, men can experience other, potentially serious health problems. Men with diminished aromatase levels will have an estradiol deficit, which can create problems similar to low-T; diminished sex drive, loss of bone mass, and increased body fat (3). Men on testosterone replacement therapy (TRT) taking higher doses of aromatase inhibitors can also experience estradiol deficit. Let’s look at recent studies finding that low estradiol can play a critical role in increasing the risk of cognitive decline and increase the odds of experiencing cardiovascular disease. Low estrogen levels in men, not testosterone increases risk of heart disease A study led by Elaine Yu, MD, MSc, addresses the suspicion held by many medical professionals that testosterone can promote cardiovascular disease in men, and that estradiol provides protection against it (4). The researchers sought to determine whether it was estradiol or testosterone that regulated men’s cardiovascular risk factors by comparing two groups whose hormone levels were changed using a combination of medications (4). They looked at 400 healthy men, between the ages of 20 and 50. Study participants were weighed, had fasting blood tests for markers of heart disease and diabetes, and also had a thigh scan using quantitative computed tomography (CT scan) to measure muscle fat content before and after the study (4). Yu’s team found that while higher levels of testosterone reduced these men’s levels of healthy (HDL) cholesterol, changes in estradiol levels had no effect at all on HDL(4). However, they also discovered that low estradiol levels did increase the markers for diabetes, like increased insulin resistance, increased fat in the muscles, and higher fasting blood sugar levels(4). Diabetes is a major risk factor for heart disease (5). Additionally, the study found that neither estradiol nor testosterone affected the levels of LDL (unhealthy) cholesterol. According to Yu, these findings indicate that in men, it’s higher testosterone levels combined with lower estradiol levels that can worsen cardiovascular risk factors, somewhat explaining differences in the incidence of heart disease between men and women. Some studies have shown that it is the ratio of testosterone to estradiol that is important, not just the level of each of those hormones. As testosterone increases with TRT, so does estradiol to balance the effects of testosterone on lipids, mood and insulin action. Androgen deprivation therapy can cause cognitive decline Androgen deprivation therapy (ADT) is an often used method to slow the growth of prostate cancer. It’s also used for men transitioning to women (6, 7). ADT is typically prescribed on an open-ended (no fixed period) basis to help treat advanced prostate cancer. An estimated 44 percent of men with prostate cancer will undergo ADT at some point as part of a strategy to slow tumor growth (6). ADT therapy is used specifically to block the male hormones, particularly testosterone, from stimulating prostate cancer cell growth. Research has confirmed that ADT can cause significant cognitive decline in women with breast cancer (8), but few studies have investigated cognitive impairment following ADT for men being treated for prostate cancer. Using formal tests, scientists recently compared the cognitive ability of 58 prostate cancer patients receiving androgen deprivation therapy to 84 prostate cancer patients who did not receive ADT, and 88 cancer-free men (9). They found that those treated with ADT were 70 percent more likely to develop cognitive impairment after six months, and over twice as likely to have significant cognitive impairment after one year(9).   Does estradiol restore cognitive function during ADT? A 2018 study published in Current Neuropharmacology has examined whether estradiol supplementation is an effective way to prevent this side effect (9). Researchers performed a literature search using PubMed and Google Scholar to identify studies on this topic and discover any evidence that estradiol supplementation has a cognitive benefit for men on ADT. They examined studies involving the effects of estradiol treatment on cognitive function in three androgen-deprived male populations; prostate cancer patients, male-to-female transsexuals, and castrated male animals (9). A review of the literature found that while some studies show that estradiol supplementation resulted in cognitive improvement (especially in spatial ability), They couldn’t determine (9): Whether estradiol will improve cognition after long-term ADT How early or delayed estradiol treatment post-castration will affect cognition If estradiol affects memory retention They conclude that for androgen-deprived males, there is some evidence that estradiol supplementation may improve both verbal and visual memory (9). However the variability between the reviewed studies resulted in significant inconsistencies, making further study necessary to determine what estradiol treatment protocol can best maximize cognitive improvement for men using ADT (9). Should high estradiol levels be treated? Men on testosterone replacement therapy can experience an increase in estradiol that can sometimes reach clinically elevated levels (10). A study published in the Journal of Sexual Medicine (11) looks at the phenomenon of increased estradiol levels in men undergoing TRT to discover whether high estradiol levels in this population should be treated. Researchers comprehensively reviewed the published literature on the role of estradiols in male sexual function and testosterone deficiency to answer this question. The study findings reveal that (11): Although estradiol have been used at pharmacologic doses to suppress serum testosterone, there is no evidence that naturally occurring elevations of estradiol will cause a reduction in testosterone levels Absent testosterone deficiency, study findings suggest that elevated estradiol levels don’t seem to be harmful. Once again, monitoring and treating the ratio of testosterone to estradiol may be more important than either hormone alone. Estradiol could help maintain some sexual function in castrated men Given the evidence uncovered by this review study, researchers report that, although further research is needed, the existing evidence doesn’t support the treatment of elevated estradiol for men on testosterone therapy (11). WATCH LECTURE ABOUT ESTRADIOL IN MEN    BUY YOUR SENSITIVE ESTRADIOL TEST   References 1) Stocco, Carlos. “Tissue Physiology and Pathology of Aromatase.” Steroids 77.1-2 (2012): 27–35. PMC. Web. 11 June 2018. 2) Araujo, Andre B., and Gary A. Wittert. “Endocrinology of the Aging Male.” Best practice & research. Clinical endocrinology & metabolism 25.2 (2011): 303–319. PMC. Web. 11 June 2018. 3) Bulun, Serdar E. “AROMATASE DEFICIENCY.” Fertility and sterility 101.2 (2014): 323–329. PMC. Web. 11 June 2018. 4) Men's heart disease risk linked to high testosterone and low estrogen. The Endocrine Society. 5) Zhang PY. Cardiovascular disease in diabetes. Eur Rev Med Pharmacol Sci. 2014;18(15):2205-14. 6) Perlmutter, Mark A, and Herbert Lepor. “Androgen Deprivation Therapy in the Treatment of Advanced Prostate Cancer.” Reviews in Urology 9.Suppl 1 (2007): S3–S8. Print. 7) Unger, Cécile A. “Hormone Therapy for Transgender Patients.” Translational Andrology and Urology 5.6 (2016): 877–884. PMC. Web. 11 June 2018. 8) Wu, Lisa M., and Ali Amidi. “Cognitive Impairment Following Hormone Therapy: Current Opinion of Research in Breast and Prostate Cancer Patients.” Current opinion in supportive and palliative care 11.1 (2017): 38–45. PMC. Web. 11 June 2018. 9) Wibowo E. Cognitive Impacts of Estrogen Treatment in Androgen-Deprived Males: What Needs to be Resolved. Curr Neuropharmacol. 2017;15(7):1043-1055. 10) Tan RS, Cook KR, Reilly WG. High estrogen in men after injectable testosterone therapy: the low T experience. Am J Mens Health. 2015 May;9(3):229-34. doi: 10.1177/1557988314539000. Epub 2014 Jun 13. 11) Ravi Kacker, Abdulmaged M. Traish, Abraham Morgentaler. Estrogens in Men: Clinical Implications for Sexual Function and the Treatment of Testosterone Deficiency. The Journal of Sexual Medicine. (2012): Volume 9, Issue 6, Pages 1681–1696