Potential Side Effects of Testosterone Replacement Therapy: Role of Estrogen, Baldness, Water Retention, and Others
Testosterone replacement therapy, or TRT, is becoming increasingly popular for treating low testosterone levels in men. However, several potential side effects are associated with testosterone therapy that should be considered before starting testosterone treatment. In this blog post, we will discuss the role of estrogen in TRT and the side effects of both high and low estrogen levels. We will also look at water retention, baldness, DHT production, prolactin levels, and SERMs. Finally, we will analyze objectively when people should consider starting TRT and when not!
Role of estrogen and side effects of low and high E2 while on testosterone treatment
Men also produce estrogen, albeit in much smaller quantities than women. Estrogen is frequently called the female hormone, which is not entirely accurate. Testosterone is converted to estrogen via the enzyme aromatase. Aromatase happens both in men and women but is more pronounced in men because they have more testosterone.
Estrogen is essential for brain and sexual function, bone health, and cardiovascular function. It also plays a role in maintaining healthy cholesterol levels. In men, too much estrogen can lead to Gynecomastia (the development of breasts), water retention, and fat gain. On the other hand, too little estrogen can lead to osteoporosis, fatigue, hot flashes, and depression.
One of the most critical determinants of estrogen (E2) being out of balance is the strength of your erections! When you cannot maintain a strong erection, it is often a sign of high E2 levels in the body! On the other side, for people with deficient levels of E2 common symptoms are sexual dysfunction (low interest in sex) and the inability to get an erection. Low estrogen can happen due to natural causes such as age or aromatase inhibitors medication!
AI medication is an abbreviation for aromatase inhibitor medication used to treat conditions such as breast cancer, water retention, and Gynecomastia. These drugs work by inhibiting the enzyme aromatase, which converts testosterone to estrogen. Arimidex is one of the most commonly prescribed AI drugs and is very effective at lowering estrogen levels in men. However, it can also lead to side effects, such as joint pain, hot flashes, and fatigue.
Arimidex is not the only AI drug available; other options include Letrozole and Anastrozole. These drugs are also effective at lowering estrogen levels but may have different side effects. Letrozole can cause hair loss, while Anastrozole can cause nausea and vomiting.
It is important to remember that AI drugs are not without their risks and should only be used under the supervision of a qualified medical professional!
What should you do to ensure E2 is under control?
Usually, the endocrinologist you are working with would take an initial blood test to check your estradiol (E2) levels to establish a baseline and then closely monitor the changes after starting the testosterone replacement therapy. Based on recommended ranges and your feedback, he would try to adjust it to the degree that works best for you!
Some usual recommendations are to keep your E2 below 80pg/ml, but I repeat, numbers are only one side of the equation. How you feel is another critical element that the doc should consider!
Pro Tip: Make sure your doctor orders a sensitive or enhanced estradiol assay (a lab test) before and after you start your testosterone therapy. The standard estrogen test often over-reads estrogen levels in men on testosterone therapy, which can cause needless anxiety.
Medications you might need on testosterone therapy.
SERMs (Selective Estrogen Receptor Modulators) and AI's (Aromatase Inhibitors) were initially designed for women to help treat breast cancer. These medications are usually well-tolerated as long as you work with a professional that knows how these drugs interact with your body! That is why when these medications are used in males. They need to be closely monitored.
Arimidex (Anastrozolone)
Arimidex is an aromatase inhibitor that should only be used when necessary to lower your estradiol. Arimidex competes with estrogen for binding to the aromatase enzyme. Arimidex prevents aromatase enzymes from binding to an androgen (testosterone), thereby blocking your body's ability to produce estrogen.
You should always start with the minimum effective dose of 0.25mg-0.5mg once daily for about three days a week. Then get off the medication as soon as your estradiol levels are balanced. Men with high body fat levels might need higher doses of AI due to the conversion of androgens to estrogens in adipose tissue.
Aromatase inhibitors can have long-term risks on your bone health, so monitor your bone density with DEXA scans every few years if you are on an AI long-term!
Important note: Arimidex reduces HDL, so-called good cholesterol levels, and therefore, should be used with caution in men with cardiovascular risks! Reducing HDL levels below 40mg/dl can lead to an increased risk of heart disease.
SERM's (Nolvadex and Clomid)
Selective estrogen receptor modulators can be used for short periods when your estradiol levels are high. These drugs will bind to the estrogen receptors in your body and prevent them from being activated.
Nolvadex
Nolvadex is usually dosed at 20-40mg per day for two weeks; however, I recommend the smallest effective dose to start at 10-15mg per day or every other day until symptoms disappear and your levels are balanced. Gradually reduce your amounts before discontinuing its use.
Nolvadex works by binding to the estrogen receptors in your breast tissue, which prevents them from being stimulated by estradiol. This can help reduce the risk of developing Gynecomastia (male breasts).
Clomid
Clomid is often dosed at 50-100mg daily for five days. However, I recommend starting with lower doses of 25-50mg per day and increasing gradually if needed. Clomid can have side effects such as hot flashes, headaches, and mood changes. These side effects are usually mild and go away after a few days.
Clomiphene pills can help males with low testosterone by boosting follicle-stimulating hormone (FSH) levels and luteinizing hormone (LH). These hormones are responsible for stimulating the testicles to produce testosterone. Clomid works by blocking estrogen's actions in the pituitary gland. As a result of the inhibition, the pituitary produces less estrogen and more LH.
Clomid is now the preferred therapy by many urologists and endocrinologists for treating low testosterone in young males! Some men respond great to Clomid while others don't, so it's essential to check your Testosterone and LH/FSH levels after starting Clomid therapy to see if it works for you!
Important Note: In some men, Clomid increases SHBG, decreasing the amount of free testosterone in the body. You need to increase your testosterone dose or switch to an AI if this happens!
What role does SHBG have when it comes to health and testosterone therapy?
SHBG is a protein that binds to testosterone in the blood and makes it unavailable to be used by the body. So, the higher your SHBG levels are, the lower your free testosterone levels will be! The liver produces SHBG, and its levels can be affected by several factors such as obesity, diabetes, and hypothyroidism. Testosterone Replacement Therapy (TRT) can also increase SHBG levels! It's essential to check your SHBG levels when starting TRT, as you might need to adjust your testosterone dose depending on the results! Your goal is to have as much free testosterone available, so your body can use it!
SHBG is also an important marker of insulin resistance, and studies have shown that it is a predictor of metabolic syndrome and type 2 diabetes. In males, around 60% of testosterone is bound to Sex Hormone Binding Globulin (SHBG). Now imagine when SHBG levels start to increase, they can pick up all the testosterone you have, so in this case, you might have to increase your testosterone dosage to compensate for the increase in SHBG.
You can drive down SHBG with medication, but I recommend adjusting your testosterone protocol to compensate! You can decrease SHBG levels by reducing your body fat, eating a fiber-rich diet, introducing 5-10mg of Boron supplementation, and avoiding excess alcohol, caffeine, and sugar! Caloric restriction can also drive your SHBG up via mechanisms still unknown to me.
What is the safest way to get my estrogen levels from high to normal?
The safest way to reduce estradiol levels in your body is to reduce your testosterone dose and alter your dosing schedule! You should forget about the old school methods of injecting once a month or once every week and injecting every other day or every third day like most of my coaching clients! That will keep your estradiol levels in check, and you will feel much better!
You can improve your estrogen metabolism by reducing your body fat, eating a fiber-rich diet, introducing cruciferous vegetables into your diet, and exercising regularly! These methods will help you eliminate excess estrogen in your body and introduce supplements like DIM and Calcium D Glucarate.
DIM is an abbreviation for Diindolylmethane, a substance found in cruciferous vegetables like broccoli, cabbage, and kale. DIM supplements have been shown to increase testosterone levels and reduce estrogen levels in males! They work by inhibiting the activity of the enzyme aromatase, which is responsible for converting testosterone into estrogen!
Recommended dosage - 200mg/daily
Calcium D Glucarate is a substance found in fruits and vegetables and works by inhibiting the activity of beta-glucuronidase. This enzyme is responsible for the reabsorption of estrogen from the gut back into circulation! Calcium D Glucarate supplements have been shown to reduce circulating estrogen levels in males!
Recommended dosage - 500mg/2x daily
HCG - Human Chorionic Gonadotropin
Human Chorionic Gonadotropin can increase testosterone levels in men with hypogonadism (low testosterone). HCG is a hormone that is structurally similar to LH. HCG works by stimulating the testicles to produce more testosterone.
The recommended dosage of HCG for men is 250-1000IU two to three times per week. Side effects of HCG include acne, fatigue, and headache.
DHT - Dihydrotestosterone
Testosterone is the primary androgen hormone that is secreted in the testes. DHT is a hormone that is similar to testosterone but is more potent. DHT does not aromatize (convert to estrogen) and supports muscle gains! Dihydrotestosterone sends signals to your brain, CNS (central nervous system), skin, and genitals.
DHT is essential for male sexual development and proper sexual function, including libido. It is also necessary for good brain chemistry. However, too much DHT can lead to hair loss, prostate enlargement, and other side effects.
Does elevated DHT lead to prostate cancer?
Elevated DHT has not been linked to an increased risk of prostate disease (e.g., prostate cancer or hyperplasia. The recommended dosage of DHT for men is 50mg per day. If you have hair loss problems, taking DHT blockers such as finasteride or dutasteride would help you with hair loss. However, DHT blockers can have side effects such as impotence, loss of libido, and decreased ejaculate volume.
Prolactin
Prolactin is mainly released from the anterior lobe of the pituitary gland in response to suckling at the breast or nipple stimulation. It is a hormone found in men and women, but elevated prolactin levels are more common in men. In men, prolactin is essential for sexual function, but high levels can lead to erectile dysfunction and reduced libido.
Excessively high prolactin levels are associated with Gynecomastia (man boobs). This hormone should be a part of your regular blood work.
Baldness
Baldness is also known as MBP (male pattern baldness). MBP is genetic, but being on testosterone optimization therapy can speed up your hair loss via testosterone conversion into DHT (dihydrotestosterone). I hope now this loop makes more sense to you?
Some medication that men take to prevent hair loss is Propecia (Proscar). The ingredient in Propecia is Finasteride, which is a 5-alpha-reductase (5AR) inhibitor.
5-alpha reductase inhibitor (5AR) inhibits the conversion of testosterone to DHT. That means that taking medication to prevent testosterone conversion into DHT might block many of the positive effects of your testosterone therapy. But not just that, it also might reduce your sex drive and weaken your erections by decreasing the amount of DHT in your body.
Finasteride (5AR inhibitor) can also cause some side neurological side effects, such as reduced libido, erectile dysfunction, and decreased ejaculate volume.
Acne and testosterone therapy
Men that used to have skin issues when in their teens, like oily skin and acne, could be more prone to having these issues come back when on testosterone therapy. That is because androgens (testosterone and DHT) can stimulate the sebaceous glands responsible for producing sebum. And can last up to a few months or sometimes stay for as long as you are on TRT.
Sebum is an oily substance that lubricates and waterproofs your skin and hair. When too much sebum is produced, it can mix with dead skin cells and dirt to clog your pores. That can lead to blackheads, whiteheads, or pimples.
To help control acne, you can not do much except keep your hygiene and use creams like benzoyl peroxide or salicylic acid. If you are bothered by acne, talk to your doctor about using some medication like spironolactone, a diuretic that can help with acne by reducing androgen levels in your body. Then again, it will have a negative impact on the benefits of TRT!
Water Retention
Another very noticeable side effect of high estrogen levels is water retention. Every male is different, and some will genetically overproduce the enzyme necessary for converting testosterone to estrogen, leading to increased estrogen production and its potentially harmful side effects.
Hematocrit & Hemoglobin association with testosterone therapy
High testosterone causes an increase in RBC (Red Blood Cells) production. That will lead to an increase in hematocrit (HCT). Hematocrit is the percentage of your blood made up of red blood cells. The normal range for men is 38-54%.
An increase in HCT can cause side effects such as headaches, dizziness, and visual changes. If your HCT gets too high (over 54%), you might have to stop your testosterone therapy or donate some blood to reduce the amount of RBC in your body. Elevated hematocrit can also increase your risk of heart attacks and strokes, so it is something that you want to avoid.
You can also improve your RBC count by reducing body fat and improving your cardiovascular capacity with a good workout program!
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Types of injectable testosterone
Here we will briefly go through the different types of injectable testosterone and explain which one might be the best option for you!
Types of injectable testosterone:
Testosterone cypionate
Testosterone cypionate is usually injected once every two weeks. Testosterone cypionate has a half-life of about eight days. That means that it will stay in your system for about three weeks.
Testosterone enanthate
Testosterone enanthate is injected once every week. Testosterone enanthate has a half-life of about seven days. That means it will stay in your system for about three and a half weeks.
Testosterone propionate
Testosterone propionate has a half-life of about four days. That means that it will stay in your system for about two weeks. Testosterone propionate is injected once every three or four days.
Testosterone undecanoate
Testosterone undecanoate is injected once every four weeks. Testosterone undecanoate has a half-life of about eight hours. That means that it will stay in your system for about four days.
Which injectable testosterone is the best?
The answer to this question depends on a few factors, such as your goals, lifestyle, and budget. Testosterone cypionate and testosterone enanthate are the most popular injectable Testosterones. Testosterone propionate is a good option if you want to inject Testosterone more frequently. Testosterone undecanoate is a good option if you want to have fewer injections.
Pro Tip: Unlike conventional recommendations to inject once a week or once every two weeks, you will see much more benefits and fewer side effects if you inject more frequently while reducing the dose! That will give you a more stable Testosterone level and minimize the peaks and valleys.
How to inject testosterone?
Testosterone injections are usually given intramuscularly, which means they are injected into the muscle. The glute (butt) muscles or the quadriceps (thigh) muscles are the most common injection sites. Testosterone injections can also be given subcutaneously, which means they are injected under the skin. Subcutaneous injections are less painful and are growing in popularity.
The recommended dose of Testosterone is 100-200mg per week. However, some people may need more Testosterone. Working with a doctor who can customize your dose based on your individual needs is essential. The dosage will vary from individual to individual based on multiple factors like:
Age
Weight
Medical history
Specific goals
Previous history of use
Your doctor will be able to determine the best dose for you.
Are testosterone gels effective when having low testosterone?
Testosterone gels can be a viable option for people who do not like injections but want to do testosterone therapy. Testosterone gels are easy to use and effective in raising testosterone levels. However, Testosterone gels have some drawbacks.
Testosterone gel can be messy and can transfer to other people if you don't take precautions. Testosterone gels also have to be applied every day, sometimes twice daily, which can be a hassle for some people.
You apply the gel to your upper arms, shoulders, or abdomen. Testosterone gel comes in small packets that contain a measured amount of testosterone. You pump the desired amount of gel into your hand and then apply it to the skin. Let the area where you applied the gel dry for at least five minutes before you put on clothing.
When to start testosterone replacement therapy?
The decision to start testosterone replacement therapy (TRT) should not be taken lightly. Testosterone is a powerful hormone and can have many side effects, both good and bad. Before starting TRT, you should consult with a doctor to see if it is right for you.
Your doctor will likely perform a physical examination and order blood tests to check your testosterone levels. They will also ask about your medical history and any medications you are currently taking.
Testosterone replacement therapy can improve your quality of life and help you live longer. TRT is not for everyone, and there are risks involved. However, for some men, the benefits of TRT may outweigh the risks. If you are considering starting TRT, talk to your doctor about the risks and benefits. They will be able to help you make an informed decision about whether or not TRT is right for you.
Click here to learn more about whether testosterone is the God particle!
Conclusion
Now you can see how sensitive the human body is. Too much or too little of any hormone or signal can lead to side effects. That is why working with a knowledgeable doctor who understands how to dose Testosterone properly and the other hormones are essential! Testosterone deficiency can have some serious impact on your health and wellbeing not just your ability to put on muscle mass so it is definitely worth looking into!
Please also remember that diet, sleep, exercise, and stress management all play a role in optimizing your health and increasing low testosterone levels, so do not even think about TRT before you fix the basics! If you need help getting back on track, do not hesitate to reach out to us! We can help you find a good doctor and support you with a carefully curated nutrition and workout plan!
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