Some men that start testosterone replacement therapy (TRT) are surprised to find out that their baseline fatigue may actually get worse.



Why Can TRT Cause Fatigue?

Testosterone replacement therapy can cause fatigue in some men for a variety of reasons, including:

  1. Overstimulation of the body: Increased testosterone levels can cause the body to overwork, leading to fatigue and exhaustion.

  2. Insomnia: Some men on testosterone therapy may experience difficulty sleeping, which can lead to fatigue.

  3. Hormonal imbalance: A sudden increase in testosterone levels can cause an imbalance with other hormones in the body, leading to fatigue and other symptoms.

  4. Side effects of the medication: Testosterone therapy can cause side effects such as acne, fluid retention, and mood changes, which can also contribute to feelings of fatigue.

It's important to note that testosterone therapy can also help improve energy levels and reduce fatigue in some men, but it's best to discuss the potential benefits and risks with a healthcare provider before starting treatment.

If no improvements in fatigue are observed after six weeks of testosterone replacement, factors beyond hypogonadism may be present. This article will review a few ways to find out what the reasons for TRT fatigue may be.


Thyroid and adrenal function should be checked to ensure that those two glands work properly. Sleep apnea can also be a factor in the failure to improve stamina. Depression may still need to be addressed with proper medications and counseling.

Suggested Blood Tests Diagnose Potential Causes for Fatigue While on TRT

Thyroid Function:

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, a hormone produced by the pituitary. Hypothyroidism, or low thyroid hormone production, can cause sexual dysfunction as well as depression, fatigue, dry skin and hair, weight gain and increased sensitivity to the cold. Blood tests to measure TSH, T4, and T3 are readily available and widely used.

The American Thyroid Association ( has great comprehensive information on how to determine if you have hypothyroidism that could be causing your fatigue.

Testosterone may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Once thyroid hormone blood levels have been normalized, testosterone tends to increase naturally.

Check your thyroid hormones here: Choose Your Test | Discounted Labs

Adrenal Function:

The adrenal glands, located in the abdomen above the kidneys, regulate stress in the human body. When the body encounters an emergency situation, the adrenal glands release hormones, such as adrenaline, that enable the body to respond accordingly. You may have encountered this reaction, called the “fight or flight” response, if you have encountered danger, fear or shock. Adrenal fatigue is the controversial idea that the adrenal glands can become worn out, creating illness, if continually overstimulated. Proponents of the “adrenal fatigue” theory hold that the adrenal glands may be overworked in some individuals and therefore become “fatigued” and unable to produce sufficient hormones. When your adrenal glands become exhausted, your natural cortisol levels drop significantly. Cortisol is your naturally occurring stress hormone. In addition to low sex drive and infertility, symptoms of adrenal fatigue may 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 corticoid steroids if your morning levels of cortisol (measure by blood, saliva or urine tests) are low. But be careful with corticoid steroids since they can increase fat mass and decrease bone density if given in doses that exceed what the healthy adrenals would produce.

Click here: Are you tired even with normal testosterone? Adrenal fatigue may be the problem.


The adrenal glands also produce dehydroepiandrosterone (DHEA), the most abundant hormone found in the bloodstream. The body uses DHEA as the starting material for producing the sex hormones testosterone and estrogen in men. Studies have shown that it only increases testosterone in women. The production of DHEA diminishes in most people after age 40. In people aged 70 years, DHEA levels will be approximately 30 percent lower than what they were at age 25. Low DHEA have been associated with many degenerative conditions.

Some controversial and non-conclusive studies have shown that people with immune deficiencies and fatigue may benefit from supplementation with this hormone. It is still available over-the-counter in the United States. This may change soon due to a new bill passed by Congress that classifies it as a performance-enhancing steroid (no studies have shown that it has such effect).

One study showed that women with the correct levels of DHEA can convert it into testosterone as their body needs while men do not benefit to the same degree. 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 to 30 mg a day, while men tend to benefit from 25-100 mg per day (to bring low levels of 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 metabolize into estradiol. This could result in gynecomastia and water retention. If you start taking DHEA, have your blood levels checked to make sure they are not above normal. There are many claims about DHEA being an anti-aging and an anti-cancer cure, but none of these claims has been substantiated with strong data.

To facilitate diagnosis, we have created this new Fatigue Panel on at a deep discount.

Click here: Comprehensive Fatigue Panel

Sleep Apnea:

Sleep apnea is a sleep disorder in which a person briefly stops breathing or breathes shallowly many times during sleep and therefore does not get enough restful sleep; oxygen levels drop in the blood, starving the brain of oxygen. In addition to causing daytime fatigue, it can increase blood pressure and cardiovascular risks. Testosterone replacement therapy has been associated with the exacerbation of sleep apnea or with the development of sleep apnea, generally in men who use higher doses of testosterone or who have other identifiable risk factors for sleep apnea (high body weight, thick necks, snoring, alcohol consumption, and others). Upper-airway narrowing does not seem to be caused by testosterone replacement therapy, suggesting that testosterone replacement contributes to sleep-disordered breathing by central mechanisms rather than by means of anatomical changes in the airway.


Tell your doctor if your spouse or partner complains that you snore loudly at night and suffer from fatigue. The only real way to find out 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 Pressure Airway Pressure (CPAP) machine can be prescribed to help you open up your airways with a small air pump while you sleep. Some people love it, while 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 is paid by insurance, Medicare, and most HMOs.

A new emerging 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.