Side Effects of Testosterone Replacement Therapy (TRT)
“Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.” – Paracelsus
The Risk/Benefit Ratio of TRT
As with any medical intervention, the benefits of Low T therapy must be weighed against the potential risk of adverse reactions or “side effects”. Just as Paracelsus indicates, whether testosterone replacement creates a poisonous or beneficial environment is largely dependent upon how the medication is delivered and dosed.
Those who abuse testosterone and other androgens may experience significant and even life threatening side effects. Somewhat similarly, if treatment of Low T is mismanaged or not carefully monitored, patients will experience a higher rate and increased severity of adverse reactions or possibly a complete lack of meaningful results.
For the most part, this discussion will deal with side effects associated with TRT in general, but some attention will be given to particular differences in the variety of methods utilized for treatment of Low T.
Why Side Effects Occur With Low T Treatment
Some side effects seen with TRT are the direct result of the use of exogenous testosterone (testosterone not made naturally in the body). Many occur only in the presence of higher testosterone levels, and still others are simply the consequences of the body’s normal metabolism of testosterone. This metabolism, or break down of testosterone, occurs in the same manner for both exogenous and endogenous testosterone (naturally produced testosterone), but because of an increased abundance of testosterone this may lead to higher than normal levels of these metabolites.
TRT Side Effects: DHT and Estradiol
Normal metabolism of testosterone results in its conversion into two primary metabolites, dihydrotestosterone (DHT) and estradiol (E2, a form of estrogen). Elevated levels of DHT can cause benign growth of the prostate, increased oiliness of the skin and acne, as well as male pattern balding. Abnormal increases in estradiol can lead to mood swings, breast tissue changes, and fluid retention that may cause swelling or increases in blood pressure. Furthermore, abnormal estradiol levels have been linked to lower testosterone levels, erectile dysfunction, and a decrease in free testosterone.
According to the 2010 update to “Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline”, the conversion rate and subsequent ratio of testosterone to estradiol and DHT does not change when treating Low T via injection of testosterone cypionate. These ratios may be negatively affected with other Low T treatments (gels, patches, pellets, etc.).
TRT Side Effects: Prostate Changes
While prostate changes can occur with testosterone replacement, a study published in The Journal of Clinical Endocrinology & Metabolism in June of 2010, which looked closely at the adverse reactions reported in 51 other studies, found there to be no increased risk of the development of prostate cancer, prostate related urinary symptoms, or elevated PSA (prostate specific antigen). That aside, because PSA is essentially a tumor marker for prostate cancer, patients with a first-degree relative who has been diagnosed with prostate cancer and those with an elevated PSA level should proceed with caution and be monitored closely.
For men with a personal history of prostate cancer, treatment for Low T is considered contraindicated according to most sources. It is important to note that testosterone replacement does not “give” you prostate cancer, but certainly elevated testosterone levels (even to the normal range) can cause an otherwise unnoticed prostate lesion grow more aggressively.
It is important to note that testosterone, in and of itself, is not a causative factor in the development of prostate cancer. That myth has finally been debunked through countless studies over several years while more recent data now indicate that a low serum testosterone levels are a potential predictor of high-risk prostate cancer. The more interesting debate at this point is the potential consequence of increasing a man’s testosterone level, even to a normal range, in the presence of an existing prostatic growth.
The findings of multiple studies over the years have ranged from testosterone appearing to be associated with promoting the transition of a common, low-grade lesion into one of a more aggressive nature, to testosterone actually contributing to cell death of the malignancy to no appreciable effect whatsoever. Obviously the current data is inconclusive, however, it is becoming more and more apparent that as we ponder the safest recommendations, while peering through the lens of risk/benefit analysis, living with testosterone deficiency may indeed be the more risky endeavor.
TRT Side Effects: Suppression of Fertility
The production of testosterone and sperm both are controlled by what is referred to as the Hypolthalamus-Pituitary-Gonadal Axis. That is, the hypothalamus ( a portion of the forebrain responsible for the control of certain autonomic nervous system actions and pituitary gland activity) “talks” to the pituitary gland by mean of a chemical messenger (GnRH – gonadotropin-releasing hormone).
The pituitary gland in turn will “talk” to the testicles (male gonads) also by means of different chemical messengers (LH – luteinizing hormone and FSH – follicular stimulating hormone).
Low T occurs when either this hormonal cycle fails to stimulate the testes to produce testosterone or more commonly when the testes themselves fail to respond to said stimulation.
When testosterone levels are normalized, either by natural means or through treatment of Low T, the brain reduces the stimulus to produce testosterone by secreting less GnRH. Since this singular hormone controls both FSH and LH, the natural suppression of GnRH that occurs can reduce fertility.
Additionally, it is this same process that is responsible for the potential reduction in size and/or change in firmness of the testicles.
TRT Side Effects: “Blood Thickening” and Other Side Effects
Other side effects, that are not part of normal functioning, are increased red blood cell counts (erythrocytosis), potential decreases in “good cholesterol” or high-density lipoproteins (HDL), and increases in diastolic blood pressure (the lower of the two numbers reported in blood pressure readings). The effects of high blood pressure are well known and the reasons for avoiding hypertension during TRT are no different from standard recommendations. Increased number of red blood cells on the other hand, can lead to significant risk if not managed appropriately.
Erythrocytosis
Think of red blood cells (RBC’s) as the solid portion of the solution that is whole blood, and your hematocrit (HCT) the percentage of blood volume made up of RBC’s. If you add more solid to any solution without proportionately increasing the volume of the liquid it is suspended within, the result is a thicker solution. Thickening of the blood then, is the end result of an increase in the number of RBC’s.
Hematocrit values greater than 52.0% increase a patient’s risk factors for abnormal clotting, spleen enlargement, heart failure and other serious conditions. If erythrocytosis does occur, it is typically rather easy to address. However if its assessment is overlooked, as is far too often the case, it can lead to potentially serious problems.
Other Side Effects
Certain side effects are preparation specific. Gels, creams, and other topical agents can cause skin irritation and secondary exposure to women and children who come into contact with the medication via direct transfer. Some untoward consequences of use of topicals is the wonderful odor (or “fragrance”, to steal Big Pharma’s term) that is associated with it. Failure rates are much, much higher for this type of medication owing to the inability of 30-40% of men to even absorb enough to improve their testosterone levels.
What Can Be Done About It?
Virtually every medical treatment can cause adverse reactions. All things considered, those side effects associated with testosterone replacement therapy are quite manageable. We know what to look for and how to intervene. With careful monitoring, it is entirely possible to treat and/or prevent significant problems these side effects may pose.
Ultimately it comes down to balance. Can we approach Low T treatment in such a way that allows for minimization of side effects while allowing for optimization of results? Absolutely!
What is necessary to achieve this is having providers that are open and honest about the benefits AND the risks associated with TRT. If you have questions, we would love the opportunity to talk with you and answer them. Please Contact Us to schedule a no-obligation consultation in our clinic. If you are suffering from Low T and are ready to improve the quality of your life, the dedicated providers at Testosterone Centers of Texas are ready to help you.
