Most UK laboratories will use reference ranges similar to this one. Testosterone tests and prescriptions have almost tripled in recent years; however, it is clear from clinical practice that there are many men who consume testosterone without a clear indication, 1-3 Some studies estimate that up to 25% of men who receive testosterone therapy do not have a testosterone test before the start of treatment, 2, 3 Of the men who receive testosterone treatment, almost half of their testosterone levels are not controlled after starting treatment, 2, 3 Although up to a A third of men who receive treatment with testosterone, almost half have their testosterone levels not controlled after starting treatment, 2, 3 Although up to a third of men who receive treatment with testosterone, almost half have their testosterone levels not controlled after starting treatment, 2, 3 Although up to a third of men who receive treatment with testosterone, almost half are not controlled, are undergoing testosterone therapy and do not meet the criteria for To diagnose testosterone deficiency, 2,3 there is a large percentage of men who need testosterone treatment who do not receive it due to medical problems, mainly related to the development of prostate cancer and cardiovascular events, although current evidence does not definitively support these concerns. Given the clinical and commercial landscape of testosterone, the American Urological Association (AUA) identified the need to produce an evidence-based document that informs doctors about the appropriate evaluation and treatment of patients with testosterone deficiency. The AUA and the Testosterone Panel are committed to creating a guideline to ensure that men who need testosterone treatment receive effective and safe treatment.
When there was sufficient evidence, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) to support strong, moderate, or conditional recommendations. In the absence of sufficient evidence, additional information is provided in the form of clinical principles and expert opinions. Testosterone tests and prescriptions have almost tripled in recent years; however, it is clear from clinical practice that there are many men who consume testosterone without a clear indication, 1-3 Some studies estimate that up to 25% of men who receive testosterone therapy do not have a testosterone test before starting treatment and almost half of them do not monitor their testosterone levels once treatment has started, 2, 3 Although up to a third of men receiving testosterone therapy do not comply According to the criteria for being diagnosed as deficient in testosterone, 2, 3 there is a large percentage of men who need testosterone therapy and do not receive it because of clinical concerns, mainly related to the development of prostate cancer and cardiovascular events, although current evidence does not definitively support these concerns. For example, several testosterone gels are available in 1%, 1.62%, and 2% formulations, each marketed under a different brand or generic name.
Within this family of modalities alone, there are three different application sites, including the upper body, thigh, and armpit, with four different dosage ranges for each gel. Samples were analyzed first thing in the morning from each subject's 3 most recent and previous visits, as well as those from 10, 15, 20, 25 and 30 years earlier (3,565 samples in total, with an average of 4 samples per patient). The men evaluated by primary care physicians underwent a single laboratory extraction before 10 in the morning and were administered a series of questionnaires. The Panel does not recommend the use of free testosterone measurements as the primary diagnostic method for testosterone deficiency. Total and free testosterone should not be considered interchangeable measures, since there is no clear data that points to consistent thresholds between the two measures below which deficiency symptoms are observed and above which therapeutic benefits occur, 15, 16 An analysis of 3,219 men (average age 58) who had their testosterone measured just one morning suggested that the use of a free testosterone level added no value to the diagnosis of testosterone deficiency when the total level of testosterone era of intra-individual variability.
The repetition of measurements can fluctuate between 65 and 53% between tests, depending on the test used,24 however, the use of 2 or 3 measures can reduce this variability between 30 and 43%, respectively. To minimize these effects, it is recommended to take two doses of testosterone in the morning before any clinical intervention. When measuring testosterone levels, acute diseases must be taken into account, the presence of which can affect the accuracy of the test and cause an artificial decrease in testosterone measurements. In a small study conducted on young men with acute respiratory infections, average total testosterone levels decreased by 10%, and some cohorts experienced reductions of up to 30%.
A meta-analysis of 4 observational studies involving 4,426 men showed that men with low testosterone levels had a higher prevalence of fatigue than men with normal testosterone levels (OR = 1.46; CI 1.16, 1.9). Testosterone deficiency is prevalent in men undergoing infertility evaluation, 159 The testicles contain germ cells that produce sperm and Leydig cells that produce testosterone; any pathology of the testicles can cause infertility and testosterone deficiency, conditions that often co-exist. A survey of 120 patients who received treatment for infertility at the University of Illinois-Chicago found that the incidence of testosterone deficiency was 45% in men with non-obstructive azoospermia, 42.9% in men with oligospermia and 16.7% in men with obstructive azoospermia, 159 varicocele. It is notable that the above conditions are included in the current guidance because both are associated with low testosterone levels and have relevance to testosterone control. For example, bone mineral density is associated with testosterone, and treating low testosterone levels can improve bone mineral density.
There are other conditions that are associated with low testosterone levels, but they are not necessarily considered direct symptoms nor do they definitely improve testosterone with subsequent treatment. An example of this is the presence of varicoceles. Although there is very limited data to suggest that varicoceles (especially grades II and III) may be associated with low testosterone levels, it is not clear if the treatment of varicoceles improves symptoms in non-infertile populations and with long-term durability.164, 165 Since infertile men probably represent a different cohort than those already recommended to be screened for low testosterone levels, current data did not consider it sufficiently justified to add varicocele as independent screening trigger. Screening questionnaires are not an appropriate tool for identifying candidates for testosterone therapy.
Their role in diagnosing testosterone deficiency is unclear and they should not be used at the expense of a full patient evaluation, including the measurement of testosterone in the laboratory. Several validated questionnaires are used as screening tools to identify men at high risk of suffering from testosterone deficiency, but there is no agreement between the questionnaires as to what symptoms are related to low testosterone levels or to what extent these symptoms they get better with treatment. The validation studies in each questionnaire use a different limit of total testosterone to define low testosterone levels; however, total testosterone has been shown to correlate poorly with most questions. 164, 165 Hypergonadotropic hypogonadism, which is not a contraindication for starting testosterone treatment, can be due to several conditions, such as congenital anomalies (KS is the most common) and iatrogenic causes (for example, the etiology is obvious) (e.g., a randomized trial with 76 men (average age 50.6 years), who had at least 1 symptom of ejaculatory dysfunction and at least 2 testosterone tests.
Men diagnosed with testosterone deficiency who are interested in preserving their current fertility should undergo a testicular exam to evaluate the size, consistency and ancestry of the testicles and measure serum follicle stimulating hormone (FSH) to assess their underlying reproductive health status (Appendix C). We studied 44 patients who were randomly assigned to receive 150 mg of testosterone enanthate intravenously (n = 2) versus a placebo (n = 1) for 6 months, 211 during treatment, the patients had their blood drawn and had a biopsy of prostate tissue to observe testosterone levels in serum and prostate tissue. At the end of the study, serum testosterone levels increased in men who received testosterone therapy; however, no increase in testosterone levels was seen in the prostate tissue itself. Another retrospective study (Morgentaler 201) followed 13 men (mean age 58.8 years) with untreated prostate cancer and testosterone deficiency (total testosterone). In contrast, a population-based, retrospective case-control study using a UK clinical database of 19,215 patients with confirmed VTE showed that there was an increased risk of VTE in the first 6 months of testosterone treatment.
The risk was 10 additional cases per 10,000 person-years, which, although low in absolute terms, raised concerns about the use of testosterone treatment in men who may be at greater risk of suffering from VTE before starting treatment. 362 Current evidence consistently shows that untreated low testosterone levels are associated with a higher risk of MACE; however, studies measuring cardiovascular benefits or harms in men receiving treatment with testosterone have shown inconsistent and controversial results. Until there is definitive evidence to demonstrate an association between testosterone therapy and subsequent MACE, the Panel recommends that doctors inform patients that the current scientific literature does not definitively prove that testosterone therapy increases risk. Men who are being treated with testosterone should be advised to report any possible cardiovascular symptoms, such as chest pain, shortness of breath, dizziness, or transient loss of consciousness, during routine follow-up visits. RCTs have failed to categorically define whether treatment with testosterone increases the incidence of MACE compared to placebo.
Some studies have suggested that testosterone therapy is associated with an increase in MACE363-366, while others have suggested a decreased risk 207, 233, 259, 367, 368 and others a neutral effect, 190, 191, 202, 327, 369-373 The results and methodology of these studies have been the subject of debate. The thresholds low testosterone levels were not universal. Evaluation criteria were incoherently defined to classify serious cardiac events, including “milder” evaluation criteria (for example, the WHO Working Group on Methods for Regulating Male Fertility) conducted a larger study to examine the contraceptive efficacy of testosterone induced azoospermia in men. 385 A total of 271 healthy and fertile men from 7 countries received 200 mg of testosterone enanthate intramuscularly every week for 12 months.
During the efficacy phase of the trial, adequate suppression of spermatogenesis occurred in 98% of the study subjects (n = 390) and 157 men became azoospermic during the 12-month follow-up period (the average time to azoospermia was 120 days).Topical testosterone preparations (e.g., populations most at risk of adverse effects from transfer include women and children); however, very limited data are available on the actual risks of transfer with topical agents. Several case reports have identified virilization and early puberty in boys, as well as hyperandrogenism in women following accidental exposure to topical testosterone, 388-391. To address the problem, the FDA includes drug guidelines with topical testosterone preparations and recommends observing the signs and symptoms of early puberty in children, as well as avoiding contact with unwashed or unwashed areas where the medication has been applied, 392 To reduce risks, patients are advised to apply the medication only to suggested areas, wash their hands after application, cover the area with clothing after drying it, wash it before the intended skin-to-skin contact and wash the areas of accidental contact in women and children. More recently, a study that evaluated the amount of residual testosterone identified in the laundered clothes of men who used testosterone liquid applied to the armpit reported the presence of 13% of a single dose in the armpit in 10 x 10 cm clothing samples. 393 After washing clothes with various other materials, up to 5.8% of a standard armpit dose was transferred to other garments. It is not clear if the transferred testosterone remained biologically active.
These findings require additional follow-up, as they demonstrate that the transfer can hypothetically occur in the absence of skin-to-skin contact. Patients who are taking long-acting intravenous testosterone (testosterone undecanoate) should have their blood tested once they have reached stable levels. Testosterone undecanoate is usually re-administered 4 weeks after the initial administration and every 10 weeks thereafter. As in the case of short-acting intramuscular testosterone injections, the general recommendation is to test mid-cycle, after balance and halfway between the two.
first injections of 10 weeks. Patients taking long-acting SQ pills require two separate testosterone evaluations to determine the required dosage and frequency. The first testosterone measurement should be performed two to four weeks after the initial implant to determine if there is a need to increase or decrease the number of granules inserted to achieve the appropriate therapeutic level. Then, patients should be tested after 10 to 12 weeks.
Patients being treated with testosterone should have their serum testosterone levels monitored every 6 to 12 months to ensure that target levels are maintained. Given anecdotal concerns about tachyphylaxis associated with clomiphene citrate, it is recommended that patients using this therapeutic approach have their total testosterone measured as described above. See Table 7 below for a summary of follow-up tests performed on men being treated for testosterone deficiency. The intervals between the tests are the opinion of the Panel's experts and are provided as a guide to assist doctors in monitoring these patients.
The unique pharmacokinetic profiles of transdermal testosterone preparations relate to several factors, including the delivery system (alcohols or other penetration enhancers), concentration, surface area applied, and site of application. 228, 412 The transdermal solubility of the drug has been variably estimated, and most studies report systemic absorption rates ranging from 13 to 20%.Topical liquid and gel formulations are capable of achieving testosterone levels in the normal range in 74-87% of men and are relatively similar among the various preparations, 421-423 Given the varying absorption profiles between patients, dose adjustment may be necessary to achieve adequate therapeutic administration. For the time being, there is no consistent data to show that one drug achieves higher serum levels than others. Specific adverse effects of topical preparations include reactions at the site of application (erythema or rash from 3 to 16%) and the risk of transfer.
Patients should be especially warned not to come into contact with women and children after applying the gel to limit the possibility of involuntary transmission. The transfer can be mitigated by washing hands, covering the application site with clothing, and washing the region before intended direct contact with others. The most common adverse effect of patches is application site reactions, which have historically been reported in up to 60% of 181 patients. Other adverse effects include pruritus, vesicles at the application site, and back pain, 431 Compared to topical gels and solutions, the transfer rate is likely to be minimal.
Absorption through the oral mucosa avoids the hepatic deactivation experienced by other formulations. Testosterone is released from the tablet in a manner similar to the normal daily rhythm of endogenous testosterone: serum levels rise rapidly after buccal absorption and peak levels are reached with the second daily dose of 12 hours. It restores the level of circulating testosterone to the physiological range. Elimination of the system causes a rapid drop in testosterone levels, 433 Dosage.
The progressive hydration tablet with a matrix containing 30 mg of testosterone is placed on the gum above the right or left canine and is held in position for approximately 30 seconds. It adheres to the oral surface as it slowly moisturizes, becoming soft and gelatinous. It is administered twice a day, 12 hours apart, with an efficacy of 432%. In a 12-week study of 82 men, 72.6% of patients achieved a total testosterone concentration within the physiological range at steady-state.
434 men treated with the agent were compared to a group of patients who were administered 5 mg of a testosterone gel formulation and there were no differences in the average serum testosterone levels between the two groups. 435 The study showed that 92% of oral patients versus 83% of gel patients achieved testosterone levels in the physiological range. In the clinical trial that led to FDA approval, side effects related to nasal administration included nasopharyngitis, rhinorrhea and epistaxis, which occurred in between 7 and 10% of men, 436 Finkle et al. The authors compared the relative risk ratio (RRR) of suffering a myocardial infarction within 90 days of receiving a prescription for a testosterone or PDE5 inhibitor with that of the previous year, when patients were not taking it no medication.
For men with no history of CVD, the RRR of having a myocardial infarction in older people The Reverse, the Shores, 367 Muraleedharan,233 and Baillargeon373 studies determined that there was no increased risk of MACE in men who were being treated with testosterone. The Shores study was an observational study involving 1,031 men (average age 62.1 years) with a total level of testosterone. In addition to natural age-related deterioration, a significant decrease in testosterone may also be due to medications (especially anabolic steroids) or damage to the testicles, such as injury, infection, radiation therapy, or chemotherapy. For example, symptoms such as fatigue, difficulty concentrating, and lack of sexual desire may be due to poor diet, lack of exercise, and lack of sleep.
Stress, anxiety, and depression can be side effects of erectile dysfunction. Increasing low testosterone levels alone won't fix these problems, says Dr. If bothersome symptoms and low testosterone levels persist after exploring these avenues, your doctor may prescribe a short-term TRT. TRT is usually given as a gel, cream, or daily patch that is applied to the skin (usually on the shoulder or thigh, places easily accessible).
TRT can also be taken as a daily oral medication or as weekly or biweekly injections. Another option is granules implanted in the buttocks that release testosterone slowly over several weeks. There's no advantage over different applications, says Dr. But injections can produce a faster change.
TRT can have short-term side effects, such as acne, breathing disorders while sleeping, breast swelling or tenderness, or ankle swelling. However, for most men who qualify for treatment, the benefits of TRT often outweigh these potential risks, says Dr. Adjusted logistic regression showed an inverse relationship between total testosterone and the presence of erectile dysfunction, as the likelihood of suffering from erectile dysfunction increases as total testosterone levels decrease. Men with a history of breast cancer are not eligible for testosterone replacement therapy (weak recommendation; moderate level of evidence)).
The type of TRT you take, whether it's injections, creams, gels or tablets, will determine when it's best to measure your testosterone level. The prevailing confusion over the diagnosis of testosterone deficiency, the inappropriate use of TRT, and recent reports that the use of TRT may increase the risk of serious adverse effects indicate that it is important for health professionals to provide guidance on the treatment of testosterone deficiency. As mentioned above, combination therapy with low doses of hCG has been described as a means of maintaining intratesticular levels of testosterone 394 and preserving spermatogenesis336 in men receiving exogenous testosterone. The challenge for doctors is that the symptoms that have been associated with low testosterone levels are very unspecific and may be manifestations of other conditions (e.g., one-off estimates that measure the difference in testosterone levels between men with and without erectile dysfunction may seem statistically significant, but these estimates are not always clinically significant).
There's no need to panic if your testosterone levels are gradually decreasing; this is a normal part of aging. However, the current literature does not define the level of LH below which these complementary tests are justified. It was decided that a limit value was essential to define testosterone deficiency and that this limit should be based on at least two total testosterone levels calculated first thing in the morning in the same laboratory and using the same analysis. Despite growing trends in testosterone therapy, there's no need to worry or obsess about your testosterone levels.
