Currently published studies have not demonstrated an increased risk of biochemical cancer recurrence in post-RP patients who are on testosterone therapy, nor does it define the optimal timing for commencement of testosterone therapy. It is the opinion of this Panel that until there is definitive evidence demonstrating that testosterone therapy is not safe for use in prostate cancer patients, the decision to commence testosterone therapy in men with a history of prostate cancer is a negotiated decision based on the perceived potential benefit of treatment. The treatment and placebo arms did not differ at baseline in terms of age (62.9 years versus 64.4 years, respectively), total testosterone level (320 ng/dL versus 344 ng/dL, respectively), or PSA measurements (1.3 ng/mL in both arms). While the FDA retains a warning regarding the potential risk of prostate cancer in patients who are prescribed testosterone products ("patients treated with androgens may be at increased risk for prostate cancer"), there is accumulating evidence against a link between testosterone therapy and prostate cancer development. Included studies had significant heterogeneity with the populations themselves, methods of assessment, study durations, baseline population characteristics, and number of participants, leading the Panel to conclude that there is currently insufficient evidence to determine if testosterone therapy impacts QoL in a meaningful way. Despite the absence of definitive evidence, the Panel recommends that patients with these symptoms be counseled regarding the possibility of improvement on testosterone therapy.
A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Where gaps in the evidence existed, the Panel provides guidance in the form of Clinical Principles or Expert Opinion with consensus achieved using a modified Delphi technique if differences of opinion emerged. Conditional Recommendations also can be supported by any evidence strength.
Generally, healthcare providers will measure total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) to get the most complete picture of your hormonal health.4 The takeaway is that free testosterone will give you the most accurate picture of what is happening in your body when investigating your testosterone levels. The difference is that total testosterone, after it is produced in your body, joins or binds with proteins — most commonly one called sex hormone binding globulin (SHBG), and sometimes albumin. Knowing the range of what is considered normal or healthy at various ages can help you and your healthcare provider better understand your hormone health. Some people are curious about their testosterone levels, especially if they are experiencing symptoms of either low testosterone or high testosterone.
Patients on topical gels, patches, and intranasal formulations should have their testosterone checked between two to four weeks after commencement of therapy. + FDA approved for use in males with hypogonadotropic hypogonadism and pediatric patients with cryptorchidism. Finally, hCG therapy alone or in combination with SERMs has been shown to facilitate recovery of testosterone production and spermatogenesis in men with a prior history of exogenous testosterone use333 or anabolic steroid abuse.334 Return of sperm to the ejaculate in these men can be highly variable, taking up to two years after cessation of exogenous testosterone in some cases, with some men never experiencing return of sperm.334 Clinicians should understand that of these agents, only hCG has been approved by the FDA for use in males, specifically to treat males with hypogonadotropic hypogonadism. While SERMs, hCG, and AIs are all categorized as "alternative therapies" to testosterone, they are actually a diverse group of agents. More recently, a study evaluating the amount of residual testosterone identified on laundered clothing from men using an axilla-applied testosterone liquid reported the presence of 13% of a single axilla dose on 10x10 cm clothing samples.393 After laundering the clothing with various other materials, as much as 5.8% of a standard dose of one axilla was transferred to other garments.
Both the free fraction and the one bound to albumin are available at the tissue level (their sum constitutes the bioavailable testosterone), while SHBG effectively and irreversibly inhibits the action of testosterone. At the tissue level, testosterone dissociates from albumin and quickly diffuses into the tissues. The part of the total hormone concentration that is not bound to its respective specific carrier protein is the free part. Specific proteins include sex hormone-binding globulin (SHBG), which binds testosterone, dihydrotestosterone, estradiol, and other sex steroids.
Gynecomastia is a benign enlargement of the male breast tissue that can occur at times of male androgen/estrogen change (alteration in testosterone/estradiol E2 ratio), infancy, adolescence, or old age, and may be a sign of low serum testosterone. At this time, identification of the optimal patient (based on age, varicocele grade, baseline testosterone level) has not been defined.75 There does appear to be a trend towards lower total testosterone and a diagnosis of ED. There are inherent challenges in testosterone measurement due to the health status of patients at the time of testing, circadian rhythms in testosterone production, intra-individual variability, and inconsistencies in the assays themselves. Given that the direct method for free testosterone measurement is also time-consuming and labor intensive, calculation derived free testosterone measurement is more commonly used, however there is considerable variation in total testosterone assays as well as the clinical conditions that affect serum albumin and SHBG, all of which impact this measurement. The Panel recommends that clinicians use the same laboratory with the same method/instrumentation for serial total testosterone measurement. There is a great deal of variability across studies with respect to the forms of testosterone measured (total versus free), the assays utilized to measure testosterone, the time of day when the sample is obtained, and the number of testosterone measurements taken.
Furthermore, the identification of other pituitary tumors or processes may have important clinical implications for the patient beyond testosterone deficiency.178 An evaluation for a prolactinoma in such patients is imperative because these benign tumors can be effectively managed using medications, such as bromocriptine or carbergoline. Hyperprolactinemia is an uncommon condition172, 173 but it is a well-established cause of secondary (central) testosterone deficiency and can lead to infertility, decreased libido, sexual dysfunction, and gynecomastia. LH, which is routinely measured by immunoassay, may help to establish the etiology of testosterone deficiency and can be an important factor in determining if adjunctive tests should be ordered (Appendix C - refer to the Appendix C section in the left menu). Their role in diagnosing testosterone deficiency is unclear, and they should not be used at the expense of a full patient evaluation, including laboratory testosterone measurement.