However, it is difficult to interpret the impact of short-acting TT on sperm parameters, as the misuse of TT for male infertility, anti-aging, and body sculpting purposes confounds study results. Generally, the use of short-acting TT causes several side effects including polycythemia, gynecomastia, suppression of spermatogenesis, and impaired fertility, though these are also side effects of long-acting TT21,22. Short-acting T therapy consists of administering one or more doses a day of T with a shorter half-life throughout the day. Currently, the AUA states that there is insufficient evidence linking testosterone therapy to the development of prostate cancer or showing an increased risk of recurrence of prostate cancer in treated men7. This means they enter the blood quickly and are used up immediately, therefore not delivering the full benefits of the treatment. As mentioned earlier, the more carbon atoms in an ester, the more it is soluble in oil. This results in an immediate blast of testosterone, but it is used up very quickly...too quickly since it takes some time to deliver the full benefits. Because studies of SC testosterone therapy are limited, this needs to be verified in future studies. In a similar study by the same investigators in 150 hypogonadal men, 125 participants experienced a treatment-emergent adverse event, with 30 discontinuing therapy as a result of these events (27). Few studies have evaluated serum concentrations of 5-dihydrotestosterone (DHT) and estradiol after SC injection compared to the standard IM route. Patients who understand the pharmacology of their treatment are more likely to adhere, report symptoms accurately, and participate actively in dosage adjustments turning therapy into a collaborative, safe, and personalized process. With undecanoate, due to its longer duration and flatter curve, timing is less critical, but a standardized sampling protocol such as just prior to the next 10–12-week injection ensures consistency. Many clinicians prefer cypionate because it offers enough flexibility for individualized regimens weekly for stable levels, or biweekly for convenience. In contrast, undecanoate users typically enjoy a flatter hormonal curve, but must attend clinic-based administrations because of its viscous formulation and risk of pulmonary microembolism if injected improperly. These include the testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and the carbon-13/carbon-12 ratio (pharmaceutical testosterone contains less carbon-13 than endogenous testosterone). However, it has been reported that AndroGel, a transdermal gel formulation of testosterone, has become the most popular form of testosterone in androgen replacement therapy for hypogonadism in the United States. Testosterone has been marketed for use by oral, sublingual, buccal, intranasal, transdermal (patches), topical (gels), intramuscular (injection), and subcutaneous (implant) administration. This treatment is referred to as hormone replacement therapy (HRT), or alternatively, and more specifically, as testosterone replacement therapy (TRT) or androgen replacement therapy (ART). As mentioned earlier, these are the two most common types of testosterone esters available in the United States. There are several different esters used in testosterone replacement therapy. "Fast-acting" kinds of testosterone contain esters that are less soluble in oil. Finally, ignoring hematocrit and PSA monitoring can turn a well-intended therapy into a risky endeavor. Given the variation in concentration among pharmaceutical and compounded products, urologists stress meticulous record-keeping and education for self-injecting patients. Conversely, testing several days too late may exaggerate trough levels and prompt unwarranted dose increases. Sleep deprivation, alcohol use, stress, and sedentary behavior amplify mood swings independent of hormonal levels. Thus, the clinician must balance psychological stability with the practicality and reversibility of each ester. The pharmacokinetics of testosterone, including its bioavailability, circulating testosterone levels, metabolism, biological half-life, and other parameters, differ by route of administration. Estrogens can reduce the effects of testosterone by increasing the hepatic production and in turn circulating levels of sex hormone-binding globulin (SHBG), a carrier protein that binds to and occupies androgens like testosterone and DHT, and thereby reducing free concentrations of these androgens. As only a very small fraction of testosterone is converted into estradiol, this does not affect testosterone levels, but it can prevent estrogenic side effects like gynecomastia that can occur when testosterone is administered at relatively high dosages. For this reason, and due to the unknown health effects and safety of testosterone therapy, its use may be inappropriate. A subsequent 2017 systematic review and meta-analysis of studies including over 3,000 postmenopausal women with HSDD similarly found that short-term transdermal testosterone therapy was effective in improving multiple domains of sexual function.
