In a prospective study, the effect of switching the route of testosterone therapy (with testosterone enanthate or cypionate) from the IM to the SC route was evaluated in 14 transgender men who had been on gender-affirming hormone therapy for at least 8 weeks (24). Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display more stable vascular absorption patterns compared to IM injection. The viability of using SC route for sex steroid administration was also shown in an elegant pharmacokinetic study in which nandrolone decanoate was administered to healthy male volunteers (30). Injections with intramuscular (IM) testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. Testosterone therapy delivered by intramuscular injection may cause blood cell counts to rise. But some studies investigating testosterone’s effect on cholesterol, blood pressure, and clot-busting ability have had mixed results. And, studies suggest that testosterone may have a positive effect on the heart. Furthermore, via binding to androgen receptors in muscle cells, testosterone stimulates protein synthesis and muscular growth, which is crucial for the regulation of muscle mass . Additionally, there is a significant correlation between bone density and testosterone levels; a decrease in testosterone can result in decreased bone density . Additionally, testosterone supports endothelial function by increasing nitric oxide production, encouraging endothelial cell growth and repair, and lowering inflammation; it also has a significant impact on the vascular endothelium, the thin layer of cells lining blood vessels, which is essential for preserving cardiovascular health . In men with hypogonadism, including elderly individuals, testosterone replacement therapy may offer antidepressant effects, providing therapeutic benefits for those with testosterone deficiency . The production of testosterone in men is primarily controlled by negative feedback mechanisms, whereby high levels of testosterone prevent the release of GnRH from the hypothalamus and LH from the pituitary, thereby limiting further testosterone synthesis; testosterone is made from cholesterol by a variety of enzymatic pathways in the testes . Additionally, it aims to clarify the effects of testosterone dysregulation on men's mental and physical wellness while advancing clinical procedures and treatment approaches. When stress levels are high, the body releases cortisol, also known as the stress hormone. Testosterone is responsible for various functions in the body, including muscle growth, bone density, sexual function, and mood regulation. When it comes to men’s health, testosterone plays a crucial role in maintaining physical and mental well-being. Small sample sizes and a dearth of studies, however, limit these findings, highlighting the need for more investigation to completely comprehend the wider impacts of testosterone on men's health. Testosterone supplements can have a good impact on a number of important aspects of men's health, such as vascular endothelial function, mood (particularly in lowering depression), muscle strength, bone health, and sexual function. Beyond these physical advantages, testosterone plays a crucial role in male reproductive health by affecting spermatogenesis (the generation of sperm), libido, and erectile function. The development and maintenance of muscular mass, bone density, and general physical strength depend heavily on testosterone, a hormone that plays a complicated and significant role in men's physiology. Similarly, patients with enzyme deficiency are less likely to be prone to male androgenic alopecia. These oily solutions contain a testosterone ester dissolved in vegetable oil (usually sesame seed, tea seed, castor seed, or cottonseed oil) with some benzyl alcohol. However, this device is expensive compared to administration of ester with conventional syringe and needles. Patches result in skin irritation in a substantial number of patients, and sweating during the summer can affect patch adherence (13). Timeline of various testosterone formulations available since Brown-Sequard’s experiments in 1889. In the mid-1950s, long-acting testosterone esters (enanthate and cypionate) were introduced, and have since been the preferred testosterone formulation thanks to their affordability, longer half-life compared to propionate, and predictable pharmacokinetics (9). We have come a long way since the days of Brown-Séquard, who self-administered an extract of animal testes by subcutaneous (SC) injection in 1889 (Fig. 1) (3). In addition, we provide guidance for clinicians on how to counsel and manage their patients who opt for the SC route.
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