Andropen 450 features Acetate and a higher total concentration (450mg/mL vs 350mg/mL), which can provide a slightly faster onset and allow for a lower injection volume to achieve the same weekly dose. The high concentration (450 mg/mL) and complex blend of esters make side effect management more challenging compared to a single-ester testosterone like Testabol Enanthate 250. The blend's design means injections can be slightly less frequent than with short-acting esters like Testosterone Propionate, but more frequent than with a single long-acting ester like Enanthate or Cypionate. This weekly total should be split into at least two injections per week (e.g., Monday and Thursday) to maintain stable blood hormone levels and minimize estrogenic side effects. This powerful 450 mg/mL blend combines five distinct testosterone esters, creating a unique release profile that offers both rapid onset and long-lasting effects. Similar to testosterone cypionate, testosterone enanthate is a slow-acting injectable form of the androgen testosterone. The primary difference between esters is the rate at which testosterone enters the bloodstream following an injection. In addition, there is no risk of sciatic injury, administration can be accomplished using smaller needles, and the pain evoked during SC administration is usually lower. To the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries because of the high rate of filtration and reabsorption of fluid across vascular capillaries (39). ARatio of AUC0-168h of DHT and estradiol to AUC0-168h of serum total T at week 6 of treatment. Serum total A, testosterone; B, 5-dihydrotestosterone; and C, estradiol concentrations after subcutaneous (SC) or intramuscular (IM) administration of 1000 mg of testosterone undecanoate. Serum testosterone concentrations (Fig. 6A) did not differ according to route of administration after adjustment for age, body mass index, and clinical diagnosis (26). Serum testosterone profile after SC injection displayed a slower time to peak concentration (8.0 vs 3.3 days) with no significant differences in model-predicted peak concentration compared with the IM route (26). In this context, SC administration of testosterone undecanoate could potentially be a safer route, because the SC compartment is less vascularized, thus reducing the chance of introducing the drug directly into the systemic circulation. Various oils of USP grade were received from Sigma-Aldrich (St. Louis, MO, USA), Tex Lab supply and Med Lab supply (USA). It should be mentioned that TEna has the lowest melting point, and in the solubility evolution process it became gelatinous even though it was assessed at 14 °C. As can be seen from this figure, the absorption bands that appear in the 2800–3050 cm−1 wavenumbers region are similar and can be attributed to the symmetric and asymmetric C-H stretching within the CH, CH2, CH3 functional groups. The solubility measurements are represented graphically in Figure 6 and listed in Table S3 (Supporting information). 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). For example, a previous study shows that a microemulsion based on soybean oil and dimethoxytetraethylene glycol supports concentrations of 3.42 mg/mL (for testosterone propionate), 31.5 mg/mL (for testosterone enanthate), and 2.16 mg/mL (for medroxyprogesterone acetate) in soybean oil. This discussion should also include cost considerations because the SC autoinjector is more expensive compared to conventional SC injections with testosterone esters. Among transgender men, patients who had previously used IM testosterone therapy with long-acting esters did not want to revert back to IM injections after they were started on SC testosterone therapy (24, 28, 51). Indeed, long-term compliance among men who are prescribed testosterone therapy with IM injections is low; approximately 69% of men on long-acting esters discontinue treatment within 3 months of therapy, and 95% discontinue it within 12 months (56). A study of transgender men receiving SC weekly doses of testosterone enanthate or cypionate (28) showed that 37 of 67 participants developed acne; 2 of these individuals needed a referral to a dermatologist, while no participant chose to decrease their testosterone dose. Because studies of SC testosterone therapy are limited, this needs to be verified in future studies. Although the published studies of SC testosterone administration have not observed serious local adverse reactions (23, 47), mild local reactions were common. The formulation contains 250 mg/mL of the ester dissolved in castor oil and is supplied in 3-mL vials in the United States, and 4-mL vials in other parts of the world. To the contrary, the group receiving the 200-mg IM injection achieved supraphysiologic levels during the first week after the injection. The decanoate ester of testosterone is one of the longest available and was found to crystallize in the orthorhombic P non-centrosymmetric space group, and consisted of two independent molecules in the asymmetric unit (Figure 4a). Testosterone esters are foundational in both clinical testosterone replacement therapy (TRT) and performance-enhancing protocols among bodybuilders. By overlapping the esters, a very good match of the steroid skeleton rings (the base of the ester structures) emerges, and the major structural differences are manifested in the orientation of the tails. The literature reports the solubility of hydroxyprogesterone caproate polymorphs in castor oil at a temperature of 20 °C, which are 278 mg/mL and 301 mg/mL . Out of the six mixtures analysed, it is observed that castor oil can support the highest solubility without crashing (crystallisation of compound) and to a lesser extent MCT (for TAce, TPro, and TPhp), at the same time behaving as solvents as well. Propionate and phenylpropionate esters have similar and slightly higher values than acetate. The shortest ester (TAce) has a total lattice energy of −159.5 kJ/mol and TPhp, which is the longest ester, has an energy of −184.5kJ/mol and the most bound structure of all five steroids. 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. Although there are a few commonly prescribed compounded ester blends, some compounding pharmacies offer unique formulations. For instance, some prescribers reported the need to change the ester in a patient to mitigate side effects or to produce a specific outcome. Over a few decades, healthcare providers who specialize in men’s hormone replacement therapies evolved their treatment protocols as more research focus was given to testosterone therapies. The ultimate goal should be to restore total Testosterone to an optimal range, with about 2%-4% free Testosterone in the blood.
