Variance in Peak and Trough T Levels in Men Using Intramuscular T Injections

[madman]

MP85-14 VARIANCE IN PEAK AND TROUGH TESTOSTERONE LEVELS IN MEN USING INTRAMUSCULAR TESTOSTERONE
Bruno Nascimento*, Helen L Bernie, Elizabeth Schofield, John P. Mulhall, New York, NY


INTRODUCTION AND OBJECTIVES

In men using intramuscular testosterone (IM T), clinical experience shows us that, despite stable dosing and frequency, total testosterone peak (Tp) and trough (Tt) levels are highly variable, thus challenging the clinician to make a decision regarding dose adjustments. The goal of this study was to define the variability in T levels in a population of men on IM T.

METHODS

Patients with 3 consecutive Tp and Tt levels available, while on a stable dose and interval of IM T cypionate were analyzed. All patients were instructed as follows: Tp levels to be checked 18 hours after IM T injection, and Tt levels to be drawn the following week on the day of injection, prior to injecting the next dose. We report on Tp, Tt, and D (Tp-Tt). T level was measured using LC/MS-MS. To assess for T level variation across the 3 cycles, we calculated mean change in Tp and Tt as well as maximal change in Tp and Tt. Distribution analysis was performed to assess for variance distribution.

RESULTS

29 patients met the inclusion criteria equating to 174 total T levels analyzed. The mean age was 52 ± 28y. Dose distribution was: 3% receiving 40mg, 10% 60mg, 35% 80mg, 38% 100mg, 7% 120mg, and 7% receiving other doses. 83% were injecting every 7 days. Averaged over 3 cycles, mean Tp was 910 ± 165 ng/dl; mean Tt was 558 ± 80 ng/dl, and mean D was 352 ± 154. Mean Tp variance was 210 ± 99 ng/dl representing a 23% change from cycle to cycle. Mean Tt variance = 102 ± 63 ng/dl (17.5% change). Averaged over all patients, maximum Tp change was 315 ± 148 ng/dl, and maximum Tt change was 152 ± 94 ng/dl, representing a maximum change of 37% and 26% respectively. In distribution analysis, 25% of patients had a maximum Tp change greater than 51% and a maximum Tt change of 35%.

CONCLUSIONS

In our population of patients on stable IM T dose, there was a wide mean variation in both Tp (23%) and Tt (17.5%). In addition to that, 25% of patients had a maximum Tp change greater than 50% and a maximum Tt change greater than 35%. Clinicians should be aware of this high variability in levels when deciding on dose adjustment.

Source of Funding: None

 

[Nelson Vergel]

Very important point. The same can happen with testosterone gels/creams. Can you check the abstract source again since the numbers seem kind of weird to me? Thanks for posting!

 

[madman]

Very important point. The same can happen with testosterone gels/creams. Can you check the abstract source again since the numbers seem kind of weird to me? Thanks for posting!

Thanks for catching that!

 

[madman]

Most Patients Liked Being Switched to Subcutaneous Testosterone Injections

Early Experience with Subcutaneous Injection of Non-Proprietary Testosterone as an Alternative Approach for Testosterone Replacement (2022) KAlter, DRoadman, CAmarasekera, LLevine Introduction Testosterone replacement therapy (TRT) has been demonstrated to benefit men with a diagnosis of...

www.excelmale.com

Key points here!

*SC administration of testosterone esters should result in a more stable absorption and release of testosterone into the circulation due to less fluctuation of lymphatic flow in the hypodermis with physical activity

*SC injections display a more stable vascular absorption patterns compared to IM injection

TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option

Abstract Context: Injections with intramuscular 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. However, they are difficult to self-administer and associated with some...

www.excelmale.com

Subcutaneous vs Intramuscular Routes

The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption.

After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). However, the hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water (40). This results in some of the esterified testosterone to enter the lymphatics, thus prolonging the secondary absorption phase.

The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism, and is drained by the lymphatics (41). Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they likely associate with small proteins and are drained via the lymphatics into the central circulation, with hydrolysis of these esters likely occurring in the central circulation (40). Therefore, pharmacokinetics of testosterone esters administered via IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. 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). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration.

Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. 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. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption patterns compared to IM injection.




Pharmacokinetics of Testosterone Esters Injected Subcutaneously

As discussed, SC administration of testosterone esters should result in a more stable absorption and release of testosterone into the circulation due to less fluctuation of lymphatic flow in the hypodermis with physical activity. This was confirmed by pharmacokinetic studies that assessed the Cmax and tmax of testosterone in the serum, and the average serum total testosterone concentration during the steady state.