Subcutaneous testosterone injections

Intramuscular testosterone injection is the most common form of androgen supplementation in hypogonadal men.

A group of 11 participants undergoing female-to-male gender transition were analyzed. Findings reveal that weekly subcutaneous testosterone (cypionate/ester) injections work well clinically.  Total and free testosterone measures were overall stable and not influenced by body mass index. 

Superiority of subcutaneous over intramuscular injections relies on improved convenience, safety, and cost. Approximately 25% lower SC than IM dose of testosterone is needed to achieve similar outcomes.

A strength of the study was the female genetic background (XY); contributing trivial amounts of endogenous testosterone to steady serum total and free measures. Alike results would be expected in hypogonadal men requiring androgen supplementation.

These findings could influence clinical practice, as the prevalence of male hypogonadism is significant.



J of the Endocrine Society

August 2017

Purpose: Intramuscular (IM) testosterone is the most common modality for testosterone therapy of both male hypogonadism and female-to-male (FTM) gender transition. However, IM injections can be painful and often are not self-administered by the patient. The objective of this study was to further characterize subcutaneous (SC) administration of testosterone as an effective and safe alternative to IM injections by evaluating the pharmacodynamics of serum total and free testosterone concentrations between weekly testosterone injections.

Methods: 11 FTM transgender patients already receiving weekly SC testosterone cypionate with documented therapeutic levels prior to enrollment had free and total serum testosterone levels measured at 8 different time points during a 1-week dosing interval.


Mean levels of total and free testosterone were stable and remained well within the normal range between injections.

Overall mean ± standard deviation levels for the seven samples taken between injections were 627 ± 206 ng/dL (range, 205 to 1410) for total testosterone and 146 ± 51 pg/mL (range, 38 to 348) for free testosterone. No adverse effects were encountered.


The results of this study support use of subcutaneous testosterone to achieve therapeutic and stable serum testosterone levels for the purpose of gender transition. It is ANTICIPATED that these results can be extended to hypogonadal men.

Subcutaneous route may be preferred over IM testosterone because it is relatively painless and easy to self-inject thus allowing for the convenience and economy of patient self-administration.

More from the publication:

For treatment of hypogonadal men and female-to-male (FTM) transgender patients, intramuscular injection of testosterone esters is standard care and is the most commonly used modality in the United States.

While on average serum testosterone levels remain within the target range, if the dosing interval is greater than 1 week, levels of testosterone rise above the normal range within the first 48 hours after the injection and fall below the normal range in the days prior to the next dose.

Variations in serum testosterone levels may be associated with concomitant fluctuation in mood, energy level, and sexual function. Furthermore, IM injections are often painful and may require administration by a trained professional, making this modality less than ideal. Another option for IM injections, testosterone undecanoate, although administered infrequently, is painful and is available only through a risk evaluation and mitigation program because of the risk of pulmonary oil microembolism. Alternatives to IM testosterone ester administration each have their own disadvantages.

Transdermal testosterone formulations (patches, gels) can also have limitations, such as local reactions, poor adhesion, fear of skin-to-skin transmission, unpleasant odor, lack of insurance coverage or high copays, and limited patient acceptance. Subcutaneous (SC) insertion of testosterone pellets is available but has been limited by the need for surgery, the possibility of infection, fibrosis or pellet extrusion, limited data regarding efficacy, inflexibility of dosing and limited acceptance.

Recent reports indicate that SC administration of testosterone esters may be an acceptable alternative to IM injections in hypogonadal men and FTM transgender patients. Only one pharmacokinetic study of SC testosterone ester injection has been reported. That study used fixed doses from an autoinjector and allowed pretreatment serum concentrations as high as 300 ng/dL in hypogonadal men thus providing a confounding factor of significant endogenous testosterone secretion to data interpretation. To further characterize SC testosterone as a practical and acceptable alternative to IM administration, we evaluated the pharmacokinetics of testosterone following manual SC injections of testosterone cypionate to patients undergoing FTM gender transition.

Genetic females undergoing gender transition provide an ideal opportunity to assess pharmacokinetics because their low endogenous secretion of testosterone contributes minimally to serum measurements of testosterone. 

Our data demonstrate that when testosterone cypionate is injected SC at a weekly interval, mean serum levels remain stable and within the normal range. A similar pattern of mean serum testosterone levels has been reported with weekly IM injections of testosterone. A slight decline in serum testosterone concentrations occurred in the 2 days prior to the injection. Near identical serum concentrations of total and free testosterone 7 days apart just prior to injections further supports consistency of serum testosterone levels with SC injections. Patients with testosterone levels within the lower half of the normal range were all receiving relatively small doses of testosterone. Thus, increasing the dose of testosterone would reasonably be anticipated to maintain serum testosterone levels well within the normal range throughout the week between injections.

Our data indicate that the dose can be monitored by a single measurement of serum total testosterone 1 to 5 days after an injection.

With respect to individual serum testosterone concentrations, overall levels were reasonably stable. Additional studies in larger populations of patient receiving either IM or SC testosterone could further define the degree of variability. However, the data in our study indicate that serum levels of testosterone are reasonably sustained between SC injections.


In our patients BMI ranged from 20-39, and increased BMI did not appear to have an adverse effect on the ability to maintain serum testosterone levels within the normal range.

We observed an inverse correlation between BMI and intraindividual variability in serum testosterone levels across the week further indicating that an increased BMI does not present a barrier to effective SC administration of testosterone. These findings regarding the lack of an effect of BMI on pharmacokinetics of SC injection of testosterone need to be further evaluated in a larger study.

The slight decline in mean serum testosterone levels just prior to an injection was not accompanied by a decline in subjective symptoms of energy or mood and is thus unlikely to have clinical significance. In the context of longer-term therapy in these patients, the SC route of testosterone administration was effective in producing deepening of the voice and appearance of facial hair and produced no adverse effects in these 11 patients, including no local reactions at the injections sites.

These data in combination with previous reports of efficacy and safety of the SC route of testosterone injections in hypogonadal men and FTM transgender patients confirm that the SC route is an acceptable alternative to the IM route.

We have previously reported greater patient acceptability of the SC route compared with the IM route. The SC route appears to be more economical than the IM route. The median dose of SC testosterone in this study (75 mg/week) and in previous studies is less than the commonly recommended dose of 100 mg/week for IM dosing. SC injections are easily self-administered. An auto injector as used in a previous pharmacokinetic study of SC injection that may increase the expense of this therapy was not necessary to produce stable levels of serum testosterone in our current study or normal levels of serum testosterone in our previous report.