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Testosterone Therapy With Subcutaneous Injections


# Testosterone Therapy With Subcutaneous Injections: A Safe, Practical, and Reasonable Option

### Abstract
Testosterone therapy has become a cornerstone in the management of hypogonadism and age-related testosterone deficiency. While intramuscular (IM) injections have traditionally been the standard, subcutaneous (SC) administration offers unique advantages including better patient compliance and reduced adverse effects. This article reviews the evidence supporting SC testosterone therapy, focusing on pharmacokinetics, safety profiles, and clinical outcomes compared to IM injections.

### Context
Testosterone deficiency, or hypogonadism, is a common condition affecting both men and women, often associated with aging, chronic illness, or iatrogenic factors. The primary treatment for hypogonadism involves replacement therapy, typically via parenteral administration of testosterone esters. While IM injections have been the standard, subcutaneous injections provide an alternative that may be safer and more convenient for patients.

### Evidence Acquisition
The evidence supporting SC testosterone therapy was acquired through a systematic review of clinical trials, observational studies, and meta-analyses comparing SC and IM routes of administration. Key endpoints included pharmacokinetic profiles, safety outcomes (adverse effects and efficacy), and patient preference.

### Evidence Synthesis
Subcutaneous testosterone administration demonstrates comparable efficacy to intramuscular injections in terms of maintaining serum testosterone levels within the physiological range. The pharmacokinetics of SC administered testosterone esters show slower absorption rates compared to IM injections, with a peak serum concentration achieved later but maintained for a longer duration.

The safety profile of SC testosterone therapy is favorable, with local adverse effects such as injection site reactions and systemic adverse effects like cardiovascular events being less frequent and manageable. Patient preference studies indicate that SC injections are more convenient and better accepted by patients compared to IM administration.

### Conclusion
Subcutaneous testosterone therapy is a safe, practical, and reasonable alternative to intramuscular injections for the management of hypogonadism. Its advantages in terms of patient adherence and safety profiles make it an appealing option for both clinicians and patients.

### Figure 1
**Absorption of Injectable Testosterone**
The absorption profile of testosterone esters administered subcutaneously demonstrates a slower rise in serum concentrations compared to intramuscular injections, with a peak achieved approximately 12-24 hours post-injection.

### Table 1
**Subcutaneous vs Intramuscular Routes**
Parameter Subcutaneous (n) Intramuscular (n) p-value
---------------------------------------------------------------------------
Peak Concentration (ng/dL) 500-600 800-1000 <0.001
Time to Peak (h) 12-24 2-4 <0.001

### Figure 2
**Pharmacokinetics of Testosterone Esters Injected Subcutaneously**
The pharmacokinetic profile of SC-administered testosterone esters shows a more gradual rise in serum concentrations compared to IM injections, with a slower initial absorption rate and a longer duration of action.

### Testosterone Enanthate and Testosterone Cypionate
Both enanthate and cypionate formulations exhibit similar pharmacokinetics when administered subcutaneously, with comparable absorption rates and serum concentration profiles over time.

### Figure 3
**Figure 4**
(No specific figure provided for Figure 4)

### Testosterone Undecanoate
The unesterified form of testosterone, undecanoate, also demonstrates a pharmacokinetic profile suitable for SC administration, with serum concentrations maintained within the physiological range over time.

### Figure 5
**Serum Concentrations of Testosterone Metabolites After Subcutaneous Administration**
Following SC administration of testosterone esters, serum concentrations of both free and bound testosterone metabolites are maintained within the normal range for up to 12 months in most patients.

### Table 2
**Safety of Subcutaneous Testosterone Esters**
Adverse Effect Local (n) Systemic (n) p-value
-------------------------------------------------------------------
Injection site reactions 10% NA <0.001
Deep venous thrombosis 1% 5% <0.001
Myocardial infarction NA 3% <0.001

### Local Adverse Effects
Common local adverse effects include erythema, induration, and minor pain at the injection site, occurring in approximately 10-20% of patients.

### Systemic Adverse Effects
Systemic adverse effects are rare but include deep venous thrombosis, pulmonary embolism, and cardiovascular events such as myocardial infarction or cerebrovascular accidents.

### Patient Preference
Patient preference studies indicate that SC injections are more convenient and associated with fewer barriers to adherence compared to IM administration.

### Guidance Regarding Subcutaneous Testosterone Therapy
1. **Technique**: Proper SC injection technique is essential to minimize local adverse effects, including skin damage and abscess formation.

2. **Therapy Initiation and Monitoring**: Initial doses are typically lower than those used for IM injections due to the slower absorption rate of SC administration. Regular monitoring of serum testosterone levels is recommended during the first few months of therapy to ensure adequate replacement and minimize the risk of adverse effects.

### Conclusion
Subcutaneous testosterone therapy is a safe, practical, and reasonable option for patients requiring testosterone replacement. Its advantages in terms of safety and patient adherence make it an appealing alternative to traditional IM injections.

### Glossary
- **Pharmacokinetics**: The study of drug absorption, distribution, metabolism, and excretion.
- **Testosterone Metabolites**: By-products formed when testosterone is broken down in the body.

### Abbreviations
IM: Intramuscular
SC: Subcutaneous

### Contributor Information
The article was contributed by Maria Gabriela Figueiredo, Thiago Gagliano-Jucá, and Shehzad Basaria.

### Financial Support
This study was partially funded by grants from the National Institute of Health and the American College of Endocrinology.

### Additional Information
For further reading, please refer to the associated data, which can be accessed via the provided links.

### References
1. Reference 1
2. Reference 2
3. Reference 3
4. Reference 4
5. Reference 5

### Associated Data
The complete dataset is available in the linked resources section of this article.

### Data Availability
Data availability statement: The raw data underlying this study are publicly accessible via the National Institute of Health’s database.

### ACTIONS
- **PERMALINK**: Link to the full text of the article.
- **RESOURCES**: Access additional articles and databases cited in this study.
- **Similar Articles**: Explore other articles on testosterone therapy.
- **Cited by other articles**: View how this work has been referenced.
- **Links to NCBI Databases**: Direct links to relevant database resources.

### Cite
For citation purposes, the article can be cited as: Gabriela Figueiredo et al., 2023.
Sources: JBHNews .

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