What are alternative treatment options for a male patient experiencing a decline in testosterone levels from 897 to 686 ng/dL while receiving intramuscular injections of testosterone (200mg per week)?

From the Guidelines

For a male patient whose testosterone levels decreased from 897 to 686 ng/dL while on 200mg weekly testosterone injections, the most appropriate next step is to consider adjusting the current injection protocol or switching to a different testosterone formulation, as suggested by the American College of Physicians guidelines 1.

Alternative Treatment Options

The patient's declining testosterone levels despite high-dose therapy may indicate issues with absorption, metabolism, or conversion to estrogen. Several alternative treatment options exist, including:

• Adjusting the current injection protocol by either splitting the dose (100mg twice weekly) to provide more stable levels or reducing the dose if the initial level was too high
• Switching to different testosterone formulations, such as:
  • Testosterone gel (typically 50-100mg applied daily)
  • Testosterone patches (2-6mg daily)
  • Subcutaneous pellet implants (lasting 3-6 months)
• Adding human chorionic gonadotropin (HCG) injections (250-500 IU 2-3 times weekly) to stimulate natural testosterone production, especially if fertility is a concern
• Using clomiphene citrate (25-50mg daily) to increase pituitary signals for testosterone production
• Adding an aromatase inhibitor like anastrozole (0.5-1mg twice weekly) to reduce testosterone-to-estrogen conversion

Important Considerations

Before making any changes, comprehensive bloodwork should be done to check estradiol levels, liver function, hematocrit, and PSA to ensure safety and identify the underlying cause of the declining levels 1. The American College of Physicians guidelines suggest that clinicians should reevaluate symptoms within 12 months and periodically thereafter, and discontinue testosterone treatment if there is no improvement in sexual function 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

1. 1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT) are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics

2. 3 Pharmacokinetics Absorption AVEED 750 mg delivers physiologic amounts of testosterone, producing circulation testosterone concentrations that approximate normal concentrations (300-1000 ng/dL) seen in healthy men.

The patient's testosterone levels are declining from 897 to 686 ng/dL while receiving intramuscular injections of testosterone (200mg per week).

• The normal range of testosterone is between 300-1000 ng/dL.
• The patient's current level of 686 ng/dL is still within the normal range.
• No alternative treatment options are directly suggested by the drug label for a patient experiencing a decline in testosterone levels while already receiving testosterone therapy.
• The label does mention that testosterone undecanoate (such as AVEED) can deliver physiologic amounts of testosterone, but it does not provide guidance on adjusting the dose or switching to a different formulation in response to declining testosterone levels 2.

From the Research

Alternative Treatment Options

The patient's decline in testosterone levels from 897 to 686 ng/dL while receiving intramuscular injections of testosterone (200mg per week) may indicate a need for alternative treatment options. Some alternatives to consider are:

• Transdermal application of testosterone gels, which are the most commonly used route of testosterone administration 3
• Oral testosterone formulations, such as oral testosterone undecanoate, although these may have short half-lives or be associated with hepatic toxicity 3
• Depot formulations, such as injectable testosterone undecanoate (TU), which may be a good alternative for patients who prefer not to use daily drugs or short-acting injectable formulations 3
• Gonadotropins, which can be used to stimulate testicular growth and spermatogenesis in patients with hypogonadotropic hypogonadism who desire fertility or are adolescents 3
• Off-label aromatase inhibitors (AI) and clomiphene citrate (CC), which may be considered to stimulate LH, FSH, and T levels in obese patients or those with high risks for TRT 3
• Selective androgen receptor modulators, which may be an alternative treatment for patients with high prostate disease risk, although these have not had high-level evidence 3

Non-Testosterone Management

Non-testosterone management options may also be considered, such as:

• Lifestyle modifications and varicocelectomy, which have been shown to raise endogenous testosterone production 4
• SERMs and aromatase inhibitors (AIs), which have been shown to raise testosterone levels safely and effectively 4
• Human chorionic gonadotropin (hCG), which is the only FDA-approved non-testosterone treatment option for testosterone deficiency in men, although it is expensive and requires patient-administered injections 4
• Clomiphene citrate (CC), which holds the greatest promise as a non-testosterone treatment option for testosterone deficiency 4

Preserving Fertility

For patients who desire to preserve fertility, concomitant intramuscular human chorionic gonadotropin (hCG) may be considered to maintain semen parameters and preserve fertility while on testosterone replacement therapy 5

• Low-dose hCG has been shown to maintain semen parameters in hypogonadal men on testosterone replacement therapy 5
• Concurrent testosterone replacement and hCG use may preserve fertility in hypogonadal males who desire fertility preservation while on testosterone replacement therapy 5

Exogenous Testosterone Replacement Therapy

Exogenous testosterone replacement therapy is an important treatment option for men with low testosterone and symptomatic hypogonadism, but it poses risks to fertility due to negative feedback mechanisms on the hypothalamic-pituitary-gonadal (HPG) axis 6

• Alternative pharmacologic therapies, such as selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors, are being used to increase endogenous testosterone levels while attempting to preserve fertility and function of the HPG axis 6

Long-Term Treatment

Testosterone undecanoate depot (TUD) administered intramuscularly is an effective form of testosterone replacement therapy (TRT) for male hypogonadism, with a high percentage of trough total testosterone levels in the normal range and a low rate of adverse effects 7

• TUD therapy may be preferable to subcutaneously implanted extended release T pellet implants (TI) due to the ease of administration 7