From the Guidelines
The optimal regimen to discontinue Testosterone Undecanoate and minimize its effects on the Hypothalamic-Pituitary-Gonadal (HPG) axis involves avoiding exogenous testosterone therapy in males pursuing or planning to pursue family building in the near future, as it provides negative feedback to the hypothalamus and pituitary gland, inhibiting gonadotropin secretion and potentially resulting in oligospermia or azoospermia 1.
Discontinuation Approach
To minimize the negative effects on the HPG axis, the following steps can be considered:
- Avoid exogenous testosterone therapy in males interested in current or future fertility, as it can suppress spermatogenesis 1.
- For patients who have been on exogenous testosterone therapy, recovery of sperm to the ejaculate can occur after cessation, but the time course may be prolonged, taking months or rarely years 1.
- In patients with non-obstructive azoospermia, clinicians may inform the patient of the limited data supporting pharmacologic manipulation with selective estrogen receptor modulators, aromatase inhibitors, and gonadotropins prior to surgical intervention 1.
Alternative Therapies
Alternative therapies that may be considered to support recovery of the natural hormonal axis include:
- Human chorionic gonadotropin (hCG) at 500-2500 IU, 2-3 times weekly, to stimulate testicular function and maintain sperm production 1.
- Selective estrogen receptor modulators, such as clomiphene citrate or tamoxifen, to restore natural testosterone production by blocking negative feedback at the hypothalamus 1.
Monitoring
Regular monitoring of testosterone, LH, FSH, and estradiol levels is essential to assess recovery and adjust the treatment plan as needed 1.
From the Research
Discontinuation of Testosterone Undecanoate and its Effects on the HPG Axis
- The optimal regimen to discontinue Testosterone Undecanoate (TU) and minimize its effects on the Hypothalamic-Pituitary-Gonadal (HPG) axis is not directly stated in the provided studies 2, 3, 4, 5, 6.
- However, it is known that TU suppresses the HPG axis, resulting in suppressed spermatogenesis 3.
- Alternatives such as clomiphene citrate and human chorionic gonadotropin have been shown to increase endogenous testosterone production and may be considered for patients who desire to minimize the effects of TU on the HPG axis 3.
Dosing Regimens of Testosterone Undecanoate
- Studies have investigated different dosing regimens of TU, including administration at extended intervals of 12 weeks 5 and every 10 weeks 4, 6.
- A population pharmacokinetic model suggested that an 8-week maintenance regimen may improve symptom management of low testosterone at the end of each dosing interval 4.
- A retrospective investigation found that 91% of men received the standard 1,000 mg TU dose with 66% at the standard dosing interval of 10-14 weekly 6.
Effects of Testosterone Undecanoate on the HPG Axis
- The use of TU has been shown to suppress the HPG axis, resulting in suppressed spermatogenesis 3.
- However, the study by 5 found that injections of TU at intervals of up to 3 months offered an excellent alternative for substitution therapy of male hypogonadism, with minimal change in serum hormone levels.
- The study by 6 found that 72% of trough total testosterone levels were in the normal range for TU therapy, indicating effective replacement therapy.