From the Guidelines
Recovery of the hypothalamic-pituitary-gonadal axis after testosterone therapy discontinuation in a 40-year-old man can take months or rarely years, with most azoospermic males experiencing recovery of sperm to the ejaculate after cessation of testosterone therapy. The time course of recovery is highly variable and depends on several factors, including the duration of testosterone therapy and individual testicular function prior to treatment 1. According to the 2024 AUA/ASRM guideline, exogenous testosterone administration provides negative feedback to the hypothalamus and pituitary gland, inhibiting gonadotropin secretion and potentially resulting in oligospermia or azoospermia 1.
Key factors influencing recovery include:
- Duration of testosterone therapy: longer use typically means slower recovery
- Formulation used: injectable testosterone may require longer recovery than topical forms
- Individual testicular function: pre-existing testicular function can impact recovery timeline
- Use of medications to support recovery: human chorionic gonadotropin (hCG) or selective estrogen receptor modulators (SERMs) may be prescribed to stimulate natural testosterone production 1.
Clinicians should counsel patients about the potential negative effects of exogenous testosterone therapy on spermatogenesis and the time course required for resumption of spermatogenesis after cessation. Regular monitoring of testosterone, luteinizing hormone, and follicle-stimulating hormone levels every 1-3 months can help track recovery progress, and medications like hCG (500-2500 IU, 2-3 times weekly) may be used to support recovery 1.
From the Research
Recovery of the Hypothalamic-Pituitary Axis
- The recovery of the hypothalamic-pituitary axis after testosterone therapy discontinuation can take up to 24 months 2.
- A study found that 79.5% of men who used androgenic anabolic steroids (AAS) had satisfying recovery of the hypothalamic-pituitary-gonadal (HPG) axis after 3 months of cessation and post-cycle therapy (PCT) 2.
- The duration of use, amount, dose, and type of AAS can negatively affect the restoration of the HPG axis 2.
- Metformin treatment may mitigate the unfavorable effect of discontinuation of testosterone treatment on hypothalamic-pituitary-testicular axis activity and sexual function in men with late-onset hypogonadism 3.
Factors Affecting Recovery
- The level of inhibin B may serve as a marker for the restoration of spermatogenic epithelium 2.
- Ambulatory early morning cortisol can be used to predict the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after prolonged glucocorticoid use 4.
- Age, gender, body mass index, indications for glucocorticoid use, and basal adrenocorticotropic hormone levels were not predictive of HPA axis recovery 4.
Individual Differences in Recovery
- Individual differences in the speed of recovery of the HPA axis after exposure to a severe stressor may not be related to individual differences in fear/anxiety or to the HPA response during exposure to the stressor 5.
- These individual differences in the capability to terminate the activation of the HPA axis after stress might be related to individual differences in the predisposition to develop stress-induced pathology 5.