Recovery of serum T levels after short-term LHRH agonist therapy

An article in the June issue of the Canadian Urological Association Journal offers preliminary evidence from a randomized clinical trial that men treated for 6 months with a short-acting LHRH agonist may recover normal serum testosterone (T) levels faster than those treated for the same time with a long-acting LHRH agonist.

Unfortunately the authors were unable to accrue the full sample of 100 patients required by the original trial design, so the data presented in this paper can only be considered to be suggestive of the  proposed effect. Clear demonstration  that longer-acting LHRH agonists delay recovery of serum T levels compared to shorter-acting LHRH agonists would require a new randomized trial with a full complement of patients.

Pai et al. actually recruited only 55 patients to their trial, in which patients with low- and intermediate-risk prostate cancer who were scheduled for brachytherapy with permanent implantation of iodine-125 seeds were randomized to either two doses of a 3-month-long-acting formulation of leuprolide acetate or six doses of a 1-month-long-acting formulation of the same LHRH agonist. LHRH agonist therapy was initiated 3 months prior to execution of brachytherapy. All patients also received daily doses of flutamide (250 mg t.i.d.) for a total of 4 weeks, starting with the first injection of leuprolide. The patients’ serum T and PSA levels were then recorded every 2 months for the following 2 years.

The results of the study were as follows:

  • Only 55 patients were actually recruited and randomized.
  • Data from just 46  patients were available for analysis.
    • 22/46 received the long-acting formulation.
    • 24/46 received the short-acting formulation.
  • The average (median) times to recovery of baseline levels of serum T (calculated from the end of androgen suppression) were
    •  8 months for the long-acting formulation
    • 4 months for the short-acting formulation
  • The average (median) time to recovery of serum T levels to the lower limit of the reference range were
    • 4 months for the long-acting formulation
    • 2 months for the short-acting formulation
  • One patient who received the long-acting formulation of leuprolide acetate did not recover serum T levels to the lower limit of the reference range within the 2 year follow-up period.
The authors conclude that this study showed a trend towards more rapid recovery of testosterone levels after the use of a shorter-acting as compared to a longer-acting formulation of leuprolide acetate for a total period of 6 months.
While The “New” Prostate Cancer InfoLink concurs with the authors that this study does not demonstrate conclusively that shorter-acting LHRH agonists are associated with faster recovery of normal levels of serum T after androgen deprivation therapy than long-acting equivalents, the trend is definitely suggestive of such an effect. We would argue that there is strong justification for a new randomized trial designed to resolve this question.

2 Responses

  1. What happened to the cancer cells once the T levels recovered?


  2. Dear Sandy:

    This paper provides no information about the post-treatment PSA levels of the 55 patients actually treated, so we can’t answer your question. However, brachytherapy with short-term neoadjuvant and adjuvant androgen deprivation is normally a very effective form of therapy for mern with low- and intermediate-risk prostate cancer. It is probably safe to assume that the majority of these patients would have had biochemical progression-free survival for a period of at least 10 years.

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