Both LHRH agonists (like Lupron, Eligard, and Zoladex) and LHRH antagonists (like Degarelix) suppress testosterone (T) equally well. But the antagonist, Degarelix, drives T down faster and does not cause an initial surge in T before T descends into the castrate range. So, what happens when one stops taking those drugs? Does T climb back into the normal range faster after ADT with an antagonist than an agonist?
Consider the situation where one is on ADT short term to improve the effectiveness of radiotherapy. Patients in that situation often hope to get their T levels back quickly when coming off ADT. A group of physicians in Okayama, Japan, explored the topic of T recovery with 112 patients going for brachytherapy to treat prostate cancer. Approximately 70% of the men were on an agonist and the rest were on an antagonist for short-term ADT.
Surprisingly, the T level climbed significantly faster after ceasing LHRH agonist ADT than LHRH antagonist ADT in the first three months post ADT. However, at the one-year mark there was no difference in the recovery between the patients on either class of drugs. In both treatment arms, there was 72 to 75% recovery of T after one year (which is comparable to what has been reported in previous studies).
It’s not clear that these results can be generalized to other populations. For instance, in North America patients going on an LHRH agonist usually start on an anti-androgen, like bicalutamide (Casodex), before starting on an LHRH agonist. However, only a few patients in this Japanese study received Casodex. Thus, we don’t know if early administration of the anti-androgen somehow influenced the rate of T recovery. What the data do suggest is that there’s not a symmetry between how fast one can drive T down and how quickly it can recover.
To read the study abstract, see: https://pubmed.ncbi.nlm.nih.gov/34955538/
Reference:
Iwata T, Maruyama Y, Kawada T, Sadahira T, Katayama S, Takamoto A, Sako T, Wada K, Edamura K, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y. Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis. Acta Med Okayama. 2021 75(6):705-711. doi: 10.18926/AMO/62810. PMID: 34955538