6-month Formulations of Androgen Deprivation Therapy for Advanced Prostate Cancer: Effectiveness and Rationale for Extended Dosing

Jason Hafron1, *, Stuart Atkinson2, Debbie Boldt-Houle2, Joseph F. Renzulli3
1 Department of Urology, Michigan Institute of Urology, Troy, MI, USA
2 Medical Affairs, Tolmar, Inc, Buffalo Grove, IL, USA
3 Department of Urology, Yale Department of Urology, New Haven, CT, USA

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Creative Commons License
© 2024 Hafron et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Urology, Michigan Institute of Urology, 130 Town Center Dr #101, Troy, MI 48084, USA;



Luteinizing hormone-releasing hormone (LHRH) agonists and GnRH antagonists are the most widely used androgen deprivation therapy to achieve castration levels of serum testosterone (T). Adherence to dosing schedules is important to avoid treatment failure. A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials.


Narrative review of LHRH therapy and evaluation of which offers optimal efficacy, safety, and practicality.


6-month LHRH agonist formulations require fewer appointments for injections than shorter-acting formulations. Therefore, the frequency of late/missed doses and overall non-adherence may be reduced compared to options requiring frequent dosing (e.g., oral therapies and shorter-acting injections). This flexibility may be preferable for patients who live in multiple locations throughout the year, live long distances from clinics, and/or lack access to reliable transportation. 6-month formulations may also have cost benefits compared to shorter-acting doses. Despite similar levels of T suppression during the labeled dosing period, individual 6-month LHRH agonist formulations appear to have unique profiles, e.g., 6-month subcutaneous leuprolide acetate (LA) results in lower T escape rates compared to 6-month intramuscular LA, if dosing is late.


The efficacy and practicality offered by 6-month LHRH formulations suggest these could reduce opportunities for late injections by requiring fewer office visits and provide greater confidence that efficacy will be maintained should there be extenuating circumstances leading to delays in therapy administration, as experienced during the recent pandemic.

Keywords: Luteinizing hormone-releasing hormone agonist, Gonadotropin-releasing hormone antagonist, Testosterone suppression, COVID-19, Pandemic, Subcutaneous leuprolide acetate.