Individual variation of hormonal recovery after cessation of luteinizing hormone-releasing hormone agonist therapy in men receiving long-term medical castration for prostate cancer
Author:
Kobayashi T, Nishizawa K and Mitsumori K.
10 August 2006
The main purpose of intermittent or interrupted androgen deprivation therapy in patients with prostate cancer is temporal androgen recovery in order to delay the hormone independence of tumour cells and to improve the patient’s quality of life. However, it has been reported that in some patients who have received long-term LHRHa therapy, serum testosterone does not recover.
This study (n=10) investigated the discontinuation of long-term LHRHa (goserelin or leuprorelin) therapy (median 39 months – 30 – 56 months), on serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and PSA. Measurements were taken before cessation of therapy and then every 4 weeks until the total testosterone level recovered to >50 ng/dl.
Scand J of Urol and Nephrol 2006; 40: 198 – 203.
The main purpose of intermittent or interrupted androgen deprivation therapy in patients with prostate cancer is temporal androgen recovery in order to delay the hormone independence of tumour cells and to improve the patient’s quality of life. However, it has been reported that in some patients who have received long-term LHRHa therapy, serum testosterone does not recover.
This study (n=10) investigated the discontinuation of long-term LHRHa (goserelin or leuprorelin) therapy (median 39 months – 30 – 56 months), on serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and PSA. Measurements were taken before cessation of therapy and then every 4 weeks until the total testosterone level recovered to >50 ng/dl.
All patients showed recovery of serum testosterone to >50 ng/ml within 26 – 327 days (median 98 days) after LHRHa cessation. LH recovery to >1.1 mIU/ml was observed within 26 – 98 days (median 53 days) and the interval between LH and testosterone recovery in each patient ranged from 0 – 274 days (median 32.5 days). FSH recovery to >10 mIU/ml paralleled the LH recovery. An increase in PSA to twice the baseline value was observed in 9 patients within 26 – 288 days (median 90 days). The total testosterone level at which the PSA increase occurred was < 20 ng/dl in one patient, 20 – 50 ng/dl in two and >50ng/dl in four. In all nine patients, with increased PSA, the PSA level returned to baseline after the resumption of LHRHa therapy.
The variable recovery of LH and FSH following long-term LHRHa therapy suggests that this results from disuse of the gonadotrophin producing cells of the pituitary gland which for individual patients require varying times to recover. Similarly the variable recovery of testosterone strongly suggests that the testicular Leydig cells require time to recover and this again varies from patient to patient. The results also identify that the variation in time from LH and FSH recovery to testosterone recovery, greatly affects the interval between cessation of LHRHa and testosterone recovery. Non-parallel recovery of PSA and testosterone add a further degree of variability to this confusing situation.
Whilst recognising that this study involved only a small number of patients the authors identify that the results suggest that the time of androgen exposure during LHRHa off-therapy period is likely to be highly variable and much shorter than expected. In fact in some patients there may only be a very small amount of androgen exposure. The authors suggest that if intermittent therapy is used to delay the acquirement of androgen independence by temporal androgen exposure, it is important that recovery of testosterone as well as PSA should be used to determine the period of “off-therapy”.
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