Note the effects of long-term androgen deprivation therapy (LTAD) on Testosterone and erectile function recovery after discontinuing.
Testosterone and erectile function recovery after radiotherapy and long-term androgen deprivation with luteinizing hormone-releasing hormone agonists
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Testosterone recovery after STAD and radiotherapy has been well described [9–12]. Shahidi et al.[9] studied the long-term effects of 3–6 months neoadjuvant treatment with either goserelin 3.6 mg or leuprorelin 3.75 mg, given at 4-week intervals before radiotherapy in 419 men with localized disease, and found that 88% recovered a normal testosterone level (10–30 nmol/L or 2.9–8.6 ng/mL) within 6–12 months. Only three of 256 men (1%) still had castrate levels of testosterone at 36, 101 and 111 weeks after the last LHRH agonist injection.
By contrast, the limited data available after LTAD therapy suggests [Size=4]the possibility of a very prolonged testosterone suppression[/size]. Hall et al.[13] studied men with LAPC who stopped LHRH agonist therapy after >2 years of treatment; four of 10 men still had castrate testosterone levels 1 year after stopping therapy. Similarly, Nejat et al. [14] in a study of 68 patients, found that testosterone recovery was significantly delayed in those on therapy for more than 2 years, rather than less (P = 0.0034).
The present study shows that men achieve supracastrate TT levels after LTAD, but there is a slow recovery of normal TT levels, and [Size=4]a significant proportion of men do not achieve supracastrate or normal levels of TT even several years after completing LTAD[/size].
[Size=4]Despite the return of supracastrate or normal levels of TT, there appears to be little return of potency, as measured by the IIEF, and little return of sexual desire[/size].
[Size=4]In the entire cohort, only 10% of men regained the ability to have an erection sufficient for intercourse, and of men who were potent before any treatment, only two of 11 regained the ability to have an erection sufficient for intercourse[/size]. The present study does not address the cause of ED in these patients, but factors other than TT levels appear to be important.
The value of the LH/TT ratio at study entry in predicting the time to TT recovery was an unexpected finding, and needs to be validated in a larger study.
A possible explanation of why this ratio could be thought of as measuring a physiological phenomenon is based on the model of the hypothalamic-pituitary-testis axis. The assumptions in this model are that when an LHRH agonist is stopped, the pituitary regains function before the testis, possibly due to Leydig cell atrophy, and a high LH/TT ratio would indicate that the pituitary is working harder, raising LH levels proportionately more, relative to the levels of TT, so that a high LH/TT ratio represents a state of prolonged subnormal TT levels.
Practically, it may be a convenient measure for clinicians to be able to counsel their patients about how soon they might recover levels of TT and, in this respect, allow the patient to feel ‘normal’ again, as opposed to the androgen-deprived state that they were subject to for several years.
The limitations of the present study include the small sample size, the lack of measurement of bioavailable testosterone, which is a better measure of the biological activity of testosterone, and the lack of measurement of pre-treatment and subsequent health-related quality of life.
It would be important to learn whether men recover their baseline level of health-related quality of life, and how levels of TT or bioavailable testosterone correlate with how patients feel. It is possible that men may feel ‘normal’ when the testosterone level is in the supracastrate range and not necessarily into the ‘normal’ range, if effects of androgen deprivation such as hot flashes, weight gain and fatigue were no longer perceived.
This type of data would be helpful to those clinicians and patients who are considering testosterone replacement after LTAD, which is still considered experimental. Another aspect that cannot be explored in the present study is whether or not different LHRH-agonist preparations lead to a more rapid recovery of testosterone, as most of the patients were on 1-month preparations.
In conclusion, most men recover supracastrate TT levels after LTAD and external beam radiotherapy, but the time to recovery of ‘normal’ TT levels is prolonged. [Size=4]Few men recover potency and sexual desire[/size]. Patient age and the LH/TT ratio, may be predictive of the time to recovery of both supracastrate and normal serum TT levels.