Sexual function and serum T levels, before, on, and after 9 months of ADT

As many readers of this news service will be aware, good data on the recovery of libido and sexual function after a period of androgen deprivation therapy (ADT) are limited. We have long known that such recovery is variable, and we also know that it can take time, but sound data from a large cohort of patients has been “missing in action,” so to speak. A new paper by Ng et al. has now remedied this problem.

Ng and his colleagues have now published detailed data from a relatively large, Phase II cohort study of men being treated with intermittent ADT. Recruitment of patients was started in July 1999. By July 2004 the authors had recruited a total of 250 patients who had been followed for 21 months or more. It is perhaps a little frustrating to note that it has taken > 7 years to publish these data in a peer-reviewed journal — although other data from this trial were published in 2006 and 2007. However, …

In this paper, Ng et al. report on two specific issues:

  • Actual testosterone levels over time in these 250 patients — before treatment, on treatment, and off treatment
  • Patients’ perceptions over time about their levels of libido, actual sexual activity, potency, and sense of masculinity

This is a complex paper containing way more data than we can encapsulate here. Many support group leaders would be well advised to seek their own copies of the full text of this paper. What we will try and do in the remainder of this commentary is summarize some of the most important points.

So first it is important to understand that all patients in this study were initially treated with maximal ADT using a 22.5 mg depot injection of leuprolide acetate every 3 months and 250 mg of flutamide three times a day. (Remember that this study was started in 1999; other forms of maximal androgen deprivation might be considered more appropriate today.)

Eligible patients were maintained on maximal ADT for a pre-scheduled period of 9 months (the “on-treatment” phase). If their PSA was ≤ 4 ng/ml at 9 months, their ADT was stopped and they moved into the “off-treatment” phase of the study. During the “off-treatment” phase, patients were returned to treatment if they met any one of the following criteria:

  • Their PSA rose to > 20 ng/ml.
  • Their PSA rose to a level higher than their PSA level at study entry (if that level was ≤ 20 ng/ml).
  • There was any other clinical manifestation of disease progression.

Here are the relevant results of the study:

  • 164/250 patients (65.6 percent) were 70 years or older and only 86 (34.4 percent) were less than 70 years of age.
  • 68/250 patients (27.2 percent) had evident, metastatic disease and 182 (72.8 percent) had locally advanced or locally recurrent disease.
  • 90 percent of all questionnaires were returned by patients.
  • With regard to the numbers of men on and off treatment
    • When men initially came “off treatment” (at the start of the serum T recovery phase), 6 percent of men had relapsed and 82 percent of the cohort completed questionnaires.
    • At 6 months “off treatment,” 8 percent of men had relapsed and 74 percent completed  questionnaires.
    • At 12 months “off treatment,” 27 percent of men had relapsed and 46 percent completed questionnaires.
    • At 18 months “off treatment,” 48 percent of patients had relapsed and only 27 percent completed questionnaires.
  • With respect to serum testosterone (T) levels
    • The average (median) testosterone levels at baseline (before treatment) was 147 ng/dl (range, 35 to 335 ng/dl).
    • After 3 months “on treatment,” 98 percent of patients achieved serum T levels < 20 ng/dl (range, 2 to 42 ng/dl).
    • During the “off-treatment” phase, the median time to recovery of a serum T level of 100 ng/dl was 10.4 months.
    • 30 percent of patients failed to achieve a serum T level of 100 ng/dl after 2 years off treatment.
  • With respect to libido (“To what extent were  you interested in sex?”)
    • 28 percent of patients expressed “major interest” at baseline.
    • 14 percent of patients still expressed “major interest” at 3 months on ADT.
    • 9.6 percent of patients still expressed “major interest” after 9 months on ADT.
    • “Major” interest recovered slowly during the “off-treatment” phase, peaking at 19 percent after 9 months off treatment.
  • With respect to actual sexual activity (with or without intercourse)
    • 112/250 patents (46 percent) claimed to be sexually active at baseline.
    • Of the men who were sexually active at baseline, only 22/112 (19.6 percent) were sexually active after 9 months on ADT.
    • Of the men who were sexually active at baseline, 26 (52 percent of those remaining in the trial) were sexually active after 12 months “off treatment.”
    • The mean testosterone level at which men recovered “major” sexual activity was 101 ng/dl.
  • With respect to potency (“Did you have difficulty getting and maintaining an erection?”)
    • 42/97 men who claimed to be sexually active at baseline (43 percent) had mild or no problems.
    • 4/27 men who claimed to be sexually active after 9 months on ADT (15 percent) had mild or no problems.
    • 6/14 men who claimed to be sexually active at 21 months “off treatment” (43 percent) had mild or no problems.

The conclusions that can be drawn from this study of sexual function in this cohort of relatively elderly men on ADT and during a first “off treatment” phase are relatively straightforward:

  • About half the men had sexual interest and some form of sexual activity at baseline (before treatment).
  • One in five (20 percent) of those men continued to have sexual interest and activity despite 9 months of ADT.
  • About one in two men who were sexually interested and active before regained that sexual interest and activity at 9 to 12 months “off treatment” (when their serum T level had increased back up to at least 100 ng/dl).

4 Responses

  1. So, the risk of sexual dysfunction post-treatment is roughly the same as surgery and radiation, the latter taking a few years to destroy the functionality of whomever it’s going to destroy.

  2. Dear Tracy:

    Actually no. The risk of sexual dysfunction after ADT is higher than it is after surgery or radiation therapy … but this has always been well understood and no one has ever pretended anything else.

  3. Dear Sitemaster,

    In my single-case experience your reply is spot-on. I shall soon complete a 3-year course of continuous ADT, using Zoladex in the large depot. This followed a period of HDR brachytherapy and EBRT, preceded by neoadjuvant hormone therapy using Zoladex and Casodex.

    A bit more than 1 month before this treatment began, I asked one urological surgeon about side-effects. His answer was “Probable impotence after 4 years,” although we were not speaking in English. I shrugged my shoulders and said “Ach, I’ll be 71 then and won’t be thinking about such things very much anyway.” He was a bit surprised and considers me a quite interesting patient (as do others).

    Perhaps I’m unusual, but this attitude seems to me to be right and proper, assuming that a man has strong interests other than mere sex.

  4. In my case I have been on ADT for 18 months, namely Eligard and a starter for 1 month on Casodex. My sexual desires started to diminish a year before starting on this treatment (about the same time that my PSA started to rise from a steady 10 to eventually 116 ng/ml). I am now 75. When the Eligard is starting to have no further effect, some sexual desires make themselves known but am unable to rise to the occasion.

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