Testosterone Levels May Decline, Then Recover, After External Beam Radiotherapy for Prostate Cancer

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer

Raisa S. Pompe, MD, Pierre I. Karakiewicz, MD, Emanuele Zaffuto, MD, Ariane Smith, MD, Marco Bandini, MD, Michele Marchioni, MD, Zhe Tian, Sami-Ramzi Leyh-Bannurah, MD, Jonas Schiffmann, MD, Guila Delouya, MD, MSc, Carole Lambert, MD, MSc, Jean-Paul Bahary, MD, MSc, Marie Claude Beauchemin, MD, Maroie Barkati, MD, Cynthia Ménard, MD, Markus Graefen, MD, Fred Saad, MD, Derya Tilki, MD, Daniel Taussky, MD

ONLINE: May 22, 2017 – The Journal of Sexual Medicine

DOI: http://dx.doi.org/10.1016/j.jsxm.2017.04.675


Introduction

Past research has shown that testosterone levels in men with localized prostate cancer decrease after radical prostatectomy or radiotherapy (when used as monotherapy). Pickles and Graham conducted one of the largest studies on the topic in 2002. Since then, smaller-scale studies have had mixed results.

The current study focused on testosterone kinetics after external beam radiation therapy (EBRT) in contemporary patients with localized prostate cancer. The authors hypothesized that these patients would have less significant decreases in serum testosterone and duration when compared to men in the previous studies.

Methods

The study population included 248 men who underwent definitive EBRT [three-dimensional conformal or intensity modulated radiation therapy (IMRT)] as monotherapy at the same institution from 2002 through 2014. The men were also participants in prospective registered phase II and III trials. All patients receiving therapy since 2007 received IMRT. None of the men had received neo- or adjuvant androgen-deprivation therapy. None had testis protection during radiation therapy.

Testosterone levels were measured according to each study’s protocol. For this study, low testosterone was defined as levels below 8 nmol/L.

Risk factors, including age, body mass index (BMI), total EBRT dose, baseline testosterone (BST), and percentage of decrease at nadir were also studied, as were any associations between testosterone decrease and recovery or biochemical recurrence.

Results

The men’s median age was 71 years. Median BST was 10.1 nmol/L. Twelve patients had low testosterone (below 8 nmol/L) at baseline and none had high testosterone (35 nmol/L or above). The median follow up time was 72 months.

Testosterone Decrease

Reported testosterone decreases from BST were as follows:

  • 75% of the men had any decrease.
  • 65.3% had at a decrease of at least 10%.
  • 44.8% had a decrease of at least 25%.
  • 13.3% had a decrease of at least 50%.
  • 1.2% had a decrease of at least 90%.

The median percentage of decrease from BST to the nadir level was 30%.

The median time frame between BST and the first decrease was 6.4 months.

About 45% of the men had levels no higher than 8 nmol/L, indicating biochemical hypogonadism. (About 5% of the men had biochemical hypogonadism at baseline.)

Testosterone decrease findings for a subgroup of 166 patients who underwent IMRT were “virtually the same findings as reported for the entire cohort,” the authors wrote.

Testosterone Recovery

Among the men who had any decrease, 62.9% had testosterone recovery to at least 90% of their BST. The median time frame from nadir to recovery was 6.1 months.

Findings were similar for a subgroup of 118 men after IMRT who had a testosterone decrease, with 61.9% recovering at least 90% in a median of 6.1 months.

Advanced age, increased BMI, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery.

Oncologic Outcome

Overall, 21.3% of the men had a biochemical recurrence during the follow-up period.

Discussion

The authors highlighted several of their findings:

  • Testosterone decrease after EBRT was confirmed in contemporary patients, but 63% saw their testosterone levels return to at least 90% of their baseline level. Forty-five percent experienced biochemical hypogonadism. Prostate cancer patients who are weighing their treatment options should be aware of these possibilities and understand that low testosterone is associated with depression, cognitive decline, decreased libido, erectile dysfunction, and inflammation.
  • The mechanisms behind testosterone decreases after radiation therapy “are multiple and can differ from one treatment to another.” It is possible that “scattered radiation” to the testes could prompt hormonal changes. Non-specific stress responses, such as those caused by cancer diagnosis and treatment, may also be involved.
  • Testosterone levels in older men naturally decline and age may have contributed to some of the decreases seen in this study. However, age would not explain the testosterone recovery experienced by 63% of the patients.
  • Patients at higher risk for non-recovery might need closer monitoring after treatment.
  • No association was found between testosterone kinetics after radiation therapy and biochemical recurrence.

The authors acknowledged limitations, including the following:

  • Because the participants were involved in different clinical trials, testosterone follow-up and laboratories were non-uniform.
  • Information on the patients’ health-related quality of life was not available.