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The Association Between Frailty, Hypogonadism, and Postoperative Outcomes Among Men Undergoing Radical Cystectomy - Beyond the Abstract

Hypogonadism is highly prevalent among the aging male population. Screening studies estimate nearly 20% of men in their 60’s and close to 50% of men in their 80’s carry this diagnosis.1 Symptoms of low testosterone, which include fatigue, reduced bone density, and sarcopenia, mirror symptoms of the frailty phenotype that are associated with low physiologic reserve and poor functional status. However, screening for hypogonadism and evaluating serum testosterone is often not performed by urologic oncologists in the preoperative setting. As our field searches for ways to identify high-risk surgical patients, improve clinical outcomes, and reduce the burden and time of postoperative recovery, testosterone may prove to be an untapped resource.

In this study, we used the IBM MarketScan database to compare postoperative outcomes between men with and without hypogonadism who underwent radical cystectomy between 2012 and 2021.2 Among over 3,700 individuals, we found that 6.1% had hypogonadism and that these patients were significantly more frail compared to men without hypogonadism. Although hypogonadism alone was not an independent risk factor for adverse clinical outcomes, we showed that frailty was associated with a higher rate of emergency department visits and inpatient readmissions after surgery. Our findings are revealing; however, we are left with two important unanswered questions that should direct future research.

First, what is the true prevalence of hypogonadism among men undergoing radical cystectomy, or other major urologic surgery? Our rate of 6.1% in this retrospective study is almost certainly a gross underestimate. As stated earlier, this is likely due to low screening rates in this population. The true prevalence can only be elucidated by conducting large-scale, prospective screening studies in the preoperative setting.

Second, does treatment of hypogonadism with testosterone replacement therapy (TRT) improve patient-reported outcomes? Aside from the physiologic benefit of testosterone supplementation, TRT improves overall mood and health-related quality of life.3 Recent studies have also shown TRT to be safe, even among high-risk patients with cardiovascular disease.4 Since radical cystectomy carries a high morbidity, with complication rates approaching 60-70% and a 5-year survival of 70%, these less tangible outcomes become even more important to patient care.5 Mood and health-related quality of life could not be assessed in the current study. However, these metrics should be prospectively evaluated in future research.

Assessment of hypogonadism can help identify frail patients. Although we did not find a significant difference in clinical outcomes between patients with and without hypogonadism, TRT is safe and likely effective at improving patient-reported outcomes. Therefore, we believe testosterone is an important biomarker that should be evaluated in the preoperative setting. Future studies are needed to determine the utility and role of frailty, testosterone, and TRT for patients undergoing major urologic surgery.

Written by:

  • Daniel R. Greenberg, MD, Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL
  • Joshua A. Halpern, MD, Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL, Posterity Health, Centennial, CO
References:

  1. Harman SM, Metter EJ, Tobin JD, et al: Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001; 86: 724–731.
  2. Greenberg DR, Rhodes S, Bhambhvani HP, et al: The association between frailty, hypogonadism, and postoperative outcomes among men undergoing radical cystectomy. Urol Oncol 2024: S1078-1439(24)00013–9.
  3. Shiraishi K, Ohmi C, and Matsuyama H: Patient-reported outcomes and biochemical alterations during hormonal therapy in men with hypogonadotropic hypogonadism who have finished infertility treatment. Endocr J 2021; 68: 221–229.
  4. Lincoff AM, Bhasin S, Flevaris P, et al: Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med 2023; 389: 107–117.
  5. Cancer Stat Facts: Bladder Cancer. National Cancer Institute; 2023.
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