Biochemical Hypogonadism in Aging Testicular Cancer Survivors: A Clinical Challenge

Abstract

Background and objective

Few longitudinal studies have described the prevalence and development of biochemical hypogonadism in aging testicular cancer survivors (TCSs) in comparison to men from the general population (control subjects).

Methods

Serum total and free testosterone (T_total, T_free) were measured in 593 TCSs median11 and 27 years after TC diagnosis (Survey-First; Survey-Last). Post-treatment adverse health outcomes (AHOs) were recorded. The results were compared to those in 578 control subjects. Treatment was stratified as surgery alone, radiotherapy alone, or platinum-based chemotherapy. Biochemical hypogonadism was defined as T_total <8 nmol/l, or as T_total <12 nmol/l and T_free <225 pmol/l. We used multivariable logistic regression analysis to explore associations with age and treatment intensity. Statistical significance was set at p <0.05.

Key findings and limitations

Between the first and last survey the prevalence of biochemical hypogonadism increased from 12% to 41% in the TSC group and from 5% to 11% in the control group. Three decades after diagnosis, the probability of biochemical hypogonadism was significantly correlated with increasing age and greater treatment intensity. The combined age- and treatment- related probability of hypogonadism was more than threefold higher in the TCS group than in the control group. At the last survey, fewer eugonadal than hypogonadal TCS men reported at least one AHO attributable to androgen deficiency (54% vs 72%; p <0.001). Limitations include the availability of only one blood sample per survey wave.

Conclusions and clinical implications

For aging TCSs, the probability of biochemical hypogonadism depends on age and prior treatment intensity and is threefold higher than for control subjects at 30 yr after diagnosis. As late hypogonadism is associated with AHO incidence, the development of hypogonadism should be monitored via regular blood tests during TCS follow-up.

Patient summary

Depending on the treatment they received, older survivors of testicular cancer (TC) are at persistent risk of lower testosterone levels. Our study revealed low testosterone in 40% of TC survivors older than 60 years compared to 10% of similarly aged men from the general population. Low testosterone is associated with chronic conditions such as diabetes, fatigue, and/or erectile dysfunction. Testosterone should be regularly monitored during follow-up for TC survivors.