Prevalence of Hypogonadism in Low-Risk Prostate Cancer Survivors
Data Collection
The study participants were asked to complete a brief validated Androgen Deficiency in the Aging Male (ADAM) questionnaire and provide a blood sample. The standard ADAM questionnaire consists of 10 yes/no questions concerning symptoms of androgen deficiency. A positive questionnaire was defined as a “yes” to any 3 questions.13 A blood sample was obtained between 7AM and 9AM for total and free testosterone level, follicle stimulating hormone, and luteinizing hormone (LH) to determine whether the hypogonadism was primary or secondary to a hypothalamicpituitary process. Additional data were collected, including age, height, weight, race, presence of diabetes mellitus (DM), tumor characteristics at diagnosis (ie, PSA, Gleason score, AJCC stage), and first course of cancer treatment.
Main Outcomes and Measures
The primary outcome was hypogonadism. Patients with serum T < 250 ng/dL were identified as having hypogonadism (the lower limit of the reference range in the EHJVA laboratory assay 250-1,100 ng/dL). The type of hypogonadism was further categorized as primary (LH > 10.6 IU/L) or secondary (LH < 10.6 IU/L). Patients with a body mass index (BMI) > 30 kg/m2 were considered obese.
The prevalence of hypogonadism was assessed overall and for subgroups of patients. The 95% confidence interval (CI) was calculated for each estimate. The correlation between BMI and serum T was also determined. Analyses were carried out using SAS 9.2 (SAS Institute Inc., Cary, North Carolina).
Results
The mean age was 69.1 years and patients were primarily white (Table 1). Half the patients were obese, and 40% had DM. The majority of patients had been diagnosed with stage I PCa, had received radiation as their primary treatment, and had completed the PCa treatment more than 5 years ago.
The prevalence of hypogonadism did not differ by race, DM, or tumor stage (Table 3). The oldest age group had the highest prevalence, but it was not statistically significant. However, obese patients were significantly more likely to have hypogonadism than were nonobese patients (57.6% vs 7.6%, P < .001). The negative association between BMI and serum T was more apparent when the correlation (r = -0.37, P < .01) between these 2 factors were examined (Figure). Patients with a higher ADAM score (> 3) were more likely to have hypogonadism than patients with a lower score (40.6% vs 20.0%, P = .14; Table 3). The prevalence of hypogonadism was higher in patients who were treated with radiation compared with patients who had surgery (41.6% vs 13.3%, P = .05). However, obese patients were more likely to have been treated with radiation (Table 4). After stratifying by obesity status, there was no difference in hypogonadism by treatment type.
Discussion
To the authors’ knowledge, this is the first study to assess the prevalence of hypogonadism in treated low-risk PCa survivors. In this sample of 52 men in an outpatient setting, about 1 in 3 had low testosterone levels. Three patients had primary hypogonadism, and 14 had secondary
(hypogonadotrophic) hypogonadism. Obese patients were significantly more likely to have hypogonadism than were nonobese patients. There was no evidence of an associationbetween PCa treatment and hypogonadism.
Estimates of prevalence of hypogonadism in the general population vary in the literature based on different patient demographics, study designs, and geography. A recent review found that the prevalence of hypogonadism in adult men ≥ 18 years had a range of 2.1% to 31.2% since the authors included studies that were population-based, community-based, and primary care or screening-based.14 The prevalence of hypogonadism was 15.0% to 78.8% in obese people and 21.4% to 33% in men with newly diagnosed PCa.14
Mulligan and colleagues estimated that 38.7% of men aged ≥ 45 years who visited primary care clinics in the U.S. had hypogonadism.15 They also found that the prevalence of hypogonadism, defined as serum T < 300 ng/dL, was significantly higher in men with obesity, DM, hypertension, hyperlipidemia, asthma or chronic obstructive pulmonary disease, and prostate disease. The prevalence of hypogonadism in this study was slightly lower (32.6%), but the authors used a different serum T level (< 250 ng/dL).15 Using the Mulligan and colleagues’ definition of serum T level, there was a prevalence of 40.3% in this study’s population of men with treated low-risk PCa.
Other patient characteristics were examined to determine whether the prevalence of hypogonadism differed by age, tumor stage, or mode of treatment. Testosterone levels drop in all men, 1% per year on average after age 30 years.15 Hypogonadism has been consistently found to increase with age and certain comorbidities. Zarotsky and colleagues found a 17% increase in the risk for hypogonadism with every 10-year increase in age.14 In this study, the authors did not find a significant difference in the prevalence of hypogonadism in this group by age or DM.
In the Prostate Cancer Outcomes Study (PCOS), the prevalence of erectile dysfunction was almost 90% in the prostatectomy and radiotherapy group after 15 years. It was unclear whether this was due to PCa and its treatment, the normal aging process, or a combination of factors, but no significant differences were observed between the treatment groups. However, it is unclear whether the PCOS men had hypogonadism, because testosterone levels were not reported.16
