Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids

Abstract

BACKGROUND Profound hypogonadism has been noted in patients receiving intrathecal opioids. The purpose of the current study was to determine whether chronic consumption of oral opioids by male survivors of cancer also would lead to central hypogonadism and whether this hypogonadism was associated with symptoms of sexual dysfunction, fatigue, anxiety, and depression. METHODS A case–control study was conducted at The University of Texas M. D. Anderson Cancer Center (Houston, TX), in which 20 patients who were chronically consuming opioids were compared with 20 matched controls. Patients completed the Sexual Desire Inventory (SDI), the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Chronic Illness Therapy with general and fatigue subscales (FACT‐G/FACIT‐F), and the Edmonton Symptom Assessment System (ESAS) questionnaires. Serum samples were collected for testosterone, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS Comparing the opioid group with the control group, 18 of the 20 patients (90%; 95% confidence interval [CI], 65–98%) exhibited hypogonadism, compared with 8 of the 20 control patients (40%; 95% CI, 19–64%). The median testosterone level was 145 ng/dL versus 399.5 ng/dL (5.0 nmol/L vs. 13.9 nmol/L; P < 0.0001), the median FSH level was 2.85 milli–International Units (mIU)/mL versus 5.3 mIU/mL (P = 0.08), the median LH level was 1.8 mIU/mL versus 4.2 mIU/mL (P = 0.0014), the median SDI‐dyadic score was 18.5 versus 40 (P = 0.01), the median SDI‐solitary score was 0 versus 5 (P = 0.007), the HADS (anxiety) score was 8.5 versus 5.5 (P = 0.053), the HADS (depression) score was 7.5 versus 1.5 (P = 0.0002), the FACT‐G score was 64 versus 96.3 (P = 0.0001), and the FACIT‐F score was 24 versus 46 (P = 0.0003). CONCLUSIONS Survivors of cancer who chronically consumed opioids experienced symptomatic hypogonadism with significantly higher levels of depression, fatigue, and sexual dysfunction. With the increasing use of opioids among patients with cancer, further research in improving quality‐of‐life outcomes is warranted. Cancer 2004;100:851–8. © 2004 American Cancer Society.

The impact of hypogonadism and autonomic dysfunction on fatigue, emotional function, and sexual desire in male patients with advanced cancer

“…The trend toward higher opioid dosage for hypogonadal patients is consistent with previous reports, 45 including our own, 44,49 of hypogonadism among cancer survivors without evidence of recurrent disease who use opioid therapy for chronic pain. Our patients with autonomic dysfunction did not seem to have a greater frequency of fatigue or, indeed, of any major symptoms except for dyspnea.…”

“…This confirms our previous observation in patients with cancer who received opioids. 44 Elevated inflammatory cytokines, particularly IL-6, are common in patients with advanced cancer and are associated with fatigue, depression, anorexia/ cachexia, reduced free testosterone, prolonged suppres-FIGURE 1. Free testosterone versus total testosterone (in ng/mL) (normal free testosterone is !34 ng/mL; normal total testosterone is !241 ng/mL).…”

Preliminary Report: Vitamin D Deficiency in Advanced Cancer Patients with Symptoms of Fatigue or Anorexia

“…Notably, in a placebo-controlled trial among overweight, otherwise healthy men, vitamin D replacement over a period of 1 year significantly increased testosterone levels [23]. In patients with cancer, chronic use of opioid analgesics can result in low testosterone [24], and in combination with low vitamin D levels this could predispose patients to loss of muscle mass and increase the insulin resistance associated with cancer cachexia [25] or obesity. Both vitamin D [26] and testosterone [27] supplementation have been reported to increase insulin sensitivity in selected noncancer populations.…”

Hypogonadism in male patients with cancer

“…49 -52 Rajagopal et al 53 reported low TT levels in 18 of 20 cancer survivors who were receiving high-dose opioids orally (Ն200 mg of morphine equivalent daily dose for Ն1 year) compared with 8 of 20 matched cancer survivors who had not received opioids, suggesting that hypogonadism is common in cancer survivors and is even more common in patients who require high doses of opioids. Nevertheless, samples were not drawn in the early morning, and neither SHBG nor FT levels were measured.…”

“…In the current study, all blood specimens were obtained in the early morning, in contrast to most of the previous studies, 45,53 in which samples were collected throughout the day. This is particularly important, because testosterone is characterized by a diurnal rhythm, with highest levels in the morning and a nadir in the late afternoon.…”