LAS VEGAS, NV—Tapentadol therapy has nominal effects on luteinizing hormone (LH) and testosterone, in contrast to the opioid-induced androgen deficiency (eg, suppression of adrenal, pituitary, hypothalamic, and gonadal hormone production) observed with other mu-opioid analgesics, according to study results presented at PAINWeek 2012.
Gary Vorsanger, MD, from Janssen Scientific Affairs, LLC, Raritan, NJ, and colleagues sought to evaluate the effects of tapentadol immediate-release (IR) and tapentadol extended-release (ER) on gonadotropin (LH and/or follicle stimulating hormone [FSH]) and testosterone levels in healthy subjects and subjects with moderate-to-severe, chronic osteoarthritis knee pain. The first study, conducted in adult male healthy subjects, was a four-way crossover, single-administration study in which subjects received a single dose of placebo, tapentadol IR (50 mg or 100 mg), or 30 mg of IR morphine in each of four 2-day periods. After 6 hours of dosing, median serum testosterone levels were comparable for placebo and tapentadol IR but lower in subjects who received 30 mg IR morphine; median serum LH levels were also similar for subjects who received placebo and tapentadol IR, but lower for subjects receiving 30 mg IR morphine during this time.
The second study, carried out in adult male and female healthy subjects, was a four-period dose-escalation study in which subjects received placebo during one 3-day treatment period and a different escalating dose of tapentadol IR during each of the other 3-day treatment periods (dose range: 75–250 mg every 6 hours). Mean testosterone levels increased slightly from baseline to 24 hours with placebo and decreased with tapentadol IR in a dose-related trend; mean changes in LH levels were comparable for placebo and all doses of tapentadol IR during this period.
The third study was performed in adult males and females with moderate-to-severe, chronic osteoarthritis knee pain. In this parallel-group, forced-titration study, subjects received either placebo, one of two titration regimens of tapentadol ER (25-50-100 mg or 100-150-200 mg), or controlled-release oxycodone (10-10-20 mg) twice daily during a 14-day titration period, followed by a 14-day fixed-dose maintenance period. No clinically important changes were seen in testosterone, LH, or FSH concentrations during the double-blind treatment portion.
The authors noted that as tapentadol has dual mechanisms of action (mu-opioid receptor agonism and norepinephrine reuptake inhibition), this might have provided an explanation regarding the minimal effects of tapentadol on sexual hormone levels.