25985806
OBJECTIVE	Opioid-induced androgen deficiency ( OPIAD ) affects patients treated with opioid analgesics .
OBJECTIVE	The norepinephrine reuptake inhibitor ( NRI ) and - opioid receptor ( MOR ) agonist activities of tapentadol may result in tapentadol having less effect on serum androgen concentrations than analgesics acting through the MOR alone , such as morphine and oxycodone .
OBJECTIVE	The objectives of this publication are to 1 ) evaluate the effects of tapentadol ( NUCYNTA and NUCYNTA extended release [ ER ] ) on sex hormone concentrations in healthy male volunteers ( vs placebo and morphine ) and patients with osteoarthritis ( vs placebo and oxycodone ) , and 2 ) present a mechanistic hypothesis explaining how the combined MOR agonist and NRI activities of tapentadol may result in less impact on androgen concentrations .
METHODS	Three clinical studies were conducted : study 1 ( single-dose comparison study vs morphine in healthy volunteers ) , study 2 ( single-dose-escalation study in healthy volunteers without an active comparator ) , and study 3 ( multiple-dose study vs oxycodone in patients with osteoarthritis ) .
METHODS	Studies 1 and 2 were conducted at medical research centers in Germany and the United Kingdom ; study 3 was conducted at primary and secondary care centers and medical research centers in the United States .
METHODS	All three studies were randomized , double blind , and placebo controlled .
METHODS	Concentrations of testosterone , luteinizing hormone ( LH ) , and follicle-stimulating hormone ( FSH ; study 3 only ) were evaluated at 6 and 24 hours postdose in studies 1 and 2 , respectively , and at varying time points postdose in study 3 .
RESULTS	In study 1 , mean serum total testosterone concentrations in healthy male volunteers were similar at baseline for all treatment periods ; 6 hours after dosing , mean concentrations were comparable between placebo ( 8.6 nmol/L ) and tapentadol immediate release ( IR ; 43 mg , 8.8 nmol/L ; 86 mg , 9.3 nmol/L ) , but were lower following administration of morphine IR 30 mg ( 5.4 nmol/L ) .
RESULTS	In study 2 , there were no or minimal changes in testosterone in the therapeutic dose range with tapentadol IR ( 75-100 mg ) , and there was a modest decrease that appeared to level off in the supratherapeutic range ( 125-175 mg ) ; mean testosterone and LH concentrations with all doses remained within normal ranges ( testosterone , 4.56-28 .2 nmol/L ; LH , 2.9-4 .6 U/L ) .
RESULTS	In study 3 , the decrease in the mean [ standard deviation ] testosterone concentration from baseline to endpoint for male patients receiving tapentadol ER ( 100 mg , -1.9 [ 0.71 ] nmol/L ; 200 mg , -2.1 [ 0.93 ] nmol/L ) was numerically smaller compared to oxycodone CR ( 20 mg , -2.7 [ 0.93 ] nmol/L ) , but higher compared to placebo ( -0.3 [ 1.62 ] nmol/L ) .
CONCLUSIONS	These results suggest that tapentadol , which has combined MOR and NRI activities , may have a lower impact on sex hormone concentrations than pure opioid analgesics , such as morphine or oxycodone .
CONCLUSIONS	The data and mechanistic rationale presented herein provide a justification for conducting additional hypothesis testing studies , and are not intended to be used as a basis for clinical decision making .
CONCLUSIONS	Future studies may help elucidate whether the observed trends are clinically significant and would translate into a reduced incidence of OPIAD .

