Opioid analgesia impairs gonadal function in healthy men and women. Methadone, a synthetic opioid is used in opioid addicts to prevent relapse due its longer-lasting effects and is known to cause hypogonadism. Little data exists on the prevalence of this and the mechanism through which this occurs.
Men (n=147), mean age 36.2 years (S.D 7.2) attending a drug-treatment rehabilitation centre for methadone maintenance therapy had early morning gonadotrophins, prolactin, thyroid hormones and sex-hormone binding-globulin (SHBG) levels measured.
35.4% (n=52) of men had total testosterone (TT) below the reference range (8.629 nmol/L). The mean TT in the hypogonadal group was 5.18 nmol/L (S.D. 2.28) compared to 18.1 nmol/L (S.D. 7.65) in the eugonadal group (P<0.001). SHBG concentrations were increased in the whole group, 62.5 U/l (S.D. 28.9) compared to the normal reference range (14.548.4 U/l). SHBG concentrations were significantly lower in the hypogonadal group compared to the eugonadal group, 49.7 U/l (S.D. 22.0) versus 69.3 U/l (S.D. 29.9) respectively (P<0.001).
There was no significant difference in methadone dose, antidepressant, benzodiazepine or anti-psychotic use between groups. Prolactin levels were normal and not significantly different in the low TT compared to the normal TT group, 223.5 mU/l and 250.6 mU/l respectively.
LH levels were significantly lower in the hypogonadal group, 4.10 U/l (S.D. 3.46) compared to the eugonadal men, 5.87 U/l (S.D. 2.97) (P<0.005). There was no difference in FSH levels. TSH was significantly greater in the hypogonadal group 5.82 mU/l (S.D. 14.92) compared to the eugonadal group 1.96 mU/l (S.D. 1.51) (P <0.05), with normal free T4 levels in both groups.
In summary, there is a high prevalence of hypogonadism in male methadone users. The whole group have high SHBG levels. However, compared to eugonadal users, hypogonadal users have significantly lower SHBG and LH levels and higher TSH levels. The clinical implications of this are not known.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology