The acute and chronic effects of heroin, and the opiate antagonist naltrexone, on integrated plasma samples analyzed for luteinizing hormone (LH) and testosterone (T) levels were studied in six adult males with a history of heroin addiction. Acute doses of heroin (10 mg i.v.) significantly suppressed LH levels. Chronic heroin use was also associated with a significant decrease in plasma T levels. LH levels after chronic heroin use were lower than control levels but the degree of LH suppression was approximately the same as after the acute doses of heroin. Acute naltrexone administration did not alter T levels appreciably but was associated with a significant elevation in LH levels. After 22 days of chronic naltrexone maintenance, T levels were in the high normal range and LH levels were in the low normal range. These data suggest the development of tolerance and supersensitivity to opiate agonist and antagonist effects on pituitary-gonadal hormones involves interaction between the direct effects of these drugs on LH followed by steroid feedback effects of T on gonadotrophin secretory activity.
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