Function of the Male Sex Organs in Heroin and Methadone Users

Cicero, Theodore J.; Bell, Roy D.; Wiest, Walter G.; Allison, James H.; Polakoski, Kenneth L.; Robins, Eli

doi:10.1056/nejm197504242921703

Cited by 231 publications

(86 citation statements)

References 11 publications

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“…Thus, again it seems to be mainly an impairment of the pulsatile component of LH secretion that occurs in response to the sustained stress of prolonged critical illness (56). Endogenous dopamine, opiates and the elevated estradiol levels (3) may be involved in the pathogenesis of hypogonadotropism, as exogenous dopamine, opioids and estrogens may further diminish blunted LH secretion (56,78).…”

Section: Luteinizing Hormone±testosterone Axismentioning

confidence: 99%

Novel insights into the neuroendocrinology of critical illness

Berghe

2000

European Journal of Endocrinology

226

104

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An unexplained hallmark of prolonged critical illness is the fact that food does not prevent or reverse protein wasting, while fat is paradoxically accrued. This`wasting syndrome' often persists after the underlying disease has been resolved and thus perpetuates intensive care dependency. Although the crucial role of an intact hypothalamus±pituitary axis for homeostasis during stress is well recognized, the differences between the neuroendocrine changes observed in acute and prolonged critical illness were only recently described. Novel insights in this area are reviewed here.The initial endocrine stress response consists primarily of a peripheral inactivation of anabolic pathways while pituitary activity is essentially ampli®ed or maintained. These responses presumably provide the metabolic substrates and host defense required for survival and to delay anabolism, and thus should be considered as adaptive and bene®cial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated, since a uniformly reduced pulsatile secretion of ACTH, TSH, LH, prolactin (PRL) and GH has been observed in protracted critical illness, causing diminished stimulation of several target organs. Impaired pulsatile secretion of anterior pituitary hormones in the chronic phase of critical illness seems to have a hypothalamic rather than a pituitary origin, as administration of relevant releasing factors evoked immediate and pronounced pituitary hormone release. A reduced availability of TRH, one of the endogenous ligands of the GH-releasing peptide (GHRP) receptor (such as the recently discovered ghrelin) and, in very long-stay critically ill men, also of GHRH, appear to be involved. This hypothesis was further explored by investigating the effects of continuous i.v. infusion of GHRH, GHRP, TRH and their combinations for several days. Pulsatile secretion of GH, TSH and PRL was re-ampli®ed by relevant combinations of releasing factors which also substantially increased circulating levels of IGF-I, GH-dependent binding proteins, thyroxine and tri-iodothyronine (T3) while avoiding a rise in reverse T3. Active feedback-inhibition loops prevented overstimulation of target organs and metabolic improvement was noted with the combined infusion of GHRP and TRH. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.

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Section: Luteinizing Hormone±testosterone Axismentioning

confidence: 99%

Novel insights into the neuroendocrinology of critical illness

Berghe

2000

European Journal of Endocrinology

226

104

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“…Moreover, other studies have suggested that monocytes provide soluble Fas, which has the potential to trigger lymphocyte apoptosis (9) . Whereas (10) provides further support for the hypothesis that morphine may be directly compromising immune function by enhancing apoptosis of T lymphocytes in patients with heroin addiction through alteration of BCl2 and BAX genes expression.Some studies demonstrated that high-dose methadone was shown to depress plasma testosterone levels (11,12) , and other clinical studies have reported decreased sexual drive and performance in male heroin addicts (13) . This study is designed for better understanding of the underlying mechanisms of heroin-induced toxicity which may allow more informed application of opioid replacement therapy as well as the development of additional novel therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Oxidative Markers, Apoptosis and Reproductive Efficiency in Heroin Addicted Rats

Othman¹

2013

iosrphr

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“…Cicero et al (9) reported that a 3 day implantation of morphine pellets in male rats produced atrophy of the male accessory reproductive organs and low plasma testosterone levels. Our experimental design differs from Cicero's experiment in that we used rats which were fully mature sexually and were administered morphine repeatedly for a longer period of time.…”

Section: Discussionmentioning

confidence: 99%

Effects of Repeated Morphine Administration on Copulation and on the Hypothalamic-Pituitary-Gonadal Axis of Male Rats

Tokunaga

Muraki

Hosoya

1977

Japanese Journal of Pharmacology

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Abstract-Adult male rats were administered morphine twice a day for 45 days and the effects of morphine on the copulation rate, the weight of various organs, and on the hypothalamic-pituitary-gonadal axis were examined. Morphine administered rats showed a loss of weight, hypertrophy of the adrenals, decreased weight of accessory sex organs, low sperm count, and decreased copulation rate. While investigating the possible teratogenicity of morphine, we found that the copulation rate of morphine-tolerant male rats was less than that of saline-treated control males sug gesting that the repeated administration of morphine inhibits gonadotropin secretion and causes regressive changes in the reproductive organs of rats (1). The present study was undertaken to determine whether or not morphine does affect the hypothalamic-pituitary gonadal axis in male rats. Some of these data have already been reported (2). MATERIALS AND METHODSTwenty sexually mature male Wistar rats, 16 weeks of age, weighing from 330 to 380 g at the start of morphine administration, and 40 adult female virgin rats of the same strain were used. The morphinized and the control groups each consisted of 10 males and 20 females. Morphine hydrochloride was administered s.c. twice daily to the male rats only.The initial dose was 20 mg/kg and the dose was increased by 20 mg/kg every three days.After the 16th day, the dose was fixed at 100 mg/kg twice daily. Control male rats were given the same amount (5 ml/kg) of physiological saline solution. After the 16th day of administration of morphine or physiological saline, each male rat was put with 2 female rats. Confirmation of copulation was made by examining vaginal smears for sperm every morning. Each male rat was housed with a virgin female in a cage until copulation for 12 days at the longest. After copulation or after 12 days' housing with its partner, when copulation was not evident, the first female was taken away and a second new female was put into the cage and copulation was checked again. The female was examined for pregnancy 3 weeks later to obtain the gestation rate. When sperms were found in the vaginal smears of the second female rat, or, after 12 days of housing with a second female rat if no sperms were found in the smear, the male rat was isolated from the female for 5 days to restore the sperm, and was decapitated 2 hr after the last administration of morphine or physiological saline. The hypothalamus, pituitary, adrenals and male reproductive organs were weighed and the reproductive organs were examined histologically. The serum was kept frozen at -70°C until the assay of hormones. To count the number of sperm in the epididymis, the caudal part of one epididymis was minced in 1 nil of physiological saline solution for 5 min and the number of sperm in the resultant cloudy solution was counted. The hypo thalamus was isolated by the method of Glowinski and Iversen (3) and was homogenized in 2 ml of 0.2 M acetic acid. The supernatant obtained by 10 min centrifugation at 2,000,-" g was lyophilize...

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Function of the Male Sex Organs in Heroin and Methadone Users

Cited by 231 publications

References 11 publications

Novel insights into the neuroendocrinology of critical illness

Novel insights into the neuroendocrinology of critical illness

Evaluation of Oxidative Markers, Apoptosis and Reproductive Efficiency in Heroin Addicted Rats

Effects of Repeated Morphine Administration on Copulation and on the Hypothalamic-Pituitary-Gonadal Axis of Male Rats

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