The hypothalamic-pituitary-luteal axis in women: Effects of long-term orally active opioid antagonist (naltrexone) administration

Abstract

Aim of our study is to assess the effect of a long-term oral opiate antagonist treatment during the luteal phase on the hypothalamic-pituitary-ovarian axis. Fourteen normovulatory women participated to the study. Immediately after the ovulation, the patients were randomly divided in two groups: in the first one women received naltrexone 50 mg/die orally (Antaxone Zambon Italy) from day 1 of the luteal phase for 7 days. In the second patients were treated with placebo for the same period and served as control group. On day 7, patients were hospitalized for a pulse pattern study followed by a GnRH test. LH, FSH, Estradiol, Progesterone were assayed. The naltrexone administration strongly increased the number as well as the amplitude of the gonadotropin pulses. The circulating P levels were also significantly higher in treated patients. The GnRH injection significantly increases the gonadotropin secretion in all patients. The stimulated LH and FSH secretion was significantly greater in treated patients when compared to controls. Such discharge of LH determined a significant increase of progesterone production in controls, but failed to stimulate the corpus luteum in treated patients. In conclusion the present paper strengthen an important role of the opioidergic system in the regulation of GnRH pulsatility in luteal phase. Moreover, our findings confirms the sensibility of the corpus luteum to LH and the possibility to stimulate the P secretion during the luteal phase.

Effects of the opioid analgesic oxymorphone hydrochloride on reproductive function in male and female rats

“…Endogenous opioids seem to play a key regulatory role in hypothalamic–pituitary–gonadal axis function in both males and females, where they exert chronic inhibitory effects on LH release. In humans, increases in serum LH occur after administration of opioid antagonists, and LH release is disrupted by morphine (Genazzani and Petraglia, 1989; Fulghesu et al, 1997). In animal studies, LH and FSH are suppressed by opioid agonists, including morphine and methadone, leading to downstream effects on reproductive steroid levels in both males and females (Cicero et al, 1977; Pang et al, 1977; Johnson and Rosecrans, 1978; Cicero, 1980).…”

Opioid dependence treatment: options in pharmacotherapy

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Enhancing Protective Antibodies against Opioids through Antigen Display on Virus-like Particles

“…A key approach to combating chronic OUD is medication-assisted treatment (MAT). , Pharmacotherapies, including methadone, buprenorphine, and naltrexone, are crucial in the treatment for individuals recovering from OUD. − However, these therapies have significant limitations, including low adherence to the medication and poor retention in the treatment regimen, especially for the opioid antagonist naltrexone. , As a result, there are substantial chances for relapse even with the therapy. , In addition, adverse events have been associated with long-term MAT, including significant hormonal effects, given that these drugs enter the brain to exert their biological activities . The unintended consequences of hormonal perturbations range from growth retardation and affective instability to increased fertility in adolescent girls.…”

“…14,15 In addition, adverse events have been associated with long-term MAT, including significant hormonal effects, given that these drugs enter the brain to exert their biological activities. 16 The unintended consequences of hormonal perturbations range from growth retardation and affective instability to increased fertility in adolescent girls. The significant increase in opioid overdose deaths in the past few years highlights the urgent need for novel treatment/prevention strategies beyond the current pharmacotherapies to stem the tide of the onset of OUD.…”