Acute dopaminergic blockade augments the naloxone-induced LH rise in estrogen-treated postmenopausal women

Objectives: To assess the effect of estrogen replacement on the simultaneous blockade of the dopaminergic (DA) and opioidergic neural control of hypothalamic-gonadotropic function in postmenopausal women. Methods: Twenty healthy postmenopausal women, 48–55 years old were randomly assigned to receive either a 4-h naloxone infusion at 2 mg/h (group 1, n = 7) or a 10 mg i.v. bolus of metoclopramide (group 2, n = 7) or both drugs, simultaneously (group 3, n = 6) before and after 3 weeks of transdermal estradiol (100 μg/day). Blood samples were obtained at 30-min intervals during 4 h and duplicate determinations of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂) and prolactin (PRL) were performed in all samples. Results: In group 1 only a mild but significant LH rise after but not before estrogen replacement was seen. In group 2 PRL had a greater rise after than before estrogen therapy, without other hormonal changes. In group 3 a greater rise in PRL occurred after than before estrogen administration and serum LH had a sustained rise throughout the test only after estrogen replacement (greater than in group 1). No FSH changes were observed. The after-estradiol PRL response was nearly similar in groups 2 and 3. Conclusions: Our results indicate that in the untreated postmenopausal women, the dopaminergic system has little and the opioidergic system has no significant input in the control of gonadotropin or prolactin release. However, following estrogen replacement, opioids are involved in the inhibition of LH release and stimulating PRL release, while the dopaminergic system acts to inhibit PRL release and modulates LH release or inhibition, depending on the levels of circulating estrogens.