Effects of opioid receptor blockade on luteinizing hormone (LH) pulses and interpuise LH concentrations in normal women during the early phase of the menstrual cycle

To determine the role of endogenous opioid peptides in regulating pulsatile luteinizing hormone (LH) release in the early follicular phase of the menstrual cycle of eumenorrheic women, we evaluated serum LH concentrations in blood collected every 10 min for 12 h in 27 women each studied during two menstrual cycles: (1) without pretreatment and (2) following oral administration of naltrexone, a mu opiate receptor blocking agent, at a dose of 1.0 mg/kg. Pulsatile LH release was assessed by the CLUSTER algorithm. The mean (±SE) integrated serum LH concentration (IU/L/min) increased following the administration of naltrexone (4715±298) in comparison to the control day (3997±381; p=0.0008). The mean number of LH pulses (/12 h) detected on the naltrexone day (10.3±0.3) was higher than on the control day (8.9±0.4; p=0.0068). Mean maximal LH peak height (IU/L) was greater on the naltrexone (7.8±0.5) vs control (6.7±0.5) days (p=0.0064) as was the interpulse valley mean serum LH concentration (IU/L; 6.3±0.4 vs 5.0±0.4; p=0.0013). No difference was noted in the mean incremental LH pulse amplitude (IU/L; 1.9±0.1 vs 2.1±0.1; p=0.13), or peak duration (min; 40±1.8 vs 45.0±2.4; p=0.06). Mean LH peak area (IU/L/min) was greater on the control (45.0±2.4) vs naltrexone (40±1.8) days (p=0.0475). These results suggest that inhibition of endogenous opioid peptide systems with naltrexone in the early follicular phase of the menstrual cycle is associated with an alteration of the gonadotropin-releasing hormone (GnRH) pulse generator firing rate as appraised indirectly by enumeration of distinct LH pulses. The enhanced maximal serum LH pulse amplitude and interpulse valley mean LH concentrations, together with no observed change in the incremental amplitude, suggest a naltrexone-associated augmentation of low levels of basal LH release, a skewing of LH secretory burst waveform, and/or a prolongation of LH half-life.