Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women
Tay, C.C.; Glasier, A.F.; McNeilly, A.S.
Human Reproduction 8(4): 532-539
ISSN/ISBN: 0268-1161 PMID: 8501180 DOI: 10.1093/oxfordjournals.humrep.a138090
The role of dopamine and opiates in the suckling-induced suppression of gonadotrophin secretion and prolactin release was investigated during lactational amenorrhoea in fully breastfeeding women at 12 weeks post-partum. A total of 26 women, 20 using non-steroidal methods of contraception and six using the progestogen-only pill, Noriday (POP), breastfed their babies on demand at a frequency of 3.6 +- 0.2 suckling episodes during the 8 h study period while blood samples were collected at 10-min intervals. Five hours after the start of sampling six women were given the dopamine antagonist metoclopramide (10 mg, i.m.) while four women received saline. In a second experiment, six women using non-steroidal contraception and three women on the POP received an i.v. infusion of the opiate antagonist naloxone (1.6 mg/h) for 2 h, while four women using non-steroidal contraception and three women on the POP were infused with saline. Two hours after the i.m. injection or start of infusion all women were given an i.v. injection of 10 mu-g gonadotrophin releasing hormone (GnRH) and samples were collected for a further 1 h. All samples were assayed for luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin. Plasma concentrations of oestradiol were lt 60 pmol/l in all women and they remained amenorrhoeic for at least 10 weeks after the study. Pulsatile release of LH was only observed over the 5 h pre-treatment period in 10 of the 20 non-steroid taking women (1-3 pulses/5 h), and in one of the six women (1 pulse/5 h) on POP. Treatment with metoclopramide caused a substantial (29-fold) increase in prolactin over baseline, 7.4 times the maximum released in response to suckling. There was no effect of metoclopramide on the pattern of release of LH or FSH or the response to GnRH. Infusion of naloxone in women using either non-steroidal contraceptives or progestogen-only pill did not affect prolactin release. Naloxone infusion did not affect LH or FSH in women using nonsteroidal contraceptives, but caused a small but significant (P lt 0.05) increase in both LH and FSH in women taking the progestogen-only pill. There was a significantly greater release of LH and FSH after GnRH in all women after naloxone infusion. These results in breastfeeding women during lactational amenorrhoea confirmed that suckling suppresses the pulsatile release of LH but not through a dopaminergic pathway, showed that prolactin remains under dopaminergic control during human lactation, but suckling does not appear to affect prolactin secretion in via an opiate pathway and indicated only a minor, if any, role for opiates in the suckling-induced suppression of GnRH/gonadotrophin secretion but a potential, previously unreported, effect of opiates in reducing pituitary responsiveness to GnRH.