Role of the Hypothalamic-Pituitary-Ovarian Axis in Puerperal Infertility

Abstract

To gain further insight into the mechanisms of postpartum infertility, plasma gonadotropins, prolactin, estradiol, and progesterone were measured following either iv LHRH or im menopausal gonadotropins (Pergonal) to postpartum women. Plasma estradiol and progesterone rose significantly between 24-72 hours following hMG injection. The response was similar in both nursing and non-nursing women throughout the intermediate and late postpartum study interval. No gonadotropin response was observed following LHRH injection in the early puerperium. Beyond five postpartum weeks, a significantly greater response following LHRH was observed in nursing compared with non-nursing women. A subsequent and significant rise in estradiol correlated with the magnitude of the LHRH-induced increment. Basal prolactin levels in nursing women were significantly greater than in non-nursing women but were unchanged after either hMG or LHRH. We conclude that the postpartum ovary is not refractory to either direct exogenous gonadotropin stimulation or to endogenously released gonadotropins, at least as far as estrogen production is concerned. Furthermore, the difference in the pituitary response to LHRH in nursing and non-nursing women may reflect a difference in the hypothalamic-pituitary axis. Elevated prolactin secretion in response to nursing may be involved in postpartum infertility, but the specific role remaine unclear.

Direct effects of prolactin and dopamine on the gonadotroph response to GnRH

“…This may explain the apparent discrepancies in the reported associations between PRL and gonadotrophin secretion during lactational amenorrhoea in humans. Specifically, whereas some studies have provided evidence for a negative correlation between gonadotrophin secretion and PRL at this time ( Jeppsson et al 1974, Le Maire et al 1974, Andreassen & Tyson 1976, Delvoye et al 1978, Duchen & McNeilly 1980 and that the duration of puerperal amenorrhoea is positively associated with the level of prolactinaemia (Diaz et al 1989(Diaz et al , 1991, others have found no correlation between the two (Nunley et al 1991, Tay et al 1992. In a study where dopamine and opioid antagonists were administered to breastfeeding women, the resulting increases in endogenous PRL secretion did not significantly affect the gonadotrophin responses to an injection of GnRH (Tay et al 1993).…”

“…PRL receptor mRNA and protein have been detected within the pituitary gland of the rat (Chiu et al 1992), and treatment of cultured pituitary fragments with PRL resulted in the suppression of both basal and GnRH-stimulated luteinizing hormone (LH) release (Cheung 1983). In humans, the pituitary LH response to GnRH is reduced during lactational amenorrhoea when PRL concentrations are elevated (Jeppsson et al 1974, Le Maire et al 1974, Andreassen & Tyson 1976, and this has been associated with LH pulses of low amplitude (Tyson et al 1978, Glasier et al 1984. Similarly, in subhuman primates, exogenous PRL was shown to suppress the LH response to GnRH (Maneckjee et al 1976).…”

Failure of Estrogen-Induced Discharge of Luteinizing Hormone in Lactating Women

“…After delivery, the pituitary responsiveness to an acute injection of LRF is reduced until the fourth postpartum week but becomes exaggerated from the fifth to eighth weeks (10,11). These results, domonstrating that the pituitary is responsive at least to exogenous LRF,, suggest that the lack of ovarian cyclicity in nursing mothers may be due to a failure of the hypothalamicf control of pituitary gonadotropin secretion.…”

Serum inhibin during lactation: relation to the gonadotrophins and gonadal steroids

“…A number of studies have attempted to establish the relations between gonadotrophins and ovarian hormones during the post partum period, in both breast-feeding and bottle-feeding mothers (Rolland et al, 1975a,b;Andreassen & Tyson, 1976;Delvoye et al, 1978;Glass et al, 1981;Howie et al, 1982a,b;Glasier et al, 1983, Gross & Eastman, 1985. These studies have mainly addressed the question of hormonal interaction, particularly involving PRL during post partum infertility, and have examined possible indicators for the return of fertility.…”