Impaired LH Release Following Exogenous Estrogen Administration in Patients with Amenorrhea-Galactorrhea Syndrome

Abstract

Serum gonadotropin levels were determined in 10 patients with the amenorrhea-galactorrhea syndrome before and following acute iv administration of synthetic LH-releasing hormone (LHRH) or conjugated estrogens, in order to clarify the hypothalamic derangements in the gonadotropin secretion in patients with hyperprolactinemia. The basal prolactin (PRL) levels were elevated in all the patients, and blunted responses to 500 mug of iv synthetic thyrotropin-releasing hormone (TRH) injection were found in 9 out of the 10 patients. The basal levels of LH and FSH were subnormal in 2 and 3 patients, respectively, while those in the remaining patients were normal or slightly elevated. Normal or excessive responses of gonadotropins to 100 mug of iv LHRH were observed in most patients, 9 for LH and 10 for FSH out of 10 patients. In 10 normal cyclic women at the mid-follicular phase (D7-9) and 10 hypothalamic amenorrhea patients without galactorrhea, LH release was found 48 to 72 h after the iv injection of 20 mg conjugated estrogens (Premarin). This LH release following Premarin injection was completely abolished in the patients with amenorrhea-galactorrhea. These data seem to indicate that in patients with hyperprolactinemia, tonic secretion of gonadotropin is maintained fairly well, while of the positive feedback effect of Premarin on the release of LH is impaired. It is suggested that impaired LH release may be partly responsible for anovulation and amenorrhea in patients with hyperprolactinemia.

Simultaneous Increases of Leptin and Gonadotropin-Releasing Hormone Following Exogenous Estrogen Administration in Women with Normally Menstrual Cycle

“…In addition, several cell lines of evidence suggest that hypothalamus is the critical target of leptin and GnRH hormones and that they are specifically bound to the hypothalamic neuron cell membrane where both receptors are expressed [13,14]. Women with inadequate nutritional intake and hypoleptinemia may develop hypothalamic amenorrhea [15,16], which has been described as a state of impaired positive feedback mechanism in previous studies [11]. Taken together with observations from this study, it seems reasonable to assume that the positive feedback mechanism of estrogen requires the cooperation of leptin to convey metabolic signal to hypothalamus for release and/or synthesis of GnRH in the hypothalamus.…”

“…An impaired positive feedback of estrogen results in the decrease of LH secretion and is responsible for hypothalamic amenorrhea [11]. However, the mechanism by which estrogen triggers the release of GnRH in hypothalamus and whether leptin links to this mechanism remains unknown in humans.…”

Pituitary Responsiveness to LH-RH in Post-partum Ewes Treated With Oestradiol-17ß and Failing to Show a Plasma LH Surge

“…Failure of the positive feedback effect of oestrogens on LH release has been associated with ovarian acyclicity in post-partum ewes (Wright and Findlay 1977), women (Baird et al 1979), monkeys (Yamaji et al 1971) and cows (Radford et al 1978), and in non-parturient amenorrhoeic women (Glass et al 1975;Aono et al 1976).…”

Stimulatory Action of Prolactin on Gonadotropin Secretion in Vitro.

“…Presumptive mechanisms of suppressed gonadotropic function by PRL have been reported to be the interruption of the release of GnRH (Bohnet et al, 1976;Aono et al, 1976;Taketani et al, 1988) and the direct inhibition of ovarian function (McNatty et al, 1974;Demura et al, 1982;Van der Schoot et al, 1982). In this context, our present data showing a stimulatory action of PRL on gonadotropin release are rather unexpected.…”

“…However, the mechanism by which prolactin (PRL) affects the gonadal function is very controversial. To date, several data suggest an action of PRL in decreasing the release of gonadotropin-releasing hormone (GnRH) which consequently influences the anterior pituitary gland to reduce the secretion of gonadotropin (Bohnet et al, 1976;Aono et al, 1976;Taketani et al, 1988). On the other hand, the capacity of the anterior pituitary gland to secrete gonadotropin in response to GnRH is intact or often rather enhanced in hyperprolactinemic women (Archer et al, 1976;Chang et al, 1977;Monroe et al, 1981).…”