Does the gonadotropin pulsatility of postmenopausal women represent the unrestrained hypothalamic—pituitary activity?

Abstract

Ovarian sex steroids profoundly modulate the gonadotropin pulsatile secretion in women. A gonadotropin pulsatility determined in the absence of any considerable ovarian sex steroid feedback, as in postmenopausal women (PMW), may thus represent the unrestrained activity of the hypothalamic-pituitary axis. We hypothesized that increases in the gonadotropin pulse frequencies and amplitudes during sex steroid replacements may be limited by those determined in the hypogonadal state of PMW. To address this assumption, we investigated the unstimulated the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in PMW before and during sequential ovarian sex steroid treatments. Seven PMW (mean age 59.4 years) were studied initially during unreplaced conditions (control studies), then on the last day of a 21-day course of oral estradiol valeriate (E2) administrations (2 mg daily) and, finally, on the last day of a 21-day course of oral estradiol-progesterone (E2/P4) replacements (2 mg of E2 and 200 mg of micronized P4 daily). On all study occasions, blood was drawn at 10-min intervals for 10 h and GnRH (25 micrograms iv) was administered 8 h after initiation of blood collections. Compared to control conditions, the basal serum estrogen (estrone and E2) and progesterone (P4) concentrations markedly increased (p < 0.001) following oral E2 or E2/P4 treatments. As determined by Cluster pulse algorithm, LH and FSH were found to be released episodically during each study condition. Mean LH and FSH release rates declined (P < 0.05 or less) during E2 and E2/P4 regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence That GnRH Decreases with Gonadal Steroid Feedback but Increases with Age in Postmenopausal Women

“…In steroid-deficient women, E administration was associated with an increase (45), decrease (14), or lack of change (46) in LH pulse frequency and no change in FAS pulse frequency (17). In steroid-deficient women, E administration was associated with an increase (45), decrease (14), or lack of change (46) in LH pulse frequency and no change in FAS pulse frequency (17).…”

Neuroendocrinology of Aging in Humans: Attenuated Sensitivity to Sex Steroid Feedback in Elderly Postmenopausal Women

“…The characteristics of these assays have been described pre viously [9,15]. To establish gonadotropin secretory profiles, luteiniz ing hormone (LH) and follicle-stimulating hormone (FSH) were determined in duplicate in all samples, using sensitive (0.2 and 0.1 U/l for LH and FSH, respectively) immunoradiomctric assays (Bio-Merieux.…”

“…In the early years after the onset of menopause, the negative feedback on the hypothalamic-pituitary axis re mains principally intact, as documented by the profound decline in circulating gonadotropin levels following estro gen supplementation to PMW [13][14][15], However, evi dence from experimental animals suggests that the neu roendocrine regulation on gonadotropin release is mark edly affected at old age [5]. In fact, aging may reduce the responsiveness to the negative feedback actions of estro gens [4,16,17].…”

Endokrinologie des Klimakteriums

“…Die Dynamik der Sekretion von Gonadotropinen ist vor und während des Klimakteriums durch Freisetzungsepisoden (ªPulseª) gekennzeichnet [15,18,25]; LH und FSH werden intermittierend in Spitzen sezerniert. Diese pulsatile Gonadotropinsekretion ist bei postmenopausalen Frauen deutlicher als vor der Menopause zu erkennen (Abb.…”

“…Diese pulsatile Gonadotropinsekretion ist bei postmenopausalen Frauen deutlicher als vor der Menopause zu erkennen (Abb. Da die Gonadotropinsekretion postmenopausaler Frauen von ovariellen Sexualsteroiden praktisch unbeeinfluût verläuft, stellt die Episodik in der Gonadotropinsekretion postmenopausaler Frauen den hypothalamisch-hypophysären Grundrhythmus mit maximaler Aktivität des zentralnervalen Pulsgebers dar [15,18]. Da die Halbwertszeit von LH (20 min) beträchtlich kürzer als von FSH (etwa 4 h) ist [8], sind die LH-Sekretionsepisoden im Serum eindeutiger als die des FSH zu bestimmen; LH-und FSH-Sekretionsepisoden treten etwa alle 90 min auf.…”