Evidence for attenuation of gonadotropin pulse frequency in hypergonadotropic women with estradiol secretion in the menopausal transition.

To investigate neuroendocrine interventions for climacteric symptoms in peri- and post-menopausal periods, the association between endocrine status and symptoms was examined in 519 peri- and post-menopausal women with climacteric symptoms. Furthermore, we evaluated the nature of putative disturbances in pulsatile gonadotropin (FSH and LH) secretion in 14 hypergonadotropic women with estradiol secretion and 16 hypergonadotropic women with hypoestrinism. We observed that 68.6% (356/519) of women with climacteric symptoms and 49.2% (121/246) of women in good health showed hypergonadotropinemia, and that 39.3% (140/356) of hypergonadotropic women with climacteric symptoms and 23.1% (28/121) of healthy women (controls) showed estradiol secretion (p < .002). In particular, the endocrinological profile of hypergonadotropinemia with estradiol secretion was observed in 67.1% (60/92) of pre-menopausal women with climacteric symptoms, approximately 2 x higher than that in healthy women (p < .005). Mental symptoms were observed at a significantly higher incidence in women with the endocrinological profile of hypergonadotropinemia with estradiol secretion compared with that in women with hypergonadotropic hypoestrinism showing a symptomatic profile, namely 25.0 versus 6.9% for mood lability (p < .001), and 21.4 versus 9.3% for anxiety symptoms (p < .001). Moreover, in vivo FSH and LH pulse frequencies were observed in only 14.3 and 18.6% of women with hypergonadotropinemia with estradiol secretion whereas such pulses were observed in all women with hypergonadotropic hypoestrinism. We also observed FSH and LH pulse frequencies in hypergonadotropinemia with estradiol secretion 0.14 +/- 0.35 and 0.29 +/- 0.45/3 h, respectively compared with those in hypergonadotropinemia without estradiol secretion 2.25 +/- 0.91 and 2.81 +/- 0.73/3 h, respectively (p < .001). Such findings are considered to be consistent with diminished hypothalamic GnRH impulse strength. In summary, we infer that decreased pulse frequencies in FSH and LH secretion are due to decreased hypothalamic GnRH impulse strength in women with the endocrinological profile of hypergonadotropinemia with estradiol secretion. As the potential mechanisms of this finding, it should be considered that specific endocrine environments damage the pulse generator mechanism in the diencephalon, and that changes occur in the pituitary responsiveness to GnRH (changes in receptor function).