Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

Abstract

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.