SERUM INHIBIN-A AND INHIBIN-B FALL DIFFERENTIALLY AS FSH RISES IN PERIMENOPAUSAL WOMEN

BACKGROUND Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to t he postmenopausal state. The contributions of decreasing levels of inh ibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclea r, as there are no reports of dimeric INH levels in relation to menopa usal status. The present study was undertaken in order to provide prel iminary data on relationships amongst the dimeric inhibins, oestradiol (E-2) and FSH in normal subjects of defined menopausal status. METHODS Single serum samples were obtained between cycle days 3 and 8 in regu larly cycling women, or at random in those with irregular cycles or am enorrhoea, in 110 women, aged 48-59 years, in the third year of a pros pective longitudinal study of the menopausal transition, 'The Melbourn e Women's Mid-Life Health Project'. Samples were assayed for FSH, E-2 INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were anal ysed following logarithmic transformation. Undetectable values were as signed the limit of sensitivity of the respective assays. The relation ships between hormones were evaluated as a function of menopausal stag e. The latter was assigned as Stage 1, premenopausal (no reported chan ge in menstrual cycle pattern), Stage 2, early peri-menopausal (report ed change in menstrual cycle frequency in the preceding year with a bl eed in the preceding 3 months), Stage 3, late peri-menopausal (no mens es in the preceding 3-11 months)and Stage 4, postmenopausal (no menses in the preceding 12 months). RESULTS The hormone concentrations in pr emenopausal subjects (geometric means, FSH 13.5 IU/l, E-2 306 pmol/l, IR-INH 217 Un, INH-A 96 ng/l, and INH-B 48 ng/l) were used as referenc e points for the other stages of menopausal status. Early peri-menopau sal subjects had significantly lower levels of IR-INH (147 U/l) and IN H-B (13.5 ng/l) in the presence of a small, statistically nonsignifica nt rise in FSH (to 21.4 Un) and no significant change in E-2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76 U/l, INH-A fell t o 4 2 ng/l, whilst INH-B was not significantly different at 14 ng/l. F SH had risen significantly to 72.2 IU/l. Oestradiol also fell signific antly to 89 pmol/l. In the postmenopausal subjects there were no furth er significant changes in the peptide hormones or FSH, but Eg fell fur ther to 41 pmol/l. There was a significant (P<0.05) inverse correlatio n between FSH and E-2 (R = -0.78), FSH and IR-INH (R = -0.66), FSH and INH-A (R = -0.53), FSH and INH-B (R = - 0.29) while IR-INH and either INH-A or INH-B were positively correlated (R = + 0.57 and + 0.35, res pectively). The data are consistent with negative feedback roles for b oth dimeric inhibins and E-2 as contributors to the regulation of FSH secretion as menopausal status changes. CONCLUSIONS The major signific ant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-B with no significant change in inhibin-A or oestradiol Pr ogression to late peri-menopausal status is accompanied by a marked fa ll in inhibin-A and oestradiol and a rise in FSH without further chang e in inhibin-B. Inhibin-B, a marker of follicle number, is a significa nt factor in the endocrinology of the menopausal transition.