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Utilizing inhibin-B levels to diagnose menopause in patients using oral contraceptive pills

2008; Elsevier BV; Volume: 90; Linguagem: Inglês

10.1016/j.fertnstert.2008.07.743

1556-5653

Jason C. Bradford, I Witt, Alicia L. Kuehl, Andrea Coffee, Thomas J. Kuehl, Patricia J. Sulak,

TGF-β signaling in diseases

OBJECTIVE: To characterize reproductive hormone levels in perimenopausal women as they discontinue oral contraceptive (OC) pills, and test the hypothesis that early follicular phase inhibin-B (InhB) levels can predict menopause when discontinuing OCs. DESIGN: A prospective cohort of 50 perimenopausal women discontinuing OCs. MATERIALS AND METHODS: Current OC users age 45 and above who desired discontinuation of pills were recruited. Patient demographics were recorded, and each patient provided a sequence of 7 blood samples measuring FSH, LH, estradiol and inhB at baseline and days 5, 8, 14, 28, 56, and 84 after the last active pill. Patients kept a daily symptom log for 84 days, and a follow up phone survey was completed at one year to assess their menopausal status. Patients with severe vasomotor symptoms were prescribed replacement if desired. Analysis of variance was used to define the points when hormone levels exceed baseline levels. ROC analysis was used to test menopause predictions. We estimated that in this age group 30 to 50% of women would be menopausal. RESULTS: 42 of 50 subjects (ages 45-55 years, average 50.1) provided interpretable data. During the first 84 days, 22 women went without bleeding and 20 experienced bleeding. At one year follow-up, only eight subjects remained without bleeding and were termed menopausal. All four hormone profiles demonstrated significant differences between groups during the first 28 days. Gonadotropin levels were higher (p<0.01) in those who did not resume bleeding, and estradiol levels were greater (p<0.01) in subjects with bleeding; however this was not until 14 days after stopping OCs. The first indicator of early bleeding status was elevated inhB levels, which demonstrated a higher pattern (p<0.01) by day 8. In spite of its usefulness early on, inhB was not a predictor of menopause. An elevated LH level at 28 days was the best predictor of menopause. FSH and estradiol lacked specificity. Only about one third (7 of 18) of subjects age 51 and above were menopausal. CONCLUSIONS: This trial demonstrates a deficiency in inhB response to increasing endogenous FSH levels in subjects who do not initially resume menstrual bleeding after discontinuing OC pills. This difference is not sufficient to serve as a predictive marker of menopause. With the exception of LH levels, other reproductive hormone tests lack specificity. This observation suggests consideration of another strategy for determining the menopausal status of women using OCs.