Contribution of the rate of change of antimüllerian hormone in estimating time to menopause for late reproductive-age women

Abstract

Objective: To determine the rate of change of antimüllerian hormone (AMH) level in the late reproductive years and its associations with time to menopause (TTM). We hypothesized that the rate of change between two measures of AMH reflects follicular atresia and varies among women independent of age.

Design: A14-year follow-up.

Setting: A randomly identified, population-based cohort (Penn Ovarian Aging Study).

Patient(s): Two measures of AMH were evaluated in survival analysis of 293 women.

Intervention(s): None.

Main outcome measure(s): Time to menopause.

Result(s): The rate of AMH change was a strong independent predictor of TTM in multivariable analysis after adjusting for AMH baseline, age, and smoking (hazard ratio for 1 SD change = 1.82, 95% confidence interval 1.56-2.14). Among women with similar AMH levels, TTM differed by approximately 2 years when compared between a slow and fast rate of AMH change. A significant interaction of AMH rate of change and age indicated that a faster decrease in AMH level was associated with an increased risk of menopause in women aged 35-39 years (hazard ratio 6.97, 95% confidence interval 3.81-12.72), with less dramatic but significant associations in women aged 40-44 and 45-48 years.

Conclusion(s): The AMH rate of change was independently associated with TTM in late reproductive-age women and increased the precision of estimates of TTM when included with an AMH baseline level and age. The rate of AMH change may be a more direct surrogate than age and increases the precision of estimates of TTM during this clinically important time period.

Figure 1

AMH rate of decline over the study interval for women with baseline AMH >=1.0 ng/mL in 5 subgroups. Subgroups are the following (starting at lower left): ages 45–49 years, fast rate of decline; 40–44 years, fast rate of decline; 35–39 years, fast rate of decline; 40–44 years, slow rate of decline; 35–39 years, slow rate of decline. The subgroups with AMH <1.0 ng/mL at baseline had little additional AMH decline and the curves of these subgroups were nearly identical (not shown).