Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women

Abstract

Study question: Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women?

Summary answer: Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women.

What is known already: Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation.

Study design, size, duration: We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007.

Participants/materials, setting, methods: Women aged 18-44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle.

Main results and the role of chance: Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03).

Limitations, reasons for caution: Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential.

Wider implications of the findings: This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase.

Study funding/competing interests: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare.

Keywords: anovulation; anti-Müllerian hormone; menstrual cycle.

Figure 1

Geometric mean AMH levels across the menstrual cycle by ovulatory category, adjusted for age. AMH levels from ovulatory cycles of women with only ovulatory cycles were significantly different from both of the other groups with anovulatory cycles (P = 0.02). No significant difference between anovulatory cycles from women with both observed cycles being anovulatory and anovulatory cycles from women with one observed anovulatory cycle and one observed ovulatory cycle were seen. There were 443 ovulatory cycles from 224 women with ovulatory cycles only, 24 ovulatory cycles from 24 women with 1 ovulatory and 1 anovulatory cycle and 42 anovulatory cycles from 35 women with any anovulatory cycle (total of 509 cycles from 259 women).

Figure 2

Geometric mean AMH across the menstrual cycle in eumenorrheic women by age category. P < 0.05 for mid-cycle comparisons (visit 3 versus visit 5) for AMH levels for all age groups (years). Age ≤20 years: n = 73 women, 20–25 years: n = 71 women, 26–30 years: n = 33 women, 31–35 years: n = 20 women, >35 years: n = 62 women. The n values reflect women in each age category; each woman contributes up to 2 cycles at each of the 8-cycle visits for a total of up to 16 possible measurements of serum AMH across the 2 menstrual cycles.

Figure 3

Geometric mean AMH levels across the menstrual cycle by ovulatory category, adjusted for age. AMH: ovulatory cycles of women with only ovulatory cycles were significantly different from both of the other groups (P = 0.02). No significant differences between ovulatory cycles of women with anovulatory cycles and anovulatory cycles. There were 443 ovulatory cycles from 224 women with ovulatory cycles only, 24 ovulatory cycles from 24 women with 1 ovulatory and 1 anovulatory cycle and 42 anovulatory cycles from 35 women with any anovulatory cycle (total of 509 cycles from 259 women).