Changes in serum collagen markers, IGF-I, and knee joint laxity across the menstrual cycle

Abstract

Variations in serum markers of collagen production (CICP) and degradation (ICTP), insulin-like growth factor I (IGF-I) and anterior knee laxity (AKL) were measured in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral contraceptives] over 5 consecutive days at menses (M1-M5, 1st pill week), the initial estrogen rise near ovulation (O1-O5, 2nd pill week), the initial progesterone rise of the early luteal phase (EL1-EL5, 3rd pill week) and post-progesterone peak of the late luteal phase (LL1-LL5, 4th pill week). ICTP was higher in oral contraceptive women (5.3 ± 1.7 vs. 3.7 ± 1.3 µg/L; p = 0.030), primarily during days near ovulation and the early luteal phase when concentrations decreased in eumenorrheic women (p = 0.04). IGF-I concentrations increased during menses then decreased and remained lower during the early and late luteal phase in oral contraceptive women, resulting in lower concentrations compared to eumenorrheic women at EL2 and LL1 (p = 0.03). CICP decreased in early and late luteal days (p <0.01), and there was a trend toward lower concentrations in eumenorrheic versus oral contraceptive women (85.7 ± 35.7 ng/ml vs. 123.2 ± 49.8 ng/ml; p = 0.07). Lower CICP and greater IGF-I concentrations predicted greater AKL across the 20 cycle days in both groups (R(2) = 0.310 and 0.400). Sex hormone concentration changes across the menstrual cycle are of sufficient magnitude to influence collagen metabolism, and may indirectly influence knee structure and function.

Figure 1

Mean endogenous sex hormone concentrations for a) eumenorrheic (NM) and b) oral contraceptive (OC) women and mean collagen markers and mediators and anterior knee laxity for c) eumenorrheic (NM) and d) oral contraceptive (OC) women during the 5 days for each of the 4 Defined Phases (M1 – M5, O1 – O5, EL1 – EL5, LL1 – LL5).

Figure 2

Comparisons of ICTP concentrations by group and day. Symbols indicate *Eumenorrheic (NM) < oral contraceptive (OC) women, †value < 1 or more Days of M, ‡value < EL2 and EL5.

Figure 3

Comparisons of IGF-I concentrations by group and day. Symbols indicate * Eumenorrhei (NM) < oral contraceptive (OC) women, †value < M1 - O5, ‡value < M1-M5, and #value < M4, M5.

Figure 4

CICP concentrations by day (cycle day main effect). Symbols indicate *value < M2, †value < M2 & M3, ‡value < M1, M3, & M5, and #value < M1-M5. Data stratified for oral contraceptive (OC) and Eumenorrheic (NM) women are also provided for descriptive purposes.

Figure 5

Comparisons of AKL by group and day. Symbols indicate * value > M1, M3, O1 and EL5, † value > M1 thru O5, and EL5, and ‡ value > M3 for Eumenorrheic (NM) women.

Figure 6

Patterns of change in CICP, IGF-I and AKL across the Menstrual Cycle in a) eumenorrheic (NM; R² = .309) and b) oral contraceptive women (OC; R² = .395).