Ethinyl oestradiol administration in women suppresses synthesis of collagen in tendon in response to exercise

Abstract

Women are at greater risk than men of sustaining certain kinds of injury and diseases of collagen-rich tissues. To determine whether a high level of oestradiol has an acute influence on collagen synthesis in tendons at rest and in response to exercise, one-legged kicking exercise was performed for 60 min at 67% of maximum power by healthy, young oral contraceptive (OC) users when circulating synthetic (ethinyl) oestradiol was high (n = 11, HE-OC) and compared to similar women who had never used OCs when circulating endogenous oestrogen was low (n = 12, LE-NOC). Interstitial fluid was collected 24 h post-exercise through microdialysis catheters placed anterior to the patellar tendon in both legs and subsequently analysed for the amino-terminal propeptide of type I collagen (PINP), a marker of tendon collagen synthesis. To determine the long-term effect of OC usage, patellar tendon cross-sectional area (CSA) was measured by magnetic resonance imaging (MRI). A lower exercise-induced increase in tendon collagen synthesis was observed in HE-OC than in LE-NOC (DeltaPINP (mean +/- s.e.m.) 1.5 +/- 5.3 versus 24.2 +/- 9.4 ng ml(-1), P < 0.05). Furthermore, serum and the interstitial peritendinous tissue concentrations of insulin-like growth factor I (IGF-I) and IGF-binding proteins showed a reduced bioavailability in HE-OC compared with results in LE-NOC. No difference in patellar tendon CSA was observed between groups. In conclusion, the selective increase in tendon collagen synthesis in LE-NOC but not HE-OC 24 h post-exercise is consistent with the hypothesis that oestradiol inhibits exercise-induced collagen synthesis in human tendon. The mechanism behind this is either a direct effect of oestradiol, or an indirect effect via a reduction in levels of free IGF-I. However, the data did not indicate any long-term effect on tendon size associated with chronic OC use.

Figure 1

N-terminal propeptide of human collagen type I (PINP, μg l⁻¹) measured at rest and after exercise in LE-NOC and HE-OC in the peritendinous tissue in front of the patellar tendon. Values are mean ±s.e.m.#P < 0.05: increase in tendon collagen synthesis (PINP) in response to exercise was significant higher in LE-NOC than HE-OC. *P < 0.05: tendon PINP higher 24 h post-exercise than at rest in LE-NOC.

Figure 2

A, concentration of insulin-like growth factor I (IGF-I) in serum (μg l⁻¹) in LE-NOC (n = 12) and HE-OC (n = 11). B, IGF-I in interstitial tissue fluid surrounding the patellar tendon in LE-NOC (n = 11) and HE-OC (n = 7) collected as paired samples from the resting leg and the contralateral leg which had performed exercise the previous day. *P < 0.05; **P < 0.01: IGF-I higher in LE-NOC than HE-OC.

Figure 3

Insulin-like binding proteins (IGFBPs) 1–4 (pixel intensity) in the interstitial tissue fluid surrounding the patellar tendon in LE-NOC (n = 9) and HE-OC (n = 9) collected as paired samples from the resting leg and the leg which had performed exercise the previous day. *P < 0.05; **P < 0.01; ***P < 0.001: IGFBP higher in LE-NOC than HE-OC at rest and/or post-exercise.