Mechanisms
Oral estrogen lowers Lp(a) by 23%, linked to a doubling of IGFBP-1, a trial of 73 postmenopausal women (Atherosclerosis 2000)
Original title: Insulin-like growth factor binding protein-1 (IGFBP-1) and IGF-I during oral and transdermal estrogen replacement therapy: relation to lipoprotein(a) levels
This double-blind, placebo-controlled trial randomised 73 hysterectomised postmenopausal women to oral estradiol valerate 2 mg/day (n=35) or transdermal estradiol gel 1 mg/day (n=38) for 6 months, measuring IGFBP-1, IGF-I and Lp(a) at baseline, 3, and 6 months. Oral therapy increased IGFBP-1 by 104% (P<0.001) and decreased IGF-I by 13% (P<0.05), while transdermal therapy left both unchanged. Lp(a) fell by 23% (median, P<0.001) with oral therapy but was unaffected by transdermal therapy, and the change in IGFBP-1 during oral therapy inversely correlated with the change in Lp(a) (r=-0.40, P<0.05). The findings suggest oral estrogen replacement raises IGFBP-1, which may partly explain its Lp(a)-lowering effect, an effect not seen with transdermal estrogen.
Original abstract
Low levels of insulin-like growth factor binding protein-1 (IGFBP-1) have recently been associated with several risk factors for cardiovascular disease. The effects of estrogen replacement therapy (ERT) on plasma IGFBP-1 levels are, however, unclear. A double-blind, placebo-controlled study for 6 months was conducted in 73 hysterectomized postmenopausal women randomized into two groups: oral estradiol (E2) valerate, 2 mg/day (n = 35) and transdermal E2 gel, 1 mg/day (n=38). Plasma IGFBP-1, insulin-like growth factor-I (IGF-I) and lipoprotein(a) (Lp(a)) were determined at baseline, 3 and 6 months. The groups were similar for age and BMI. The baseline levels of estrone (E1), E2, IGFBP-1, IGF-I and Lp(a) did not differ between the groups. During treatment, serum estradiol concentrations increased in both groups. During oral ERT, IGFBP-1 levels increased by 104% (P<0.001), whereas IGF-I levels decreased by 13% (mean, P<0.05). IGF-I and IGFBP-1 levels remained unchanged in the transdermal group. Lp(a) levels decreased by 23% (median, P<0.001) in the oral group, but were unaffected by transdermal therapy. The change in IGFBP-1 concentrations during oral ERT showed an inverse correlation to that in Lp(a) (r = -0.40, P<0.05, Spearman correlation). In conclusion, oral ERT seems to enhance plasma levels of IGFBP-1, which may be one reason for the reduced Lp(a) levels.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.