SUN-535 Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and Mediators of these Effects

Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligo-amenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. Whereas IGF-1 is bone anabolic, sclerostin, preadipocyte factor-1 (Pref-1) and brain derived neurotropic factor (BDNF) inhibit bone formation, and an effect of estrogen on these factors has been demonstrated in other populations. However, few studies have examined the impact of route of estrogen administration on these factors in adolescents and young adults. Further, it is unclear how the route of estrogen administration impacts bioavailable testosterone, which in turn may impact bone outcomes in young oligo-amenorrheic women. 73 OA 14-25 years old received (i) a 17β-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12-months. We evaluated fasting morning levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption [N-telopeptide (NTX)], IGF-1, insulin-like growth factor binding protein 3 (IGFBP3), total testosterone, estradiol, sex hormone-binding globulin (SHBG), sclerostin, Pref-1, BDNF, calcium, 25(OH) vitamin D, and parathyroid hormone (PTH) at baseline and 12-months. Groups did not differ for age, weight, exercise activity or markers of bone formation at baseline. We have previously reported increases in areal BMD Z-scores at the spine and femoral neck in the PATCH compared to PILL and NONE groups (Ackerman et al: BJSM Oct. 2018). Over 12 months, between group analysis showed greatest decreases of P1NP in the PILL group (p=0.03) associated with a decrease in IGF-1 and IGF1/IGFBP-3 ratio (r=0.33, p≤0.05), and an increase in SHBG (r=-0.28;p=0.02). Within group analysis showed that sclerostin, Pref-1 and BDNF decreased in the PATCH group over 12 months (p=0.01, 0.01 and 0.04 respectively). PATCH group had the greatest increases in estradiol (p=0.0009), and estradiol increases were associated with increases in BMD. Groups did not differ for changes in NTX. Transdermal 17β-estradiol does not cause the decrease in IGF-1 and SHBG observed with oral ethinyl estradiol. It leads to decreases in sclerostin, Pref-1 and BDNF. These effects may mediate the beneficial effects of transdermal estrogen on bone in young women.