Bone; Disorder, Development and Growth Clinical Trial
Official title:
Primary Mechanisms Underlying the Effects of Oral vs. Non-oral Contraceptives on the GH/IGF-1 Axis and Bone Metabolism in Young Women
This study will determine whether the negative effects of combined oral contraceptive (COC) therapy on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and bone turnover are dependent on the route of administration such that an attenuation of these effects is observed when a comparable dose of non-oral transdermal contraceptive (TDC) and contraceptive vaginal ring therapy (CVR) are also tested.
This study is a preclinical, multi-site trial (Penn State University and Purdue University)
that will determine whether the negative effects of combined oral contraceptive (COC) therapy
on bone turnover are dependent on the route of administration such that an attenuation of
these effects is observed when a comparable dose of non-oral transdermal contraceptive (TDC)
therapy and contraceptive vaginal ring (CVR) therapy are also tested. Millions of women use
COC therapy for birth control purposes or regulation of menstrual cycles. TDC and CVR
therapies are relatively new FDA-approved contraceptive alternatives to COC. The purpose of
the proposed project is to address the potential mechanism(s) by which oral ethinyl estradiol
(EE) may negatively impair bone via "first pass" effects on the liver and compare these
effects to transdermally-administered and vaginally-administered EE in young women. We will
assess mechanistic effects by way of 2-day serial sampling and by an insulin-like growth
factor (IGF-1) generation test. The IGF-1 generation test was developed over 20 years ago and
is currently used to diagnose growth hormone (GH) insensitivity. IGF-1 generation tests may
also be used to amplify effects not observable by the assessment of fasting or serial
concentrations of systemic IGF-1(secreted by the liver) and its associated binding proteins.
This study will be the first study to examine the physiological mechanisms whereby the route
of estrogen administration affects the GH/IGF-1 axis and bone turnover in young women.
The overall purpose of this study is to explore differences in liver metabolism and bone
turnover of oral versus transdermal and vaginal contraceptive therapy. In an effort to expose
the route-dependent effects of oral versus transdermal and vaginal contraceptive therapy on
liver and bone metabolism, we will examine the effects of ethinyl estradiol on
serially-assessed fasting concentrations of the GH/IGF-1 axis and bone turnover and explore
physiological mechanisms underlying hepatic responsiveness to oral versus transdermal and
vaginal contraceptive therapy using an IGF-1 Generation Test as a probe.
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