Effects of Oral vs. Non-oral Contraceptives on the GH/IGF-1 Axis
Condition: Bone; Disorder, Development and Growth
MeSH terms: Bone Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Combined Oral Contraceptive; Transdermal Contraceptive; Contraceptive Vaginal Ring
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism. Using a prospective repeated measures design, we will test the effects of 2 cycles of combined oral contraceptive (Apri or Reclipsen) on the GH/IGF-1 axis.; The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism. Using a prospective repeated measures design, we will test the effects of 2 cycles of a transdermal contraceptive (Xulane) on the GH/IGF-1 axis.; The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism. Using a prospective repeated measures design, we will test the effects of 2 cycles of vaginal ring contraceptive (Nuva Ring) on the GH/IGF-1 axis.
Other intervention name(s): Apri (Reclipsen); Xulane; Nuva Ring
Intervention MeSH terms: Contraceptive Agents; NuvaRing; Contraceptives, Oral; Contraceptives, Oral, Combined
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin-like growth factor-1; Combined oral contraceptive; Contraceptive Vaginal Ring; Transdermal Contraceptive