Effects of Oral vs. Non-oral Contraceptives on the GH/IGF-1 Axis

NCT02367833 | Completed Phase 4 Results

• 1 other identifier: STUDY00000053
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bone; Disorder, Development and Growth

Keywords

Insulin-like growth factor-1; Combined oral contraceptive; Contraceptive Vaginal Ring; Transdermal Contraceptive

Outcome Measures

Primary Outcomes (1)

• Changes in Insulin-like Growth Factor-1 (IGF-1), IGF Binding Proteins (IGFBP-1, IGFBP-3), and Acid Labile Subunit (ALS)

  Changes in serially-sampled fasting serum concentrations of insulin-like growth factor-1 (IGF-1) before and after 49 days of contraceptive therapy. Data were only collected for IGF-1 levels, no assays were performed for IGFBP-1, IGFBP-3, and acid labile subunit (ALS) and no raw data were collected due to insufficient funds.

  Baseline and post-49 days of contraceptive therapy

Secondary Outcomes (2)

• Changes in Bone Turnover Markers

  Baseline and post-49 days of contraceptive therapy

• Changes in GH-stimulated IGF-1 Secretion

  49 days of contraceptive therapy

Study Arms (4)

Combined Oral Contraceptives (COC)

EXPERIMENTAL

Apri (or generic equivalent - Reclipsen) (30µg/d EE, 150 µg/d desogestrel) is a monophasic dosing regimen of 21 active and 7 placebo pills. On Day 1 of the Intervention, participants in the COC group will begin taking the COC pill. Each participant in this group will ingest active pills from the first pack each day for the first 21 days. Pills ingested on days 22 through 28 are placebo pills. A second pill pack will begin on day 29 and pills with active ingredients will be ingested from the second pack each day for days 29-49. On day 50, the participants will immediately begin a 3rd pill pack, if the post-study testing is still occurring, and will ingest a pill with active ingredients from the third pack for days 50-56 (or for as long as the post-study testing is occurring).

Drug: Combined Oral Contraceptive

Transdermal Contraceptive (TDC)

EXPERIMENTAL

Participants in the TDC group will apply a 20 cm2 patch (Xulane: 20µg/d EE,150µg/d norelgestromin) to the abdomen, upper arm or buttock. The patch will be changed once weekly on the same day each week for weeks 1-3 (days 1-21, removed on day 22) and weeks 5-8 (days 29-56). Week 4 (days 22-28) will be a patch-free week. As soon as the post-study testing is complete, subjects will remove the patch.

Drug: Transdermal Contraceptive

Contraceptive Vaginal Ring (CVR)

EXPERIMENTAL

Participants in the CVR group (NuvaRing - 15µg/d EE/120µg/d etonogestrel) will insert a vaginal ring into the vagina on Day 1 of the intervention. The vaginal ring will be removed and discarded after 3 weeks of continuous use (days 1-21 of continuous use and removed on day 22). There will be one week (days 22-28) that will be ring-free. A new ring will be inserted for days 29-49. On day 50, the second ring will be removed, and a third ring will be immediately inserted into the vagina (if the post-study testing is still occurring). The third ring will remain in the vagina for the last week of the post-study period (days 50-56). As soon as the post-study testing is complete, subjects will remove the ring.

Drug: Contraceptive Vaginal Ring

Control Group

NO INTERVENTION

The Control group will complete all procedures with the exception of contraceptive therapy.

Interventions

Combined Oral Contraceptive DRUG

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.

Also known as: Apri (Reclipsen)

Combined Oral Contraceptives (COC)

Transdermal Contraceptive DRUG

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.

Also known as: Xulane

Transdermal Contraceptive (TDC)

Contraceptive Vaginal Ring DRUG

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.

Also known as: Nuva Ring

Contraceptive Vaginal Ring (CVR)

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female
• Age 18-30 yrs
• BMI 18-29 kg/m2
• Non-smoking
• Not using hormonal contraceptives for at least 6 months prior
• Not currently pregnant nor intending to become pregnant in the next 6 months
• Not lactating
• No apparent metabolic, endocrine, musculoskeletal, or severe psychiatric disease
• Willing to adhere to maintenance of current exercise training and diet and remain weight stable (±2 kg) during study
• Variable physical activity acceptable, but mode must be primarily weight bearing
• At least 9 menses in past 12 months
• Willing to quit taking any current nutritional supplements and take Calcium and Vitamin D supplements for the duration of the study.
• If 21 or older, a normal Pap smear must be confirmed.

You may not qualify if:

• Non-weight bearing exercise as primary mode of physical activity
• Known or suspected metabolic or endocrine disease
• Pregnant
• Currently consuming large amounts of soy products
• Regular consumption of grapefruit juice
• Current clinical eating disorder or other axis 1 psychiatric or bipolar disorders
• Oral or hormonal contraceptive use in the last 6 months
• Currently amenorrheic
• Hyperparathyroidism
• Liver or renal disease
• Evidence of malabsorption or skeletal disorder
• Thyroid abnormalities (controlled hypothyroidism acceptable)
• Chronic use of non-steroidal anti-inflammatory drugs (NSAIDS)
• Taking medications known to have interactions with contraceptive therapy
• Division I Athlete, on or off season

Sponsors & Collaborators

• Penn State University: lead
• Massachusetts General Hospital: collaborator
• Purdue University: collaborator

Study Sites (1)

Women's Health and Exercise Laboratories, The Pennsylvania State University

University Park, Pennsylvania, 16802, United States

Location

Related Publications (2)

• Grossman D, White K, Hopkins K, Amastae J, Shedlin M, Potter JE. Contraindications to combined oral contraceptives among over-the-counter compared with prescription users. Obstet Gynecol. 2011 Mar;117(3):558-565. doi: 10.1097/AOG.0b013e31820b0244.

  PMID: 21343758 BACKGROUND

• Allaway HCM, Misra M, Southmayd EA, Stone MS, Weaver CM, Petkus DL, De Souza MJ. Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis? Front Endocrinol (Lausanne). 2020 Jun 16;11:334. doi: 10.3389/fendo.2020.00334. eCollection 2020.

  PMID: 32612574 DERIVED

MeSH Terms

Interventions

Contraceptives, Oral, Combined; Desogestrel; Ortho Evra

Intervention Hierarchy (Ancestors)

Drug Combinations; Pharmaceutical Preparations; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Mary Jane De Souza
• Organization: Penn State University

mjd34@psu.edu

8148630045

Study Officials

• Mary Jane De Souza, PhD

  The Pennsylvania State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Kinesiology and Physiology

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: February 20, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: March 9, 2020
• Results First Posted: February 6, 2019

Record last verified: 2020-02

Locations

US (1)