Assessing the Impact of Contraceptives on Bone Health Using 41Ca

Phase 4Active Not RecruitingNCT02367846

Penn State University6 enrolled

Overview

This preclinical randomized crossover study will examine the effects of oral versus non-oral contraceptive therapy on bone turnover in young exercising women. In an effort to expose the route-dependent effects of oral versus non-oral contraceptive therapy on bone turnover, the investigators will examine 1) the effects of ethinyl estradiol on bone calcium balance using the 41Ca technology and 2) the underlying physiological mechanisms associated with the effects of oral versus non-oral contraceptive therapy on net bone calcium balance.

This study is a preclinical, multi-site study (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 contraceptive therapy, such as vaginal contraceptive (CVR) therapy is also tested. Millions of women use COC therapy for birth control purposes or regulation of menstrual cycles. CVR therapy is a relatively new FDA-approved contraceptive alternative to COC. The purpose of the proposed project is to investigate whether oral ethinyl estradiol (EE) may negatively impair bone turnover when compared to vaginally-administered EE in young physically-active women. A novel calcium tracer technology suitable to rapidly assess changes in net bone calcium balance in a small sample size will be applied to evaluate the effects of COC and CVR therapy on bone turnover. The radioisotope Calcium-41 (41Ca) demonstrates increased sensitivity when compared to dual x-ray absorptiometry (DXA) and increased specificity for bone mineralization and precision when compared to biochemical markers of bone turnover. This study will be the first study to examine how the route of estrogen administration affects bone turnover in young physically active women by assessing changes in net bone calcium balance with different forms of contraceptive therapy. The overall purpose of this study is to explore the effects of oral versus vaginal contraceptive therapy on bone turnover in young exercising women using 41Ca technology. In an effort to expose the route-dependent effects of oral versus non-oral contraceptive therapy on bone turnover, the investigators will examine 1) the effects of ethinyl estradiol on bone calcium balance using the 41Ca technology and 2) the underlying physiological mechanisms associated with the effects of oral versus vaginal contraceptive therapy on net bone calcium balance.

Study Type

INTERVENTIONAL

Allocation

Conditions

Other Disorders of Bone Development and Growth

Interventions

Combined Oral Contraceptive (COC)DRUG

The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral vs. non-oral ethinyl estradiol on net bone calcium balance. A prospective crossover study with repeated measures and a simple random assignment will be used to test the effects of 49 days of COC use on bone metabolism using 41Ca to determine net bone calcium balance. Subjects will be randomized to receive COC during either the first or second intervention period.

Contraceptive Vaginal Ring (CVR)DRUG

The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral vs. non-oral ethinyl estradiol on net bone calcium balance. A prospective crossover study with repeated measures and a simple random assignment will be used to test the effects of 49 days of CVR use on bone metabolism using 41Ca to determine net bone calcium balance. Subjects will be randomized to receive CVR during either the first or second intervention period.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 25 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female 2. Age 18-25 yrs 3. BMI 18-29 kg/m2 4. Non-smoking 5. Willing to refrain from using hormonal contraceptives for the equilibration + baseline period of the study (\~150 days) 6. Availability to frequently visit the laboratory in the next 12 months 7. Not currently pregnant nor intending to become pregnant in the next 12 months 8. Not lactating 9. No apparent metabolic, endocrine, musculoskeletal, or severe psychiatric disease 10. Willing to maintain consistent exercise (aerobic, weight-bearing) and dietary habits during pre-intervention and intervention periods 11. Willing to refrain from supplements other than those provided by study staff in the next 12 months 12. Variable physical activity acceptable, but mode must be primarily weight bearing 13. At least 9 menses in the past 12 months Exclusion Criteria: 1. Non-weight bearing exercise as primary mode of physical activity 2. Resistance exercise training (≥ 2 times 30 minutes per week of resistance exercise) 3. Complete seasonal change of impact mode of physical activity 4. Known or suspected metabolic or endocrine disease 5. Smoking 6. Pregnant 7. Currently consuming large amounts of soy products 8. Current clinical eating disorder or other axis 1 psychiatric disorder or bipolar disorders 9. Oral or hormonal contraceptive use in the last 6 months 10. Hyperparathyroidism 11. Liver or renal disease 12. Evidence of malabsorption or skeletal disorder 13. Thyroid abnormalities (controlled hypothyroidism acceptable) 14. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDS) 15. Taking medications known to have interactions with oral or vaginal contraceptive therapy 16. Other Exclusion Criteria proposed by the World Health Organization COC Contraindications (Grossman et al., 2011).

Locations (1)

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

University Park, Pennsylvania, United States

Outcomes

Primary Outcomes

Changes in 41Ca:Ca ratio

Changes in the 41Ca:Ca ratio in 24-h urine samples measured every 10-14 days during and after oral and non-oral contraceptive therapy as determined by Accelerometer Mass Spectrometry

Time frame: 49 days of contraceptive therapy

Secondary Outcomes

Changes in serum concentrations of insulin-like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP-1, IGFBP-3), and acid labile subunit (ALS)

Changes in fasting serum concentrations of IGF-1, IGFBP-1, IGFBP-3, and ALS after oral and non-oral contraceptive therapy

Time frame: 49 days of contraceptive therapy

Changes in serum concentrations of markers of bone formation and bone resorption

Changes in fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (CTx) after oral and non-oral contraceptive therapy

Time frame: 49 days of contraceptive therapy

Data from ClinicalTrials.gov

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