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.

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).