Differential bone calcium retention with the use of oral versus vaginal hormonal contraception: A randomized trial using calcium-41 radiotracer

Objectives: This study aimed to assess if hormonal contraception administered orally (combined oral contraceptive pill, COC) or vaginally (contraceptive vaginal ring) differentially affected bone calcium retention in young females.

Study design: Reproductive aged females (18-35 years) not using hormonal contraception were dosed with 50 nCi ⁴¹Ca as CaCl₂ in 10 mL of sterile saline (0.9%). Following an equilibration phase of ≥100 days and a baseline of two menstrual cycles, participants used COC and the ring for two cycles (49 days) each, in a randomized order, separated and followed by washouts of two menstrual cycles. Twenty-four-hour urine samples were collected monthly during equilibration and every around 10 days during baseline, interventions, and washouts to assess bone calcium retention through accelerator mass spectrometry analysis of the ⁴¹Ca:Ca ratio in urine. The effect of each contraception was determined by comparing ⁴¹Ca:Ca measured during each contraception intervention to ⁴¹Ca:Ca measured during the "control" (baseline and washout) phases using linear models and generalized linear mixed models.

Results: Eight reproductive aged females were studied. Compared with control phases (baseline and washouts), COC resulted in greater bone calcium retention (11.3%, 95% CI: 6.7%, 15.6%). The ring did not alter bone calcium retention (4.2%, 95% CI: -6.6%, 13.9%). COC produced a greater change in calcium retention than the ring (p = 0.03).

Conclusion: Although many factors contribute to bone health, short-term COC improved bone calcium retention, suggesting a potential benefit of COC to bone in females. Conversely, the ring did not alter calcium retention, and may be neither beneficial nor deleterious for bone.

Implications: In this study, the effects of oral (pill) vs. vaginal (ring) hormonal contraception on bone calcium retention were assessed in young females. The pill improved bone calcium retention, suggesting a potential beneficial effect on bone health; the ring did not change bone calcium retention compared with control (no contraception).