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Bone impact after two years of low-dose oral contraceptive use during adolescence

Objective: Data regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC).

Methods: A total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 μg Ethinylestradiol (EE)/150 μg Desogestrel and the COC2 group used 30 μg EE/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni's multiple comparison test.

Results: Incorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U/L (± 11.6) for the control group, 34.95 U/L (± 10.8) for COC1, and 30.29 U/L for COC 2 (± 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng/mL (± 7.3), 6.44 ng/mL (± 4.6), and 9.48 ng/mL (± 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up.

Conclusion: Bone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 μg EE.

 

Comments:

The objective of the present study was to evaluate the effect of combined oral contraceptives (COC) on bone metabolism in healthy adolescents. The study was conducted as a non-randomized clinical trial, and a total of 168 adolescents were recruited between 2014 and 2020 and divided into three groups. The COC1 group used a combination of 20 μg Ethinylestradiol (EE) and 150 μg Desogestrel, while the COC2 group used 30 μg EE and 3 mg Drospirenone. These two COC groups were compared to a control group of adolescent non-COC users.

The participants underwent bone densitometry using dual-energy X-ray absorptiometry and measurement of bone biomarkers, specifically bone alkaline phosphatase (BAP) and osteocalcin (OC), at the beginning of the study and 24 months later. The data from the three groups were compared using statistical analysis.

The results of the study showed that the incorporation of bone mass was greater in non-users compared to adolescents in the COC1 and COC2 groups. Specifically, the lumbar bone mineral content (BMC) increased by 4.85 g in non-users, while the increase was 2.15 g in the COC1 group and there was a loss of 0.43 g in the COC2 group. When comparing the subtotal BMC, the control group increased by 100.83 g, the COC1 group increased by 21.46 g, and the COC2 group showed a reduction of 1.47 g.

Regarding the bone biomarkers, the levels of bone alkaline phosphatase (BAP) were similar among the three groups after 24 months. However, the levels of osteocalcin (OC) differed significantly. The control group had a mean OC level of 13.59 ng/mL, while the COC1 and COC2 groups had mean OC levels of 6.44 ng/mL and 9.48 ng/mL, respectively.

It is important to note that there were participants lost to follow-up in all three groups, but there were no significant differences between the variables in the adolescents who remained in the study and those who were excluded or lost to follow-up.

In conclusion, the study found that the acquisition of bone mass was compromised in healthy adolescents using combined hormonal contraceptives compared to the control group. The negative impact on bone mass acquisition appears to be more pronounced in adolescents using contraceptives containing 30 μg of Ethinylestradiol.

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