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. CLINICAL TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br, RBR-5h9b3c. "Low-dose combined oral contraceptive use is associated with lower bone mass in adolescents".

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives / Alterações na densidade mineral óssea e nos marcadores de formação óssea em adolescentes usuárias ou não de contraceptivos hormonais orais combinados por período de um ano

Abstract Objective: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. Methods: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. Results: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. Conclusion: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Resumo: Objetivo: O objetivo deste estudo foi avaliar os efeitos de dois contraceptivos orais combinados de baixa dosagem por um ano sobre o metabolismo ósseo em adolescentes. Métodos: Este foi um estudo quase experimental. As adolescentes foram divididas em três grupos: contraceptivos orais 1 (n = 42) (20 µg de EE/150 µg de desogestrel), contraceptivos orais 2 (n = 66) (30 µg EE/3 mg de drospirenona) e grupo controle (n = 70). As adolescentes foram submetidas à avaliação antropométrica e densitometria (raio-X de dupla energia). Foram avaliados a idade óssea e os marcadores de formação óssea (osteocalcina e fosfatase alcalina óssea). As usuárias de contraceptivos orais foram novamente avaliadas após 12 meses. A análise de regressão linear foi utilizada para estudar, indiretamente, o efeito de cada ano adicional da idade cronológica sobre as variáveis antropométricas e densitométricas e sobre os marcadores ósseos no grupo de controle. Resultados: No início do estudo, não foram observadas diferenças significativas nas variáveis analisadas entre as usuárias de contraceptivos orais 1, contraceptivos orais 2 e o grupo controle. A análise de regressão linear mostrou um aumento na densidade mineral óssea e no conteúdo mineral ósseo para cada ano adicional. Houve uma redução significativa nos níveis de fosfatase alcalina óssea e não foi observada diferença significativa para osteocalcina nos indivíduos controles. A comparação das variáveis do raio-X de dupla energia no início e após um ano não mostrou diferença significativa no grupo de contraceptivos orais 1 ou contraceptivos orais 2. Foi observada uma redução significativa nos níveis de fosfatase alcalina óssea e osteocalcina nos dois grupos contraceptivos orais 1 e contraceptivos orais 2. Conclusão: As adolescentes atingiram o pico de massa óssea durante essa fase da vida. Duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de uso, se associaram a menor incremento na densidade mineral óssea e menor concentração de marcadores de formação óssea quando confrontados com resultados de adolescentes não usuárias de contraceptivos.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives.

OBJECTIVE: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. METHODS: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n=42) (20µg EE/150µg desogestrel), oral contraceptives 2 (n=66) (30µg EE/3mg drospirenone), and a control group (n=70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. RESULTS: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. CONCLUSION: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.

BACKGROUND: Low-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 µg/desogestrel 150 µg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs. METHODS: This was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 µg ethinylestradiol/150 µg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann-Whitney test with the significance level fixed at 5% or p < 0.05. Comparisons between the groups at the study onset and after 12 months were based on variations in the median percentages for bone mass variables. RESULTS: The COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p < 0.05) was seen for the BMC percentage variation between COC users and non-users. CONCLUSIONS: Use of a low-dose COC (ethinylestradiol 20 µg/desogestrel 150 µg) was associated with lower bone mass acquisition in adolescents during the study period. TRIAL REGISTRATION: Registry Number, RBR-5h9b3c.

Relationship between chronological and bone ages and pubertal stage of breasts with bone biomarkers and bone mineral density in adolescents / Relação entre as idades cronológica e óssea e o estágio puberal das mamas com os biomarcadores ósseos e a densidade mineral óssea em adolescentes

OBJECTIVE: To study bone mineral density (BMD) in adolescent females according to five groups of chronological age (CA), bone age (BA), and breast development stage (B), and to correlate these parameters with plasma bone biomarkers (BB). METHODS: This was a cross-sectional study performed in 101 healthy adolescent females between 10 and 20 years old. The study variables were: weight, height, body mass index (BMI), CA, B, BA, calcium intake, BMD, and BB. Osteocalcin (OC), bone alkaline phosphatase (BAP), and C-terminal telopeptide (S-CTx) were evaluated for BB. BMD was measured using dual energy X-ray absorptiometry (DXA). RESULTS: BMD in lumbar spine, proximal femur, and total body increased with age, and the respective observed averages were: in CA1 (10 years old), 0.631, 0.692, 0.798 g/cm2; in CA2 (11 to 12 years old), 0.698, 0.763, 0.840 g/cm2; in CA3 (13 to 14 years old), 0.865, 0.889, 0.972 g/cm2; in CA4 (15 to 16 years old), 0.902, 0.922, 1.013 g/cm2; and in CA5 (17 to 19 years old), 0.944, 0.929, 1.35 g/cm2. These results showed significant differences between 13 and 14 years of age (CA3) or when girls reached the B3 stage (0.709, 0.832, 0.867 g/cm2). The highest median concentrations of BB were between 10 and 12 years of age when adolescents were in the B2-B3 (p < 0.001). Median BB concentrations decreased in advanced BA and B. CONCLUSIONS: BB concentrations were positively correlated with the peak height velocity and negatively correlated with BMD in the study sites. Increased BMD and BB concentrations were observed in B3. .

OBJETIVO: Avaliar a densidade mineral óssea (DMO) em adolescentes do sexo feminino de acordo com a idade cronológica (IC), idade óssea (IO) e desenvolvimento das mamas (M) e suas correlações com biomarcadores de remodelação óssea em plasma (BO). MÉTODOS: Este foi um estudo transversal prospectivo feito em 101 adolescentes saudáveis do sexo feminino com idade entre 10 e 20 anos. As variáveis estudadas foram: peso, altura, índice de massa corpórea (IMC), IC, IO, M, ingestão de cálcio, DMO e BO. A osteocalcina (OC), fosfatase alcalina óssea (BAP) e o telopeptídeo C terminal (S-CTx) foram os biomarcadores de remodelação óssea avaliados. A DMO foi obtida por absorciometria de raios-X de dupla energia (DXA). RESULTADOS: A DMO de coluna lombar, fêmur proximal e corpo total aumentou com a idade, e as respectivas médias observadas foram: IC1 = 0,631, 0.692, 0,798 g/cm2; IC2, 0,698, 0,763, 0,840 g/cm2; IC3, 0,865, 0,889, 0,972 g/cm2; IC4, 0,902, 0,922, 1,013 g/cm2; e IC5, 0,944, 0,929, 1,35 g/cm2. Observou-se diferença significativa entre 13 e 14 anos (IC3) ou quando as meninas estavam em M3 (0,709, 0,832, 0,867 g/cm2). Os valores dos BO apresentaram elevação entre 10 e 12 anos e quando as adolescentes estavam em M2-M3 (p < 0,001). Os valores das medianas dos BO diminuíram com o avançar da IO e M. CONCLUSÕES: Os BOs mostraram paralelismo com o pico de velocidade de crescimento e demonstraram correlação negativa com a DMO no sítios avaliados. O aumento da DMO e dos BOs foi observado em M3. .

Relationship between chronological and bone ages and pubertal stage of breasts with bone biomarkers and bone mineral density in adolescents.

OBJECTIVE: To study bone mineral density (BMD) in adolescent females according to five groups of chronological age (CA), bone age (BA), and breast development stage (B), and to correlate these parameters with plasma bone biomarkers (BB). METHODS: This was a cross-sectional study performed in 101 healthy adolescent females between 10 and 20 years old. The study variables were: weight, height, body mass index (BMI), CA, B, BA, calcium intake, BMD, and BB. Osteocalcin (OC), bone alkaline phosphatase (BAP), and C-terminal telopeptide (S-CTx) were evaluated for BB. BMD was measured using dual energy X-ray absorptiometry (DXA). RESULTS: BMD in lumbar spine, proximal femur, and total body increased with age, and the respective observed averages were: in CA1 (10 years old), 0.631, 0.692, 0.798 g/cm(2); in CA2 (11 to 12 years old), 0.698, 0.763, 0.840 g/cm(2); in CA3 (13 to 14 years old), 0.865, 0.889, 0.972 g/cm(2); in CA4 (15 to 16 years old), 0.902, 0.922, 1.013 g/cm(2); and in CA5 (17 to 19 years old), 0.944, 0.929, 1.35 g/cm(2). These results showed significant differences between 13 and 14 years of age (CA3) or when girls reached the B3 stage (0.709, 0.832, 0.867 g/cm(2)). The highest median concentrations of BB were between 10 and 12 years of age when adolescents were in the B2-B3 (p<0.001). Median BB concentrations decreased in advanced BA and B. CONCLUSIONS: BB concentrations were positively correlated with the peak height velocity and negatively correlated with BMD in the study sites. Increased BMD and BB concentrations were observed in B3.

Densidade mineral óssea em adolescentes usuárias de anticoncepcional oral combinado / Bone mineral density in adolescents users of combined oral contraceptive

Avaliar a densidade mineral óssea (DMO) e o conteúdo mineral ósseo (CMO) de adolescentes do sexo feminino, usuárias de anticoncepcional oral combinado (AOC) de baixa dosagem padronizado (EE 20 μg/ Desogestrel 150 μg), por período de um ano de seu uso e comparar os dados obtidos aos de adolescentes saudáveis da mesma faixa etária, não usuárias. Trata-se de um estudo controlado paralelo não randomizado. Sessenta e sete adolescentes, de 12 a 20 anos de idade, foram divididas em grupo de usuárias de AOC (n=41) e grupo controle (n=26). As adolescentes pertencentes aos dois grupos foram submetidas a exame físico geral e especial para obtenção de peso, estatura, índice de massa corpórea (IMC), avaliação dos caracteres sexuais secundários (critérios de Tanner), obtenção de idade óssea (IO) pelo método de Greulich & Pyle, ingestão de cálcio obtida pelo recordatório de 3 dias e obtenção da idade do evento menarca. As usuárias de AOC foram submetidas ao exame de Densitometria Óssea por atenuação de raio x de dupla energia (DXA), no momento de inclusão no trabalho; 6 e 12 meses depois, para obtenção de CMO (g) e DMO (g/cm2) em região lombar (L1-L4), fêmur proximal total, corpo total e corpo subtotal. O grupo controle foi avaliado através da DXA, no momento inicial; 12 meses depois, para obtenção de DMO e CMO, nos mesmos locais. A comparação entre as variáveis dos grupos de não usuárias e usuárias de AOC, no momento zero, foi realizada através do teste de Mann-Whitney, fixado o nível de significância de 5% ou utilizado o p-valor correspondente, enquanto para a comparação evolutiva dos grupos utilizou-se a variação das porcentagens das medianas das variáveis relativas à massa óssea, nos momentos inicial e final...

To evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low dose (EE 20μg/ Desogestrel 150μg) combination oral contraceptive (COC) over a one year period and comparing them to healthy adolescents from the same age group not taking COC’s. A non-randomized parallel control study with 67 adolescents from 12 to 20 years of age divided into user (COC; n=41) and control (n=26) groups. Both groups were submitted to a general physical and specific examination for weight, height, body mass index (BMI), secondary sexual characteristics evaluation (Tanner criteria), bone age (BA) by the Greulich & Pyle method, calcium intake by 3 days diet recording, and obtaining age at menarche. COC users underwent bone density exam by dual-energy X-ray absorptiometry (DXA) at time of inclusion in the study and at 6 and 12 months, to obtain BMC (g) and BMD (g/cm2) in the lumbar (L1-L4) and total proximal femur regions, for whole body and subtotal whole body. The Control group underwent DXA at inclusion and 12 months to obtain BMD and BMC in the same locations. Comparisons between groups at moment zero was through the Mann-Whitney test with significance level fixed at 5% or corresponding p value; evolutive group comparisons used variations in median percentages for bone mass variables at start and final moments. There were no statistical differences in chronological (CA) and BA, anthropometric variables, and bone densitometry results at the initial moment between COC and control groups. However after 12 months follow-up, COC users presented low bone mass acquisition in the lumbar spine BMD and BMC median variation percentages between initial and final moments (+2.07% and +1.57% respectively) while the control group presented expressive variations (+12.16% and +16.84% respectively)...