Takaisin Tulosta

Combined oral contraceptives and bone mineral density

Evidence summaries
Heidi Alenius

Level of evidence: D

Low-dose estrogen (under 30 μg ethinyl estradiol) combined oral contraceptives might possibly decrease physiological bone mineral density acquisition in adolescents compared with nonusers, but the evidence is insufficient.


In a prospective study «Cibula D, Skrenkova J, Hill M et al. Low-dose estr...»1 56 healthy females (15-19.5 years) in Czech Republic were randomized to combined oral contraceptives (COC) with either 30 μg ethinyl estradiol (EE) plus 75 μg gestodene or 15 μg EE plus 60 μg gestodene in crossover design of 9-month intervention. Nonusers of the same age (n=28) served as controls. Bone mineral density (BMD) at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months. In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). A difference between the 30 μg EE and 15 μg EE users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg EE COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months.

In another RCT «Gai L, Jia Y, Zhang M et al. Effect of two kinds o...»2 in China 450 adolescents (16-18 years) were randomized to EE 30 μg plus desogestrel 150 μg or EE 35 μg plus cyproterone acetate 2 mg for 2 years, and 150 women were using nonhormonal contraception as control subjects. Lumbar spine and femoral neck mean BMD values in women who used EE/desogestrel were slightly lower compared with baseline, but these effects did not reach statistical significance. The mean LS and femoral neck BMD values in women who used EE/cyproterone acetate were slightly higher compared with baseline, but there was no statistical significance (p=.789 and p=.756, respectively). The increases in mean percent change in LS and femoral neck BMD in the EE/cyproterone acetate group were less than those in the control group (1.88% vs. 0.30% and 0.98% vs. 0.49%, respectively). There were no significant differences in mean BMD of the LS and femoral neck between the users of EE/desogestrel or EE/cyproterone acetate and nonusers (p>.05).

A prospective study «Polatti F, Perotti F, Filippa N et al. Bone mass a...»3 assessed the bone metabolism in young women taking oral monophasic contraceptives (EE 20 μg + desogestrel 0.150 mg) over 5 years. Healthy women (n = 200, 19 - 22 years) were divided into two groups, one receiving COCs and the other receiving none. All the subjects underwent a BMD evaluation at spinal level L2-L4 with Dexa (Norland XR-26) and a measurement of the serum alkaline phosphatase levels and urinary excretion of OH-proline at baseline and every 12 months over 5 years. The COC group did not show any significant BMD change after 5 years, while controls demonstrated a significant increase (p < 0.01) in the bone mass content at the end of the time of observation (+7.8% after 5 years).

In another study «Pikkarainen E, Lehtonen-Veromaa M, Möttönen T et a...»4 in Finland 122 adolescents (12-19 years) were divided into three groups based on estrogen-progestin contraceptive (COC; EE 35 μg or less) use: nonusers, 1-2 years of use, and use for more than 2 years. Height, weight, and the amount of exercise (ratio of work metabolic rate, h/week) as well as bone mineral content (BMC) of lumbar spine and femoral neck were measured repeatedly. There was a significant trend showing less of an increase in the mean adjusted BMC of LS in the group of adolescent women who had used COC for more than 2 years compared with the two other groups. In the mean adjusted BMC of the femoral neck, there was a significant trend of a smaller increase in COC users for more than 2 years compared with 1-2 years of use.

In an observational, prospective cohort study «Cromer BA, Bonny AE, Stager M et al. Bone mineral ...»5 in USA 433 postmenarcheal girls (12-18 years), who had chosen to use depot medroxyprogesterone acetate (DMPA; n = 58), oral contraceptives (COC, 20 μg EE plus 100 μg levonorgestrel ; n = 187), or were untreated (n = 188) were followed up for 24-months. Measurements of BMD at spine and femoral neck were obtained by using dual x-ray absorptiometry at baseline and 6-month intervals. Over 24 months, mean percentage change in spine BMD was as follows: DMPA, -1.5%; OC, +4.2%; and untreated, +6.3%. Mean percentage change in femoral neck BMD was as follows: DMPA, -5.2%; OC, +3.0%; and untreated, +3.8%. Statistical significance was found between the DMPA group and the other two groups.


  1. Cibula D, Skrenkova J, Hill M et al. Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence. Eur J Endocrinol 2012;166(6):1003-11. «PMID: 22436400»PubMed
  2. Gai L, Jia Y, Zhang M et al. Effect of two kinds of different combined oral contraceptives use on bone mineral density in adolescent women. Contraception 2012;86(4):332-6. «PMID: 22364818»PubMed
  3. Polatti F, Perotti F, Filippa N et al. Bone mass and long-term monophasic oral contraceptive treatment in young women. Contraception 1995;51(4):221-4. «PMID: 7796586»PubMed
  4. Pikkarainen E, Lehtonen-Veromaa M, Möttönen T et al. Estrogen-progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study. Contraception 2008;78(3):226-31. «PMID: 18692613»PubMed
  5. Cromer BA, Bonny AE, Stager M et al. Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertil Steril 2008;90(6):2060-7. «PMID: 18222431»PubMed