Skip to main content

Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females

Abstract

Introduction

The purpose of this study was to compare bone mineral density (BMD) and bone turnover markers between combined oral contraceptive (COC) and non-COC users over 12 months.

Materials and methods

COC users (n = 34, age = 19.2 ± 0.5) and non-COC users (n = 28, age = 19.3 ± 0.6) provided serum at baseline, 6 months, and 12 months. C-terminal telopepetides (CTX) and pro-collagen type 1 N-terminal propeptides (P1NP) were determined using ELISA. BMD was measured at the three time points using dual-energy x-ray absorptiometry (DXA).

Results

COC users had greater CTX than non-COC users at baseline (18.6 ± 8.2 vs. 13.8 ± 5.3 ng/mL, P = 0.021) and 6 months (20.4 ± 10.3 vs. 14.2 ± 8.5 ng/mL, P = 0.018). Controlling for lean mass, groups were similar in BMD. Over 12 months, non-COC users maintained BMD at the spine, while the COC users declined 2.2% in lateral spine BMD (0.773 ± 0.014 to 0.756 ± 0.014 g/cm2, P = 0.03) and 0.7% in anterior–posterior spine BMD (1.005 ± 0.015 to 0.998 ± 0.015 g/cm2, P = 0.069). Non-COC users increased in BMD of the whole body over 12 months (P < 0.001) while COC users had no change. Women who began COCs within 4 years after menarche had lower BMD at the hip and whole body. Women taking very low dose COCs (20 mcg ethinyl estradiol, EE) significantly declined in CTX, P1NP, and lateral spine BMD in comparison to participants using low dose COCs (30/35 mcg EE).

Conclusion

College-aged women who did not use COCs increased BMD of the whole body, while COC users had elevated bone turnover, declines in spinal BMD, and lack of bone acquisition of the whole body over 12 months. Young females who initiate COC use early after menarche may experience skeletal detriments.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. United Nations, Department of Economic and Social Affairs, Population Division (2015) Trends in Contraceptive Use Worldwide 2015 (ST/ESA/SER.A/349)

  2. Abma JC, Martinez GM (2017) Sexual activity and contraceptive use among teenagers in the United States, 2011–2015. Natl Health Stat Report, pp 1–23

  3. Manolagas SC (2000) Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137. https://doi.org/10.1210/edrv.21.2.0395

    CAS  Article  PubMed  Google Scholar 

  4. Herrmann M, Seibel MJ (2010) The effects of hormonal contraceptives on bone turnover markers and bone health. Clin Endocrinol (Oxf) 72:571–583. https://doi.org/10.1111/j.1365-2265.2009.03688.x

    CAS  Article  Google Scholar 

  5. Cibula D, Skrenkova J, Hill M, Stepan JJ (2012) Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence. Eur J Endocrinol 166:1003–1011. https://doi.org/10.1530/EJE-11-1047

    CAS  Article  PubMed  Google Scholar 

  6. Ackerman KE, Singhal V, Baskaran C, Slattery M, Campoverde Reyes KJ, Toth A, Eddy KT, Bouxsein ML, Lee H, Klibanski A, Misra M (2019) Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial. Br J Sports Med 53:229–236. https://doi.org/10.1136/bjsports-2018-099723

    Article  PubMed  Google Scholar 

  7. Ludicke F, Sullivan H, Spona J, Elstein M (2001) Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene. Contraception 64:243–248

    CAS  Article  Google Scholar 

  8. Southmayd EA, De Souza MJ (2017) A summary of the influence of exogenous estrogen administration across the lifespan on the GH/IGF-1 axis and implications for bone health. Growth Horm IGF Res 32:2–13. https://doi.org/10.1016/j.ghir.2016.09.001

    CAS  Article  PubMed  Google Scholar 

  9. Elkazaz AY, Salama K (2015) The effect of oral contraceptive different patterns of use on circulating IGF-1 and bone mineral density in healthy premenopausal women. Endocrine 48:272–278. https://doi.org/10.1007/s12020-014-0290-2

    CAS  Article  PubMed  Google Scholar 

  10. Hartard M, Kleinmond C, Luppa P, Zelger O, Egger K, Wiseman M, Weissenbacher ER, Felsenberg D, Erben RG (2006) Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles. Contraception 74:367–375. https://doi.org/10.1016/j.contraception.2006.06.005

    CAS  Article  PubMed  Google Scholar 

  11. Taraborrelli S (2015) Physiology, production and action of progesterone. Acta Obstet Gynecol Scand 94:8–16. https://doi.org/10.1111/aogs.12771

    CAS  Article  PubMed  Google Scholar 

  12. NIH Consensus Panel (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  13. Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS (2016) The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int 27:1281–1386. https://doi.org/10.1007/s00198-015-3440-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Berger C, Goltzman D, Langsetmo L, Joseph L, Jackson S, Kreiger N, Tenenhouse A, Davison KS, Josse RG, Prior JC, Hanley DA, CaMos Research G (2010) Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis. J Bone Miner Res 25:1948–1957. https://doi.org/10.1002/jbmr.95

    Article  Google Scholar 

  15. Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK (2017) The determinants of peak bone mass. J Pediatr 180:261–269. https://doi.org/10.1016/j.jpeds.2016.09.056

    Article  PubMed  Google Scholar 

  16. Sabatier JP, Guaydier-Souquieres G, Laroche D, Benmalek A, Fournier L, Guillon-Metz F, Delavenne J, Denis AY (1996) Bone mineral acquisition during adolescence and early adulthood: a study in 574 healthy females 10–24 years of age. Osteoporos Int 6:141–148

    CAS  Article  Google Scholar 

  17. Henry YM, Fatayerji D, Eastell R (2004) Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: Relative contributions of bone size and volumetric bone mineral density. Osteoporos Int 15:263–273

    Article  Google Scholar 

  18. Walsh JS, Henry YM, Fatayerji D, Eastell R (2009) Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study. Osteoporos Int 20:355–362. https://doi.org/10.1007/s00198-008-0672-5

    CAS  Article  PubMed  Google Scholar 

  19. Gambacciani M, Levancini M (2014) Hormone replacement therapy and the prevention of postmenopausal osteoporosis. Prz Menopauzalny 13:213–220. https://doi.org/10.5114/pm.2014.44996

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR (2006) Longitudinal evaluation of perimenopausal bone loss: Effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas 54:176–180. https://doi.org/10.1016/j.maturitas.2005.10.007

    CAS  Article  PubMed  Google Scholar 

  21. Nappi C, Di Spiezio SA, Greco E, Tommaselli GA, Giordano E, Guida M (2005) Effects of an oral contraceptive containing drospirenone on bone turnover and bone mineral density. Obstet Gynecol 105:53–60. https://doi.org/10.1097/01.AOG.0000148344.26475.fc

    CAS  Article  PubMed  Google Scholar 

  22. Kuohung W, Borgatta L, Stubblefield P (2000) Low-dose oral contraceptives and bone mineral density: an evidence-based analysis. Contraception 61:77–82

    CAS  Article  Google Scholar 

  23. Nappi C, Di Spiezio SA, Acunzo G, Bifulco G, Tommaselli GA, Guida M, Di Carlo C (2003) Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: A prospective controlled randomized study. Contraception 67:355–359

    CAS  Article  Google Scholar 

  24. Tremollieres F (2013) Impact of oral contraceptive on bone metabolism. Best Pract Res Clin Endocrinol Metab 27:47–53. https://doi.org/10.1016/j.beem.2012.09.002

    CAS  Article  PubMed  Google Scholar 

  25. Almstedt Shoepe H, Snow CM (2005) Oral contraceptive use in young women is associated with lower bone mineral density than that of controls. Osteoporos Int 16:1538–1544

    CAS  Article  Google Scholar 

  26. Biason TP, Goldberg TB, Kurokawa CS, Moretto MR, Teixeira AS, Nunes HR (2015) Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period. BMC Endocr Disord 15:15. https://doi.org/10.1186/s12902-015-0012-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Gai L, Jia Y, Zhang M, Gai P, Wang S, Shi H, Yu X, Liu Y (2012) Effect of two kinds of different combined oral contraceptives use on bone mineral density in adolescent women. Contraception 86:332–336. https://doi.org/10.1016/j.contraception.2012.01.009

    CAS  Article  PubMed  Google Scholar 

  28. Gersten J, Hsieh J, Weiss H, Ricciotti NA (2016) Effect of extended 30 ug ethinyl estradiol with continuous low-dose ethinyl estradiol and cyclic 20 ug ethinyl estradiol oral contraception on adolescent bone density: a randomized trial. J Pediatr Adolesc Gynecol 29:635–642. https://doi.org/10.1016/j.jpag.2016.05.012

    Article  PubMed  Google Scholar 

  29. Pikkarainen E, Lehtonen-Veromaa M, Mottonen T, Kautiainen H, Viikari J (2008) Estrogen-progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study. Contraception 78:226–231. https://doi.org/10.1016/j.contraception.2008.05.002

    CAS  Article  PubMed  Google Scholar 

  30. Scholes D, Ichikawa L, LaCroix AZ, Spangler L, Beasley JM, Reed S, Ott SM (2010) Oral contraceptive use and bone density in adolescent and young adult women. Contraception 81:35–40. https://doi.org/10.1016/j.contraception.2009.07.001

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. LaBrie JW, Boyle S, Earle A, Almstedt HC (2018) Heavy episodic drinking is associated with poorer bone health in adolescent and young adult women. J Stud Alcohol Drugs 79:391–398

    Article  Google Scholar 

  32. Block G, Subar AF (1992) Estimates of nutrient intake from a food frequency questionnaire: the 1987 National Health Interview Survey. J Am Diet Assoc 92:969–977

    CAS  PubMed  Google Scholar 

  33. Pereira MA, FitzerGerald SJ, Gregg EW, Joswiak ML, Ryan WJ, Suminski RR, Utter AC, Zmuda JM (1997) A collection of physical activity questionnaires for health-related research. Med Sci Sports Exerc 29:S1–205

    CAS  Article  Google Scholar 

  34. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR Jr, Tudor-Locke C, Greer JL, Vezina J, Whitt-Glover MC, Leon AS (2011) 2011 Compendium of physical cctivities: a second update of codes and MET values. Med Sci Sports Exerc 43:1575–1581. https://doi.org/10.1249/MSS.0b013e31821ece12

    Article  Google Scholar 

  35. Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O, Frediani B, Rossini M (2008) Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 82:341–347. https://doi.org/10.1007/s00223-008-9126-5

    CAS  Article  PubMed  Google Scholar 

  36. Gargano V, Massaro M, Morra I, Formisano C, Di Carlo C, Nappi C (2008) Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception 78:10–15. https://doi.org/10.1016/j.contraception.2008.01.016

    CAS  Article  PubMed  Google Scholar 

  37. Lattakova M, Borovsky M, Payer J, Killinger Z (2009) Oral contraception usage in relation to bone mineral density and bone turnover in adolescent girls. Eur J Contracept Reprod Health Care 14:207–214. https://doi.org/10.1080/13625180902838828

    CAS  Article  PubMed  Google Scholar 

  38. Endrikat J, Mih E, Dusterberg B, Land K, Gerlinger C, Schmidt W, Felsenberg D (2004) A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 microg or 30 microg ethinylestradiol in combination with levonorgestrel on bone mineral density. Contraception 69:179–187. https://doi.org/10.1016/j.contraception.2003.10.002

    CAS  Article  PubMed  Google Scholar 

  39. de Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, Rosenberg E, Reitz RE (2007) A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 40:1222–1230. https://doi.org/10.1016/j.bone.2007.01.008

    Article  PubMed  Google Scholar 

  40. WHO (1994) Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis, vol 843. World Health Organisation Tehnical Report Series, World Health Organisation, Geneva

    Google Scholar 

  41. Hartard M, Kleinmond C, Wiseman M, Weissenbacher ER, Felsenberg D, Erben RG (2007) Detrimental effect of oral contraceptives on parameters of bone mass and geometry in a cohort of 248 young women. Bone 40:444–450. https://doi.org/10.1016/j.bone.2006.08.001

    CAS  Article  PubMed  Google Scholar 

  42. de Melo NR, Aldrighi JM, Faggion D Jr, Reyes VR, Souza JB, Fernandes CE, Larson E (2004) A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet (gestodene75/EE20) on body fat. Contraception 70:65–71. https://doi.org/10.1016/j.contraception.2003.10.016

    CAS  Article  PubMed  Google Scholar 

  43. Rosenberg M (1998) Weight change with oral contraceptive use and during the menstrual cycle. Results of daily measurements. Contraception 58:345–349

    CAS  Article  Google Scholar 

  44. Rosenberg MJ, Waugh MS, Meehan TE (1995) Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation. Contraception 51:283–288

    CAS  Article  Google Scholar 

  45. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine S (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930. https://doi.org/10.1210/jc.2011-0385

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This research was funded by the National Institute of Alcohol Abuse and Alcoholism at the National Institute of Health with Grant number R21AA022942. Support was also provided by the Frank R. Seaver College of Science and Engineering, the Bellarmine College of Liberal Arts, and the Rains Research Assistance program at Loyola Marymount University. We are grateful for all of the participants who volunteered for the investigation. We acknowledge Sarah Boyle, Andrew Earle, Angie Flores, Nicole Froidevaux, Danielle Good, Carolyn Jackson, Caitlin Jennings, Shantay Pierre, Todd Shoepe, and Liam Shorrock for their valuable contributions to this project. We also appreciate the many people who worked as part of the SELFY research team including Olivia Abdoo, Kate Collins, Kelsey Crispeno, Christa Demos, Zoe Daily, Isabella Kuroyama, Stephanie Lee, Haley Loeffler, Allison Leggett, Diana Martinez, Sydnie Maltz, Grant Mello, Savannah Mersola, Nhandi Scott, Fiona Shorrock, Alejandra Silva, Daniel Smith, and Lauren Sutherlin.

Author information

Authors and Affiliations

Authors

Contributions

HCA developed methodology and performed conceptualization, formal analysis, investigation, data curation, writing, project administration, and funding acquisition. MMC and LFB were responsible for data curation, formal analysis, and contributed to writing. DVD contributed to methodology, formal analysis, investigation, and writing. JWL was involved with data curation, methodology, supervision, project administration, and funding acquisition.

Corresponding author

Correspondence to Hawley C. Almstedt.

Ethics declarations

Conflict of interest

All authors have no conflicts of interest.

Ethical approval

All the procedures performed in this study were in accordance with the ethical standards of the Human Subject’s Institutional Review Board at Loyola Marymount University and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

All volunteers provided informed consent for procedures and scientific data use before initiating participation, as is standard at our University.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Almstedt, H.C., Cook, M.M., Bramble, L.F. et al. Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females. J Bone Miner Metab 38, 544–554 (2020). https://doi.org/10.1007/s00774-019-01081-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-019-01081-1

Keywords

  • Peak bone mass
  • Menarche
  • Premenopausal
  • CTX
  • P1NP