Status of bone mineral density after the long-standing application of contraception Depo-Provera

Authors: S. Zeman 1;  P. Havlík 2;  J. Zemanová 1;  D. Němec 3
Authors‘ workplace: Gynekologická ambulance, Velké Meziříčí, MUDr. S. Zeman 1;  Osteocentrum, Brno, MUDr. MVDr. J. Slesinger 2;  Gynekologicko-porodnické oddělení, Nemocnice Nové Město na Moravě, přednosta prim. MUDr. J. Hrdina 3
Published in: Ceska Gynekol 2013; 78(1): 116-124

Dynamika kostních změn před, po nasazení a po vysazení depotníhomedroxyprogesteron acetátu ve všech věkových skupinách. Rebound fenomén.
Recentní pohledy na preskripci tohoto generika.


The objective of this study was to assess bone mineral density (BMD) on a cohort of women who used depot medroxyprogesterone acetate (DMPA) (Depo-Provera) contraception uninterruptedly between 3 and 10 years.

Retrospective study with review of the literature.

Office gynecology Velké Meziříčí; Osteocentrum Brno; Department of Obstetrics and Gynecology, Hospital Nové Město na Moravě.

The study included 21 healthy women aged between 26 and 43 years (the mean age 31 years) who started long-term continual application of depot medroxyprogesterone acetate (DMPA) in contraception (Depo-Provera) (the mean time of using 7 years, range 3–10 years). The women underwent lumbar spine, hip, femoral neck and forearm BMC (g) (bone mass content), BMD (g/cm2)(bone mass density), T-score, PR (%) (peak reference), Z-score, AM (%)(age matched) evaluation using Hologic dual-energy X-ray absorptiometry.

Age of women, time of application of Depo-Provera and body mass index (BMI) were collected.

Randomly from this cohort of users DMPA (n = 11) were determined levels of serum folicle stimulating hormone (FSH) and estradiol (E2), mostly shortly before next application of DMPA.

At average 7 years of treatment, as compared to baseline, the mean BMD of DMPA users was in total lumbar spine AM (age matched) 96.48%, total hip AM 100%, femoral neck AM 97.62%, total forearm (radius+ulna) AM 99.81%.

Concentrations of serum estradiol varied from 94.3–294 pmol/l (25.7–80.1 pg/ml) with average level 190.3 pmol/l(51.9 pg/ml), seen in the early follicular phase.

There are probably several reasons, but not at least, why mean bone loss even after long use of DMPA is low.

The loss of BMD is more pronounced during the first 2 years of use DMPA and its fall subsequently gradually stabilises due to new balance between extrinsic and intrinsic factors that influence bone resorption and formation. After the two years bone loss in DMPA users nears under 1% per year and practically copies level of physiological bone loss.

Another hypothetical compensation mechanisms of bone remodelling in the hypoestrogenic time during DMPA use may be reason of higher levels of BMD 4–5 years after discontinuing the use of contraceptive injections than that of nonusers (rebound phenomenon).

depot medroxyprogesterone acetate (DMPA) – bone mineral density (BMD) – long-term use – Depo-Provera – skeletal health – rebound phenomenon – contraception


1. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 415: depot medroxyprogesterone acetate and bone effects. Obstet Gynecol, 2008, 112, p. 727–730.

2. Bahamondes, L., Trevisan, M., Andrade, L., et al. The effect upon the human vaginal histology of the long-term use of the injectable contraceptive Depo-Provera. Contraception, 2000, 62, p. 23–27.

3. Bailey, DA., McKay, HA., Mirwald, RL., et al. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. J Bone Miner Res, 1999, 14, p. 1672–1679.

4. Baxter-Jones, AD., Faulkner, RA., Mirwald, RL., et al. Bone mineral accrual and age of attainment of adult bone mass: a 15-year longitudinal study from pre-adolescence into adulthood [Abstract, 4th International Conference on Children‘s Bone Health, Montreal, 2007. Bone, 2007, 40, S25.

5. Berenson, AB., Breitkopf, CR., Grady, JJ., et al. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol, 2004, 103, p. 899–906.

6. Berenson, AB., Rahman, M., Breitkopf, CR., Bi, LX. Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives on bone mineral density. Obstet Gynecol, 2008, 112, p.788–799.

7. Black, A. Ad Hoc DMPA Committee of the Society of Obstetricians and Gynaecologists of Canada. Canadian contraception consensus—update on depot medroxyprogesterone acetate (DMPA). J Obstet Gynaecol Can, 2006, 28, p. 305–313.

8. Bonny, AE., Secic, M. Cromer, BA. Relationship between weight and bone mineral density in adolescents on hormonal contraception. J Pediatr Adolesc Gynecol, 24, 2011, 24, p. 35–38.

9. Busen, NH., Britt, RB., Dianin, N. Bone mineral density in a cohort of adolescent women using depot medroxprogesterone acetate for one to two years. J Adolesc Health, 2003, 32, p. 257–259.

10. Clark, MK., Sowers, M., Levy, BT., et al. Magnitude and variability of sequential estradiol and progesteron concentrations in women using depot medroxyprogesterone acetate for contraception. Fertil Steril, 2001, 75, p. 871–877.

11. Clark, MK., Sowers, M., Levy, B., Nichols, S. Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate. Fertil Steril, 2006, 86, p. 1466–1474.

12. Clark, MK., Sowers, MR., Nichols, S., Levy, B. Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate. Fertil Steril, 2004, 82, p. 1580–1586.

13. Clarke, BL, Khola, S. Female reproductive system and bone. Arch Biochem Biophys, 2010, 503, p. 118–128.

14. Cromer, AC., Scholes, D., Berenson, A., et al. Depot medroxyprogesterone acetate and bone mineral density in adolescents – the black box warning: A position paper of the Society for Adolescent Medicine. J Adol Health, 2006, 39, p. 296–301.

15. Cromer, BA., Blair, JM., Mahan, JD., et al. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr, 1996, 129, p. 671–676.

16. 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, p. 2060–2067.

17. Cromer, BA., Stager, M., Bonny, A., et al. Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls. J Adolesc Health, 2004, 35, p. 434–441.

18. Cundy, T., Cornish, J., Roberts, H., et al. Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception. Am J Obstet Gynecol, 2002, 186, p. 978–983.

19. Curtis, KM., Martins, SL. Progestogen-only contraception and bone mineral density: a systematic review. Contraception, 2006, 73, p. 470–487.

20. Glasier, A., Yan, Y., Wellings, K. How do health care professionals respond to advice on adverse side effects of contraceptive methods? The case of Depo Provera. Contraception, 2007, 76, p. 18–22.

21. Gai, L., Zhang, J., Zhang, H., et al. The effect of depot medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) and evaluating changes in BMD after discontinuation of DMPA in Chinese women of reproductive age. Contraception, 2011, 83, p. 218–222.

22. Gomez-Ambrosi, J., Rodriguez, A., Catalan, V., et al. The bone-adipose axis in obesity and weight loss. Obes Surg, 2008, 18, p. 1134.

23. Guilbert, ER., Brown, JP., Kaunitz, AM., et al. The use of depot medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception, 2009, 79, p. 167–177.

24. Harel, Z., Johnson, CC., Gold, MA., et al. Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception, 2010, 81, p. 281–291.

25. Harel, Z., Wolter, K., Gold, AM., et al. Biopsychosocial variables associated with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate in adolescents: adolescents who lost 5% or more from baseline vs. those who lost less than 5%. Contraception, 2010, 82, p. 503–512.

26. Jeppsson, S., Gershagen, S., Johansson, EDB., Rannevik, G. Serum medroxyprogesterone (MPA), sex hormone binding globulin, gonadal steroids, gonadotrophins and prolactin in women during long-term use of depo-MPA as a contraceptive. Acta Endocrinol, 1982, 99, p. 339–343.

27. Kaunitz, AM. Long-acting injectable contraception with depot medroxyprogesterone acetate. Am J Obstet Gynecol, 1994, 170(5Pt2), p. 154–159.

28. Kaunitz, AM., Arias, R., McClung, MR. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception, 2008, 77, p. 67–76.

29. Kaunitz, AM., Darney, PD., Ross, D., et al. Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density. Contraception, 2009, 80, p. 7–17.

30. Kaunitz, AM., Miller, PD., Rice, VM., et al. Bone mineral density in women aged 25-35 years receiving depot medroxyprogesterone acetate recovery following discontinuation. Contraception, 2006, 74, p. 90–99.

31. Klein, KO., Larmore, KA., de Lancey, E., et al. Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children. J Clin Endocrinol Metab, 1998, 83, p.3469–3475.

32. Lara-Torre, E., Edwards, CP., Perlman, S., Hertweck, SP. Bone mineral density in adolescent females using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol, 2004, 17, p. 17–21.

33. Leopard, MB., Shults, J., Wilson, BA., et al. Obesity during child-hood and adolescence augments bone mass and bone dimensions. Am J Clin Nutr, 2004, 80, p. 514–523.

34. Manolagas, SC. Birth and death of bone cells: basic regulatory mechanism and implication for the pathogenesis and treatment of osteoporosis. Endocr Rev, 2000, 21, p. 115–137.

35. Marcus, R. New perspectives on the skeletal role of estrogen.J Clin Endocrinol Metab, 1998, 83, p. 2236–2238.

36. Marshall, D., Johnell, O., Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ, 1996, 312, p. 1254–1259.

37. Ott, SM., Scholes, D., LaCroix, AZ., et al. Effects of contraceptive use on bone biochemical markers in young women. J Clin Endocrinol Metanol, 2001, 86, p. 179.

38. Paschall, S., Kaunitz, AM. Depo-Provera and skeletal health: a survey of Florida obstetrics and gynecologist physicians. Contraception, 2008, 78, p. 370–376.

39. Petitti, DB., Piaggio, G., Mehta, S., et al. Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol, 2000, 95, p. 736–744.

40. Planning, California Department of Health Services. Family PACT Clinical Practice Alert. Resources/Documents/CPA_Depo- provera_and_Bone_Density_ Aug_2005. Accessed June 22, 2011.

41. Rahman, M., Berenson, AB. Predictors of higher bone mineral density loss and use of depot medroxyprogesterone acetate. Obstet Gynecol, 2010, 115, p. 35–40.

42. Reid, IR. Relationships between fat and bone. Osteoporos Int, 2008, 19, p. 595.

43. Rome, E., Ziegler, J., Secic, M., et al. Bone biochemical markers in adolescent girls using either depot medroxyprogesterone acetate or an oral contraceptive. J Pediatr Adolesc Gynecol, 2004, 17, p. 373.

44. Rosenberg, L., Zhang, Y., Konstant, D., et al. Bone status after cessation of use of injectable progestin contraceptives. Contraception, 2007, 76, p. 425–431.

45. Shaarawy, M., El-Mallah, SY., Scoudi, S., et al. Effects of the long-term use of depot medroxyprogesterone acetate as hormonal contraceptive on bone mineral density and biochemical markers of bone remodeling. Contraception, 2006, 74, p. 297–302.

46. Scholes, D., LaCroix, AZ., Ichikawa, LE., et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med, 2005, 159, p. 139–144.

47. Scholes, D., LaCroix, AZ., Ichikawa, LE., et al. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology, 2002, 13, p. 581–587.

48. Sirola, J., Kroger, H., Honkanen, R., et al. Factors affecting bone loss around menopause in women without HRT: a prospective study. Maturitas, 2003, 45, p. 159–167.

49. Tang, OS., Tang, G., Yip, P., et al. Long-term depot medroxyprogesterone acetate and bone mineral density. Contraception, 1999, 59, p. 25–29.

50. Tang, OS., Tang, G., Yip, PS., Li, B. Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study. Contraception, 2000, 62, p. 161–164.

51. The National Collaborating Centre for Women’s and Children’s Health. Long-Acting Reversible Contraception—Clinical Guideline 30. London, United Kingdom: National Institute for Health and Clinical Excellence, 2005, p. 1–176.

52. Theintz, G., Buchs, B., Rizzoli, R., et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab, 1992, 75, p. 1060–1065.

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