Advertisement

Bone density recovery after depot medroxyprogesterone acetate injectable contraception use

      Abstract

      Background

      While depot medroxyprogesterone acetate (DMPA) is a highly effective contraceptive used by millions of women, its use is associated with bone mineral density (BMD) loss, raising concerns about long-term risk of osteoporosis and/or fractures.

      Study Design

      We conducted a systematic review of studies published in PubMed�� from 1996 to 2006, evaluating changes in BMD after discontinuation of DMPA. Ten primary clinical or observational studies were identified addressing this issue.

      Results

      BMD consistently returned toward or to baseline values following DMPA discontinuation in women of all ages. This recovery in BMD was seen as early as 24 weeks after stopping therapy and persisted for as long as women were followed up; BMD in past DMPA users was similar to that in nonusers.

      Conclusions

      Bone loss occurring with DMPA use is reversible and is not likely to be an important risk factor for low bone density and fractures in older women, although data on fracture risk in DMPA users are lacking.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Westhoff C.
        Depot-medroxyprogesterone acetate injection (Depo-Provera��): a highly effective contraceptive option with proven long-term safety.
        Contraception. 2003; 68: 75-87
        • Cromer B.A.
        Bone mineral density in adolescent and young adult women on injectable or oral contraception.
        Curr Opin Obstet Gynecol. 2003; 15: 353-357
        • Chiou C.F.
        • Trussell J.
        • Reyes E.
        • et al.
        Economic analysis of contraceptives for women.
        Contraception. 2003; 68: 3-10
        • Kaunitz A.M.
        Depo-Provera's black box: time to reconsider?.
        Contraception. 2005; 72: 165-167
        • Mosher W.D.
        • Martinez G.M.
        • Chandra A.
        • Abma J.C.
        • Willson S.J.
        Use of contraception and use of family planning services in the United States: 1982-2002. Advance data from vital and health statistics; No. 350.
        National Center for Health Statistics, Hyattsville, MD2004
        • Shelton J.
        FDA Approval of SC Depo-Provera. Center for Communication Programs Pearl of the Week.
        The Johns Hopkins University, Baltimore2006 (www.jhuccp.org/pearls. Accessed August 29)
        • Jain J.
        • Jakimiuk A.J.
        • Bode F.R.
        • Ross D.
        • Kaunitz A.M.
        Contraceptive efficacy and safety of DMPA-SC.
        Contraception. 2004; 70: 269-275
      1. Depo-Provera [physician information].
        Pfizer Inc, New York2004
        • Mishell Jr., D.R.
        Pharmacokinetics of depot medroxyprogesterone acetate contraception.
        J Reprod Med. 1996; 41: 381-390
        • Hergenroeder A.C.
        Bone mineralization, hypothalamic amenorrhea, and sex steroid therapy in female adolescents and young adults.
        J Pediatr. 1995; 126: 683-689
        • Gbolade B.A.
        Depo-Provera and bone density.
        J Fam Plann Reprod Health Care. 2002; 28: 7-11
        • Curtis K.M.
        • Martins S.L.
        Progestogen-only contraception and bone mineral density: a systematic review.
        Contraception. 2006; 73: 470-487
        • Tang O.S.
        • Tang G.
        • Yip P.
        • Li B.
        • Fan S.
        Long-term depot-medroxyprogesterone acetate and bone mineral density.
        Contraception. 1999; 59: 25-29
        • Scholes D.
        • Lacroix A.Z.
        • Ichikawa L.E.
        • Barlow W.E.
        • Ott S.M.
        Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.
        Arch Pediatr Adolesc Med. 2005; 159: 139-144
        • Scholes D.
        • Lacroix A.Z.
        • Ichikawa L.E.
        • Barlow W.E.
        • Ott S.M.
        Injectable hormone contraception and bone density: results from a prospective study.
        Epidemiology. 2002; 13: 581-587
        • Scholes D.
        • Lacroix A.Z.
        • Ott S.M.
        • Ichikawa L.E.
        • Barlow W.E.
        Bone mineral density in women using depot medroxyprogesterone acetate for contraception.
        Obstet Gynecol. 1999; 93: 233-238
        • Paiva L.C.
        • Pinto-Neto A.M.
        • Faundes A.
        Bone density among long-term users of medroxyprogesterone acetate as a contraceptive.
        Contraception. 1998; 58: 351-355
        • Lara-Torre E.
        • Edwards C.P.
        • Perlman S.
        • Hertweck S.P.
        Bone mineral density in adolescent females using depot medroxyprogesterone acetate.
        J Pediatr Adolesc Gynecol. 2004; 17: 17-21
        • Gbolade B.
        • Ellis S.
        • Murby B.
        • Randall S.
        • Kirkman R.
        Bone density in long term users of depot medroxyprogesterone acetate.
        Br J Obstet Gynaecol. 1998; 105: 790-794
        • Cromer B.A.
        • Lazebnik R.
        • Rome E.
        • Bonny A.
        • Ziegler J.
        • Debanne S.M.
        Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception.
        Am J Obstet Gynecol. 2005; 192: 42-47
        • Cromer B.A.
        • 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: 434-441
        • Cromer B.A.
        • Blair J.M.
        • Mahan J.D.
        • Zibners L.
        • Naumovski Z.
        A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives.
        J Pediatr. 1996; 129: 671-676
        • Clark M.K.
        • Sowers M.F.R.
        • Nichols S.
        • Levy B.
        Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate.
        Fertil Steril. 2004; 82: 1580-1586
        • Berenson A.B.
        • Radecki C.M.
        • Grady J.J.
        • Rickert V.I.
        • Thomas A.
        A prospective, controlled study of the effects of hormonal contraception on bone mineral density.
        Obstet Gynecol. 2001; 98: 576-582
        • Bahamondes L.
        • Perrotti M.
        • Castro S.
        • Faundes D.
        • Petta C.
        • Bedone A.
        Forearm bone density in users of Depo-Provera as a contraceptive method.
        Fertil Steril. 1999; 71: 849-852
        • Cundy T.
        • Evans M.
        • Roberts H.
        • Wattie D.
        • Ames R.
        • Reid I.R.
        Bone density in women receiving depot medroxyprogesterone acetate for contraception.
        BMJ. 1991; 303: 13-16
        • Cundy T.
        • Cornish J.
        • Roberts H.
        • Elder H.
        • Reid I.R.
        Spinal bone density in women using depot medroxyprogesterone contraception.
        Obstet Gynecol. 1998; 92: 569-573
        • Cundy T.
        • Cornish J.
        • Roberts H.
        • Reid I.R.
        Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception.
        Am J Obstet Gynecol. 2002; 186: 978-983
        • Cundy T.
        • Ames R.
        • Horne A.
        • Roberts H.
        • Gamble G.
        • Reid I.R.
        A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate.
        J Clin Endocrinol Metab. 2003; 88: 78-81
        • Berenson A.B.
        • Breitkopf C.R.
        • Grady J.J.
        • Rickert V.I.
        • Thomas A.
        Effects of hormonal contraception on bone mineral density after 24 months of use.
        Obstet Gynecol. 2004; 103: 899-906
        • Kaunitz A.M.
        • Miller P.D.
        • Rice V.M.
        • Ross D.
        • McClung M.R.
        Bone mineral density in women aged 25���35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation.
        Contraception. 2006; 74: 90-99
        • Naessen T.
        • Olsson S.E.
        • Gudmundson J.
        Differential effects on bone density of progestogen-only methods for contraception in premenopausal women.
        Contraception. 1995; 52: 35-39
        • Tang O.S.
        • Tang G.
        • Yip P.S.
        • Li B.
        Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study.
        Contraception. 2000; 62: 161-164
        • Virutamasen P.
        • Wangsuphachart S.
        • Reinprayoon D.
        • Kriengsinyot R.
        • Leepipatpaiboon S.
        • Gua C.
        Trabecular bone in long-term depot-medroxyprogesterone acetate users.
        Asia Oceania J Obstet Gynaecol. 1994; 20: 269-274
        • Taneepanichskul S.
        • Intaraprasert S.
        • Theppisai U.
        • Chaturachinda K.
        Bone mineral density in long-term depot medroxyprogesterone acetate acceptors.
        Contraception. 1997; 56: 1-3
        • Taneepanichskul S.
        • Intaraprasert S.
        • Theppisai U.
        • Chaturachinda K.
        Bone mineral density during long-term treatment with Norplant implants and depot medroxyprogesterone acetate. A cross-sectional study of Thai women.
        Contraception. 1997; 56: 153-155
        • Orr-Walker B.J.
        • Evans M.C.
        • Ames R.W.
        • Clearwater J.M.
        • Cundy T.
        • Reid I.R.
        The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women.
        Clin Endocrinol (Oxf). 1998; 49: 615-618
        • Merki-Feld G.S.
        • Neff M.
        • Keller P.J.
        A prospective study on the effects of depot medroxyprogesterone acetate on trabecular and cortical bone after attainment of peak bone mass.
        BJOG. 2000; 107: 863-869
        • Merki-Feld G.S.
        • Neff M.
        • Keller P.J.
        A 2-year prospective study on the effects of depot medroxyprogesterone acetate on bone mass-response to estrogen and calcium therapy in individual users.
        Contraception. 2003; 67: 79-86
        • Petitti D.B.
        • Piaggio G.
        • Mehta S.
        • Cravioto M.C.
        • Meirik O.
        Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population.
        Obstet Gynecol. 2000; 95: 736-744
        • Busen N.H.
        • Britt R.B.
        • Rianon N.
        Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years.
        J Adolesc Health. 2003; 32: 257-259
        • Beksinska M.E.
        • Smit J.A.
        • Kleinschmidt I.
        • Farley T.M.
        • Mbatha F.
        Bone mineral density in women aged 40���49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception.
        Contraception. 2005; 71: 170-175
        • Scholes D.
        • Lacroix A.Z.
        • Ichikawa L.E.
        • Barlow W.E.
        • Ott S.M.
        The association between depot medroxyprogesterone acetate contraception and bone mineral density in adolescent women.
        Contraception. 2004; 69: 99-104
        • Tharnprisarn W.
        • Taneepanichskul S.
        Bone mineral density in adolescent and young Thai girls receiving oral contraceptives compared with depot medroxyprogesterone acetate: a cross-sectional study in young Thai women.
        Contraception. 2002; 66: 101-103
        • Wanichsetakul P.
        • Kamudhamas A.
        • Watanaruangkovit P.
        • Siripakarn Y.
        • Visutakul P.
        Bone mineral density at various anatomic bone sites in women receiving combined oral contraceptives and depot-medroxyprogesterone acetate for contraception.
        Contraception. 2002; 65: 407-410
        • Schlaff W.D.
        • Carson S.A.
        • Luciano A.
        • Ross D.
        • Bergqvist A.
        Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain.
        Fertil Steril. 2006; 85: 314-325
        • Ryan P.J.
        • Singh S.P.
        • Guillebaud J.
        Depot medroxyprogesterone and bone mineral density.
        J Fam Plann Reprod Health Care. 2002; 28: 12-15
        • 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: 373-377
        • Perrotti M.
        • Bahamondes L.
        • Petta C.
        • Castro S.
        Forearm bone density in long-term users of oral combined contraceptives and depot medroxyprogesterone acetate.
        Fertil Steril. 2001; 76: 469-473
        • Crosignani P.G.
        • Luciano A.
        • Ray A.
        • Bergqvist A.
        Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain.
        Hum Reprod. 2006; 21: 248-256
        • Shaarawy M.
        • El Mallah S.Y.
        • Seoudi S.
        • Hassan M.
        • Mohsen I.A.
        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: 297-302
        • Clark M.K.
        • 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;
        • Cundy T.
        • Cornish J.
        • Evans M.C.
        • Roberts H.
        • Reid I.R.
        Recovery of bone density in women who stop using medroxyprogesterone acetate.
        BMJ. 1994; 308: 247-248
        • Albertazzi P.
        • Bottazzi M.
        • Steel S.A.
        Bone mineral density and depot medroxyprogesterone acetate.
        Contraception. 2006; 73: 577-583
        • Cundy T.
        • Ames R.
        • Clearwater J.
        • et al.
        Bone density in long-term DMPA users: a double-blind randomised controlled trial of estrogen replacement therapy.
        J Bone Miner Res. 2001; 16 (Abstract F390): S221
        • World Health Organization
        WHO Statement on Hormonal Contraception and Bone Health. WHO Epidemiological Record No. 35.
        World Health Organization, Geneva, Switzerland2005
        • McClung M.R.
        The relationship between bone mineral density and fracture risk.
        Curr Osteoporos Rep. 2005; 3: 57-63
        • Kanis J.A.
        • Borgstrom F.
        • De Laet C.
        • et al.
        Assessment of fracture risk.
        Osteoporos Int. 2005; 16: 581-589
        • Kanis J.A.
        • Johnell O.
        • Oden A.
        • Dawson A.
        • De Laet C.
        • Jonsson B.
        Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds.
        Osteoporos Int. 2001; 12: 989-995
        • Black A.
        Canadian contraception consensus���update on depot medroxyprogesterone acetate (DMPA).
        J Obstet Gynaecol Can. 2006; 28: 305-313
        • Banks E.
        • Berrington A.
        • Casabonne D.
        Overview of the relationship between use of progestogen-only contraceptives and bone mineral density.
        BJOG. 2001; 108: 1214-1221
        • Kalkwarf H.J.
        • Specker B.L.
        Bone mineral loss during lactation and recovery after weaning.
        Obstet Gynecol. 1995; 86: 26-32
        • Polatti F.
        • Capuzzo E.
        • Viazzo F.
        • Colleoni R.
        • Klersy C.
        Bone mineral changes during and after lactation.
        Obstet Gynecol. 1999; 94: 52-56
        • Karlsson C.
        • Obrant K.J.
        • Karlsson M.
        Pregnancy and lactation confer reversible bone loss in humans.
        Osteoporos Int. 2001; 12: 828-834
        • Chantry C.J.
        • Auinger P.
        • Byrd R.S.
        Lactation among adolescent mothers and subsequent bone mineral density.
        Arch Pediatr Adolesc Med. 2004; 158: 650-656
        • Carranza-Lira S.
        • Mera J.P.
        Influence of number of pregnancies and total breast-feeding time on bone mineral density.
        Int J Fertil. 2002; 47: 169-171
        • Prentice A.
        • Jarjou L.M.
        • Cole T.J.
        • Stirling D.M.
        • Dibba B.
        • Fairweather-Tait S.
        Calcium requirements of lactating Gambian mothers: effects of a calcium supplement on breast-milk calcium concentration, maternal bone mineral content, and urinary calcium excretion.
        Am J Clin Nutr. 1995; 62: 58-67
        • Ritchie L.D.
        • Fung E.B.
        • Halloran B.P.
        • et al.
        A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses.
        Am J Clin Nutr. 1998; 67: 693-701
        • Krebs N.F.
        • Reidinger C.J.
        • Robertson A.D.
        • Brenner M.
        Bone mineral density changes during lactation: maternal, dietary, and biochemical correlates.
        Am J Clin Nutr. 1997; 65: 1738-1746
        • Lopez J.M.
        • Gonzalez G.
        • Reyes V.
        • Campino C.
        • Diaz S.
        Bone turnover and density in healthy women during breastfeeding and after weaning.
        Osteoporos Int. 1996; 6: 153-159
        • Sowers M.
        • Corton G.
        • Shapiro B.
        • et al.
        Changes in bone density with lactation.
        JAMA. 1993; 269: 3130-3135
        • Paton L.M.
        • Alexander J.L.
        • Nowson C.A.
        • Frame M.G.
        • Kaymakci B.
        • Wark J.D.
        Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: a twin study.
        Am J Clin Nutr. 2003; 77: 707-714
        • Henderson III, P.H.
        • Sowers M.F.
        • Kutzko K.E.
        • Jannausch M.L.
        Bone mineral density in grand multiparous women with extended lactation.
        Am J Obstet Gynecol. 2000; 182: 1371-1377
        • Kolthoff N.
        • Eiken P.
        • Kristensen B.
        • Nielsen S.P.
        Bone mineral changes during pregnancy and lactation: a longitudinal cohort study.
        Clin Sci (Lond). 1998; 94: 405-412
        • Hayslip C.C.
        • Klein T.A.
        • Wray H.L.
        • Duncan W.E.
        The effects of lactation on bone mineral content in healthy postpartum women.
        Obstet Gynecol. 1989; 73: 588-592
        • More C.
        • Bettembuk P.
        • Bhattoa H.P.
        • Balogh A.
        The effects of pregnancy and lactation on bone mineral density.
        Osteoporos Int. 2001; 12: 732-737
        • Holmberg-Marttila D.
        • Sievanen H.
        Prevalence of bone mineral changes during postpartum amenorrhea and after resumption of menstruation.
        Am J Obstet Gynecol. 1999; 180: 537-538
        • Kalkwarf H.J.
        Lactation and maternal bone health.
        Adv Exp Med Biol. 2004; 554: 101-114
        • Honda A.
        • Kurabayashi T.
        • Yahata T.
        • Tomita M.
        • Takakuwa K.
        • Tanaka K.
        Lumbar bone mineral density changes during pregnancy and lactation.
        Int J Gynecol Obstet. 1998; 63: 253-258
        • Hillier T.A.
        • Rizzo J.H.
        • Pedula K.L.
        • et al.
        Nulliparity and fracture risk in older women: the study of osteoporotic fractures.
        J Bone Miner Res. 2003; 18: 893-899
        • Michaelsson K.
        • Baron J.A.
        • Farahmand B.Y.
        • Ljunghall S.
        Influence of parity and lactation on hip fracture risk.
        Am J Epidemiol. 2001; 153: 1166-1172
        • Cromer B.A.
        • Scholes D.
        • Berenson A.
        • Cundy T.
        • Clark M.K.
        • Kaunitz A.M.
        Depot medroxyprogesterone acetate and bone mineral density in adolescents-the black box warning: a position paper of the Society for Adolescent Medicine.
        J Adolesc Health. 2006; 39: 296-301
        • American College of Obstetricians and Gynecologists
        ACOG Practice Bulletin No. 73: Use of hormonal contraception in women with coexisting medical conditions.
        Obstet Gynecol. 2006; 107: 1453-1472