Use of Depot Medroxyprogesterone Acetate and Fracture Risk
Open accessAbstract
CONTEXT: Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited. OBJECTIVE: We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk. DESIGN: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. SETTING AND PARTICIPANTS: Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008. MAIN OUTCOME MEASURES: Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders. RESULTS: We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1. CONCLUSIONS: This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures.
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DMPA use is associated with a modest increase in fracture risk, particularly in long-term users, with odds ratios no greater than 1.5.
“two large-scale, population-based, case-control studies [69,70] showed a modest increase in the risk in DMPA users, particularly in long term users (ORs ≤ 1.5).”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [70]
Cites
Body mass index as a predictor of fracture risk: A meta-analysis
De Laet, C., Kanis, J. A., Odén, A., Johanson, H., Johnell, O., Delmas, P., Eisman, J. A., Kroger, H., Fujiwara, S., Garnero, P., et al. (2005) · Osteoporosis International · doi:10.1007/s00198-005-1863-y · Cited by 1,622 · see citing works
Jick, H., Jick, S. S., & Derby, L. E. (1991) · BMJ · doi:10.1136/bmj.302.6779.766 · Cited by 839 · cited 1× · see citing works
“The recorded information on drug exposure and diagnoses has been validated and proven to be of high quality (30, 31).”
BackgroundSelf-citationOral corticosteroids and fracture risk: relationship to daily and cumulative doses
van Staa, T. P., Leufkens, H. G. M., Abenhaim, L., Zhang, B., & Cooper, C. C. (2000) · Lara D. Veeken · doi:10.1093/rheumatology/39.12.1383 · Cited by 699 · cited 1× · see citing works
“Based on previous record reviews by ourselves (32) and others (35), we have determined that the diagnosis of fracture in the GPRD is very accurate, with a confirmed proportion of at least 90% after comparing computer-recorded diagnoses with hospital discharge letters and/or questionnaire information provided by GP.”
MethodValidity of the General Practice Research Database
Jick, S. S., Kaye, J. A., Vasilakis‐Scaramozza, C., Rodríguez, L. A. G., Ruigómez, A., Meier, C. R., Schlienger, R. G., Black, C., & Jick, H. (2003) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.23.5.686.32205 · Cited by 584 · cited 1× · see citing works
“The recorded information on drug exposure and diagnoses has been validated and proven to be of high quality (30, 31).”
BackgroundSelf-citationUse of the UK General Practice Research Database for pharmacoepidemiology
Rodríguez, L. A. G., & Perez‐Gutthann, S. (1998) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1998.00701.x · Cited by 559 · cited 1× · see citing works
“Data were derived from the United Kingdom-based GPRD, which has been described previously (28, 29).”
MethodHMG-CoA Reductase Inhibitors and the Risk of Fractures
Meier, C. R. (2000) · JAMA · doi:10.1001/jama.283.24.3205 · Cited by 447 · see citing works
Self-citationUse of Thiazolidinediones and Fracture Risk
Meier, C., KRAENZLIN, M. E., Bodmer, M., Jick, S. S., Jick, H., & Meier, C. R. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.8.820 · Cited by 353 · see citing works
Self-citationUse of β-Blockers and Risk of Fractures
Schlienger, R. G. (2004) · JAMA · doi:10.1001/jama.292.11.1326 · Cited by 342 · see citing works
The General Practice Research Database
Wood, L., & Martínez, C. (2004) · Drug Safety · doi:10.2165/00002018-200427120-00004 · Cited by 330 · see citing works
Bone density in women receiving depot medroxyprogesterone acetate for contraception.
Cundy, T., Evans, M. C., Roberts, H., Wattie, D. J., Ames, R. W., & Reid, I. R. (1991) · BMJ · doi:10.1136/bmj.303.6793.13 · Cited by 249 · cited 1× · see citing works
“…is of special interest because it has been reported that DMPA users are less likely to be educated beyond 16 yr and more likely to have a low calcium intake and to become pregnant at a younger age and more frequently than their peers, all of which may have an effect on bone health (15, 20–21, 41).”
BackgroundFracture Risk Associated with Use of Antiepileptic Drugs
Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.18804.x · Cited by 241 · cited 1× · see citing works
“Of note, these reports are not necessarily representative of the entire female population, because women with developmental disorders may be more likely to have epilepsy-related fractures (36), and stress fractures are a greater hazard for army recruits than for the general population.”
BackgroundCromer, B. A., Blair, J. M., Mahan, J. D., Zibners, L., & Naumovski, Z. (1996) · The Journal of Pediatrics · doi:10.1016/s0022-3476(96)70148-8 · Cited by 241 · see citing works
The Impact of Lifestyle Factors on Stress Fractures in Female Army Recruits
Lappe, J. M., Stegman, M. R., & Recker, R. R. (2001) · Osteoporosis International · doi:10.1007/s001980170155 · Cited by 212 · cited 1× · see citing works
“(25) found an increased risk of stress fractures among nonHispanic White female army recruits with a history of DMPA use who were completing basic training (relative risk 1.”
BackgroundInjectable Hormone Contraception and Bone Density: Results from a Prospective Study
Scholes, D., LaCroix, A. Z., Ichikawa, L. E., Barlow, W. E., & Ott, S. M. (2002) · Epidemiology · doi:10.1097/00001648-200209000-00015 · Cited by 187 · see citing works
Progestogen-only contraception and bone mineral density: a systematic review
Curtis, K. M., & Martins, S. L. (2006) · Contraception · doi:10.1016/j.contraception.2005.12.010 · Cited by 170 · cited 2× · see citing works
“In contrast to estrogen-containing oral contraceptives, which do not appear to have negative effects on biochemical markers of bone turnover or bone mineral density (BMD) (6), use of DMPA has been associated with accelerated bone turnover (7–10) and with a decline in BMD (3, 7, 11–18).”
BackgroundInfluentialSteroidal contraceptives: effect on bone fractures in women
Lopez, L. M., Grimes, D. A., Schulz, K. F., Curtis, K. M., & Chen, M. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006033.pub5 · Cited by 168 · see citing works
A Prospective, Controlled Study of the Effects of Hormonal Contraception on Bone Mineral Density
Berenson, A. B., Radecki, C. M., Grady, J. J., Rickert, V. I., & Thomas, A. R. (2001) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(01)01495-8 · Cited by 149 · see citing works
Bone density recovery after depot medroxyprogesterone acetate injectable contraception use
Kaunitz, A. M., Arias, R., & McClung, M. R. (2008) · Contraception · doi:10.1016/j.contraception.2007.10.005 · Cited by 148 · see citing works
Cromer, B. A., Scholes, D., Berenson, A. B., Cundy, T., Clark, M. K., & Kaunitz, A. M. (2006) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2006.03.011 · Cited by 143 · cited 1× · see citing works
“By one year of use, most women become amenorrheic (4), and there has been concern over potential negative effects on bone (5).”
BackgroundBone mineral density in women using depot medroxyprogesterone acetate for contraception
Scholes, D. (1999) · Obstetrics & Gynecology · doi:10.1016/s0029-7844(98)00447-5 · Cited by 141 · cited 1× · see citing works
“…is of special interest because it has been reported that DMPA users are less likely to be educated beyond 16 yr and more likely to have a low calcium intake and to become pregnant at a younger age and more frequently than their peers, all of which may have an effect on bone health (15, 20–21, 41).”
BackgroundBone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate
Clark, M. K., Sowers, M. R., Nichols, S., & Levy, B. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.04.064 · Cited by 126 · see citing works
Effects of Hormonal Contraception on Bone Mineral Density After 24 Months of Use
Berenson, A. B., Breitkopf, C. R., Grady, J. J., Rickert, V. I., & Thomas, A. R. (2004) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000117082.49490.d5 · Cited by 118 · see citing works
Kaunitz, A. M., Miller, P. D., Rice, V. M., Ross, D., & McClung, M. R. (2006) · Contraception · doi:10.1016/j.contraception.2006.03.010 · Cited by 118 · see citing works
Bone mineral density in adolescent females using depot medroxyprogesterone acetate
Lara-Torre, E., Edwards, C. P., Perlman, S., & Hertweck, S. P. (2004) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2003.11.017 · Cited by 117 · see citing works
Cromer, B. A., Bonny, A. E., Stager, M., Lazebnik, R., Rome, E. S., Ziegler, J., Camlin-Shingler, K., & Secic, M. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.10.070 · Cited by 116 · cited 3× · see citing works
“0 J Clin Endocrinol Metab, November 2010, 95(11):4909–4916 jcem.”
BackgroundInfluentialDepot medroxyprogesterone acetate
Paul, C., Skegg, D. C. G., & Williams, S. (1997) · Contraception · doi:10.1016/s0010-7824(97)00140-6 · Cited by 103 · see citing works
Combined hormonal contraception and bone health: a systematic review
Martins, S. L., Curtis, K. M., & Glasier, A. F. (2006) · Contraception · doi:10.1016/j.contraception.2006.01.003 · Cited by 80 · cited 1× · see citing works
“Combined oral contraceptives do not appear to affectbonemassorboneturnoverasaresultofmaintained estrogen exposure (6, 38).”
BackgroundMetabolic parameter, bleeding, and weight changes in U.S. women using progestin only contraceptives
Mainwaring, R., Hales, H. A., Stevenson, K., Hatasaka, H. H., Poulson, A. M., Jones, K. P., & Peterson, C. M. (1995) · Contraception · doi:10.1016/0010-7824(95)00011-x · Cited by 79 · cited 1× · see citing works
“By one year of use, most women become amenorrheic (4), and there has been concern over potential negative effects on bone (5).”
BackgroundEffects of Contraceptive Use on Bone Biochemical Markers in Young Women1
Ott, S. M., Scholes, D., LaCroix, A. Z., Ichikawa, L., Yoshida, C. K., & Barlow, W. E. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.1.7118 · Cited by 78 · see citing works
Contraception and sexual health
SHULMAN, L. P. (2008) · Current Sexual Health Reports · doi:10.1007/s11930-008-0026-5 · Cited by 65 · see citing works
The effects of hormonal contraceptives on bone turnover markers and bone health
Herrmann, M., & Seibel, M. J. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03688.x · Cited by 58 · cited 1× · see citing works
“In contrast to estrogen-containing oral contraceptives, which do not appear to have negative effects on biochemical markers of bone turnover or bone mineral density (BMD) (6), use of DMPA has been associated with accelerated bone turnover (7–10) and with a decline in BMD (3, 7, 11–18).”
BackgroundWalsh, J., Eastell, R., & Peel, N. F. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2201 · Cited by 58 · see citing works
Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2008) · Contraception · doi:10.1016/j.contraception.2008.07.014 · Cited by 51 · see citing works
Shaarawy, M., El-Mallah, S. Y., Seoudi, S., Hassan, M. S., & Mohsen, I. A. (2006) · Contraception · doi:10.1016/j.contraception.2006.04.003 · Cited by 49 · see citing works
Contraception and sexual health, 2003.
Dawe, F., & Rainford, L. (2004) · Cited by 36 · see citing works
Watson, K. C., Lentz, M. J., & Cain, K. C. (2006) · Women s Health Issues · doi:10.1016/j.whi.2006.09.003 · Cited by 34 · see citing works
Use of hormonal contraceptive methods by women with diabetes
Shawe, J., Mulnier, H. E., NICHOLLS, P. G., & Lawrenson, R. A. (2008) · Primary care diabetes · doi:10.1016/j.pcd.2008.10.003 · Cited by 32 · cited 1× · see citing works
“The authors of a previous GPRD-based study explored use of hormonal contraception among diabetic women and concluded that recording of hormonal methods was at a high level when compared with official United Kingdom statistics; there was evidence only for low recording of nonhormonal contraceptive methods (40).”
ResultCromer, B. A., Berg‐Kelly, K., van GRONINGEN, J. P., Seimer, B. S., & Ruusuvaara, L. (1998) · Journal of Adolescent Health · doi:10.1016/s1054-139x(98)00030-5 · Cited by 21 · cited 1× · see citing works
“DMPA is used by more than 9 million women worldwide and has a high usage in the United Kingdom and the United States (3).”
BackgroundBeksinska, M. E., Kleinschmidt, I., Smit, J. A., & Farley, T. M. M. (2007) · Contraception · doi:10.1016/j.contraception.2007.02.001 · Cited by 21 · see citing works
Injectable Contraception with Depot Medroxyprogesterone Acetate
Kaunitz, A. M., & Rosenfield, A. G. (1993) · Drugs · doi:10.2165/00003495-199345060-00001 · Cited by 19 · cited 1× · see citing works
“Low estrogen levels are seen in women using depot medroxyprogesterone acetate (DMPA) for contraception, a long-acting progestin-only contraceptive, administered by 3-monthly im injection (2).”
BackgroundHarkins, G., Davis, G. D., Dettori, J. R., Hibbert, M. L., & Hoyt, R. A. (1999) · PubMed · Cited by 5 · see citing works
Spinal fracture in a young Depo-Provera user
Searle, E. (2005) · Journal of Family Planning and Reproductive Health Care · doi:10.1783/1471189054483726 · Cited by 2 · cited 1× · see citing works
“A few case reports have suggested an association between DMPA use and fractures in adult women (22, 23), as did three observational studies (24– 26).”
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U.S. Medical Eligibility Criteria for Contraceptive Use, 2016
Curtis, K. M., Tepper, N. K., Jatlaoui, T. C., Berry-Bibee, E., Horton, L. G., Zapata, L. B., Simmons, K. B., Pagano, H. P., Jamieson, D. J., & Whiteman, M. K. (2016) · MMWR. Recommendations and Reports · doi:10.15585/mmwr.rr6503a1 · Cited by 1,456 · see citing works
“Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).”
BackgroundOtt, M. A., Sucato, G. S., COMMITTEE ON ADOLESCENCE, Braverman, P. K., Adelman, W. P., Alderman, E. M., Breuner, C. C., Levine, D. A., Marcell, A. V., & O’Brien, R. F. (2014) · PEDIATRICS · doi:10.1542/peds.2014-2300 · Cited by 402 · see citing works
U.S. Medical Eligibility Criteria for Contraceptive Use, 2024
Nguyen, A. T., Curtis, K. M., Tepper, N. K., Kortsmit, K., Brittain, A. W., Snyder, E. M., Cohen, M. A., Zapata, L. B., Whiteman, M. K., Contributors, et al. (2024) · MMWR Recommendations and Reports · doi:10.15585/mmwr.rr7304a1 · Cited by 286 · see citing works
Medication-induced osteoporosis: screening and treatment strategies
Panday, K., Gona, A., & Humphrey, M. B. (2014) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x14546350 · Cited by 201 · see citing works
“Studies have shown that prescribing low-dose estrogen replacement to DMPA users can prevent bone loss in premenopausal women on DMPA [Cundy et al.”
BackgroundInfluentialSteroidal contraceptives: effect on bone fractures in women
Lopez, L. M., Grimes, D. A., Schulz, K. F., Curtis, K. M., & Chen, M. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006033.pub5 · Cited by 168 · see citing works
Current and Emerging Therapeutics for the Management of Endometriosis
Ferrero, S., Barra, F., & Maggiore, U. L. R. (2018) · Drugs · doi:10.1007/s40265-018-0928-0 · Cited by 135 · see citing works
The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens
Mills, E., Yang, L. Y., Nielsen, M. F., Kassem, M. S., Dhillo, W. S., & Comninos, A. N. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab015 · Cited by 131 · see citing works
“These would be particularly useful given that by contrast to the aforementioned preclinical and interventional studies identifying positive effects, depot medroxyprogesterone acetate at contraceptive doses has consistently been shown to result in reversible BMD loss in longitudinal studies (216, 217) and possible incr…”
ResultSecondary Causes of Osteoporosis
Hudec, S. M. D., & Camacho, P. M. (2012) · Endocrine Practice · doi:10.4158/ep12059.ra · Cited by 113 · see citing works
Bone health in estrogen-free contraception
Hadji, P., Colli, E., & Regidor, P. (2019) · Osteoporosis International · doi:10.1007/s00198-019-05103-6 · Cited by 111 · see citing works
Barra, F., Scala, C., & Ferrero, S. (2018) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2018.1461840 · Cited by 100 · see citing works
Hormonal contraception and bone metabolism: a systematic review
Nappi, C., Bifulco, G., Tommaselli, G. A., Gargano, V., & Carlo, C. D. (2012) · Contraception · doi:10.1016/j.contraception.2012.04.009 · Cited by 107 · see citing works
Regidor, P. (2018) · Oncotarget · doi:10.18632/oncotarget.26015 · Cited by 107 · see citing works
“However, many studies have shown that the bone loss is reversible and the best evidence available at present indicates that that DMPA does not reduce peak bone mass and does not increase the risk of osteoporotic fractures in later life in women with an average risk of osteoporosis [16, 17, 18, 19].”
BackgroundCommittee Opinion No. 602: Depot Medroxyprogesterone Acetate and Bone Effects
(2014) · Obstetrics & Gynecology · doi:10.1097/01.aog.0000450758.95422.c8 · Cited by 107 · see citing works
Steroidal contraceptives and bone fractures in women: evidence from observational studies
Lopez, L. M., Chen, M., Long, S., Curtis, K. M., & Helmerhorst, F. M. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009849.pub3 · Cited by 102 · see citing works
RETIRED: Cancer and contraception
Patel, A. A., & Schwarz, E. B. (2012) · Contraception · doi:10.1016/j.contraception.2012.05.008 · Cited by 83 · see citing works
Use of Depot Medroxyprogesterone Acetate Contraception and Incidence of Bone Fracture
Lanza, L. L., McQuay, L. J., Rothman, K. J., Bone, H. G., Kaunitz, A. M., Harel, Z., Ataher, Q., Ross, D., Arena, P. L., & Wolter, K. D. (2013) · Obstetrics & Gynecology · doi:10.1097/aog.0b013e318283d1a1 · Cited by 78 · see citing works
Hormone replacement and contraceptive therapy in autoimmune diseases
Lateef, A., & Petri, M. (2012) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.11.002 · Cited by 80 · see citing works
Contraception in women over 40 years of age
Allen, R. H., Cwiak, C. A., & Kaunitz, A. M. (2013) · Canadian Medical Association Journal · doi:10.1503/cmaj.121280 · Cited by 70 · see citing works
Update on hormonal contraception and bone density
Isley, M. M., & Kaunitz, A. M. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9180-6 · Cited by 67 · see citing works
“Meier et al performed another large population-based case-control study, this time in the UK [57].”
Oral and depot progestin therapy for endometriosis: towards a personalized medicine
Buggio, L., Somigliana, E., Barbara, G., Frattaruolo, M. P., & Vercellini, P. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1381086 · Cited by 58 · see citing works
“of fracture, two large-scale, population-based, case-control studies [69,70] showed a modest increase in the risk in DMPA users, particularly in long-term users (Odds Ratio (ORs)”
BackgroundPrescribing Contraceptives for Women with Schizophrenia
Seeman, M. V., & ROSS, R. W. (2011) · Journal of Psychiatric Practice · doi:10.1097/01.pra.0000400263.52913.dc · Cited by 58 · see citing works
Chwalisz, K., Surrey, E., & Stanczyk, F. Z. (2012) · Reproductive Sciences · doi:10.1177/1933719112438061 · Cited by 58 · see citing works
Shah, D., Patil, M., & On behalf of the National PCOS Working Group (2018) · Journal of Human Reproductive Sciences · doi:10.4103/jhrs.jhrs_72_18 · Cited by 51 · see citing works
Cheewadhanaraks, S., Choksuchat, C., Dhanaworavibul, K., & Liabsuetrakul, T. (2012) · Gynecologic and Obstetric Investigation · doi:10.1159/000337713 · Cited by 50 · see citing works
The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK
Kyvernitakis, I., Kostev, K., Nassour, T., Thomasius, F. E., & Hadji, P. (2016) · Osteoporosis International · doi:10.1007/s00198-016-3714-4 · Cited by 48 · see citing works
“metabolism, resulting in impaired bone mineral acquisition during adolescence and accelerated bone loss in adult life [9].”
BackgroundMethodResultInfluentialNovel drug delivery methods for improving efficacy of endometriosis treatments
Garzon, S., Laganà, A. S., Barra, F., Casarin, J., Cromi, A., Raffaelli, R., Uccella, S., Franchi, M. P., Ghezzi, F., & Ferrero, S. (2020) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2021.1829589 · Cited by 42 · see citing works
Watts, N. B., Binkley, N., Owens, C. D., Al-Hendy, A. A., Puscheck, E. E., Shebley, M., Schlaff, W. D., & Simon, J. A. (2021) · Journal of Women s Health · doi:10.1089/jwh.2020.8989 · Cited by 39 · see citing works
“53,55 Moreover, percent changes from baseline in BMD observed with DMPA and GnRH antagonist use are modest, particularly during short-term treatment, and may not be detectable at the individual level due to the innate variability of densitometry (Table 4).”
Clinical relevance in present day hormonal contraception
Regidor, P.-A. (2019) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0030 · Cited by 33 · see citing works
Steroidal contraceptives: effect on bone fractures in women
Lopez, L. M., Grimes, D. A., Schulz, K. F., & Curtis, K. M. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006033.pub4 · Cited by 33 · see citing works
Steroidal contraceptives and bone fractures in women: evidence from observational studies
Lopez, L. M., Chen, M., Mullins, S., Curtis, K. M., & Helmerhorst, F. M. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009849.pub2 · Cited by 32 · see citing works
Pitts, S., Feldman, H. A., Dorale, A., & Gordon, C. M. (2011) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2011.07.014 · Cited by 31 · see citing works
Canadian Contraception Consensus (Part 3 of 4): Chapter 8 – Progestin-Only Contraception
Black, A., Guilbert, É., Costescu, D., Dunn, S., Fisher, W. A., Kives, S. L., Mirosh, M., Norman, W. V., Pymar, H. C., Reid, R. L., et al. (2016) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/j.jogc.2015.12.003 · Cited by 32 · see citing works
Approach to the Adolescent Requesting Contraception
Gordon, C. M., & Pitts, S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1780 · Cited by 29 · see citing works
“Several studies in adults have demonstrated an increased risk of fracture with history of DMPA use, although these studies did not control for calcium or vitamin D intake (31, 32).”
BackgroundBone health and HIV in resource-limited settings
Kiweewa, F. M., Wattanachanya, L., Beksinska, M. E., Pettifor, J. M., & Ruxrungtham, K. (2016) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000274 · Cited by 29 · see citing works
Adolescent Contraception: Review and Guidance for Pediatric Clinicians
Hartman, L. B., Monasterio, E., & Hwang, L. Y. (2012) · Current problems in pediatric and adolescent health care · doi:10.1016/j.cppeds.2012.05.001 · Cited by 28 · see citing works
Unrecognized and Unappreciated Secondary Causes of Osteoporosis
Miller, P. D. (2012) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2012.05.005 · Cited by 28 · see citing works
Removing the black box warning for depot medroxyprogesterone acetate
Kaunitz, A. M., & Grimes, D. A. (2011) · Contraception · doi:10.1016/j.contraception.2011.01.009 · Cited by 27 · see citing works
“Two recently published case–control studies, one using a national Danish National Patient Registry [13] and one based on the United Kingdom Family Practice Research database [14], have suggested that use of DMPA is associated with an elevated risk of fractures in reproductive-age women.”
ResultOral Contraceptive Use and Bone
Wei, S., Winzenberg, T. M., Laslett, L. L., Venn, A., & Jones, G. (2010) · Current Osteoporosis Reports · doi:10.1007/s11914-010-0037-9 · Cited by 25 · see citing works
“[9] conducted a case–control study in a large population-based sample (20–44 years of age) to evaluate the relationship between use of hormonal contraceptives (particularly depot medroxyprogesterone acetate but also OC) and fracture risk.”
BackgroundGarbe, E., & Suissa, S. (2013) · Springer eBooks · doi:10.1007/978-0-387-09834-0_31 · Cited by 22 · see citing works
Depot Medroxyprogesterone Acetate, Oral Contraceptive, Intrauterine Device Use, and Fracture Risk
Raine‐Bennett, T. R., Chandra, M., Armstrong, M. A., Alexeeff, S., & Lo, J. C.-M. (2019) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000003414 · Cited by 18 · see citing works
Bone health and hormonal contraception
Rocca, M. L., Palumbo, A., BITONTI, G., BRISINDA, C., & Carlo, C. D. (2021) · Minerva Obstetrics and Gynecology · doi:10.23736/s2724-606x.20.04688-2 · Cited by 18 · see citing works
Premenopausal Reproductive and Hormonal Characteristics and the Risk for Osteoporosis
Randolph, J. F., & Sowers, M. R. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415853-5.00030-3 · Cited by 18 · see citing works
Contraception for midlife women: a review
Miller, T. A., Allen, R. H., Kaunitz, A. M., & Cwiak, C. A. (2018) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001073 · Cited by 16 · see citing works
Effect of depot medroxyprogesterone acetate on bone mineral density in adolescent women
Zhang, M., Zhang, W., Zhang, A., Yang, Y. L., & Gai, L. (2013) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.20130885 · Cited by 15 · see citing works
“But it may reduce bone mineral density (BMD) and increase the risk of fractures.(1,2) In 2004, the Food and Drug Administration (FDA) in the United States issued a Black Box Warning that “women who use Depo-Provera Contraceptive Injection may lose significant bone mineral density.”
BackgroundHormonally Active Contraceptives Part I: Risks Acknowledged and Unacknowledged
Williams, W. V., BRIND, J. L., Haynes, L., Manhart, M. D., Klaus, H., Lanfranchi, A., Migeon, G., Gaskins, M., Šeman, E. I., Ruppersberger, L. A., et al. (2021) · The Linacre Quarterly · doi:10.1177/0024363920982709 · Cited by 15 · see citing works
“Virtually all the studies evaluating POCs show an elevated risk (Lanza et al. 2013; Vestergaard, Rejnmark, and Mosekilde 2008a; Meier et al. 2010; Kyvernitakis et al. 2017).”
BackgroundInfluentialContraception and Cancer Treatment in Young Persons
Laurence, V., & Rousset‐Jablonski, C. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2492-1_4 · Cited by 14 · see citing works
“potential decrease of bone density with prolonged use of DMPA [54–58] and the potential increase of fracture risk [59].”
BackgroundHormonal contraceptive prescriptions in the UK Armed Forces
Double, R. L., Wardle, S. L., O’Leary, T. J., Weaden, N., Bailey, G., & Greeves, J. P. (2021) · BMJ Military Health · doi:10.1136/bmjmilitary-2020-001594 · Cited by 13 · see citing works
Viola, A. S., Castro, S., Bahamondes, M. V., Fernandes, A. M. D. S., Viola, C. F. M., & Bahamondes, L. G. (2011) · Contraception · doi:10.1016/j.contraception.2011.06.012 · Cited by 12 · see citing works
“The other case–control study [27] from the UK also evaluated the relationship between DMPA use and fracture risk.”
BackgroundMethodInjectable contraception: issues and opportunities
Kaunitz, A. M., Peipert, J. F., & Grimes, D. A. (2014) · Contraception · doi:10.1016/j.contraception.2014.03.014 · Cited by 12 · see citing works
Augustine, M., Boudreau, R. M., Cauley, J. A., Majchel, D., Nagaraj, N., Roe, L. S., Sood, P., Stewart, A. F., & Horwitz, M. J. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01125-9 · Cited by 10 · see citing works
“While it can prevent pregnancy, DMPA is known to cause bone loss and has been associated with increased fracture risk [38].”
BackgroundAdverse skeletal effects of drugs – beyond Glucocorticoids
O’Sullivan, S., & Grey, A. B. (2014) · Clinical Endocrinology · doi:10.1111/cen.12549 · Cited by 9 · see citing works
“[48,49] Given that absolute fracture risk in premenopausal women is very low, the putative increase that accompanies DMPA use is of limited clinical importance, particularly when weighed against the risks associated with unplanned or unwanted pregnancy.”
BackgroundDey, M., & Bukhari, M. A. S. (2019) · Osteoporosis and Sarcopenia · doi:10.1016/j.afos.2019.03.001 · Cited by 9 · see citing works
“Depo-Provera use is also associated with a slightly increased risk of fracture [18].”
BackgroundQuintino‐Moro, A., Zantut‐Wittmann, D. E., dos Santos, P. D. N. S., Silva, C. A., Bahamondes, L. G., & Fernandes, A. M. D. S. (2019) · International Journal of Gynecology & Obstetrics · doi:10.1002/ijgo.12958 · Cited by 9 · see citing works
Segall‐Gutierrez, P., Agarwal, R., Ge, M. X., Lopez, C. M., Hernandez, G. D., & Stanczyk, F. Z. (2013) · The European Journal of Contraception & Reproductive Health Care · doi:10.3109/13625187.2013.774358 · Cited by 8 · see citing works
Kiweewa, F. M., Nabwana, M., Kiwanuka, N., Scholes, D., Isingel, E., Nolan, M. L., Fowler, M. G., Musoke, P., Pettifor, J. M., Brown, T. T., et al. (2020) · JBMR Plus · doi:10.1002/jbm4.10446 · Cited by 6 · see citing works
“001 Median duration of breast feeding 26 (15, 43) 27 (15, 42) 30 (18, 48) 24 (15, 42) 28 (18, 50) 0.”
La contraception après 40 ans. RPC Contraception CNGOF
Lambert, M., Begon, E., & Hocké, C. (2018) · Gynécologie Obstétrique Fertilité & Sénologie · doi:10.1016/j.gofs.2018.10.008 · Cited by 6 · see citing works
Controversies in Contraception
Kiley, J. W., Armstrong, W. A., & SHULMAN, L. P. (2020) · Springer eBooks · doi:10.1007/978-3-030-46391-5_19 · Cited by 6 · see citing works
Black, A., Guilbert, É., Costescu, D., Dunn, S., Fisher, W. A., Kives, S. L., Mirosh, M., Norman, W. V., Pymar, H. C., Reid, R. L., et al. (2016) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/j.jogc.2016.03.005 · Cited by 4 · see citing works
Hormonal contraception and bone mineral density
Beksinska, M. E., & Smit, J. A. (2011) · Expert Review of Obstetrics & Gynecology · doi:10.1586/eog.11.19 · Cited by 4 · see citing works
Controversies in Contraception
Kiley, J. W., & SHULMAN, L. P. (2015) · Springer eBooks · doi:10.1007/978-3-319-20185-6_15 · Cited by 5 · see citing works
Depot Medroxyprogesterone Acetate
McCullough, D. C., Eraso, K. M., & Kaunitz, A. M. (2020) · Springer eBooks · doi:10.1007/978-3-030-46391-5_6 · Cited by 3 · see citing works
Hormonal Contraception and Bone
Birkhaeuser, M. H. (2021) · Trends in andrology and sexual medicine · doi:10.1007/978-3-030-70932-7_21 · Cited by 3 · see citing works
Thai Interest Group for Endometriosis (TIGE) consensus statement on endometriosis-associated pain
Wisawasukmongchol, W., Chalermchockcharoenkit, A., Panyakhamlerd, K., Ratchanon, S., Luanratanakorn, S., Sophonsritsuk, A., Rungruxsirivorn, T., Choksuchat, C., Lertvikool, S., & Pantasri, T. (2022) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2022.2036965 · Cited by 3 · see citing works
“At laparoscopy, the endometriotic lesions can present with a variety of appearances ranging from white, yellow, or nonpigmented lesions, to blue, powder-burn black, red or brown lesions (Mishra et al. 2017).”
BackgroundContraception in Medically Complex Adolescents and Young Adults
Addison, J., Hassan, A., & DiVasta, A. D. (2024) · Open Access Journal of Contraception · doi:10.2147/oajc.s424068 · Cited by 2 · see citing works
“19”
Contraceptive use and fracture risk in active-duty females - A case control study
Ryan, B., Brezovec, A., Ying, S., Stahlman, S. L., & Pier, B. D. (2025) · Contraception · doi:10.1016/j.contraception.2025.111239 · Cited by 2 · see citing works
A practical guide to contraception. Part 2: Long-acting reversible methods
Stewart, M., McNamee, K. M., & Harvey, C. (2013) · Cited by 2 · see citing works
Formulation Development and Evaluation of Injectable Depot Suspension
Bodhe, R., Deshmukh, R. K., Shinde, R., & Patil, K. K. (2021) · doi:10.51521/ijmhr.2021.1105 · Cited by 2 · see citing works
“MPA act on the gonadotropin and it inhibit the secretion of gonadotropin there by prevent the follicular maturation and ovulation result in endometrial thinning, this action of MPA produce its contraceptive effect [10].”
BackgroundProgestin-Only Contraception and Bone Health
Isley, M. M. (2017) · Current Obstetrics and Gynecology Reports · doi:10.1007/s13669-017-0201-7 · Cited by 2 · see citing works
Bone Health and Hormonal Contraception
Dragoman, M. V., Kaunitz, A. M., & McClung, M. R. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1233-9_16 · Cited by 2 · see citing works
Garbe, E., Suissa, S., & Douros, A. (2022) · Springer eBooks · doi:10.1007/978-1-4614-6625-3_31-1 · Cited by 2 · see citing works
Reproductive and hormonal factors and the risk for osteoporosis
Randolph, J. F., & Karvonen-Gutierrez, C. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00023-x · Cited by 1 · see citing works
Contraception for adolescent and young women. A consensus conference results
Fruzzetti, F., Cagnacci, A., Farris, M., Dei, M., Caruso, S., Fidecicchi, T., Paolo, G. D., Londero, A. P., & for the Italian Society of Contraception (S.I.C.) (2025) · The European Journal of Contraception & Reproductive Health Care · doi:10.1080/13625187.2025.2586091 · Cited by 1 · see citing works
Rabe, T., Ludwig, M. Z., Merkle, E., Hj, A., Kj, B., Hadji, P., Ao, M., Merki, G., Egarter, C., König, K., et al. (2013) · Journal für Reproduktionsmedizin und Endokrinologie · Cited by 1 · see citing works
Lanza, L. L., McQuay, L. J., Rothman, K. J., Bone, H. G., Kaunitz, A. M., Harel, Z., Ataher, Q., Ross, D., Arena, P. L., & Wolter, K. D. (2013) · Journal of Family Planning and Reproductive Health Care · doi:10.1136/jfprhc-2013-100759 · Cited by 1 · see citing works
Secondary Causes of Osteoporosis: Other Medications
Biskobing, D. M. (2013) · doi:10.1002/9781118316290.ch7 · Cited by 1 · see citing works
Vallim, J. H. (2019) · doi:10.47749/t/unicamp.2019.1096821 · Cited by 1 · see citing works
Contraception hormonale au présent
Gronier, H., Robin, G., Catteau-Jonard, S., Sonigo, C., & Letombe, B. (2012) · Elsevier eBooks · doi:10.1016/b978-2-294-70154-2.00015-7
A practical guide to contraception2
Bayer Australia Ltd (2013)
Does Injectable Contraception Raise Fracture Risk
Kaunitz, A. M. (2010) · Journal watch · doi:10.1056/wh201009230000002
Family Planning Services and Birth Control
Morse, J. E., & Darney, P. D. (2013) · doi:10.1093/obo/9780199756797-0055
Der Einfluss der Gestagene auf die Knochengesundheit
Kashiwagi, M., & Seifert‐Klauss, V. (2019) · Journal für Gynäkologische Endokrinologie/Schweiz · doi:10.1007/s41975-019-00101-7
Der Einfluss der Gestagene auf die Knochengesundheit
Kashiwagi, M., & Seifert‐Klauss, V. (2020) · Journal für Gynäkologische Endokrinologie/Österreich · doi:10.1007/s41974-020-00125-z
Vinogradova, Y., Iyen, B., Masud, T., Taylor, L. R., & Kai, J. (2024) · medRxiv · doi:10.1101/2024.05.15.24307422
Gynecologic and Reproductive Health Considerations in the Adult Solid Organ Transplant Recipient
Tan, N., & McClintock, A. H. (2025) · Springer eBooks · doi:10.1007/978-3-031-98076-3_13
Tassi, A., Londero, A. P., Xholli, A., Lanzolla, G., Bertozzi, S., Savelli, L., Prefumo, F., & Cagnacci, A. (2025) · Pharmaceuticals · doi:10.3390/ph18091402
Controversies in Contraception
Patel, P. M., & Nguyen, B. T. (2026) · Current clinical practice · doi:10.1007/978-3-032-22510-8_20
Progestin only contraception and bone health
Dvořáková, V. (2026) · Clinical Osteology · doi:10.36290/clo.2026.010
Ostéoporose: traitements par stade & innovations en biologie cellulaire
Birkhäuser, M., Geyter, C. D., FINKENSTEDT, G., Hofbauer, L., Meier, C., SCHARLA, S. H., Stute, P., Ziller, & Hadji, P. (2012) · Journal für Kardiologie (Krause & Pachernegg GmbH)
Self-citationcheng, S.-C. J. (2014) · USF Scholarship Repository (University of San Francisco)
- Authors
- Meier, C., Brauchli, Y. B., Jick, S. S., Kraenzlin, M. E., & Meier, C. R.
- Affiliations
- University Hospital of Basel (CH)
- University of Basel (CH)
- Boston University (US)
- Corresponding author
- Meier, Christoph R.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-11
- Volume
- 95
- Issue
- 11
- Pages
- 4909-4916
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2106188080
- Cited by
- 90
- References
- 42
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- depot medroxyprogesterone acetate, fracture risk, hormonal contraception, combined oral contraceptives, osteoporosis, bone loss, treatment duration, women
- MeSH terms
- Adult, Contraceptive Agents, Female, Female, Humans, Risk, Bone Density, Incidence, Odds Ratio, Medroxyprogesterone Acetate, Fractures, Bone
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