Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections
Abstract
Background Depot medroxyprogesterone acetate (DMPA) is a highly effective progestin-only contraceptive that is widely used by adolescents. We investigated bone mineral density (BMD) changes in female adolescents during and following use of this method.Study design A multicenter, prospective, non-randomized observational study in 98 healthy female adolescents aged 12-18 years who initiated DMPA intramuscular injections for contraception and provided BMD data for up to 240 weeks while receiving DMPA and for up to 300 weeks after DMPA cessation. BMD at the lumbar spine (LS), total hip (TH) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry. A mixed model analysis of variance was used to examine BMD changes.Results At the time of their final DMPA injection, participants had mean BMD declines from baseline of 2.7% (LS), 4.1% (TH) and 3.9% (FN) (p<.001 at all three sites). Within 60 weeks of discontinuation of DMPA, mean LS BMD had returned to baseline levels, and 240 weeks after DMPA discontinuation, the mean LS BMD was 4.7% above baseline. Mean TH and FN BMD values recovered to baseline values more slowly: 240 weeks and 180 weeks, respectively, after the last DMPA injection.Conclusions BMD loss in female adolescents receiving DMPA for contraception is substantially or fully reversible in most girls following discontinuation of DMPA, with faster recovery at the LS than at the hip.
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The negative impact of DMPA on bone mineral density is reversible toward or to baseline values within two years after discontinuation.
“reversibility of the negative impact of DMPA on BMD toward or to baseline values within two years after discontinuation has been demonstrated in numerous studies [59,61,65,68].”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [65]
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“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.”
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“However, there is also evidence that, after DMPA discontinuation, a full recovery of BMD occurs in adolescent and adult women at approximately 1 to 2 years or 3 years, respectively, after discontinuation [31–35].”
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“About half of the adolescents in this cohort continued to be followed after discontinuation of DMPA, and their recovery data are published in a separate paper [21].”
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“Weight gain is reported in up to 54% of adolescent DMPA users and is another commonly cited reason for discontinuation.(22) Weight gain is a particularly difficult issue to research in adolescents who may not have reached their adult height and weight and thus may experience an increase in both.”
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“Upon cessation of DMPA, BMD significantly or totally recovers [36].”
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Depot Medroxyprogesterone Acetate
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“The explanation for the skeletal malformations is that progesterone can reduce Ca++ deposition in the bone, enhance bone resorption in pregnant dams, and increase fecal Ca++ excretion from fetuses, thus reduces their bone Ca++ deposition (Harel et al., 2010).”
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“For example, injectable DMPA, which requires a single injection once every 3 months, has a typical-use failure rate of 6%3, while the hormonal IUD failure rate is 0.2% for both perfect and typical use, making it the most effective choice for reversible contraception (Trussell, 2007, 2011).”
BackgroundInfluentialBone Health in Adolescents with Multiple Fractures
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Controversies in Contraception
Patel, P. M., & Nguyen, B. T. (2026) · Current clinical practice · doi:10.1007/978-3-032-22510-8_20
Motafeghi, F., Naz, M. S. G., Tehrani, F. R., & Behboudi‐Gandevani, S. (2026) · Frontiers in Global Women s Health · doi:10.3389/fgwh.2026.1895443
“In the treatment of endometriosis, progestins are divided into two groups: DMPA is known to be a bone-damaging drug, while drugs such as DNG and NETA are often described as bone-neutral or low-risk (54 – 56).”
- Authors
- Harel, Z., Johnson, C. C., Gold, M. A., Cromer, B., Peterson, E., Burkman, R., Stager, M., Brown, R., Bruner, A., Coupey, S., Hertweck, P., Bone, H., Wolter, K., Nelson, A., Marshall, S., & Bachrach, L. K.
- Affiliations
- Brown University (US)
- Henry Ford Health (US)
- University of Pittsburgh (US)
- Tufts University (US)
- Baystate Medical Center (US)
- Johns Hopkins University (US)
- Albert Einstein College of Medicine (US)
- University of Louisville (US)
- Pfizer (United States) (US)
- University of California, Los Angeles (US)
- Wayne State University (US)
- Hasbro Children's Hospital (US)
- Corresponding author
- Harel, Zeev
- ORCID
- Venue
- Contraception
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 81
- Issue
- 4
- Pages
- 281-291
- ISSN
- 0010-7824 (ISSN-L)
- OpenAlex
- W1973237319
- Cited by
- 100
- References
- 44
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 7 · 2012: 12
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Contraception (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- depot medroxyprogesterone acetate, bone mineral density, adolescents, contraceptive side effects, bone loss, progestin-only contraception, lumbar spine, hip, femoral neck, contraceptive discontinuation
- MeSH terms
- Adolescent, Alcohol Drinking, Child, Contraceptives, Oral, Synthetic, Delayed-Action Preparations, Female, Humans, Longitudinal Studies, Pregnancy, Pregnancy in Adolescence, Prospective Studies, Smoking, Bone Density, Body Mass Index, Medroxyprogesterone Acetate
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