Review articleProgestogen-only contraception and bone mineral density: a systematic review
Introduction
Questions have been raised about the effects of progestogen-only contraceptive use on fracture risk and bone mineral density (BMD), particularly among young women who have not yet reached peak bone mass and among perimenopausal women who may be starting to lose bone mass. Concern is greatest for women using depot medroxyprogesterone acetate (DMPA), due to its relatively hypoestrogenic effect. A systematic review published in 2001 reviewed 10 cross-sectional and 7 longitudinal studies and concluded that mean BMD was lower in DMPA users than in nonusers, but that the difference was within 1 SD from the nonusers [1]. Results from that review for Norplant use were conflicting. In addition to concern about bone loss, a key issue is whether women can regain sufficient bone mass after discontinuing use of progestogen-only contraceptives.
The objective of this systematic review was to determine whether progestogen-only contraceptive use has an adverse effect on fracture risk or BMD, especially among younger (<18 years) women and older (>45 years) women. The review examined the following progestogen-only contraceptive methods: DMPA, norethisterone enantate (NET-EN), levonorgestrel and etonogestrel implants, and progestogen-only pills.
Section snippets
Materials and methods
The MEDLINE and EMBASE databases were searched for all articles published between 1966 and July 2005 by using the following search terms: [Medroxyprogesterone 17-Acetate/ and (contracept: or inject: or depo or depot)] or [(depot medroxyprogesterone or depo medroxyprogesterone or depotmedroxyprogesterone or depomedroxyprogesterone) or dmpa.tw.] or [net en.tw. or norethisterone-enantate] or [(norplant: or uniplant or jadelle or implanon) or ((levonorgestrel or etonogestrel) and (implant:))] or
Results
From 163 articles identified by the search strategy, 39 met the inclusion criteria. One study examined fracture as an outcome [6]. The other 38 studies examined BMD (Table 1, Table 2). Thirty-two studies examined use of DMPA [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], eight reports of seven studies examined levonorgestrel implants [15], [18], [23], [31]
Does use of progestogen-only contraceptives affect fracture risk?
Information on progestogen-only contraceptive use and fracture risk is limited to one study that did not find a significant association between DMPA use and risk of stress fracture in female military recruits, after controlling for baseline bone density, as measured by quantitative ultrasound [6]. It is possible that at study entry, DMPA users had lower bone density than nonusers, which may have led to greater fracture risk in the DMPA users. Unfortunately, no information on the association
Conclusion
Depot medroxyprogesterone acetate users have lower BMD than nonusers, but deficits are usually within 1 SD of the mean BMD of nonusers, so the clinical significance of these findings is unclear. The differences in BMD among adults were almost completely due to decreased BMD in DMPA users; in adolescents, differences in BMD were due to decreased BMD in DMPA users as well as increased BMD in nonusers. Recovery of BMD occurs after discontinuation of DMPA, most likely at rates higher than those in
Acknowledgments
This review was supported by resources from the World Health Organization, the US Centers for Disease Control and Prevention (CDC), the US Agency for International Development (USAID) and the US National Institute of Child Health and Human Development (NICHD).
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agencies.
References (51)
- et al.
Overview of the relationship between use of progestogen-only contraceptives and bone mineral density
BJOG
(2001) - et al.
A prospective, controlled study of the effects of hormonal contraception on bone mineral density
Obstet Gynecol
(2001) - et al.
Bone mineral density in women using depot medroxyprogesterone acetate for contraception
Obstet Gynecol
(1999) - et al.
Bone mineral density at various anatomic bone sites in women receiving combined oral contraceptives and depot-medroxyprogesterone acetate for contraception
Contraception
(2002) - et al.
Spinal bone density in women using depot medroxyprogesterone acetate contraception
Obstet Gynecol
(1998) - et al.
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) - et al.
Forearm bone density in long-term users of oral combined contraceptives and depot medroxyprogesterone acetate
Fertil Steril
(2001) - et al.
Bone mineral density during long-term treatment with Norplant implants and depot medroxyprogesterone acetate. A cross-sectional study of Thai women
Contraception
(1997) - et al.
Bone mineral density in long-term depot medroxyprogesterone acetate acceptors
Contraception
(1997) - et al.
Forearm bone density in users of Depo-Provera as a contraceptive method
Fertil Steril
(1999)
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
Long-term depot-medroxyprogesterone acetate and bone mineral density
Contraception
Bone mineral density in women aged 40–49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception
Contraception
Differential effects on bone density of progestogen-only methods for contraception in premenopausal women
Contraception
Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate
Fertil Steril
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
The association between depot medroxyprogesterone acetate contraception and bone mineral density in adolescent women
Contraception
Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years
J Adolesc Health
A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives
J Pediatr
Bone mineral density in adolescent females using depot medroxyprogesterone acetate
J Pediatr Adolesc Gynecol
Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls
J Adolesc Health
Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception
Am J Obstet Gynecol
Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study
Contraception
Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception
Am J Obstet Gynecol
Effects of levonorgestrel-releasing subdermal contraceptive implants on bone density and bone metabolism
Contraception
Cited by (119)
Cardio-Obstetrics and Heart Failure: JACC: Heart Failure State-of-the-Art Review
2023, JACC: Heart FailureIntramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda
2022, The Lancet Global HealthCitation Excerpt :In women living with HIV, DMPA-IM does not have pharmacokinetic interactions with antiretroviral drugs.11 However, DMPA-IM induces a hypo-oestrogenic state, accelerating bone turnover, leading to bone loss12,13 and an increased risk of fractures.14 Women using DMPA-IM have a lower BMD than non-users, with the greatest BMD loss occurring particularly in younger women and in the first few years of use.15
Gynecologic health care for females with cystic fibrosis
2021, Journal of Clinical and Translational EndocrinologyFeatures of Menstruation and Menstruation Management in Individuals with Rett Syndrome
2021, Journal of Pediatric and Adolescent GynecologyBone Health in Women
2018, Primary Care - Clinics in Office PracticeCitation Excerpt :Women using Depo-Provera (DMPA) may lose some bone density transiently but they regain bone density over a short time after stopping DMPA. Although DMPA effect on adolescent bone density loss seems more severe, their loss is reversible with complete recovery within 1 year to 2 years of discontinuation.24 The Food and Drug Administration added a black box warning on DMPA label cautioning against long-term use (>2 years) in 2004.25
Secondary osteoporosis
2018, Encyclopedia of Endocrine Diseases