Elsevier

Contraception

Volume 73, Issue 5, May 2006, Pages 470-487
Contraception

Review article
Progestogen-only contraception and bone mineral density: a systematic review

https://doi.org/10.1016/j.contraception.2005.12.010Get rights and content

Abstract

Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.

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.

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