Steroidal contraceptives: effect on bone fractures in women

[Intervention Review]
Steroidal contraceptives: effect on bone fractures in women

Laureen M Lopez1, David A Grimes1, Kenneth F Schulz2, Kathryn M. Curtis3

1Behavioral and Biomedical Research, Family Health International, Research Triangle Park, North Carolina, USA. 2Quantitative Sciences, Family Health International, Research Triangle Park, North Carolina, USA. 3Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Contact address: Laureen M Lopez, Behavioral and Biomedical Research, Family Health International, P.O. Box 13950, Research Triangle Park, North Carolina, 27709, USA. llopez@fhi.org. (Editorial group: Cochrane Fertility Regulation Group.)

Cochrane Database of Systematic Reviews, Issue 2, 2009 (Status in this issue: New search for studies completed, conclusions not changed)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD006033.pub3
This version first published online: 15 April 2009 in Issue 2, 2009. Last assessed as up-to-date: 23 November 2008. (Help document - Dates and Statuses explained).

This record should be cited as: Lopez LM, Grimes DA, Schulz KF, Curtis KM. Steroidal contraceptives: effect on bone fractures in women. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006033. DOI: 10.1002/14651858.CD006033.pub3.
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Abstract


Background
Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally.


Objectives
To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women


Search strategy
We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as in clinical trials databases (ClinicalTrials.gov and ICTRP). We wrote to investigators to find additional trials.


Selection criteria
Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo.


Data collection and analysis
We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The mean difference was computed with 95% confidence interval (CI) using a fixed-effect model.


Main results
We found 13 RCTs, 2 of which used a placebo. No trial had fracture as an outcome but most measured BMD. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo.


Authors' conclusions
Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.


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Plain language summary

Hormone contraceptives and bone health in women
Hormone contraceptives have been related to bone changes in women. Whether such changes lead to more bone fractures later in life is not clear. However, bone health is a major public health concern. Bone density declines with age, and the change increases the risk of fracture. Due to concern about bone health, health care providers may not suggest hormone contraceptives and women may not want to use them.

We did a computer search for studies of birth control methods containing hormones and risk of fractures. Outcomes could also be bone mineral density or markers of bone changes. Birth control pills included types with both estrogen and progestin. Also included were implants and injectables with only progestin. We wrote to researchers to find other trials. We included randomized trials in any language that had at least three treatment cycles. The studies had to compare two types of birth control or one type of birth control or supplement with a placebo or 'dummy' method.

We found 13 trials. Eleven studies compared one birth control method with another type or a different dose. Two trials used a placebo or 'dummy.' None had fractures as an outcome but most had bone density. Birth control methods with both estrogen and progestin did not appear to affect bone health. In contrast, 'depo,' a progestin-only injectable, was related to lower bone mineral density. The two trials with placebos showed increased bone density when some estrogen was given to women on depo. Bone density decreased in women who got a 'dummy' with the depo. Whether this decrease is clinically important is not known.

Whether hormone contraceptives affect fracture risk cannot be judged from current data. Hormone contraceptives work well for birth control. Health-care providers and women should think about the costs and benefits. For instance, injectable use can occur without a partner's knowledge, and is simpler than taking pills daily. Also, progestin-only methods are suggested for some women with health problems who should avoid estrogen.






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