Hormonal contraceptives and bone health in women

Hormonal 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 hormonal contraceptives and women may not want to use them.

Through April 2014, we did computer searches 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 a supplement with a placebo or 'dummy' method.

We found 19 trials. Fifteen studies compared one birth control method with another hormone method. Two trials used a placebo or 'dummy.' One compared a hormone method to a method without hormones. None had fractures as an outcome and most looked at bone density. Birth control methods with both estrogen and progestin did not appear to affect bone health. However, 'depo,' which is injected and has only progestin, was related to lower bone density. The two depo 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 important to the woman's health is not known. For implants, an etonogestrel implant with one rod showed a greater decrease in bone density than a two-rod levonorgestrel implant. However, other implants studied did not show the same pattern.

The studies had data of moderate quality. Whether hormonal contraceptives affect fracture risk cannot be judged from current information. These contraceptive methods 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 every day. Also, progestin-only methods are suggested for some women with health problems who should avoid estrogen.

Authors' conclusions: 

Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. The evidence quality was considered moderate overall, largely due to the trials of DMPA, implants, and the patch versus ring. The COC evidence varied in quality but was low overall. Many trials had small numbers of participants and some had large losses. 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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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. 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: 

Our aim was to evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women.

Search strategy: 

Through April 2014, we searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We examined reference lists of relevant articles for other trials. For the initial review, we wrote to investigators to find additional trials.

Selection criteria: 

Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover markers in women with hormonal contraceptive use prior to menopause. Eligible interventions included comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive that differed in terms of drug, dosage, or regimen. They also included providing a supplement to one group.

Data collection and analysis: 

We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to differing interventions, no trials could be combined for meta-analysis. We applied principles from GRADE to assess the evidence quality and address confidence in the effect estimates. In addition, a sensitivity analysis included trials that provided sufficient data for this review and evidence of at least moderate quality.

Main results: 

We found 19 RCTs that met our eligibility criteria. Eleven trials compared different combined oral contraceptives (COCs) or regimens of COCs; five examined an injectable versus another injectable, implant, or IUD; two studied implants, and one compared the transdermal patch versus the vaginal ring. No trial had fracture as an outcome. BMD was measured in 17 studies and 12 trials assessed biochemical markers of bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density (BMD). The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo supplement. COCs did not appear to negatively affect BMD, and some formulations had more positive effects than others. However, no COC trial was placebo-controlled. Where studies showed differences between groups in bone turnover markers, the results were generally consistent with those for BMD. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group but results were not consistent across all implant comparisons.

The sensitivity analysis included 11 trials providing evidence of moderate or high quality. Four trials involving DMPA showed some positive effects of an estrogen supplement on BMD, a negative effect of DMPA-subcutaneous on lumbar spine BMD, and a negative effect of DMPA on a bone formation marker. Of the three COC trials, one had a BMD decrease for the group with gestodene plus EE 15 μg. Another indicated less bone resorption in the group with gestodene plus EE 30 μg versus EE 20 μg.

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