Steroidal contraceptives: effect on bone fractures in women
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. 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 methods
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 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 in women with hormonal contraceptive use prior to menopause. Interventions could include comparing a hormonal contraceptive with a placebo or another hormonal contraceptive or could compare providing a supplement versus a placebo.
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 different interventions, no trials could be combined for meta‐analysis.
Main results
Of the 16 RCTs we found, 2 used a placebo and 1 used a non‐hormonal method as the comparison, while 13 compared two hormonal contraceptives. No trial had fracture as an outcome. Most measured BMD and several assessed bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density. The placebo‐controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. Combination contraceptives did not appear to negatively affect bone health, but none were placebo‐controlled. For implants, the single‐rod etonogestrel group showed a greater BMD decrease versus the two‐rod levonorgestrel group. However, results were not consistent across all implant comparisons.
Authors' conclusions
Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. 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.
PICOs
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 a supplement with a placebo or 'dummy' method.
We found 16 trials. Thirteen 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 but 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 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.
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.
