title: 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.
  
  
  OBJECTIVE
  To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women
  
  
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors: Clinical Sciences, FHI, P.O. Box 13950, Research Triangle Park, North Carolina, USA, 27709.
authors: Laureen M
authors: LM
authors: Lopez
authors: David A
authors: DA
authors: Grimes
authors: Kenneth F
authors: KF
authors: Schulz
authors: Kathryn M
authors: KM
authors: Curtis
mesh_terms: D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000494:pharmacology; D017697:Premenopause; D011372:Progestins / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic
chemical_list: D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D011372:Progestins; D017258:Medroxyprogesterone Acetate