New data suggest that women who use Depo-Provera® for long-term contraception may lose significant bone mineral density (BMD)

Depo-Provera® (medroxyprogesterone acetate, Pfizer) is a progestogen-only injection. It was registered in Singapore in 1989 and is indicated for use in contraception, treatment of endometriosis, menopausal vasomotor symptoms, palliative treatment for recurrent endometrial or renal carcinoma and treatment of hormonal-dependent, recurrent breast cancer in postmenopausal women.

Several international regulatory authorities including the US Food & Drug Administration, UK Committee on Safety of Medicines and Health Canada have issued advisories on the new prescribing information of Depo-Provera® on BMD changes. Several new studies have revealed that prolonged use of Depo-Provera® may result in significant loss of bone density, and the loss is greater the longer the drug is administered. This BMD loss may not be completely reversible after discontinuation of the drug.

In a controlled clinical study, adult women using Depo-Provera® Injection (150 mg IM) for up to 5 years for contraception showed spine, femoral neck and hip BMD mean decrease of 5–6% compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the first 2 years of use, with smaller declines in subsequent years. After stopping use of Depo-Provera®, there was partial recovery of BMD toward baseline values during the 2-year post-therapy period. A longer duration of treatment was associated with a slower rate of BMD recovery.

Preliminary results from an ongoing, open-label, non-randomised clinical study of adolescent females (12–18 years) also showed that Depo-Provera® (150 mg IM every 12 weeks for up to 5 years) was associated with a significant decline in BMD from baseline. The mean decline in lumbar spine BMD was 4.2% after 5 years; mean decreases for the total hip and femoral neck were 6.9% and 6.1%, respectively. It is unknown if use of Depo-Provera® during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk of osteoporotic fracture in later life.

Rare cases of osteoporosis including osteoporotic fracture have been reported post-marketing in patients on Depo-Provera®.

• Since loss of BMD may occur in premenopausal women who use medroxyprogesterone acetate (MPA) injection long-term, a risk-benefit assessment should be considered.
  
  
• MPA injection should be used as a long-term (e.g. longer than 2 years) birth control methods or endometrial treatment only if other treatments are inadequate.
  
  
• Other birth control methods or endometrial treatments should be considered in the risk/benefit analysis for the use of MPA injection in women with osteoporotic risk factors.