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

The local package insert of Depo-Provera® will be updated to include the following warnings:

• Since loss of BMD may occur in premenopausal women who use medroxyprogesterone acetate injection long-term, a risk-benefit assessment should be considered.

• Medroxyprogesterone acetate 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.

Reference: Health Science Authority (HSA). Product Safety Alert 17 March 2005 at http://www.hsa.gov.sg/cda/safetyalerts