Advice on Effect of Depo-Provera Contraception on Bones, UK

Main Category: Bones / Orthopedics
Article Date: 21 Nov 2004 - 13:00 PDT

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This is a document from the Medicines and Healthcare products Regulatory Agency (MHRA), UK, to doctors regarding updated prescribing advice on the effect of Depo-Provera contraception on bones.

Dear Colleague

"I am sending you this updated advice in advance of its general release to enable you to prepare for any questions that you may receive.

The effect of Depo-Provera in reducing bone mineral density (BMD) has been recognised for many years and a warning is included in prescribing information. Several new studies, especially involving adolescents, have been completed. Following careful review of the available data the Committee on Safety of Medicines has today updated its advice."

NEW ADVICE FOR PRESCRIBERS

The CSM advises that:

_ In adolescents, Depo-Provera may be used as first-line contraception but only after other methods have been discussed with the patient and considered to be unsuitable or unacceptable;

_ In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out in those who wish to continue use for more than 2 years;

_ In women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered.

THE EFFECT OF DEPO-PROVERA ON BONE MINERAL DENSITY

The key points to note are that:

_ It is well established that Depo-Provera reduces BMD in many women who use it.

_ It is not yet known whether the effect on BMD increases the risk of osteoporosis and fractures in later life.

_ The reduction in BMD is duration-dependent for the first few years of use after which the effect appears to plateau.

_ There is some evidence that BMD starts to recover when Depo-Provera is stopped but the extent of recovery is currently unknown and may be related to duration of exposure.

_ The effect of Depo-Provera may be more important in adolescents in whom the usual process of bone mineral accretion may be reversed. In this population, the effect of Depo-Provera on attainment on peak bone mass is not known.

Background

Depo-Provera is a long-acting, progestogen-only contraceptive that is administered intra-muscularly every 12 weeks. Many of those who use DepoMHRA\PublicHealthLink\Depo-Provera\16Nov2004\final

Provera may do so because they are oestrogen-intolerant or because they are unable to comply with a daily contraceptive regimen.

Previous studies have shown that Depo-Provera causes a reduction in BMD in users1,2 and warnings have been included in product information for several years.

In adult women, BMD appears to start to recover when Depo-Provera is stopped3,4 and limited data suggest that, at menopause, the bone density of previous users may be no different from that of women who have never used Depo-Provera5-7. However, there are some data to suggest that the rate of recovery is dependent on the duration of use.

In adolescents it is recognised that attaining peak bone mass is an important factor in minimising the risk of future osteoporosis. There is now evidence that Depo-Provera causes a loss of BMD in adolescents, at a time when BMD is normally increasing8,9. For this reason it is possible that the effect of Depo-Provera in adolescents may be more significant than in adults. As in adults, there is some evidence for reversibility of effect in adolescents, but it is not known whether BMD recovers to the level attainable if Depo-Provera had not been used. Whilst the reversal of BMD gain has been consistently observed, the clinical implications of these findings remain unknown.

There is currently no evidence to say whether use of Depo-Provera at any age is associated with an increased risk of osteoporosis and fracture in later life, but this possibility should be considered when prescribing Depo-Provera. Further research is being pursued.

Sources of Further Information

An information sheet for women is attached and may also be found on the MHRA website (http://www.mhra.gov.uk).

For telephone enquiries, please call the Medicines and Healthcare products Regulatory Agency 020 7084 2000.

Professor Gordon Duff
Chairman
Committee on Safety of Medicines

References

1) Cundy T et al., BMJ 1991;303:13-16

2) Cromer BA et al., J Paediatrics 1996;129:671-6

3) Pettiti DB et al., Obs & Gynaecol 2000;95:736-744

4) Scholes D et al., Epidemiology 2002;13:581-7

5) Cundy T et al., BMJ 1994;308:1567-8

6) Orr-Walker BJ et al., Clin Endocrinol. 1998;49:615-618

7) Cundy T et al., Am J Obs Gynae. 2002;186:978-983

8) Edwards CP et al., J Paediatr Adolesc Gynaecol 1998;11:201-210

9) Lara-Torre E at al., J Paediatr Adolesc Gynaecol 2004;17

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Suspected ADRs should be reported via the Yellow Card scheme (http://www.yellowcard.gov.uk).
For additional reporting advice refer to the MHRA website
http://medicines.mhra.gov.uk.

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