Notice type: 3rd Party Publications

Date: 31/01/2005


Product name or type:
Depo-Provera (Medroxyprogesterone) MIMS Advisory

MIMS Publication January 2005

Prescription Required:

Problem Or Issue:
Depo-Provera is a long-acting, progestogen-only contraceptive containing medroxyprogesterone acetate, that is administered intra-muscularly every 12 weeks. By suppressing oestradiol levels Depo-Provera is known to adversely affect BMD in women of all ages, as evidenced in previous studies1,2. 

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. 

The key points to note are as follows: 
• It is 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 of peak bone mass is not known. 

 • 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. 

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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