Medroxyprogesterone acetate (Depo-Provera) and bone mineral density loss

Reason for posting : Medroxy- progesterone acetate is an in- jectable agent widely used for contraception and the treatment of endometriosis. However, a warning was recently issued that patients taking this drug may experience a significant loss of bone mineral density. 1 The drug: Medroxyprogesterone acetate is injected intramuscu- larly in a standard dose (150 mg) once every 3 months. It confers its reversible contraceptive ef- fect by inhibiting gonadotropin secretion, preventing follicle maturation and ovulation, and causing endometrial thinning. Disrupted menses (bleeding, amenorrhea or both), fluid re- tention, weight changes, dizzi- ness, headache, weakness and fa- tigue are frequently experienced by women taking the drug. Other rare but serious adverse effects include mood changes, thromboembolic diseases, ocu- lar disorders (including vision loss, proptosis, diplopia or mi- graine) and reduced glucose tol- erance. About 3 in 1000 women taking the drug will experience an accidental pregnancy in the first year of continuous use. It is contraindicated in pregnant wo- men, women who have undiag- nosed vaginal bleeding, malig- nant breast disease, active thrombophlebitis, past throm- boembolic disorders or cerebral vascular disease, and in women with significant liver disease. Medroxyprogesterone ace- tate decreases serum estrogen levels, which can lead to bone mineral density loss. In an un- published study involving women above the age of 18 who used the drug for up to 5 years, bone mineral density in the spine and hip was reduced by 5% to 6% below baseline. 2 In contrast, women in the control group, who were not using hor- monal contraception, had no significant change in bone min- eral density. Loss of density was greatest in the first 2 years of use. Two years after stopping the drug, bone mineral density was only partially recovered. Preliminary results from an on- going open-label self-selected nonrandomized group of ado- lescent women aged 12–18 years showed a similar decrease in bone mineral density of 4%–6.9% after 4.6 years of study. 2 This decline was not seen in a group of unmatched adolescents not receiving the drug. It is unknown whether use of medroxyprogesterone acetate will lead to osteoporotic frac- tures later in life. What to do: This drug, which is widely taken by patients for whom compliance is an issue (e.g., adolescents and young adults), may cause a loss of bone density that may not be fully re- versible in a group that is least able to afford such a loss. A patient’s risk factors for osteo- porosis (a family history of osteoporosis; long-term use of glucocorticoids, heparin or anti- convulsant therapy; malabsorp- tion states; hyperparathyroidism; hyperthyroidism; smoking; low dietary calcium intake; excessive caffeine or alcohol intake; weight < 57 kg; anorexia or bulemia) 2,3 should be part of the risk–benefit analysis of prescribing the drug. Only if other methods of birth control are inappropriate should the drug be used as a contracep- tive for the long term (> 2 years). Women who take the drug for more than 2 years should have their bone mineral density moni- tored. When interpreting bone mineral density test results in adolescents, the patient’s age and degree of skeletal maturation should be taken into account. Studies are lacking on how best to prevent and treat medroxy- progesterone acetate-associated bone mineral density loss; how- ever, it may be wise to routinely recommend regular weight- bearing exercise, smoking cessa- tion, and calcium and vitamin D supplementation to women pre- scribed the drug. Eric Wooltorton Associate Editor, CMAJ References 1. Health Canada endorsed important safety information on Depo-Provera (medroxyprogesterone acetate) [letter]. Nov. 22, 2004. Available: www.hc-sc .gc.ca/hpfb-dgpsa/tpd-dpt/depo-provera _hpc_e.html (accessed 2005 Feb 8). 2. Depo-Provera (medroxyprogesterone acetate injectable suspension) revised product monograph, Pfizer. Available: www.fda.gov/medwatch/SAFETY/20 04/safety04.htm#Depo [click on: No- vember, 2004 - Label - Pfizer] (ac- cessed 2005 Feb 8). 3. Brown JP, Josse RG, for the Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical prac- tice guidelines for the diagnosis and management of osteoporosis in Cana- da. CMAJ 2002;167(10 Suppl):S1-34. Medroxyprogesterone acetate (Depo-Provera) and bone mineral density loss PRACTICE HEALTH AND DRUG ALERTS DOI:10.1503/cmaj.050158 746 JAMC • 15 MARS 2005; 172 (6) © 2005 CMA Media Inc. or its licensors Canadian Adverse Reaction Newsletter Bulletin canadien des effets indésirables To receive the Newsletter and health product Advisories by email, join Health Canada’s Health_Prod_Infomailing list. Go to www.hc-sc.gc.ca/hpfb-dgpsa /tpd-dpt/subscribe_e.html. Inscrivez-vous à la liste Info_Prod_Santé de Santé Canada pour recevoir par courriel le Bulletin et les Avis au sujet des produits de santé. Rendez-vous à l’adresse www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt /subscribe_f.html. 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