{"paper_id":"50ef6b22-0adc-4529-bc6e-e1f38e64fe2f","body_text":"Reason for posting : Medroxy-\nprogesterone acetate is an in-\njectable agent widely used for\ncontraception and the treatment\nof endometriosis. However, a\nwarning was recently issued that\npatients taking this drug may\nexperience a significant loss of\nbone mineral density.\n1\nThe drug: Medroxyprogesterone\nacetate is injected intramuscu-\nlarly in a standard dose (150 mg)\nonce every 3 months. It confers\nits reversible contraceptive ef-\nfect by inhibiting gonadotropin\nsecretion, preventing follicle\nmaturation and ovulation, and\ncausing endometrial thinning.\nDisrupted menses (bleeding,\namenorrhea or both), fluid re-\ntention, weight changes, dizzi-\nness, headache, weakness and fa-\ntigue are frequently experienced\nby women taking the drug.\nOther rare but serious adverse\neffects include mood changes,\nthromboembolic diseases, ocu-\nlar disorders (including vision\nloss, proptosis, diplopia or mi-\ngraine) and reduced glucose tol-\nerance. About 3 in 1000 women\ntaking the drug will experience\nan accidental pregnancy in the\nfirst year of continuous use. It is\ncontraindicated in pregnant wo-\nmen, women who have undiag-\nnosed vaginal bleeding, malig-\nnant breast disease, active\nthrombophlebitis, past throm-\nboembolic disorders or cerebral\nvascular disease, and in women\nwith significant liver disease. \nMedroxyprogesterone ace-\ntate decreases serum estrogen\nlevels, which can lead to bone\nmineral density loss. In an un-\npublished study involving\nwomen above the age of 18 who\nused the drug for up to 5 years,\nbone mineral density in the\nspine and hip was reduced by\n5% to 6% below baseline.\n2 In\ncontrast, women in the control\ngroup, who were not using hor-\nmonal contraception, had no\nsignificant change in bone min-\neral density. Loss of density was\ngreatest in the first 2 years of\nuse. Two years after stopping\nthe drug, bone mineral density\nwas only partially recovered.\nPreliminary results from an on-\ngoing open-label self-selected\nnonrandomized group of ado-\nlescent women aged 12–18 years\nshowed a similar decrease in\nbone mineral density of\n4%–6.9% after 4.6 years of\nstudy.\n2 This decline was not\nseen in a group of unmatched\nadolescents not receiving the\ndrug. It is unknown whether use\nof medroxyprogesterone acetate\nwill lead to osteoporotic frac-\ntures later in life. \nWhat to do: This drug, which is\nwidely taken by patients for\nwhom compliance is an issue\n(e.g., adolescents and young\nadults), may cause a loss of bone\ndensity that may not be fully re-\nversible in a group that is least\nable to afford such a loss. A\npatient’s risk factors for osteo-\nporosis (a family history of\nosteoporosis; long-term use of\nglucocorticoids, heparin or anti-\nconvulsant therapy; malabsorp-\ntion states; hyperparathyroidism;\nhyperthyroidism; smoking; low\ndietary calcium intake; excessive\ncaffeine or alcohol intake; weight\n< 57 kg; anorexia or bulemia)\n2,3\nshould be part of the risk–benefit\nanalysis of prescribing the drug.\nOnly if other methods of birth\ncontrol are inappropriate should\nthe drug be used as a contracep-\ntive for the long term (> 2 years).\nWomen who take the drug for\nmore than 2 years should have\ntheir bone mineral density moni-\ntored. When interpreting bone\nmineral density test results in\nadolescents, the patient’s age and\ndegree of skeletal maturation\nshould be taken into account.\nStudies are lacking on how best\nto prevent and treat medroxy-\nprogesterone acetate-associated\nbone mineral density loss; how-\never, it may be wise to routinely\nrecommend regular weight-\nbearing exercise, smoking cessa-\ntion, and calcium and vitamin D\nsupplementation to women pre-\nscribed the drug.\nEric Wooltorton\nAssociate Editor, CMAJ\nReferences\n1. Health Canada endorsed important\nsafety information on Depo-Provera\n(medroxyprogesterone acetate) [letter].\nNov. 22, 2004. Available: www.hc-sc\n.gc.ca/hpfb-dgpsa/tpd-dpt/depo-provera\n_hpc_e.html (accessed 2005 Feb 8).\n2. Depo-Provera (medroxyprogesterone\nacetate injectable suspension) revised\nproduct monograph, Pfizer. Available:\nwww.fda.gov/medwatch/SAFETY/20\n04/safety04.htm#Depo [click on: No-\nvember, 2004 - Label - Pfizer]  (ac-\ncessed 2005 Feb 8).\n3. Brown JP, Josse RG, for the Scientific\nAdvisory Council of the Osteoporosis\nSociety of Canada. 2002 clinical prac-\ntice guidelines for the diagnosis and\nmanagement of osteoporosis in Cana-\nda. CMAJ 2002;167(10 Suppl):S1-34.\nMedroxyprogesterone acetate (Depo-Provera) and\nbone mineral density loss\nPRACTICE\nHEALTH AND DRUG ALERTS\nDOI:10.1503/cmaj.050158\n746 JAMC • 15 MARS 2005; 172 (6)\n© 2005  CMA Media Inc. or its licensors\nCanadian Adverse \nReaction Newsletter\nBulletin canadien \ndes effets indésirables\nTo receive the Newsletter and health\nproduct Advisories by email, join Health\nCanada’s Health_Prod_Infomailing list.\nGo to www.hc-sc.gc.ca/hpfb-dgpsa\n/tpd-dpt/subscribe_e.html.\nInscrivez-vous à la liste\nInfo_Prod_Santé de Santé Canada\npour recevoir par courriel le Bulletin et\nles Avis au sujet des produits de santé.\nRendez-vous à l’adresse \nwww.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt\n/subscribe_f.html.\nReport adverse reactions toll free to\nHealth Canada • Signaler sans frais des\neffets indésirables à Santé Canada\nTel./Tél. : 866 234-2345 \nFax/Téléc. : 866 678-6789\nEmail/Courriel: cadrmp@hc-sc.gc.ca","source_license":"CC0","license_restricted":false}