This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cundy, T. Articles by Reid, I. R. Search for Related Content PubMed PubMed Citation Articles by Cundy, T. Articles by Reid, I. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

A Randomized Controlled Trial of Estrogen Replacement Therapy in Long-Term Users of Depot Medroxyprogesterone Acetate

Department of Medicine, Faculty of Medicine & Health Science (T.C., R.A., A.H., J.C., G.G., I.R.R.), University of Auckland, and the Family Planning Association (H.R.), 1001 Auckland, New Zealand

Address all correspondence and requests for reprints to: Dr. Tim Cundy, Department of Medicine, Faculty of Medical & Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: t.cundy{at}auckland.ac.nz.

Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched for demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven subjects completed at least 18 months in the study, and 26 the full 2 yr, with similar numbers dropping out from each group (mainly for personal reasons). In the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at 12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P < 0.002). Differences of lesser statistical magnitude were seen at the femoral neck (between group differences at 2 yr: 2.7%, P = 0.24), Ward’s triangle (5.0%, P = 0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy.

The study was supported by the Health Research Council of New Zealand.

Abbreviations: BMD, Bone mineral density; DMPA, depot medroxyprogesterone acetate.

This article has been cited by other articles:

				M. K Dhanjal Contraception in women with medical problems Obstet Med, December 1, 2008; 1(2): 78 - 87. [Abstract] [Full Text] [PDF]

				S. M. Ott Reproductive Hormones and Skeletal Health in Young Women J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1175 - 1177. [Full Text] [PDF]

				J. S. Walsh, R. Eastell, and N. F. A. Peel Effects of Depot Medroxyprogesterone Acetate on Bone Density and Bone Metabolism before and after Peak Bone Mass: A Case-Control Study J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1317 - 1323. [Abstract] [Full Text] [PDF]

				J. R. Meendering, B. N. Torgrimson, N. P. Miller, P. F. Kaplan, and C. T. Minson Estrogen, medroxyprogesterone acetate, endothelial function, and biomarkers of cardiovascular risk in young women Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1630 - H1637. [Abstract] [Full Text] [PDF]

				D. Scholes, A. Z. LaCroix, L. E. Ichikawa, W. E. Barlow, and S. M. Ott Change in Bone Mineral Density Among Adolescent Women Using and Discontinuing Depot Medroxyprogesterone Acetate Contraception Arch Pediatr Adolesc Med, February 1, 2005; 159(2): 139 - 144. [Abstract] [Full Text] [PDF]

				Estrogen Add-Back May Benefit DMPA-Associated Osteoporosis Journal Watch Women's Health, March 25, 2003; 2003(325): 5 - 5. [Full Text]