Abstract
OBJECTIVE--To determine if the use of the injectable contraceptive depot medroxyprogesterone (DMPA), which reduces ovarian oestrogen production, is associated with changes in bone density. DESIGN--Population study. DMPA users were compared with two control groups selected from larger population studies and individually matched for several putative determinants of bone density (age, race, body mass index, and years of oestrogen deficiency). Controls and DMPA users were matched without prior knowledge of their bone density measurements. SETTING--Teaching hospital and community family planning clinics. SUBJECTS--30 current users of DMPA with a minimum five years' previous use, 30 premenopausal controls, and 30 postmenopausal controls. MAIN OUTCOME MEASURE--Lumbar spine and femoral neck bone mineral density assessed by dual energy x ray absorptiometry. RESULTS--Compared with premenopausal controls matched for age, race, and body mass index, DMPA users had significantly reduced bone density in the lumbar spine (mean difference 7.5% (95% confidence interval 1.9% to 13.1%), p = 0.002) and in the femoral neck (6.6%, (0.8% to 12.3%), p = 0.007). Compared with postmenopausal controls matched for body mass index and duration of oestrogen deficiency, DMPA users had greater bone density in the lumbar spine (8.9% (4.3% to 13.5%), p = 0.001), but in the femoral neck the difference in bone density was less (4.0% (-0.4% to 8.5%), p = 0.04). CONCLUSIONS--Women using DMPA have bone density values intermediate between those of normal premenopausal and postmenopausal controls; thus, the degree of oestrogen deficiency induced by DMPA may have an adverse effect on bone density.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abdalla H. I., Hart D. M., Lindsay R., Leggate I., Hooke A. Prevention of bone mineral loss in postmenopausal women by norethisterone. Obstet Gynecol. 1985 Dec;66(6):789–792. [PubMed] [Google Scholar]
- Adami S., Suppi R., Bertoldo F., Rossini M., Residori M., Maresca V., Lo Cascio V. Transdermal estradiol in the treatment of postmenopausal bone loss. Bone Miner. 1989 Aug;7(1):79–86. doi: 10.1016/0169-6009(89)90064-0. [DOI] [PubMed] [Google Scholar]
- Cann C. E., Genant H. K., Ettinger B., Gordan G. S. Spinal mineral loss in oophorectomized women. Determination by quantitative computed tomography. JAMA. 1980 Nov 7;244(18):2056–2059. [PubMed] [Google Scholar]
- Cann C. E., Martin M. C., Genant H. K., Jaffe R. B. Decreased spinal mineral content in amenorrheic women. JAMA. 1984 Feb 3;251(5):626–629. [PubMed] [Google Scholar]
- Crilly R. G., Jones M. M., Horsman A., Nordin B. E. Rise in plasma alkaline phosphatase at the menopause. Clin Sci (Lond) 1980 Apr;58(4):341–342. doi: 10.1042/cs0580341. [DOI] [PubMed] [Google Scholar]
- Drinkwater B. L., Nilson K., Chesnut C. H., 3rd, Bremner W. J., Shainholtz S., Southworth M. B. Bone mineral content of amenorrheic and eumenorrheic athletes. N Engl J Med. 1984 Aug 2;311(5):277–281. doi: 10.1056/NEJM198408023110501. [DOI] [PubMed] [Google Scholar]
- Gallagher J. C., Kable W. T., Goldgar D. Effect of progestin therapy on cortical and trabecular bone: comparison with estrogen. Am J Med. 1991 Feb;90(2):171–178. [PubMed] [Google Scholar]
- Hodgkinson A., Thompson T. Measurement of the fasting urinary hydroxyproline: creatinine ratio in normal adults and its variation with age and sex. J Clin Pathol. 1982 Aug;35(8):807–811. doi: 10.1136/jcp.35.8.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horsman A., Jones M., Francis R., Nordin C. The effect of estrogen dose on postmenopausal bone loss. N Engl J Med. 1983 Dec 8;309(23):1405–1407. doi: 10.1056/NEJM198312083092301. [DOI] [PubMed] [Google Scholar]
- Jarman H., Kovacs G. T., Westcott M. Depo Provera: a profile of current users. Aust N Z J Obstet Gynaecol. 1990 Feb;30(1):74–76. doi: 10.1111/j.1479-828x.1990.tb03202.x. [DOI] [PubMed] [Google Scholar]
- Jensen J., Christiansen C., Rødbro P. Cigarette smoking, serum estrogens, and bone loss during hormone-replacement therapy early after menopause. N Engl J Med. 1985 Oct 17;313(16):973–975. doi: 10.1056/NEJM198510173131602. [DOI] [PubMed] [Google Scholar]
- Jeppsson S., Gershagen S., Johansson E. D., Rannevik G. Plasma levels of medroxyprogesterone acetate (MPA), sex-hormone binding globulin, gonadal steroids, gonadotrophins and prolactin in women during long-term use of depo-MPA (Depo-Provera) as a contraceptive agent. Acta Endocrinol (Copenh) 1982 Mar;99(3):339–343. doi: 10.1530/acta.0.0990339. [DOI] [PubMed] [Google Scholar]
- Jeppsson S., Johansson E. D., Sjörberg N. O. Plasma levels of estrogens during long-term treatment with depo-medroxyprogesterone acetate as a contraceptive agent. Contraception. 1973 Aug;8(2):165–170. doi: 10.1016/0010-7824(73)90122-4. [DOI] [PubMed] [Google Scholar]
- Klibanski A., Greenspan S. L. Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N Engl J Med. 1986 Aug 28;315(9):542–546. doi: 10.1056/NEJM198608283150903. [DOI] [PubMed] [Google Scholar]
- Koppelman M. C., Kurtz D. W., Morrish K. A., Bou E., Susser J. K., Shapiro J. R., Loriaux D. L. Vertebral body bone mineral content in hyperprolactinemic women. J Clin Endocrinol Metab. 1984 Dec;59(6):1050–1053. doi: 10.1210/jcem-59-6-1050. [DOI] [PubMed] [Google Scholar]
- Lewis A. Empirical or rational? The nature and basis of psychiatry. Lancet. 1967 Jul 1;2(7505):1–9. doi: 10.1016/s0140-6736(67)90055-4. [DOI] [PubMed] [Google Scholar]
- Lobo R. A., McCormick W., Singer F., Roy S. Depo-medroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women. Obstet Gynecol. 1984 Jan;63(1):1–5. [PubMed] [Google Scholar]
- Matta W. H., Shaw R. W., Hesp R., Evans R. Reversible trabecular bone density loss following induced hypo-oestrogenism with the GnRH analogue buserelin in premenopausal women. Clin Endocrinol (Oxf) 1988 Jul;29(1):45–51. doi: 10.1111/j.1365-2265.1988.tb00248.x. [DOI] [PubMed] [Google Scholar]
- Mazess R., Collick B., Trempe J., Barden H., Hanson J. Performance evaluation of a dual-energy x-ray bone densitometer. Calcif Tissue Int. 1989 Mar;44(3):228–232. doi: 10.1007/BF02556569. [DOI] [PubMed] [Google Scholar]
- Melton L. J., 3rd, Kan S. H., Wahner H. W., Riggs B. L. Lifetime fracture risk: an approach to hip fracture risk assessment based on bone mineral density and age. J Clin Epidemiol. 1988;41(10):985–994. doi: 10.1016/0895-4356(88)90036-4. [DOI] [PubMed] [Google Scholar]
- Nordin B. E., Need A. G., Chatterton B. E., Horowitz M., Morris H. A. The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab. 1990 Jan;70(1):83–88. doi: 10.1210/jcem-70-1-83. [DOI] [PubMed] [Google Scholar]
- Powers M. S., Schenkel L., Darley P. E., Good W. R., Balestra J. C., Place V. A. Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement. Am J Obstet Gynecol. 1985 Aug 15;152(8):1099–1106. doi: 10.1016/0002-9378(85)90569-1. [DOI] [PubMed] [Google Scholar]
- Prior J. C. Progesterone as a bone-trophic hormone. Endocr Rev. 1990 May;11(2):386–398. doi: 10.1210/edrv-11-2-386. [DOI] [PubMed] [Google Scholar]
- Prior J. C., Vigna Y. M., Schechter M. T., Burgess A. E. Spinal bone loss and ovulatory disturbances. N Engl J Med. 1990 Nov 1;323(18):1221–1227. doi: 10.1056/NEJM199011013231801. [DOI] [PubMed] [Google Scholar]
- Redman J. R., Bajorunas D. R., Wong G., McDermott K., Gnecco C., Schneider R., Lacher M. J., Lane J. M. Bone mineralization in women following successful treatment of Hodgkin's disease. Am J Med. 1988 Jul;85(1):65–72. doi: 10.1016/0002-9343(88)90504-9. [DOI] [PubMed] [Google Scholar]
- Reid I. R., Mackie M., Ibbertson H. K. Bone mineral content in Polynesian and white New Zealand women. Br Med J (Clin Res Ed) 1986 Jun 14;292(6535):1547–1548. doi: 10.1136/bmj.292.6535.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richelson L. S., Wahner H. W., Melton L. J., 3rd, Riggs B. L. Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med. 1984 Nov 15;311(20):1273–1275. doi: 10.1056/NEJM198411153112002. [DOI] [PubMed] [Google Scholar]
- Rigotti N. A., Nussbaum S. R., Herzog D. B., Neer R. M. Osteoporosis in women with anorexia nervosa. N Engl J Med. 1984 Dec 20;311(25):1601–1606. doi: 10.1056/NEJM198412203112503. [DOI] [PubMed] [Google Scholar]
- Riis B. J., Christiansen C., Johansen J. S., Jacobson J. Is it possible to prevent bone loss in young women treated with luteinizing hormone-releasing hormone agonists? J Clin Endocrinol Metab. 1990 Apr;70(4):920–924. doi: 10.1210/jcem-70-4-920. [DOI] [PubMed] [Google Scholar]
- Selby P. L., Peacock M., Barkworth S. A., Brown W. B., Taylor G. A. Early effects of ethinyloestradiol and norethisterone treatment in post-menopausal women on bone resorption and calcium regulating hormones. Clin Sci (Lond) 1985 Sep;69(3):265–271. doi: 10.1042/cs0690265. [DOI] [PubMed] [Google Scholar]