- Email: [email protected]
Long-term oral contraceptive use does not affect trabecular bone density
Louv et al.
22. Eschenbach DA, Harnisch JP, Holmes KK. Pathogenesis of acute pelvic inflammatory disease: role of contraception and other risk factors. AM J OBSTET GYNECOL 1977; 128:838-50. 23. Keith L, Moss W, Berger GS, Gonorrhea detection in a family planning clinic: a cost-benefit analysis of 2,000 triplicate cultures. AM J OBSTET GYNECOL 1975;121:399404. 24. Krauss RM. Effects of progestational agents on serum lipids and lipoproteins. J Reprod Med 1982;27:503-10. 25. Edgren RA, Sturtevant FM. Potencies of oral contraceptives. AMJ OBSTET GYNECOL 1976;125:1029-38. 26. Perlman JA, Russell-Briefel R, Ezzati T, Lieberknecht G.
February 1989 Am J Obstet Gynecol
27. 28. 29. 30.
Oral glucose tolerance and the potency of contraceptive progestins. J Chronic Dis 1985;38:85764. Gray RH. Reduced risk of pelvic inflammatory disease with injectable contraceptives. Lancet 1985; 1: 1046. Rubin GL, Ory HW, Layde PM. Oral contraceptives and pelvic inflammatory disease. AM J OBSTET GYNECOL 1982; 144:630-5. Cramer DW, Goldman MB, Schiff I. The relationship of tubal infertility to barrier method and oral contraceptive use. JAMA 1987;257;2446-50. Svensson L, Westrom L, Mardh P-A. Contraceptives and acute salpingitis. JAMA 1984;251 :2553-5.
Long-term oral contraceptive use does not affect trabecular bone density Tom Lloyd, PhD,James R. Buchanan, MD, Gregory R. Ursino, BS, Cathleen Myers, RN, Gerald Woodward, MD, PhD, and David R. Halbert, MD Hershey, Pennsylvania To determine whether long-term exposure to exogenous estrogen in oral contraceptives influences trabecular bone mass in premenopausal women, we studied 25 closely matched, healthy, premenopausal women, who were recruited from an active obstetrics and gynecology practice. Eleven women had never used oral contraceptives, and 14 women had used oral contraceptives for a minimum of 67 months. All oral contraceptive users had used preparations that provided a minimum of 50 I1g mestranol per day. Trabecular bone density was determined by quantitative single-energy computerized tomography of the L1-3 lumbar vertebral bodies. Trabecular bone density was similar for both the control group and the oral contraceptive users, 160.6 ± 6.9 versus 161.2 ± 7.4 mg/ml, respectively. The power to detect a 15% difference in bone density between these two samples was 0.87. We concluded that long-term, premenopausal oral contraceptive use has no effect on vertebral bone denSity. (AM J QBSTET GYNECOL 1989;160:402-4.)
Key words: Oral contraceptives, premenopausal bone density, estrogen status Long-term oral contraceptive use has been implicated as a risk factor in coronary vascular disease, breast disease, and thrombophlebitis. However, the risk-tobenefit assessments have generally favored the oral contraceptive user. Oral contraceptive use results in marked decreases in ovarian steroidogenesis, yet this has not been considered as a risk factor for oral contraceptive use. l -3 During oral contraceptive use, circulating estrogen levels are lower than levels found in the early follicular phase of normal ovulating cycles and somewhat higher than levels found in postmenopausal women. l Reduced circulating estrogen levels at me noFrom the Departments of Obstetrics and Gynecology, Surgery, and Radiology, College of Medicine, Pennsylvania State University. Received for publication April 9, 1988; revised July 20, 1988; accepted July 29, 1988. Reprint requests: Tom Lloyd, PhD, Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.
402
pause have been established as a principal determinant of loss in trabecular and cortical bone density. Recently, several groups have demonstrated that significant bone density loss occurs in premenopausal hypoestrogenic women,,-8 Because estrogen status appears to play a major lifetime role in maintenance of bone density in women, we designed the present study to determine whether long-term premenopausal estrogen administration, through the use of oral contraceptives, affects the trabecular bone density of the spine. Material and methods All procedures for this study were approved by the Institutional Review Board of the Pennsylvania State University College of Medicine. Informed consent was obtained from all participants. The medical records of patients in an active obstetrics and gynecology practice were reviewed to obtain closely matched study participants. Women were selected so that all factors known
Oral contraceptive use does not affect bone density 403
Volume 160 Number 2
Table I. Comparison of two study groups Oral contraceptive
users
Controls
(N = 14)
(N = 11)
Age (yr)
Height (cm) Weight (kg) Ideal body weight (%) Body fat (%) Parity Gravidity Trabecular bone density (mg/ml) Mestranol (f.Lg/mo) Norethindrone (mg/mo)
33.3 165.4 55.0 90.4 20.2 1.7 1.6 160.6
± 0.9 ± 1.6
± 1.3
± 2.1 ± 1.4
± 0.3 ± 0.2 ± 6.9
31.9 160.3 56.0 96.5 21.9 0.6 0.5 161.2 1267.0 20.1
± 0.8 ± 1.7 ± 1.7 ± 3.3 ± 1.6 ± 0.3 ± 0.2 ± 7.4 ± 27.0 ± 0.1
p Value
NS NS NS NS
NS O.oI
0.004 NS
Results shown are mean ± SEM.
to influence bone mass could be controlled. All participants were white, were nonsmokers, consumed less than 1.0 ounce of alcohol per day, had no history of drug abuse, and did not have any remarkable general medical history. We excluded women who had more than three term pregnancies. All women had normal gynecologic histories and were of reproductive age. Percent body fat composition was determined by measurement of the skin-fold thickness at ten different sites, as previously described." A power analysis was performed (in the context of an independent sample t test) prior to initiating this study to predict what size study group would be necessary to detect significant differences in bone density between oral contraceptive users and controls. This analysis indicated that with the study populations used the power to detect a 15% difference in bone density between the two subject groups was 0.87. The 14 oral contraceptive users had taken mestranolcontaining preparations for a minimum of 67 continuous months. The maximum usage was 186 months and the mean was 120 months. The 11 control women had used barrier contraceptives and had never used oral contraceptives. Trabecular bone density was determined by quantitative computerized tomography of the lumbar spine, and is expressed as mg/ml dipotassium phosphate. This method accurately measures true trabecular mass and density, and is uniformly reproducible throughout the bone density range. 10. II Our precision, determined from repeated measurements of a cadaver spine over 12 months, was 1.7%. Statistical analysis was performed with SAS software on an IBM 4381 computer. Data distributions are expressed as the mean ± SEM. All P values are two-tailed.
Results A summary of our findings is presented in Table I. The controls and oral contraceptive users were closely matched to eliminate as many potentially confounding variables as possible. Within the oral contraceptive user
group, exposure to estrogen and progestogen was very similar. As would be expected, the control group had more pregnancies and live births than the oral contraceptive user group. Fig. 1 shows no difference between the two groups with respect to trabecular bone density.
Comment The major finding of this study is that, despite the fact that oral contraceptives cause a depression of circulating estrogen to near postmenopausal levels, the long-term use of oral contraceptives does not lead to a reduction (or an increase) in trabecular bone density. Our control group was slightly taller and had more children than our oral contraceptive user group. Because both pregnancy and increased height are known to be associated with increased bone mass, we also analyzed our data after height and pregnancy were controlled and still found no difference in vertebral bone density. We believe that the findings of this study apply to the general population because rigorous screening criteria were used to closely match our study groups, thereby eliminating confounding variables, and normal premenopausal trabecular bone loss occurs at 1% to 2% per year. 12 Accordingly, if a significant aberration of the normal rate of loss had occurred in the oral contraceptive user group, it would have been detected over the lO-year mean of oral contraceptive use. Previous studies on the effects of oral contraceptive use on bone mineral density used different methods and end points than those used in this report, and direct comparisons would be difficult. Goldsmith and Johnston l3 measured cortical bone density with singlephoton absorptiometry of the distal radius and used retrospective questionnaires for a large, mixed population enrolled in a prepaid health plan. They described bone mineral class qualitatively (low, moderate, and high) and suggested that some oral contraceptive users had higher overall levels of bone mineral. More recently, Lindsay et al. I ' measured integral vertebral bone density by dual-photon absorptiometry and observed
404
Lloyd at al.
February 1989 Am J Obstet Gynecol
250
•
225 ~
.....E
01
E ....,
>.
'iii c:
200 175 150
Q)
0
125
I
•
• __ 1_•
--,-.I
•
I
-_&--
••
----I I
100
01~----~----~-----Controls OC Users Fig. 1. Trabecular bone densities of control subjects and oral contraceptive users. Bone densities of LI-3 vertebral bodies were determined by quantitative computed tomography. The solid bar represents the mean value, and the dashed line represents the SEM for each group.
an insignificant increase in the bone mass of the oral contraceptive users group. Although this study was controlled for age, height, and weight, the study populations contained a sizable percentage of women who smoked, and their bone density values reflect 76% cortical and 24% trabecular bone. '5 It is interesting that the two previous reports have set forth the notion that exogenous estrogen administration, as occurs in oral contraceptive use, might be expected to increase bone density, inasmuch as postmenopausal oral estrogen use can arrest, and possibly reverse, bone loss.'6 In designing our study, we thought that the question to be addressed might be stated as follows: Two effects of oral contraceptives on circulating estrogen status are (1) abolition of estrogen fluctuations during the normal menstrual cycle and (2) establishment of a relatively constant estrogen level similar to normal early follicular phase levels. How do these two events affect bone remodeling and ultimately bone density? Our study used quantitative computed tomography and measured only the trabecular portion of vertebral bone, which is known to respond more rapidly than cortical bone to metabolic stimuli. The fact that we observed no difference in bone density between our highly matched study groups suggests to us that premenopausal oral contraceptive use has neither a
beneficial effect on bone density nor an appreciable negative effect on bone density after long-term use. Therefore it appears that if a threshold estrogen level is required for normal premenopausal bone remodeling, such a threshold is not reached by the depression of plasma estrogen levels during oral contraceptive use . REFERENCES 1. Mishell DR, Thorneycroft IH, Nakamura RM, et al. Serum estradiol in women ingesting combination oral contraceptive steroids. AM J OBSTET GYNECOL 1972; 114: 923-8. 2. Briggs M, Briggs M. Plasma hormone concentrations in women receiving steroid contraceptives. J Obstet Gynecol 1972;70:946-50. 3. Carr BR, Parker R, Madden JD, et al. Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. J Clin Endocrinol Metab 1979;49:346-9. 4. Marcus R, Cann C, Madvig P, et al. Menstrual function and bone in elite women distance runners, endocrine and metabolic features. Ann Intern Med 1985;102:158-63. 5. Jones KP, Ravnikar VA, Tulchinsky D, et al. Comparison of bone density in amenorrheic women due to athletics, weight loss and premature menopause. Obstet Gynecol 1985;66:5-8. 6. Drinkwater BL, Nilson K, Chestnut CH, et al. Bone mineral content of amenorrheic and eumenorrheic women. N EnglJ Med 1984;311:277-81. 7. Cann C, Martin M, Genant HK, et al. Decreased spinal mineral content in amenorrheic women. JAMA 1984; 251:626-9. 8. Lloyd T, Buchanan JR, Bitzer S, et al. Interrelationships of diet, athletic activity, menstrual status and bone density in collegiate women. Am J Clin Nutr 1987;46:681-4. 9. Allen TH, Peng MT, Chen KP, et al. Prediction of the total adiposity from skin folds and the curvilinear relationship between external and internal adiposity. Metabolism 1956;51:346-52. 10. Genant HK, Cann CEo Spinal osteoporosis: advanced assessment using quantitative computed tomography. In: Genant HK, ed. J Spine Update, 1984. San Francisco: Radiology Research and Education Foundation, 1983: 331-4. II. Elasser U, Reeve J. Bone density measurement with computed tomography. Br Med Bull 1980;36:293-6. 12. Pacifici R, Susman N, Carr PL, Birge SJ, Avioli LV. Single and dual energy tomographic analysis of spinal trabecular bone: a comparative study in normal and osteoporotic women. J Clin Endocrinol Metab 1987;64:209-14. 13. Goldsmith NF, Johnston JO. Bone mineral: effects of oral contraceptives, pregnancy and lactation. J Bone Joint Surg [Am]1975;57A:657-68. 14. Lindsay R, Tohme J, Kanders B. The effect of oral contraceptive use on vertebral bone mass in pre- and postmenopausal women. Contraception 1986;34:333-40. 15. Nottestad SY, BaumelJJ, Kimmel DB. The proportion of trabecular bone in human vertebrae. J Bone Joint Surg [Am] 1987;22:221-9. 16. Ettinger B, Genant HK, Cann CEo Longterm estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 1985;102:319-24.
22. Eschenbach DA, Harnisch JP, Holmes KK. Pathogenesis of acute pelvic inflammatory disease: role of contraception and other risk factors. AM J OBSTET GYNECOL 1977; 128:838-50. 23. Keith L, Moss W, Berger GS, Gonorrhea detection in a family planning clinic: a cost-benefit analysis of 2,000 triplicate cultures. AM J OBSTET GYNECOL 1975;121:399404. 24. Krauss RM. Effects of progestational agents on serum lipids and lipoproteins. J Reprod Med 1982;27:503-10. 25. Edgren RA, Sturtevant FM. Potencies of oral contraceptives. AMJ OBSTET GYNECOL 1976;125:1029-38. 26. Perlman JA, Russell-Briefel R, Ezzati T, Lieberknecht G.
February 1989 Am J Obstet Gynecol
27. 28. 29. 30.
Oral glucose tolerance and the potency of contraceptive progestins. J Chronic Dis 1985;38:85764. Gray RH. Reduced risk of pelvic inflammatory disease with injectable contraceptives. Lancet 1985; 1: 1046. Rubin GL, Ory HW, Layde PM. Oral contraceptives and pelvic inflammatory disease. AM J OBSTET GYNECOL 1982; 144:630-5. Cramer DW, Goldman MB, Schiff I. The relationship of tubal infertility to barrier method and oral contraceptive use. JAMA 1987;257;2446-50. Svensson L, Westrom L, Mardh P-A. Contraceptives and acute salpingitis. JAMA 1984;251 :2553-5.
Long-term oral contraceptive use does not affect trabecular bone density Tom Lloyd, PhD,James R. Buchanan, MD, Gregory R. Ursino, BS, Cathleen Myers, RN, Gerald Woodward, MD, PhD, and David R. Halbert, MD Hershey, Pennsylvania To determine whether long-term exposure to exogenous estrogen in oral contraceptives influences trabecular bone mass in premenopausal women, we studied 25 closely matched, healthy, premenopausal women, who were recruited from an active obstetrics and gynecology practice. Eleven women had never used oral contraceptives, and 14 women had used oral contraceptives for a minimum of 67 months. All oral contraceptive users had used preparations that provided a minimum of 50 I1g mestranol per day. Trabecular bone density was determined by quantitative single-energy computerized tomography of the L1-3 lumbar vertebral bodies. Trabecular bone density was similar for both the control group and the oral contraceptive users, 160.6 ± 6.9 versus 161.2 ± 7.4 mg/ml, respectively. The power to detect a 15% difference in bone density between these two samples was 0.87. We concluded that long-term, premenopausal oral contraceptive use has no effect on vertebral bone denSity. (AM J QBSTET GYNECOL 1989;160:402-4.)
Key words: Oral contraceptives, premenopausal bone density, estrogen status Long-term oral contraceptive use has been implicated as a risk factor in coronary vascular disease, breast disease, and thrombophlebitis. However, the risk-tobenefit assessments have generally favored the oral contraceptive user. Oral contraceptive use results in marked decreases in ovarian steroidogenesis, yet this has not been considered as a risk factor for oral contraceptive use. l -3 During oral contraceptive use, circulating estrogen levels are lower than levels found in the early follicular phase of normal ovulating cycles and somewhat higher than levels found in postmenopausal women. l Reduced circulating estrogen levels at me noFrom the Departments of Obstetrics and Gynecology, Surgery, and Radiology, College of Medicine, Pennsylvania State University. Received for publication April 9, 1988; revised July 20, 1988; accepted July 29, 1988. Reprint requests: Tom Lloyd, PhD, Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.
402
pause have been established as a principal determinant of loss in trabecular and cortical bone density. Recently, several groups have demonstrated that significant bone density loss occurs in premenopausal hypoestrogenic women,,-8 Because estrogen status appears to play a major lifetime role in maintenance of bone density in women, we designed the present study to determine whether long-term premenopausal estrogen administration, through the use of oral contraceptives, affects the trabecular bone density of the spine. Material and methods All procedures for this study were approved by the Institutional Review Board of the Pennsylvania State University College of Medicine. Informed consent was obtained from all participants. The medical records of patients in an active obstetrics and gynecology practice were reviewed to obtain closely matched study participants. Women were selected so that all factors known
Oral contraceptive use does not affect bone density 403
Volume 160 Number 2
Table I. Comparison of two study groups Oral contraceptive
users
Controls
(N = 14)
(N = 11)
Age (yr)
Height (cm) Weight (kg) Ideal body weight (%) Body fat (%) Parity Gravidity Trabecular bone density (mg/ml) Mestranol (f.Lg/mo) Norethindrone (mg/mo)
33.3 165.4 55.0 90.4 20.2 1.7 1.6 160.6
± 0.9 ± 1.6
± 1.3
± 2.1 ± 1.4
± 0.3 ± 0.2 ± 6.9
31.9 160.3 56.0 96.5 21.9 0.6 0.5 161.2 1267.0 20.1
± 0.8 ± 1.7 ± 1.7 ± 3.3 ± 1.6 ± 0.3 ± 0.2 ± 7.4 ± 27.0 ± 0.1
p Value
NS NS NS NS
NS O.oI
0.004 NS
Results shown are mean ± SEM.
to influence bone mass could be controlled. All participants were white, were nonsmokers, consumed less than 1.0 ounce of alcohol per day, had no history of drug abuse, and did not have any remarkable general medical history. We excluded women who had more than three term pregnancies. All women had normal gynecologic histories and were of reproductive age. Percent body fat composition was determined by measurement of the skin-fold thickness at ten different sites, as previously described." A power analysis was performed (in the context of an independent sample t test) prior to initiating this study to predict what size study group would be necessary to detect significant differences in bone density between oral contraceptive users and controls. This analysis indicated that with the study populations used the power to detect a 15% difference in bone density between the two subject groups was 0.87. The 14 oral contraceptive users had taken mestranolcontaining preparations for a minimum of 67 continuous months. The maximum usage was 186 months and the mean was 120 months. The 11 control women had used barrier contraceptives and had never used oral contraceptives. Trabecular bone density was determined by quantitative computerized tomography of the lumbar spine, and is expressed as mg/ml dipotassium phosphate. This method accurately measures true trabecular mass and density, and is uniformly reproducible throughout the bone density range. 10. II Our precision, determined from repeated measurements of a cadaver spine over 12 months, was 1.7%. Statistical analysis was performed with SAS software on an IBM 4381 computer. Data distributions are expressed as the mean ± SEM. All P values are two-tailed.
Results A summary of our findings is presented in Table I. The controls and oral contraceptive users were closely matched to eliminate as many potentially confounding variables as possible. Within the oral contraceptive user
group, exposure to estrogen and progestogen was very similar. As would be expected, the control group had more pregnancies and live births than the oral contraceptive user group. Fig. 1 shows no difference between the two groups with respect to trabecular bone density.
Comment The major finding of this study is that, despite the fact that oral contraceptives cause a depression of circulating estrogen to near postmenopausal levels, the long-term use of oral contraceptives does not lead to a reduction (or an increase) in trabecular bone density. Our control group was slightly taller and had more children than our oral contraceptive user group. Because both pregnancy and increased height are known to be associated with increased bone mass, we also analyzed our data after height and pregnancy were controlled and still found no difference in vertebral bone density. We believe that the findings of this study apply to the general population because rigorous screening criteria were used to closely match our study groups, thereby eliminating confounding variables, and normal premenopausal trabecular bone loss occurs at 1% to 2% per year. 12 Accordingly, if a significant aberration of the normal rate of loss had occurred in the oral contraceptive user group, it would have been detected over the lO-year mean of oral contraceptive use. Previous studies on the effects of oral contraceptive use on bone mineral density used different methods and end points than those used in this report, and direct comparisons would be difficult. Goldsmith and Johnston l3 measured cortical bone density with singlephoton absorptiometry of the distal radius and used retrospective questionnaires for a large, mixed population enrolled in a prepaid health plan. They described bone mineral class qualitatively (low, moderate, and high) and suggested that some oral contraceptive users had higher overall levels of bone mineral. More recently, Lindsay et al. I ' measured integral vertebral bone density by dual-photon absorptiometry and observed
404
Lloyd at al.
February 1989 Am J Obstet Gynecol
250
•
225 ~
.....E
01
E ....,
>.
'iii c:
200 175 150
Q)
0
125
I
•
• __ 1_•
--,-.I
•
I
-_&--
••
----I I
100
01~----~----~-----Controls OC Users Fig. 1. Trabecular bone densities of control subjects and oral contraceptive users. Bone densities of LI-3 vertebral bodies were determined by quantitative computed tomography. The solid bar represents the mean value, and the dashed line represents the SEM for each group.
an insignificant increase in the bone mass of the oral contraceptive users group. Although this study was controlled for age, height, and weight, the study populations contained a sizable percentage of women who smoked, and their bone density values reflect 76% cortical and 24% trabecular bone. '5 It is interesting that the two previous reports have set forth the notion that exogenous estrogen administration, as occurs in oral contraceptive use, might be expected to increase bone density, inasmuch as postmenopausal oral estrogen use can arrest, and possibly reverse, bone loss.'6 In designing our study, we thought that the question to be addressed might be stated as follows: Two effects of oral contraceptives on circulating estrogen status are (1) abolition of estrogen fluctuations during the normal menstrual cycle and (2) establishment of a relatively constant estrogen level similar to normal early follicular phase levels. How do these two events affect bone remodeling and ultimately bone density? Our study used quantitative computed tomography and measured only the trabecular portion of vertebral bone, which is known to respond more rapidly than cortical bone to metabolic stimuli. The fact that we observed no difference in bone density between our highly matched study groups suggests to us that premenopausal oral contraceptive use has neither a
beneficial effect on bone density nor an appreciable negative effect on bone density after long-term use. Therefore it appears that if a threshold estrogen level is required for normal premenopausal bone remodeling, such a threshold is not reached by the depression of plasma estrogen levels during oral contraceptive use . REFERENCES 1. Mishell DR, Thorneycroft IH, Nakamura RM, et al. Serum estradiol in women ingesting combination oral contraceptive steroids. AM J OBSTET GYNECOL 1972; 114: 923-8. 2. Briggs M, Briggs M. Plasma hormone concentrations in women receiving steroid contraceptives. J Obstet Gynecol 1972;70:946-50. 3. Carr BR, Parker R, Madden JD, et al. Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. J Clin Endocrinol Metab 1979;49:346-9. 4. Marcus R, Cann C, Madvig P, et al. Menstrual function and bone in elite women distance runners, endocrine and metabolic features. Ann Intern Med 1985;102:158-63. 5. Jones KP, Ravnikar VA, Tulchinsky D, et al. Comparison of bone density in amenorrheic women due to athletics, weight loss and premature menopause. Obstet Gynecol 1985;66:5-8. 6. Drinkwater BL, Nilson K, Chestnut CH, et al. Bone mineral content of amenorrheic and eumenorrheic women. N EnglJ Med 1984;311:277-81. 7. Cann C, Martin M, Genant HK, et al. Decreased spinal mineral content in amenorrheic women. JAMA 1984; 251:626-9. 8. Lloyd T, Buchanan JR, Bitzer S, et al. Interrelationships of diet, athletic activity, menstrual status and bone density in collegiate women. Am J Clin Nutr 1987;46:681-4. 9. Allen TH, Peng MT, Chen KP, et al. Prediction of the total adiposity from skin folds and the curvilinear relationship between external and internal adiposity. Metabolism 1956;51:346-52. 10. Genant HK, Cann CEo Spinal osteoporosis: advanced assessment using quantitative computed tomography. In: Genant HK, ed. J Spine Update, 1984. San Francisco: Radiology Research and Education Foundation, 1983: 331-4. II. Elasser U, Reeve J. Bone density measurement with computed tomography. Br Med Bull 1980;36:293-6. 12. Pacifici R, Susman N, Carr PL, Birge SJ, Avioli LV. Single and dual energy tomographic analysis of spinal trabecular bone: a comparative study in normal and osteoporotic women. J Clin Endocrinol Metab 1987;64:209-14. 13. Goldsmith NF, Johnston JO. Bone mineral: effects of oral contraceptives, pregnancy and lactation. J Bone Joint Surg [Am]1975;57A:657-68. 14. Lindsay R, Tohme J, Kanders B. The effect of oral contraceptive use on vertebral bone mass in pre- and postmenopausal women. Contraception 1986;34:333-40. 15. Nottestad SY, BaumelJJ, Kimmel DB. The proportion of trabecular bone in human vertebrae. J Bone Joint Surg [Am] 1987;22:221-9. 16. Ettinger B, Genant HK, Cann CEo Longterm estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 1985;102:319-24.