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Oral alendronate induces progressive increases in bone mass of the spine, hip and total body over 3 years in postmenopausal women with osteoporosis
80
Abstract
section
i Maturitas
0.001 vs. baseline) in the combined oestrogen medroxyprogesterone therapy group, compared to 4.0% (C.I. 2.445.7, PC 0.001 vs. baseline) in the unopposed oestrogen group (difference between means 2.6% (C.I. 0.8-4.4, P < 0.01). Conclusion: In osteoporotic postmenopausal women, I year of continuous combined oestrogenlmedroxyprogesterone therapy is associated with a 65’% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic postmenopausal women who have undergone hysterectomy, in order to maximizc the skeletal protection provided by hormone replacement therapy. Leisure, home and occupational physical activity and cardiovascular risk factors in postmenopausal women: The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study Greendale G.A. Bodin-Dunn L. lngles S. Haile R. BarrettConnor E. Div. o/’ GeneraI Internal Medicirle. UCLA School oj Medicine, 10833 Le Conte Aw, Los Angeles, CA 90024-l 736, USA .4RCH INTERN MED 1996: 156 (4): 418.-424. Objective: To examine the associations between self-reported leisure. home and occupational physical activity and selected cardiovascular risk factors. Methods: A cross-sectional analysis of baseline data from the Postmenopausal EstrogenProgestins Intervention Trial was performed in 851 women aged 45 -64 years. Outcomes were levels of high-density lipoprotein cholesterol, insulin (2 h after challenge), fibrinogen and systolic blood pressure. Race-stratified models were adjusted for age, smoking, alcohol and previous non-contraceptive estrogen use. Models were also run with body mass index as an additional covariate. Results: In white women, leisure physical activity was positively associated with levels of high-density lipoprotein cholesterol (P = 0.001) and inversely associated with levels of insulin (P= 0.04) and fibrinogen (P = 0.02). Compared with high-density lipoprotein cholesterol levels in the inactive and light leisure physical activity groups, moderate (P c 0.001) and heavy (P = 0.004) leisure activities were associated with higher high-density lipoprotein cholesterol levels. High-density lipoprotein cholesterol levels in the heavy leisure physical activity group were significantly higher than those in the moderate group (P = 0.01). Compared with lessrr levels of leisure physical activity. significantly lower mean values of fibrinogen (P = 0.02) and insulin (P = 0.01) were associated with the highest-intensity leisure physical activity. Home physical activity was positively related to highdensity lipoprotein cholesterol level (P = 0.01); relative to lower levels of home physical activity, the heavy home physical activity group demonstrated significantly higher mean highdensity lipoprotein cholesterol levels. The effects of leisure and home physical activities were independent of each other. Systolic blood pressure did not vary by leisure, occupational or home physical activity. Conclusion: The unique relationships between type of physical activity and cardiac risk factors underscore the necessity of including multiple domains of activity in epidemiologic studies of physical activity in women.
25 (1996)
77-82
Long term compliance with hormone replacement treatment following screening for postmenopausal osteoporosis by bone density measurements Ahmed AIH, Ryan PJ. Snelling T. Blake GM, Rymer J, Fogelman 1. Department of’ Obstetrics Gynaecology. 2nd Floor, New Guv k House, Guyk Hospital, St. Thomas Street, London SE1 9RT. UK J OBSTET GYNAECOL (GBr) 1996; 16 (1): 41-44. We contacted 352 postmenopausal women (mean age 52 years, range 45-80 years) by questionnaire 4 years after bone density measurements (all had responded to a previous postal survey 8 months after screening). Changes in compliance with hormone replacement and reasons for these changes were evaluated. Replies were received from 301 women (85%). One-hundred-and-thirteen (37%) were advised to take hormone replacement for skeletal protection and 90 (79%) complied. At 8 months, 69 (61%) were taking hormone treatment and at 46 months 52 (46%) were continuing treatment. Compliance was limited by uncertainties surrounding the risks vs. the benefits of treatment and the return of vaginal bleeding. Of those who commenced hormone replacement in response to advice, 53 (75%) were asymptomatic and low bone density was the only rationale for treatment. We conclude that recommendations for hormone replacement based on bone density measurements leads to markedly improved compliance with treatment compared with background use in the postmenopausal population and targets the group of women at highest risk for fracture. Oral alendronate induces progressive increases in bone mass of the spine, hip and total body over 3 years in postmenopausal women with osteoporosis Devogelaer JP, Broll H, Correa-Rotter R, Cumming DC, Nagant de Deuxchaisnes C. Geusens P, Hosking D, Jaegar P. Kaufman JM, Leite M, Leon J. Liberman U, Menkes CJ. Meunier PJ, Reid I, Rodriguez J, Romanowicz A. Seeman E. Vermeulen A. et al. Arthritis Unit. St. Luc Unicersity Hospital. Arenue Hippocrate IO, Brusse1.c B 1200, Belgium BONE 1996; 18 (2): 141ll50. To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, I9 centers enrolled 5 16 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 S.D. below the mean for young premenopausal women in a 3-year, double-blind. placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate. 5 or IO mg/day for 3 years: or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mgiday of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites, Non-significant mean decreases in BMD of the spine, femoral neck and trochanter of 0.6, 0.7 and 0.4%. respectively, occurred in the placebo group at 3 years. Relative to placebotreated patients, spine BMD increased by 5.4, 7.4 and 8.4% in the 5. IO and 20’5 mg ALN groups, respectively. Increases at
Absrrut
section
/I Muturitus
the femoral neck were 3.5. 5.5 and 4.3%. and those at the trochanter were 5.1. 7.2 and 7.2% respectively. Thus. efficacy of IO and 2015 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire j-year study duration in the ALN-treated groups and. compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confilmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary. IO mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women. Psychosexual adjustment among women receiving hormone replacement therapy for premature menopause following cancer treatmentMoadel AB, Ostroff JS, Lesko LM, Bajorunas DR. Psychiatry Service, Memorial Sloan-Kettering Cancer Ctr., 1275 York Avmrte, New York, NY, USA PSYCHO-ONCOLOGY 1995; 4 (4): 273-282. As a result of their cancer treatment, many young cancer survivors experience primary ovarian failure and subsequent premature menopause. This study examined the psychosexual adjustment of women who experience premature menopause due to cancer therapy. Severity of menopausal symptoms, relationship adjustment, body image and psychological distress were also assessed. Participants were 34 women (mean age 36 years) receiving hormone replacement therapy (HRT) for at least 3 months for early menopause following non-surgical treatment for cancer. Twenty-four healthy female peers with normal menses served as a comparison sample. Prematurely menopausal women demonstrated a higher prevalence of sexual dysfunction (P < 0.01 ), greater psychological distress (P -=z 0.02) and more distressing menopausal symptoms (P < 0.003) than the healthy women with normal menses. Twenty-eight women (82%) reported reduced sexual functioning, with I3 women (38%) meeting DSM-IV criteria for one or more sexual dysfunctions. Prematurely menopausal cancer survivors with diagnosable sexual dysfunctions tended to have greater menopausal symptoms, which itself was associated with higher psychologicd distress (P < 0.001). Menopausal symptoms and relationship adjustment together were the best predictors of sexual dysfunction (P < 0.07). Further exploration is needed of the factors contributing to psychosexual dysfunction and the development of clinical interventions for the psychosexual needs of women with cancer treatment-induced menopause. Sex hormones and alcohol withdrawal: Does a good supply of testosterone prevent serious symptoms during detoxification? Ruusa J, Bergman B. Department of Psychiutry, Karolinska institute, Huddinge Hospital. S- 141 86 Hudditlge, Sbceden ALCOHOL 1996: I3 (2): 139-145. Owing to the clinical similarity between the male climacteric syndrome and the results of previous studies on the alcohol withdrawal syndrome in relation to sex hormones, we
2.5 (1996)
77--&Z
XI
hypothesized that alcoholics with a poor supply of testoaterone will develop more pronounced symptoms during alcohol withdrawal than alcoholics with high levels of testosterone. Fifty-two male alcoholics were atudied. To test our hypothesis we entered the mean values of the hormones. the mean age and the mean consumption of liquor (CL) the week before admittance as regressors in a multiple forward stepwise regression analysis with four subclass constructed from the CPRS as dependent variables. Our results indicate that patients with low levels of testosterone develop more neurotic-asthenic symptoms. such as indecision, worrying about tribes, fatigability and lassitude during alcohol withdrawal. Further, high levels of SHBG were related to a history of seizures and younger alcoholics received higher ratings on the paranoid-aggressive subscale. It is concluded that there is a relation between levels of testosterone and symptoms during alcohol withdrawal. The question of a causal relationship remains to be answered, however. One way to illuminate this would be to add testosterone during detoxification. which may reduce the symptoms mentioned above analogous to the male climacteric syndrome. which could be prosperously treated by a supplement of testosterone. This treatment strategy would have obvious advantages compared to benzodiazepine detoxification as such drugs are potentially addictive. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy Ayton RA. Darling GM, Murkies AL. Farrell EA, Weisberg E, Selinus I, Fraser IS. 376 Albert Street. East Melbourne. Vie. 3002, Australia BR J OBSTET GYNAECOL 1996; 103 (4): 351-358. Objective: To compare the safety, efficacy and acceptability of a continuous low dose oestradiol releasing vaginal ring with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Design: An open, parallel. comparative multicentre trial. Setting: Sydney and Melbourne, Australia. Participants and Interventions: Onehundred-and-ninety-four postmenopausal women with symptoms and signs of urogenital atrophy were randomised on a 2:1 basis to I2 weeks of treatment with an oestrogen vaginal ring vs. an oestrogen cream. Main outcome measures and results: Equivalence (95% C.I.) was demonstrated between the two treatments for relief of vaginal dryness and dyspareunia. resolution of atrophic signs, improvement in vaginal mucosal maturation indices and reduction in vaginal pH. No significant difference was demonstrated in endometrial response to a progestogen challenge test and equivalence was demonstrated in the incidence of intercurrent bleeding episodes. The vaginal ring was significantly more acceptable than the cream (P < 0.0001). and was preferred to the cream (P < 0.001). Conclusion: With equivalent efficacy and safety and superror acceptability to vaginal cream. the low dose oestradiol vaginal ring is an advance in vaginal delivery systems for the treatment of urogenital atrophy.
Abstract
section
i Maturitas
0.001 vs. baseline) in the combined oestrogen medroxyprogesterone therapy group, compared to 4.0% (C.I. 2.445.7, PC 0.001 vs. baseline) in the unopposed oestrogen group (difference between means 2.6% (C.I. 0.8-4.4, P < 0.01). Conclusion: In osteoporotic postmenopausal women, I year of continuous combined oestrogenlmedroxyprogesterone therapy is associated with a 65’% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic postmenopausal women who have undergone hysterectomy, in order to maximizc the skeletal protection provided by hormone replacement therapy. Leisure, home and occupational physical activity and cardiovascular risk factors in postmenopausal women: The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study Greendale G.A. Bodin-Dunn L. lngles S. Haile R. BarrettConnor E. Div. o/’ GeneraI Internal Medicirle. UCLA School oj Medicine, 10833 Le Conte Aw, Los Angeles, CA 90024-l 736, USA .4RCH INTERN MED 1996: 156 (4): 418.-424. Objective: To examine the associations between self-reported leisure. home and occupational physical activity and selected cardiovascular risk factors. Methods: A cross-sectional analysis of baseline data from the Postmenopausal EstrogenProgestins Intervention Trial was performed in 851 women aged 45 -64 years. Outcomes were levels of high-density lipoprotein cholesterol, insulin (2 h after challenge), fibrinogen and systolic blood pressure. Race-stratified models were adjusted for age, smoking, alcohol and previous non-contraceptive estrogen use. Models were also run with body mass index as an additional covariate. Results: In white women, leisure physical activity was positively associated with levels of high-density lipoprotein cholesterol (P = 0.001) and inversely associated with levels of insulin (P= 0.04) and fibrinogen (P = 0.02). Compared with high-density lipoprotein cholesterol levels in the inactive and light leisure physical activity groups, moderate (P c 0.001) and heavy (P = 0.004) leisure activities were associated with higher high-density lipoprotein cholesterol levels. High-density lipoprotein cholesterol levels in the heavy leisure physical activity group were significantly higher than those in the moderate group (P = 0.01). Compared with lessrr levels of leisure physical activity. significantly lower mean values of fibrinogen (P = 0.02) and insulin (P = 0.01) were associated with the highest-intensity leisure physical activity. Home physical activity was positively related to highdensity lipoprotein cholesterol level (P = 0.01); relative to lower levels of home physical activity, the heavy home physical activity group demonstrated significantly higher mean highdensity lipoprotein cholesterol levels. The effects of leisure and home physical activities were independent of each other. Systolic blood pressure did not vary by leisure, occupational or home physical activity. Conclusion: The unique relationships between type of physical activity and cardiac risk factors underscore the necessity of including multiple domains of activity in epidemiologic studies of physical activity in women.
25 (1996)
77-82
Long term compliance with hormone replacement treatment following screening for postmenopausal osteoporosis by bone density measurements Ahmed AIH, Ryan PJ. Snelling T. Blake GM, Rymer J, Fogelman 1. Department of’ Obstetrics Gynaecology. 2nd Floor, New Guv k House, Guyk Hospital, St. Thomas Street, London SE1 9RT. UK J OBSTET GYNAECOL (GBr) 1996; 16 (1): 41-44. We contacted 352 postmenopausal women (mean age 52 years, range 45-80 years) by questionnaire 4 years after bone density measurements (all had responded to a previous postal survey 8 months after screening). Changes in compliance with hormone replacement and reasons for these changes were evaluated. Replies were received from 301 women (85%). One-hundred-and-thirteen (37%) were advised to take hormone replacement for skeletal protection and 90 (79%) complied. At 8 months, 69 (61%) were taking hormone treatment and at 46 months 52 (46%) were continuing treatment. Compliance was limited by uncertainties surrounding the risks vs. the benefits of treatment and the return of vaginal bleeding. Of those who commenced hormone replacement in response to advice, 53 (75%) were asymptomatic and low bone density was the only rationale for treatment. We conclude that recommendations for hormone replacement based on bone density measurements leads to markedly improved compliance with treatment compared with background use in the postmenopausal population and targets the group of women at highest risk for fracture. Oral alendronate induces progressive increases in bone mass of the spine, hip and total body over 3 years in postmenopausal women with osteoporosis Devogelaer JP, Broll H, Correa-Rotter R, Cumming DC, Nagant de Deuxchaisnes C. Geusens P, Hosking D, Jaegar P. Kaufman JM, Leite M, Leon J. Liberman U, Menkes CJ. Meunier PJ, Reid I, Rodriguez J, Romanowicz A. Seeman E. Vermeulen A. et al. Arthritis Unit. St. Luc Unicersity Hospital. Arenue Hippocrate IO, Brusse1.c B 1200, Belgium BONE 1996; 18 (2): 141ll50. To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, I9 centers enrolled 5 16 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 S.D. below the mean for young premenopausal women in a 3-year, double-blind. placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate. 5 or IO mg/day for 3 years: or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mgiday of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites, Non-significant mean decreases in BMD of the spine, femoral neck and trochanter of 0.6, 0.7 and 0.4%. respectively, occurred in the placebo group at 3 years. Relative to placebotreated patients, spine BMD increased by 5.4, 7.4 and 8.4% in the 5. IO and 20’5 mg ALN groups, respectively. Increases at
Absrrut
section
/I Muturitus
the femoral neck were 3.5. 5.5 and 4.3%. and those at the trochanter were 5.1. 7.2 and 7.2% respectively. Thus. efficacy of IO and 2015 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire j-year study duration in the ALN-treated groups and. compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confilmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary. IO mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women. Psychosexual adjustment among women receiving hormone replacement therapy for premature menopause following cancer treatmentMoadel AB, Ostroff JS, Lesko LM, Bajorunas DR. Psychiatry Service, Memorial Sloan-Kettering Cancer Ctr., 1275 York Avmrte, New York, NY, USA PSYCHO-ONCOLOGY 1995; 4 (4): 273-282. As a result of their cancer treatment, many young cancer survivors experience primary ovarian failure and subsequent premature menopause. This study examined the psychosexual adjustment of women who experience premature menopause due to cancer therapy. Severity of menopausal symptoms, relationship adjustment, body image and psychological distress were also assessed. Participants were 34 women (mean age 36 years) receiving hormone replacement therapy (HRT) for at least 3 months for early menopause following non-surgical treatment for cancer. Twenty-four healthy female peers with normal menses served as a comparison sample. Prematurely menopausal women demonstrated a higher prevalence of sexual dysfunction (P < 0.01 ), greater psychological distress (P -=z 0.02) and more distressing menopausal symptoms (P < 0.003) than the healthy women with normal menses. Twenty-eight women (82%) reported reduced sexual functioning, with I3 women (38%) meeting DSM-IV criteria for one or more sexual dysfunctions. Prematurely menopausal cancer survivors with diagnosable sexual dysfunctions tended to have greater menopausal symptoms, which itself was associated with higher psychologicd distress (P < 0.001). Menopausal symptoms and relationship adjustment together were the best predictors of sexual dysfunction (P < 0.07). Further exploration is needed of the factors contributing to psychosexual dysfunction and the development of clinical interventions for the psychosexual needs of women with cancer treatment-induced menopause. Sex hormones and alcohol withdrawal: Does a good supply of testosterone prevent serious symptoms during detoxification? Ruusa J, Bergman B. Department of Psychiutry, Karolinska institute, Huddinge Hospital. S- 141 86 Hudditlge, Sbceden ALCOHOL 1996: I3 (2): 139-145. Owing to the clinical similarity between the male climacteric syndrome and the results of previous studies on the alcohol withdrawal syndrome in relation to sex hormones, we
2.5 (1996)
77--&Z
XI
hypothesized that alcoholics with a poor supply of testoaterone will develop more pronounced symptoms during alcohol withdrawal than alcoholics with high levels of testosterone. Fifty-two male alcoholics were atudied. To test our hypothesis we entered the mean values of the hormones. the mean age and the mean consumption of liquor (CL) the week before admittance as regressors in a multiple forward stepwise regression analysis with four subclass constructed from the CPRS as dependent variables. Our results indicate that patients with low levels of testosterone develop more neurotic-asthenic symptoms. such as indecision, worrying about tribes, fatigability and lassitude during alcohol withdrawal. Further, high levels of SHBG were related to a history of seizures and younger alcoholics received higher ratings on the paranoid-aggressive subscale. It is concluded that there is a relation between levels of testosterone and symptoms during alcohol withdrawal. The question of a causal relationship remains to be answered, however. One way to illuminate this would be to add testosterone during detoxification. which may reduce the symptoms mentioned above analogous to the male climacteric syndrome. which could be prosperously treated by a supplement of testosterone. This treatment strategy would have obvious advantages compared to benzodiazepine detoxification as such drugs are potentially addictive. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy Ayton RA. Darling GM, Murkies AL. Farrell EA, Weisberg E, Selinus I, Fraser IS. 376 Albert Street. East Melbourne. Vie. 3002, Australia BR J OBSTET GYNAECOL 1996; 103 (4): 351-358. Objective: To compare the safety, efficacy and acceptability of a continuous low dose oestradiol releasing vaginal ring with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Design: An open, parallel. comparative multicentre trial. Setting: Sydney and Melbourne, Australia. Participants and Interventions: Onehundred-and-ninety-four postmenopausal women with symptoms and signs of urogenital atrophy were randomised on a 2:1 basis to I2 weeks of treatment with an oestrogen vaginal ring vs. an oestrogen cream. Main outcome measures and results: Equivalence (95% C.I.) was demonstrated between the two treatments for relief of vaginal dryness and dyspareunia. resolution of atrophic signs, improvement in vaginal mucosal maturation indices and reduction in vaginal pH. No significant difference was demonstrated in endometrial response to a progestogen challenge test and equivalence was demonstrated in the incidence of intercurrent bleeding episodes. The vaginal ring was significantly more acceptable than the cream (P < 0.0001). and was preferred to the cream (P < 0.001). Conclusion: With equivalent efficacy and safety and superror acceptability to vaginal cream. the low dose oestradiol vaginal ring is an advance in vaginal delivery systems for the treatment of urogenital atrophy.