TY - JOUR
T1 - Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study.
AU - Nielsen, Therese F
AU - Ravn, Pernille
AU - Bagger, Yu Z
AU - Warming, Lise
AU - Christiansen, Claus
PY - 2004/2/1
Y1 - 2004/2/1
N2 - The aim of this study was to evaluate the efficacy of pulsed estrogen therapy (intranasal 17beta-estradiol) in the prevention of postmenopausal bone loss. A total of 386 women (40-65 years old), less than 5 years past menopause, were randomized to intranasal placebo, 17beta-estradiol 150 micro g, or 300 micro g daily for 2 years. Women with an intact uterus received micronised progesterone 200 mg per day, 14 days of each 28-day cycle. Women randomised to placebo-treatment received placebo progesterone. The primary endpoints were changes in BMD at the spine (L2-L4) and femoral neck. Secondary endpoints were changes in bone turnover markers: serum osteocalcin (sOC) as a marker of bone formation and urinary C-terminal telopeptides (uCTX) as a marker of bone resorption. BMD increased at all measured sites in women receiving active treatment in a dose-related manner, the difference compared to placebo being 5.2% and 6.7% at the spine, and 3.2% and 4.7 % at the hip, respectively, with 150 microg and 300 microg ( P<0.001). On the other hand, a decrease versus baseline of -3.2% and -3.3% at the spine and hip, respectively, was observed in women receiving placebo ( P<0.001). In the patients with at least one risk factor for osteoporotic fracture, the difference between placebo and 150 microg or 300 micro g was even higher at the spine (5.4% and 7.4%, respectively), and at the femoral neck (4.0% and 5.2%, respectively). Correspondingly, uCTX decreased from baseline by 39% and 46 %, and sOC by 22% and 27%, in the 150 micro g group and 300 micro g group (all P<0.001 versus placebo). A strong correlation was found between variations of bone turnover markers after 1 year and BMD after 2 years, emphasizing that bone markers can predict BMD response during hormonal treatment. Acceptability and general tolerance were good. This study demonstrates that pulsed estrogen therapy at the dose of 150 microg and 300-microg per day prevents bone loss in a dose-dependant manner at each site studied, and normalizes bone turnover markers to premenopausal levels.
AB - The aim of this study was to evaluate the efficacy of pulsed estrogen therapy (intranasal 17beta-estradiol) in the prevention of postmenopausal bone loss. A total of 386 women (40-65 years old), less than 5 years past menopause, were randomized to intranasal placebo, 17beta-estradiol 150 micro g, or 300 micro g daily for 2 years. Women with an intact uterus received micronised progesterone 200 mg per day, 14 days of each 28-day cycle. Women randomised to placebo-treatment received placebo progesterone. The primary endpoints were changes in BMD at the spine (L2-L4) and femoral neck. Secondary endpoints were changes in bone turnover markers: serum osteocalcin (sOC) as a marker of bone formation and urinary C-terminal telopeptides (uCTX) as a marker of bone resorption. BMD increased at all measured sites in women receiving active treatment in a dose-related manner, the difference compared to placebo being 5.2% and 6.7% at the spine, and 3.2% and 4.7 % at the hip, respectively, with 150 microg and 300 microg ( P<0.001). On the other hand, a decrease versus baseline of -3.2% and -3.3% at the spine and hip, respectively, was observed in women receiving placebo ( P<0.001). In the patients with at least one risk factor for osteoporotic fracture, the difference between placebo and 150 microg or 300 micro g was even higher at the spine (5.4% and 7.4%, respectively), and at the femoral neck (4.0% and 5.2%, respectively). Correspondingly, uCTX decreased from baseline by 39% and 46 %, and sOC by 22% and 27%, in the 150 micro g group and 300 micro g group (all P<0.001 versus placebo). A strong correlation was found between variations of bone turnover markers after 1 year and BMD after 2 years, emphasizing that bone markers can predict BMD response during hormonal treatment. Acceptability and general tolerance were good. This study demonstrates that pulsed estrogen therapy at the dose of 150 microg and 300-microg per day prevents bone loss in a dose-dependant manner at each site studied, and normalizes bone turnover markers to premenopausal levels.
KW - Administration, Intranasal
KW - Aged
KW - Biological Markers
KW - Bone Density
KW - Bone Remodeling
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Estradiol
KW - Estrogen Replacement Therapy
KW - Female
KW - Femur Neck
KW - Humans
KW - Lumbar Vertebrae
KW - Middle Aged
KW - Osteoporosis, Postmenopausal
U2 - 10.1007/s00198-003-1535-8
DO - 10.1007/s00198-003-1535-8
M3 - Journal article
C2 - 14647880
SN - 0937-941X
VL - 15
SP - 168
EP - 174
JO - Osteoporosis International
JF - Osteoporosis International
IS - 2
ER -