Levonorgestrel and 17beta-estradiol given transdermally for the prevention of postmenopausal osteoporosis.
OBJECTIVE
To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis.


METHODS
212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S.D. of the premenopausal mean value) postmenopausal women aged 45-65 years participated in a 2-year prospective study. Treatments were 45 microg 17beta-estradiol combined with 30 (n = 69) or 40 microg (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day patch. All received a daily supplement of 500 mg calcium. BMD at lumbar spine (L2-L4), hip and total body, as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase (sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured regularly.


RESULTS
BMD at the lumbar spine, hip and total body increased by 8, 6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from baseline (all P < 0.001)), except for uCa that did not change significantly. No significant dose-related effect of levonorgestrel was found. Vaginal bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the study period. Skin tolerance was good in 84% of the women with no difference between the study groups. No incidences of endometrial hyperplasia, uterine or mammary cancer occurred.


CONCLUSIONS
The transdermal combination of 17beta-estradiol and levonorgestrel has a positive effect on BMD in an osteopenic postmenopausal population. Furthermore, a high safety profile was observed.
Warming
L
L
Center for Clinical and Basic Research A/S, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. ig@ccbr.dk
Ravn
P
P
Christiansen
C
C
D000279:Administration, Cutaneous; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D003094:Collagen / Q000652:urine; D003280:Contraceptives, Oral, Synthetic / Q000627:therapeutic use*; D004311:Double-Blind Method; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000627:therapeutic use*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010446:Peptide Fragments / Q000652:urine; D011446:Prospective Studies; D016896:Treatment Outcome
D015415:Biomarkers; D003280:Contraceptives, Oral, Synthetic; D010446:Peptide Fragments; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D004958:Estradiol; D016912:Levonorgestrel; D003094:Collagen; D000469:Alkaline Phosphatase