Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.
OBJECTIVE
To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis.


METHODS
A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily.


RESULTS
BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo).


CONCLUSIONS
The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.
Warming
L
L
Center for Clinical and Basic Research A/S, Ballerup, Denmark.
Ravn
P
P
Nielsen
T
T
Christiansen
C
C
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000736:Androstenes / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010446:Peptide Fragments / Q000097:blood / Q000652:urine; D045167:Progesterone Congeners / Q000627:therapeutic use; D011446:Prospective Studies; D014463:Ultrasonography
D000736:Androstenes; D015415:Biomarkers; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D045167:Progesterone Congeners; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D004958:Estradiol; D003094:Collagen; D002784:Cholesterol; D000469:Alkaline Phosphatase; C035144:drospirenone