Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate.
OBJECTIVE
To evaluate the effect on bone mineral density of vaginal rings delivering estradiol acetate at two systemic doses versus a locally active vaginal ring in healthy postmenopausal women.


METHODS
A total of 174 postmenopausal women (younger than age 65 years) were randomly assigned to a 0.05 mg/day vaginal ring, 0.1 mg/day vaginal ring, or 0.0075 mg/day vaginal ring (active comparator), and treated for 96 weeks. Of these, 170 took a study drug; 85 taking the study drug had data at 96 weeks, and 132 women were included in the intent-to-treat analysis. Non-hysterectomized women received 1 mg of norethisterone taken on the last 12 days of each 28-day monthly cycle. The primary endpoint was change in lumbar spine bone mineral density (L2-L4); change in total hip bone mineral density was a secondary endpoint.


RESULTS
At 96 weeks, mean lumbar spine bone mineral density increased 2.7% and 3.3% from baseline, respectively, in the 0.05-mg and 0.1-mg groups (P < 0.001 for both) compared with an 0.3% increase in the 0.0075-mg group (P = 0.56). Mean total hip bone mineral density increased 1.7% and 1.8% from baseline, respectively, in both the 0.05-mg and 0.1-mg groups (P < 0.001) and decreased 1.2% in the 0.0075-mg group (P = 0.001). All vaginal ring doses were well tolerated.


CONCLUSIONS
Vaginal rings delivering systemic doses of estradiol increase bone mineral density of the lumbar spine and total hip in healthy postmenopausal women. Safety and acceptability were similar to existing estradiol therapies.
Al-Azzawi
Farook
F
Gynecology Research Unit, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK. farookalazzawi@yahoo.co.uk
Lees
Belinda
B
Thompson
John
J
Stevenson
John C
JC
D000282:Administration, Intravaginal; D000328:Adult; D000465:Algorithms; D015519:Bone Density / Q000187:drug effects*; D003274:Contraceptive Devices, Female; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D017698:Postmenopause; D011355:Prodrugs; D011446:Prospective Studies; D006113:United Kingdom
D011355:Prodrugs; D004958:Estradiol