Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response.
OBJECTIVE
The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E2-valerate.


METHODS
One-year prospective multicentre randomised control trial.


METHODS
Four outpatient clinics in Oulu, Helsinki and Jyväskylä, Finland.


METHODS
A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT).


METHODS
Subjects were randomly allocated to receive a new intrauterine system releasing 10 microg of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20 microg of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E2-valerate.


METHODS
Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy.


RESULTS
Insertion of the smaller 10 microg levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10 microg levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20 microg levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10 microg and 20 microg of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel.


CONCLUSIONS
Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10 microg system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.
Raudaskoski
T
T
Department of Obstetrics and Gynaecology, Oulu University Hospital, Finland.
Tapanainen
J
J
Tomás
E
E
Luotola
H
H
Pekonen
F
F
Ronni-Sivula
H
H
Timonen
H
H
Riphagen
F
F
Laatikainen
T
T
D000282:Administration, Intravaginal; D000284:Administration, Oral; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage*; D008525:Medroxyprogesterone / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D045167:Progesterone Congeners / Q000008:administration & dosage*; D011446:Prospective Studies; D014592:Uterine Hemorrhage / Q000517:prevention & control
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D045167:Progesterone Congeners; D004958:Estradiol; D016912:Levonorgestrel; D005640:Follicle Stimulating Hormone; D008525:Medroxyprogesterone; D015232:Dinoprostone