[Comparative study on two different dosages of conjugated equine estrogen continuously combined with medroxyprogesterone in prevention of postmenopausal osteoporosis].
OBJECTIVE
To investigate the effects of two dosages of conjugated equine estrogen (CEE) in preventing bone loss in early postmenopausal women.


METHODS
Two hundreds and thirty six early postmenopausal women were randomly given one of the following regimens for two years. Groups A (GA): CEE 0.625 mg + medroxyprogesterone (MPA domestic made) 2 mg + caltrate-D (Ca-D) 1 tablet daily; Group B (GB): CEE 0.3 mg + MPA 2 mg + Ca-D 1 tablet daily; Group C (GC): Ca-D 1 tablet daily alone. The observation endpoints included: (1) bone mineral density (BMD) of lumbar 2 - 4 (L(2 - 4)) measured by duel energy X-ray absorptiometry (DEXA, Lunar DPX-L) before and 1, 2 years after treatment; (2) vaginal bleeding recorded daily and endometrium thickness yearly by transvaginal ultrasonography. Endometrium biopsies were performed if its thickness greater than 5 mm.


RESULTS
Two hundreds and thirteen (90%) cases completed 1-year study, 176 (75%) 2 year study. In GA L(2 - 4) BMD significantly increased both after 1 and 2 year treatment as compared with pretreatment value (P < 0.001). While in GB, L(2 - 4) BMD significantly elevated only after 1 year treatment, but did not reach significance during the end of 2 year therapy. In contrast, L(2 - 4) BMD decreased by 0.4% and 1.6% respectively after 1, 2 year of GC although without significance. Compared among the three group, the increments of mean L(2 - 4) BMD after 1 year treatment in GA and GB were significantly different from, that in GC (+2.3%, +2.7% versus -0.4%, P < 0.001, P < 0.05 respectively). So were the values after 2 year treatment (+3.7%, +0.7% versus -1.6%, P < 0.001, P < 0.05 respectively). As compared the mean L(2 - 4) BMD between GA and GB, the difference reached significance only after 2 year (P < 0.01), but not after 1 year treatment (P > 0.05). The vaginal bleeding rate in GA during the first month and 1, 2 year after treatment were higher than those in GB and GC (52% versus 16%, 9%; 43% versus 12%, 2.8%; 34% versus 8%, 3.3%). Endometrium biopsies were carried in 153 cases (27 had endometrium thicker than 5 mm) in GA and GB. No atypical hyperplasia was found, but 2 cases showed simple hyperplasia in the GA. One case in GA developed superficial thromphlebitis during the 1 year treatment.


CONCLUSIONS
Both 0.625 mg and 0.3 mg daily of CEE continuously combined with domestic MPA are effective in preventing postmenopausal osteoporosis. The former has more stronger effect than the latter, but needs higher dose of MPA when combined continuously in order to decrease the vaginal bleeding rate and preventing endometrium hyperplasia.
Department of Obstetrics and Gynecology, Beijing Hospital, Beijing 100730, China.
Yiyong
Y
Wu
Jianli
J
Liu
Shumin
S
Xing
Rulan
R
Xu
Zhonglan
Z
Zhang
Ying
Y
Wang
D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006736:Horses; D006801:Humans; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology / Q000517:prevention & control*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D000469:Alkaline Phosphatase; D008525:Medroxyprogesterone