Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.
OBJECTIVE
To compare the effects of a 12-week treatment with 17ss-estradiol given alone and in sequential combination with 3.75 mg of nomegestrol acetate (Naemis), or a placebo on biochemical markers of bone turnover in menopausal women.


METHODS
A double-blind, randomized, placebo and estradiol-controlled multicenter study was conducted. A total of 176 patients who had been menopausal for 1-10 years, hysterectomized or not, having no contraindications to hormone replacement therapy, without any risks factors for osteoporosis, received one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E(2)) or 1.5 mg E(2)/3.75 mg nomegestrol acetate (E(2)/NOMAC). The primary efficacy variables were the change in bone markers (total alkaline phosphatase, bone alkaline phosphatase and osteocalcin; urinary type-I collagen peptides).


RESULTS
The four biochemical markers decreased only in the E(2)/NOMAC group. Bone alkaline phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the E(2) group. For both active treatment groups compared to the placebo group, the changes were statistically significant after a 12-week treatment. There were no statistically significant differences between the E(2) and the E(2)/NOMAC groups except for total serum alkaline phosphatase, whose mean value decreased in the E(2)/NOMAC group but increased slightly in the E(2) group (p < 0.001). Furthermore, after a 6-week treatment, the changes in biochemical markers of bone turnover were similar to those found after 12 weeks. Safety data were satisfactory with regard to estradiol given alone or in combination with nomegestrol acetate.


CONCLUSIONS
These results demonstrated that 1.5 mg E(2) is effective in reducing bone turnover in postmenopausal women and proved that the combination of 1.5 mg E(2) and 3.75 mg nomegestrol acetate has no deleterious effect on bone remodelling.
Nguyên-Pascal
M L
ML
Laboratoire Théramex, Paris, France.
Thomas
J L
JL
Bergougnoux
L
L
Garnero
P
P
Drapier-Faure
E
E
Delmas
P D
PD
D000469:Alkaline Phosphatase / Q000032:analysis; D015415:Biomarkers; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008535:Megestrol / Q000494:pharmacology*; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009649:Norpregnadienes / Q000494:pharmacology*; D015675:Osteocalcin / Q000032:analysis; D010455:Peptides / Q000652:urine; D045167:Progesterone Congeners / Q000494:pharmacology; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D015415:Biomarkers; D024042:Collagen Type I; D009649:Norpregnadienes; D010455:Peptides; D045167:Progesterone Congeners; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D004958:Estradiol; C038501:nomegestrol acetate; D003094:Collagen; D008535:Megestrol; D000469:Alkaline Phosphatase