Continuous-combined treatment of the menopause with combinations of oestradiol valerate and dienogest - a dose-ranging study.
OBJECTIVE
To determine the progestational efficacy of continuous treatment with various doses of dienogest, combined with oestradiol valerate, on the basis of endometrial histology, effect on climacteric symptoms and bleeding profile in postmenopausal women.


METHODS
Patients were randomised to one of five fixed-combination treatments, oestradiol valerate 2.0 mg plus dienogest 0.5, 1.0, 2.0, 3.0 or 4.0 mg. Efficacy was assessed by endometrial biopsy, menstrual charts and change in climacteric symptoms.


RESULTS
The endometrium was classified as atrophic in 20.0, 31.3, 25.0, 55.6 and 57.1% of patients in the 0.5, 1.0, 2.0, 3.0 and 4.0 mg dienogest groups, respectively. The frequency of uterine bleeding was dose-dependent. The most favourable bleeding profile was seen in the 3.0 mg dienogest group, whereas the lower doses of dienogest had advantages with respect to the efficacy of the combined preparation.


CONCLUSIONS
Dienogest 2.0 and 3.0 mg are the optimal doses for combination with 2.0 mg oestradiol valerate for continuous-combined hormone replacement therapy.
Gräser
T
T
Department of Clinical Research, Jenapharm GmbH & Co. KG, Otto-Schott-Strasse 15, 07745, Jena, Germany. thomas.graeser@jenapharm.de
Müller
A
A
Mellinger
U
U
Mück
A O
AO
Lippert
T H
TH
Oettel
M
M
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005858:Germany; D020249:Hormone Replacement Therapy; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045167:Progesterone Congeners / Q000008:administration & dosage* / Q000627:therapeutic use
D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; C023635:dienogest; D004958:Estradiol; D009277:Nandrolone