Menopause
Conditions
Brief summary
To investigate, relative to placebo and conjugated oestrogens, the efficacy, safety and tolerability of a 12 weeks peroral treatment twice daily with a cimicifuga racemosa extract corresponding to 20 mg, 75 mg or 150 mg plant material on menopause-related neurovegetative and mental complaints
Interventions
DRUGLow dose of Klimadynon®
DRUGMedium dose of Klimadynon®
DRUGHigh dose of Klimadynon®
DRUGOestrofeminal®
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Only postmenopausal (amenorrhea for 6 months at least) women may be enrolled in the study * Women after ovariectomy may also be enrolled if surgery was carried out at least 6 months prior to the enrollment. Only women between the age of 40 and 60 may be included * 2 weeks (control -1, week -2, day -14) before the beginning of the treatment the following hormone values must have been analyzed: * estradiol-17ß ≤ 0.15 nmol/l corresponding to ≤ 40 pg/ml and follicle stimulating hormone (FSH) ≥ 25 milliunits per milliliter (mU/ml) * These hormone analyses must be carried out at the competent local laboratory * In addition to other menopausal complaints the women must have hot flushes / outbreaks of sweating: * Diary: During the run-in period daily ≥ 3 hot flushes / outbreaks of sweating * Modified Menopause Rating Scale, 1st item twofold (week -2 and 0) ≥ 0.3 * A sum score taken twice from the modified (only items 1 - 6) Menopause Rating Scale within 2 weeks (week - 1 and 0) before the beginning of treatment must be ≥ 1.7 * In case of a pretreatment with estrogen a wash-out phase of 6 weeks is necessary in case of oral or transdermal administration. After the 4th week of wash-out the patient may be included in the run-in period
Exclusion criteria
* General criteria for exclusion: * Non-responder (= no therapeutic success) under a pretreatment with estrogen * Amenorrhea for \< 6 months * In case of an estrogen pretreatment last menstruation (menopause) \> 3 years earlier * Sum score of the modified Menopause Rating Scale (items 1 - 6) during the run-in period twice (week -2 and 0) \< 1.7 * No hot flushes / outbreaks of sweating (see Inclusion criteria) * At one of the appointments of the run-in period (week -2 and 0) more than one question of items 1 - 6 of the modified Menopause Rating Scale (MMRS) not answered * During the run-in period at the appointment week -2: estradiol-17ß \> 40 pg/ml corresponding to \> 0.15 nmol/l and FSH \< 25 mU/ml * Condition after hysterectomy * Simultaneous ingestion of estrogen-containing products in addition to the test products * Any addition ingestion of psychotropic drugs, antidepressants and sleeping aids (hypnotics / sedatives) * Treatment with another study drug in the 2 months preceding the beginning of the study * Considerable overweight (exceeding the target body weight \[height in cm minus 100\] by more than 30%) * Poor general condition * Alcohol or drug abuse * Poor compliance *
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of score in menopause-related symptom categories of the modified menopausal rating scale (MRS) | baseline, week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of menopause index according to Kupperman | Baseline up to day 98 | a 4 point numerical scale rating of 11 weighted menopause-related symptom complexes |
| Changes in daily frequency of menopausal lead symptoms | Up to day 105 | diary information |
| Changes from baseline in serum concentration of oestradiol-17ß | Up to day 98 | — |
| Changes from baseline in serum concentration of FSH | Up to day 98 | — |
| Changes from baseline in serum concentration of luteinising hormone | Up to day 98 | — |
| Changes from baseline in serum concentration of osteocalcin | Up to day 98 | — |
| Changes from baseline in serum concentration of ß-CrossLaps | Up to day 98 | — |
| Changes from baseline in serum concentration of bone specific alkaline phosphatase | Up to day 98 | — |
| Changes from baseline in serum concentration of cholesterol | Up to day 98 | — |
| Changes from baseline in serum concentration of high density lipoproteins | Up to day 98 | — |
| Changes from baseline in serum concentration of low density lipoproteins | Up to day 98 | — |
| Changes from baseline in serum concentration of triglycerides | Up to day 98 | — |
| Changes from baseline in serum concentration of glucose | Up to day 98 | — |
| Change of score of MRS items 7-10 and items 1-10 | baseline, week 12 | — |
| Assessment of global efficacy evaluated by patient and investigator on a 4-point rating scale | At day 98 | — |
| Changes from baseline in thickness of endometrium | Baseline, day 84 | measured in millimeters, assessed by transvaginal ultrasonography |
| Diary information regarding frequency, duration and intensity of vaginal bleeding on treatment | Up to day 105 | — |
| Changes from baseline for mammography/ ultrasonography assessment of the breasts | Baseline, day 98 | — |
| Changes from baseline in vital signs (blood pressure, heart rate) | Baseline up to day 98 | — |
| Number of patients with adverse events | Up to day 105 | — |
| Changes from baseline in clinical laboratory including coagulation parameters | Baseline, day 56, day 98 | — |
| Assessment for incidence of withdrawal bleeding upon peroral gestagen administration | At day 105 | — |
| Assessment of global tolerability evaluated by patient and investigator (4-point rating scale) | At day 98 | — |
| Change in scores of major climacteric complaints (MRS items 1, 4, 9, 10) | baseline, week 12 | — |
| Change in scores of somatic complaints (MRS items 1, 2, 8, 9, 10) | baseline, week 12 | — |
| Changes from baseline in body weight | Baseline up to day 98 | — |
| Changes from baseline in maturity index of the vaginal epithelium | Baseline, day 84 | — |
Outcome results
None listed