Efficacy of Gynodian® Depot in Women With Impaired Well-being
Efficacy of Gynodian® Depot in Women With Impaired Well-being
The typical menopausal symptoms that are associated with a variety of physical and
 psychological changes (e.g. nervousness, anxiety, and depression) and also with impaired
 sexual interest and enjoyment are caused by a lack of estrogen, a female sex hormone produced
 inside the body. To treat these symptoms, women who are postmenopausal can receive a therapy
 called 'hormone replacement therapy' (the dosage of hormones to replace the body's deficient
 hormones), for instance, with estrogen preparations injected into a muscle.In women with a
 uterus estrogen use causes the lining of the womb (endometrium) to grow (thicken) as before
 the menopause. With long-term use this may lead to pathological changes of the endometrium.
 That is why this therapy should be complemented by the estrogens' natural counterbalance,
 progesterone (progestogen), at a certain interval. This causes the lining of the womb to
 shed, with monthly bleeding like a normal period, thus avoiding excessive endometrial
 growth.Estrogen treatment is well known to relieve psychological complaints. The combination
 of an estrogen with a weak androgen (in this case Dehydroepiandrosterone (DHEA)) is presumed
 to clearly increase this effect. The present clinical study is to prove that Gynodian? Depot
 as a combination of estrogen and androgen has a better effect on psychological complaints and
 sexuality in postmenopausal women than has treatment with the estrogen Estradiol valerate
 alone.All patients will receive the same therapy, but differing in sequence. Either they
 receive Gynodian? Depot during the first five cycles and the estrogen-only preparation during
 cycles 6-10 (treatment group 1) or they receive the study medication in reverse order
 (treatment group 2). Patients will be assigned to one of the two groups at random. In either
 case they will be given an injection into the gluteal muscle every four weeks.Women with an
 intact uterus, in addition to the injections (the day of the injection being the 1st day of a
 cycle) have to take a tablet containing 5 mg Medroxyprogesterone acetate (MPA) (progestogen)
 per day for 14 days (cycle days 15-28) to enable the endometrium to shed in a monthly
 period.The study will extend over a total period of about 11 months, during which the patient
 will have 16 appointments for examinations.After patient has signed on the informed consent
 form for participation in this clinical study, the investigator will ask her, which diseases
 she has at the moment or has had during the past 12 months and which medicinal products she
 has been taking. Subsequently, she will have a gynecological examination (including the
 breasts) as well as a general physical examination. Blood pressure, heart rate as well as
 body height and weight will be measured and noted down. In addition, the doctor will question
 her about physical and psychological menopausal complaints by means of two different, short
 questionnaires. Only if the evaluation of these two questionnaires shows that she is eligible
 for the participation in this clinical study, will the following actions be carried
 through.Approx. 40 ml blood will be taken from the patient for a thorough laboratory test
 including her hormone levels, and she will be asked for a urine sample. Additionally, she
 will have a vaginal ultrasound examination of the womb lining, a cervical smear test (unless
 already done during the last three months), and an x-ray examination of the breasts
 (mammography) (unless already done during the last 12 months).These measures will be repeated
 at Final visit.About 3 weeks after visit 1, when the investigator has the results of all
 tests prescribed at visit 1, the patient will be asked to appear for visit 2.If the patient
 is eligible for a participation in this clinical study, she will be given the first injection
 of the study medication.During the following visits, injections will be given, blood pressure
 and pulse rate as well as body weight will be measured and blood will be drawn to measure the
 hormone levels.All procedures will apply also during the second treatment period. When
 switching to the second treatment period a physical and gynecological examination will
 additionally be performed.Questionnaires have to be filled in by the patient at different
 time points during the study.
The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been
 renamed to Bayer Schering Pharma AG, Germany.Bayer Schering Pharma AG, Germany is the sponsor
 of the trial.
Inclusion Criteria:

 -  Written informed consent

 -  Postmenopausal status (amenorrhea for at least 12 months)

 -  45 - 65 years of age

 -  Application of estrogen or cyclic estrogen/progestin preparation other than the study
 medication for at least 6 months prior to Visit 1

 -  Relevant impairment of well-being and mood inspite of estrogen therapy (confirmed by
 questionnaire scores)

 -  BMI<33kg/m2

 Exclusion Criteria:

 -  Uterine bleeding of unknown etiology within the last 2 years

 -  Previous or existing or suspected carcinoma of the breast

 -  Any malignant disease in the last 5 years

 -  Endometrial double layer thickness > 5 mm

 -  History of thromboembolic events or existing thromboembolic processes

 -  Prior hormone replacement therapy with androgens within 12 months prior to Visit 1

 -  Major life events within the last 12 months prior to Visit 1