Conditions: Menopause
Keywords: Vasomotor symptoms Hot flashes Endometrial protection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1845
Healthy volunteers: no

Brief summary:
This study will be a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial of postmenopausal subjects with an intact uterus.

Detailed description:
Postmenopausal subjects with an intact uterus who meet the study entry criteria will be randomized to one of five treatment arms (four active and one placebo) and followed for 12 months. During the Screening period all subjects will be provided with a diary to self-assess the frequency and severity of their vasomotor symptoms. Subjects experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will participate in a VMS Substudy during the first 12 weeks of treatment. The Substudy subjects will be stratified by treatment arm within the sites, and only Substudy subjects have the possibility of being randomized to placebo. Subjects who qualify for the study except for experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will be stratified within sites to one of the four active treatment arms and followed for 12 months, but will not participate in the VMS Substudy. (However, VMS information will be collected from all subjects during the first 12 weeks of treatment.) All Study Subjects: Postmenopausal women with an intact uterus who seek relief from hot flushes and meet all other inclusion/exclusion criteria are eligible for 12 months of study treatment.

VMS Substudy Subjects: A subset of All Study Subjects who have ≥7 per day or ≥50 per week moderate to severe hot flushes (as determined during Screening) are eligible for the 12-week VMS Substudy and for a total of 12 months of study treatment.

Clinical evaluations will be performed at the following time points:

* Screening Period (Week: - 8.5) (up to -60 Days)
* Visit 1 Randomization (Week 0) (Day 1)
* Visit 2 Interim (Week 4)
* Visit 3 Interim (Week 8)
* Visit 4 Interim (Week 12)
* Visit 5 Interim (Month 6)
* Visit 6 Interim (Month 9)
* Visit 7 End of Treatment (Month 12)

Arms:
arm 1: Combined Estradiol 1 mg / Progesterone 100 mg softgel capsule formulation and placebo taken orally once a day for twelve months. arm 2: Combined Estradiol 0.5 mg / Progesterone 100 mg softgel capsule formulation and placebo taken orally once a day for twelve months. arm 3: Combined Estradiol 0.5 mg / Progesterone 50 mg softgel capsule formulation and placebo, taken orally once a day for twelve months. arm 4: Combined Estradiol 0.25 mg / Progesterone 50 mg softgel capsule formulation and placebo, taken orally once a day for twelve months. arm 5: Two Placebo softgel capsules taken orally once a day for twelve months.

Interventions: intervention 1: Estradiol intervention 2: Progesterone intervention 3: Placebo
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document: