Hormone Replacement Therapy for Use in Postmenopausal Women for Relief of Hot Flushes and Urogenital Symptoms.
Condition: Hormone Replacement Therapy
MeSH terms: Hot Flashes
Intervention: Estradiol acetate; Estradiol; Conjugated equine estrogens
Intervention description: Tablet containing 0.9 mg E3A, daily oral administration.; Tablet containing 1 mg estradiol, daily oral administration.; Tablet containing 0.625 mg CEE, daily oral administration.
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Estrogens; Estrogens, Conjugated (USP)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 249.0
Sex: Female
Minimum age: 35 Years
Healthy volunteers: No

Summary:

      Multicenter, double-blind, controlled, parallel group, randomized study to compare the
      clinical benefit of Estradiol acetate tablets, estradiol tablets and conjugated equine
      estrogen tablets, each administered orally, once daily, to postmenopausal women.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 40 years of age; bilateral oophorectomy ≥ 35 years of age.

          2. Non-hysterectomized women:

               -  Amenorrhea for ≥ 12 months or

               -  Amenorrhea for ≤ 12 months, but longer than 6 months, and serum FSH (follicle
                  stimulating hormone) levels > 40 units/L and serum estradiol levels < 20 pg /mL,

             Hysterectomized women:

               -  Bilateral oophorectomy - subjects may enter the study 6 weeks after surgery or

               -  History of removal of ovaries may be confirmed by - serum FSH levels > 40 units/L
                  and serum estradiol levels < 20 pg/mL or via surgical report / ultrasound.

          3. Seven or more moderate or severe hot flushes daily for 1 week or 60 or more moderate
             or severe flushes in 1 week during the 2 week screening period prior to study entry.

        Exclusion Criteria:

          1. Hormone therapy administered via the following routes and during the specified
             timeframes: oral within 8 weeks, vaginal (rings, creams, gels) within 1 week,
             transdermal within 4 weeks, intramuscular within 6 weeks, progestational implants,
             estrogen or estrogen/progestational injectable drug therapy within 3 months, estrogen
             pellet or progestational injectable within 6 months.

          2. Abnormal Pap smear suggestive of low grade squamous intraepithelial lesion (LGSIL) or
             worse. Enrollment of subjects with an ASCUS (atypical squamous cells of undetermined
             significance) interpretation must be discussed with the sponsor prior to
             randomization.

          3. Urinary tract infection

          4. Congestive heart failure

          5. Uncontrolled hypertension; sitting systolic BP ≥ 160 mmHg or diastolic ≥ 95 mmHg

          6. History of stroke or transient ischemic attacks

          7. Treatment with anticoagulants (heparin or warfarin).

          8. Uncontrolled thyroid disorders.

          9. Insulin-dependent diabetes mellitus.

         10. Increase frequency or severity of headaches including migraines during previous
             estrogen therapy.