Clinical trial NCT02224313 (phase 3, status: completed)
Conditions: menopause
ICD codes: E28.310, E28.319
Drugs: oral estradiol 1.0 mg, oral progesterone 100 mg
SMILES: [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3, [H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Eligibility criteria:

        Inclusion Criteria:

          -  Premenopausal and Postmenopausal women:

               1. Female between the ages of 20 and 40 years (premenopausal arm), OR be a female
                  between the ages of 45 and 65 years (postmenopausal arm) willing to participate
                  in the study, as documented by signing the informed consent form.

               2. Postmenopausal women with an intact uterus and at least 12 months of spontaneous
                  amenorrhea (postmenopausal arm), OR be a premenopausal women with regular
                  menstrual cycle with interval of 24-35 days and duration of 2-7 days
                  (premenopausal arm).

               3. No oral hormone therapy for 8 weeks and transdermal or vaginal hormone therapy
                  for 4 week prior to the study.

               4. Willing to use oral hormone therapy during the study period (postmenopausal women
                  only).

               5. Willing to abstain from using products (other than study medication) that contain
                  estrogen, progestin, or progesterone throughout study participation.

               6. Have general good health.

               7. Willing to refrain from sexual intercourse for 48 hours before vaginal sample
                  collection.

               8. Willing to abstain from use of vaginal product 7 days before vaginal sample
                  collection.

        Exclusion Criteria:

          -  To participate in the study, a subject must NOT

               1. Be allergic to estrogen or progesterone products

               2. Have active genital infection or inflammation based on vaginal wet preparation,
                  power of hydrogen (pH), whiff test and potassium hydroxide (KOH) preparation 2.1
                  Vulvovaginal candidiasis, trichomonas vaginitis or bacterial vaginitis 2.2
                  Sexually transmitted diseases including herpes simplex viral infection, gonorrhea
                  and Chlamydia

               3. Have a known contraindication for oral hormone therapy or allergy to use of
                  estradiol and/or progesterone

               4. Have used estrogen alone or estrogen/progestin for any of the following time
                  periods:

                  4.1 Vaginal hormone products (ring, cream, gels) within 30 days prior to
                  screening 4.2 Transdermal estrogen alone or estrogen/progestin products within 4
                  weeks prior to screening 4.3 Oral estrogen and/or progestin therapy within 8
                  weeks prior to screening 4.4 Progestational implants, estrogen or
                  estrogen/progestational injectable drug therapy within 3 months prior to
                  screening 4.5 Estrogen pellet therapy or progestational injectable drug therapy
                  within 6 months prior to screening 4.6 Percutaneous estrogen lotions/gels within
                  4 weeks prior to screening

               5. Have used tamoxifen, raloxifene or other selective estrogen receptor modulators
                  (SERMs) therapy within 8 weeks prior to screening

               6. Have used an intrauterine device (IUD) within 8 weeks prior to screening

               7. Have used vaginal products (pessary, tampon, tablets, douching) within 7 days
                  prior to screening

               8. Have evidence of cervical, vaginal, or vulvar intraepithelial neoplasia or cancer

               9. Have a past or current history breast cancer, endometrial cancer or endometrial
                  hyperplasia, hypertriglyceridemia or venous thromboembolism

              10. Be an immuno-compromised patient including those with human immunodeficiency
                  viral infection, chronic glucocorticoid use or active treatment with
                  immunosuppressive agents

              11. Have a history of or current evidence of thromboembolism

              12. Have evidence of uncontrolled Hypertension Blood pressure >140/100 mmHg

              13. Have confirmed Diabetes Mellitus

              14. Currently smoking

              15. For sexually active premenopausal women, should be protected against pregnancy by
                  sterilization, condom use, abstinence, or same sex relationship