Effect of Oral Estradiol and Progesterone Therapy on Vaginal Cytokines in Postmenopausal Women

This research project recruits 10 healthy, premenopausal women (aged 20-40 years-old) with
regular menstrual cycle with interval of 24-35 days and duration of 2-7 days and 10 healthy
postmenopausal women (aged 45-60 years-old) with an intact uterus and at least 12 months but
not more than 36 months of spontaneous amenorrhea.

Premenopausal women will not receive any study medication(s). Postmenopausal women will be
assigned the intervention described below.

• Oral "estradiol" 1.0 mg tablet for 14 days, then oral "estradiol" 1.0 mg tablet and
"progesterone" 100 mg capsule for 14 days

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,
pH, whiff test and 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