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

Phase 3

Completed

Conditions: Menopause

Interventions: Drug: oral estradiol 1.0 mg
Drug: oral progesterone 100 mg

Registration Number: NCT02224313

Lead Sponsor: Intira Sriprasert

Brief Summary: The purpose of this study is to compare the vaginal health between premenopausal and postmenopausal women before and after using oral "estradiol" for 14 days then "estradiol" and "progesterone" for 14 days.

Detailed Description: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 20

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2.Postmenopausal women with hormones	oral estradiol 1.0 mg	Oral hormone therapy will be given to women in this group. Daily dose of oral "estradiol" 1 mg will be given the first 14 days after enrollment. Then a daily dose of oral "estradiol" 1 mg and "progesterone" 100 mg for 14 days will be given during the following 14 days.
2.Postmenopausal women with hormones	oral progesterone 100 mg	Oral hormone therapy will be given to women in this group. Daily dose of oral "estradiol" 1 mg will be given the first 14 days after enrollment. Then a daily dose of oral "estradiol" 1 mg and "progesterone" 100 mg for 14 days will be given during the following 14 days.

Primary Outcome Measures

Name	Time	Method
Vaginal Cytokines at Baseline	At baseline visit	Determine the differences in vaginal cytokines: interleukin (IL)-1β and IL-8 between premenopausal and postmenopausal women.

Secondary Outcome Measures

Name	Time	Method
Vaginal Cytokines During Follow-up	At 14 days and 28 days follow-up	Determine the changes in vaginal cytokines in postmenopausal women following treatment with estradiol then estradiol and progesterone compared to the normal menstrual cycle changes in young premenopausal women.