Study of DARE-HRT1 Over 12 Weeks in Healthy PostMenopausal Women

Inclusion Criteria: 1. Postmenopausal women with a body mass index (BMI) ≥ 18 and ≤ 38 kg/m2. BMI = weight (kg)/(height \[m\])2 Postmenopausal is defined as 12-months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy (although participants who have had a hysterectomy are not eligible for this study). The investigator will need to determine if a participant's BMI falling within the obese-severely obese range could potentially interfere with the protocol-required procedures, specifically the pelvic examinations described in Inclusion Criterion #2. Any participant whose BMI is determined to fall into this category should be excluded from trial participation. 2. Normal cervix, vagina, uterus, and adnexa based on speculum examination and bimanual examination. 3. Normal transvaginal ultrasound, and endometrial biopsy results as follows: * If endometrial thickness is ≤ 4.0 mm in a participant without postmenopausal vaginal bleeding, an endometrial biopsy is not indicated for the purposes of screening, * If endometrial thickness is \> 4.0 mm ≤ 6.0 mm in a participant without postmenopausal vaginal bleeding, an acceptable result from an evaluable screening endometrial biopsy, evaluated by a pathologist, is required for inclusion into the study. Tissue must be read as benign, inactive, or atrophic endometrium by at least 1 pathologist, 4. Current on all Australian screening requirements for cervical cancer. 5. Able and willing to correctly and independently complete all study procedures. 6. Able and willing to stop any ongoing HRT in accordance with the appropriate washout periods (see Section 4.1 for washout requirements). Participants who are using HRT that requires more than 8 weeks to wash out (e.g., progestogen implants or progestogen injectable drug therapy, estrogen alone injectable drug therapy or estrogen pellet therapy) will not be eligible. 7. Able to read, understand, and provide written informed consent after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures. 8. Normal mammogram report within 24 months of screening. Exclusion Criteria: 1. Prior abnormal cervical screening test or Papanicolaou result within 2 years of screening. Participant can have atypical squamous cells of undetermined significance, if human papillomavirus negative. 2. Participants with any self-reported active sexually transmitted disease and/or evidence of infection based on vaginal visual examination by the investigator. 3. Participants with a urinary tract infection during screening as assessed by urine dipstick test with abnormal test findings (any positive result for leukocytes AND any positive result for nitrites). 4. Have a history of endometrial hyperplasia or cervical or uterine carcinoma. 5. Participants with indwelling catheters or requiring intermittent catheterization. 6. Participants with multiple or unsuccessful (e.g., still having symptoms) pelvic reconstructive surgery, or who suffer from pelvic relaxation. 7. Participants who have had a hysterectomy. 8. Participants taking any estrogen and/or progesterone products who are not willing to stop this treatment during their participation in this trial (see Section 4.1 for washout requirements). Participants who are using HRT that requires more than 8 weeks to wash out (e.g., progestogen implants or progestogen injectable drug therapy, estrogen alone injectable drug therapy or estrogen pellet therapy) will not be eligible. 9. Participants with concomitant use of personal lubricants (water-based lubricants are allowed) or any intravaginal product or medication, either by prescription or over-the-counter (OTC) (e.g., Femring \[estradiol acetate vaginal ring\], ESTRING® \[estradiol vaginal ring\]) with the exception of those who agree not to use these products during the IVR use period. 10. Self-reported or observed vaginal irritation unrelated to VVA; vaginal, vulvar, or cervical lesions, undiagnosed vaginal bleeding; or tenderness. 11. Participants with a finding of clinically significant uterine fibroids at screening. 12. Participants with a known hypersensitivity to progesterone, estradiol, Femring, or the components of the IVR (e.g., ethylene vinyl acetate). 13. Participants with prior pelvic malignancies. 14. Participants with a history of any severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or study treatment administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into the trial. This includes but is not limited to the following: 1. Human immunodeficiency virus (HIV) infection (confirmed by medical history/ serology testing), 2. Active chronic hepatitis B or hepatitis C infection including hepatitis B surface antigen and hepatitis C antibody positive participants with or without abnormal liver enzymes (confirmed by medical history/serology testing), 3. Concurrent neurodegenerative disease, 4. Cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 6 months, serious uncontrolled cardiac arrhythmia, use of Class 1 antiarrhythmic medications, or history of venous thromboembolism or stroke, 5. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol, 6. Participants with known thrombophilias may not participate in this study because estrogen-based products are contraindicated for them, 7. Symptomatic bacterial vaginosis. 15. Fasting triglyceride of \> 3.39 mmol/L and/or total cholesterol of \> 7.77 mmol/L. 16. Aspartate aminotransferase or alanine aminotransferase \> 1.5 times the upper limit of normal. 17. Fasting glucose \> 6.94 mmol/L. 18. Evidence of current alcohol or drug abuse in the past 60 days including a positive result from the urine drugs of abuse or alcohol screen, or history of drug or alcohol dependence in the last 2 years, as assessed by principal investigator. Alcohol abuse is defined as greater than 14 standard units/week for females and drug abuse is defined as known psychiatric or substance abuse disorder that would interfere with participation with the requirements of this study, including current use of any illicit drugs. Use of medical cannabis is not exclusionary. 19. Participation in any other investigational drug or device trial in which administration of an investigational study drug/device occurred within 30 days or placement of a non-drug eluting medical device within 15 days prior to screening.