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

Inclusion Criteria

• 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.

• Normal cervix, vagina, uterus, and adnexa based on speculum examination and bimanual examination.
• 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,
• Current on all Australian screening requirements for cervical cancer.
• Able and willing to correctly and independently complete all study procedures.
• 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.
• 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.
• Normal mammogram report within 24 months of screening.

Exclusion Criteria

• 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.
• Participants with any self-reported active sexually transmitted disease and/or evidence of infection based on vaginal visual examination by the investigator.
• 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).
• Have a history of endometrial hyperplasia or cervical or uterine carcinoma.
• Participants with indwelling catheters or requiring intermittent catheterization.
• Participants with multiple or unsuccessful (e.g., still having symptoms) pelvic reconstructive surgery, or who suffer from pelvic relaxation.
• Participants who have had a hysterectomy.
• 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.
• 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 IV