Effect of Estradiol Topical Products

The aim of the present study is to determine if two products can deliver bioequivalent amounts of estrogen (estradiol, estriol, and estrone).

Inclusion Criteria:Postmenopausal women, who are of any ethnic background, between the age of 45 to 65 years oldProvide written informed consent before initiation of any of the study proceduresAble to adhere to the study restrictions and study scheduleVolunteer has mid thighs of at least 42 cm (16.5 in) in circumference to accommodate the products to be tested at an area of 400 cm2 per thighVolunteer has legs that measure ≥46 cm (18.1 in) in length from the iliac crest to the top of the patella or large enough to accommodate the products to be tested at an area of 400 cm2 per thigh with the subject being comfortable with the template placementVolunteer deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination, and medication historyNegative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)Have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb), platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), and aspartate aminotransferase (AST)Have normal screening laboratories for urine protein and urine glucoseNaturally postmenopausal (absence of periods for ≥ 1 year or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy (menopause induced by removal of ovaries)Agree not to participate in another clinical trial/study or to participate in an investigational drug study for at least one month after the last procedure dayAgrees not to donate blood to a blood bank throughout participation in the study and for at least three months after last procedure dayHave a normal ECG; must not have the following to be acceptable: pathologic Q wave abnormalities, significant ST-T wave changes, left ventricular hypertrophy, right bundle branch block, left bundle branch block. (sinus rhythm is between 55-100 beats per minute)Have normal vital signs:Temperature 35-37.9°C (95-100.3°F)Systolic blood pressure 90-140 mmHgDiastolic blood pressure 60-90 mmHgHeart rate 55-100 beats per minuteRespiration rate 12-20 breaths per minuteExclusion Criteria:Smokers/tobacco users (current use or use over the previous 2 months of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patches, or electronic cigarettes)Participation in any ongoing clinical drug trial/studyHereditary skin disorders or any skin inflammatory conditions as reported by the volunteer or evident to the MAIHistory of significant dermatologic cancers (e.g., melanoma, squamous cell carcinoma) except basal cell carcinomas that were superficial and did not involve the investigative sitesHistory as either reported by the volunteer or evident to the investigator of infectious disease or skin infection or of chronic skin disease (e.g., psoriasis, atopic dermatitis)Use of chronic prescription medications during the period 0 to 30 days; or over-the-counter medications (e.g. antihistamines, topical corticosteroids) and short term (<30 days) prescription medications during the period 0-3 days before a procedure day vitamin and herbal supplements not included)Active positive Hepatitis B, C and/or HIV serologiesPositive urine drug screening testUse of estrogen-containing implants, topical, or oral productsDonation or loss of greater than one pint of blood within 60 days of entry to the studyAny prior allergies to estradiol and its products or other ingredients in the applied gel or creamReceived an experimental agent (vaccine, drug, biologic, device, blood product or medication) within one month before enrollment in this study or expects to receive an experimental agent during the studyAny condition that would, in the opinion of the Medically Accountable Investigator (MAI), place the volunteer at an unacceptable risk of injury or render the volunteer unable to meet the requirements of the protocolHistory of diabetesBreast cancer or history of breast cancerUndiagnosed abnormal genital bleedingEstrogen-dependent neoplasia (tumor)Active arterial thromboembolic disease (example, stroke or heart attack), or a history of these conditionsActive DVT (blood clots in deep vein such as lower leg, thigh, pelvis or can occur in arm), PE (blood clot in blood vessel; often leg), or history of these conditionsHepatic (liver) impairment or diseaseProtein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders (tendency to form blood clots)At application site, volunteer has an obvious difference in skin color between thighs, presence of a skin condition, excessive hair, sunburn, raised moles and scars, open sores, scar tissue, tattoo, or coloration that would interfere with placement of products, skin assessment, or reactions to estradiolBMI ≥30 kg/m2