Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women

Inclusion Criteria:

• Signed Informed Consent Form

• Woman aged ≥ 41 and ≤ 59 years

• Weight ≥ 50 kg and ≤ 98 kg

• BMI ≥ 18.5 and ≤ 34.9 kg/m²

• Hysterectomy (with or without oophorectomy)

• Hypoestrogenism defined by serum total estradiol concentration ≤ 50 pg/mL and serumFSH concentration ≥ 25 mIU/mL, both determined by immunoassays

• Presence of climacteric symptoms

• Absence of signs and symptoms and propedeutics suggestive of breast cancer evidencedby mammography report (woman aged > 40 years) for less than 12 months = BI-RADS1 orBI-RADS2

• Agreement not to use other hormones (estrogens, androgens and/or progestogens) inany pharmaceutical form during the study

Exclusion Criteria:

• Contraindications to the use of menopausal hormone therapy: Bleeding vaginal ofunknown cause; personal history of hormone-dependent neoplasm including breastcancer, precursor lesions of breast cancer; liver disease; porphyria; personalhistory of coronary artery disease, cerebrovascular and venous thromboembolism;systemic lupus erythematosus with high thromboembolic risk and meningioma

• Comorbidities associated with increased cardiovascular risk: smoking, uncontrolleddiabetes, dyslipidemia, and uncontrolled hypertension

• Serious chronic disorders, including metastatic malignancies, kidney disease in theend-stage with or without dialysis, clinically unstable heart disease, or anyanother disorder that, in the opinion of the investigator, excludes the participantfrom the study

• Immunocompromise or suspected or confirmed diagnosis of immunodeficiency based onhistory and/or physical or laboratory examination

• Active liver disease or dysfunction

• Benign or malignant tumors of the liver

• Clinical diagnosis of polycystic ovary syndrome

• Use of other hormones (estrogens, androgens and/or progestogens) in anypharmaceutical form in the last month

• Current use of drugs that alter cytochrome P450 and metabolization of Estrogens

• Current use of tamoxifen, aromatase inhibitors, or agonists/antagonists GnRH forcancer or any other condition

• Current use of phytoestrogens

• Participation in another clinical study within 30 days prior to the start of theStudy treatment