Hormonal Therapy, Hypoestrogenism, Menopause
Conditions
Keywords
Menopause; Hypoestrogenism; Climacteric; Subdermal implant; Estradiol
Brief summary
An open-label, prospective clinical study will be conducted to monitor serum concentration and pharmacokinetic profiles following the subcutaneous implantation of six silicone hormone implants (delivering a total dose of 300 mg of estradiol) versus the use of transdermal estradiol gel (at a daily dose of 3.0 mg). Assessment of total serum estradiol concentration and determination of pharmacokinetic parameters will be performed in eligible participants before and after hormone implant insertion and transdermal estradiol gel use, at various sampling time points (within the first 24 hours, weekly during the first month, and monthly up to 6 full months). Additionally, the concentrations of other hormones influenced by estradiol activity (total testosterone, estrone, FSH, LH, SHBG, and prolactin) will be determined. Medical consultations for clinical assessment and participant follow-up will be conducted at baseline and at 1, 3, and 6 months. The primary outcome assessment will be performed 6 months after the crossover between hormone implant insertion and transdermal estradiol gel use.
Interventions
DRUGimplantable estradiol
The assessment will include medical history, a physical examination, routine screening laboratory tests, a mammogram, and, when necessary, a transvaginal ultrasound. Each subject's body weight, height, and blood pressure will be recorded by an investigator. Subsequently, each of the 50 women will receive six (6) estradiol implants, each with a dose of 50 mg, totaling 300 mg (Elmeco, Salvador, Brazil). Each implant (40 mm in diameter) will be inserted subcutaneously into the buttock under local anesthesia. Following insertion, the patient will remain under observation at the clinic for the collection of multiple blood samples; these will be taken prior to the insertion of the Silastic implants and at 2, 4, 6, 8, 10, and 12 hours post-insertion. Patients will be instructed regarding their follow-up visits, which are scheduled for 24 hours, 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days, and 168 days.
DRUGOESTROGEL - transdermal gel
Medical consultations for clinical assessment will be conducted, involving the completion of a questionnaire on menopausal symptoms and participant follow-up at baseline (t0) and at 1, 3, and 6 months. The Menopause Rating Scale (MRS) (Heinemann et al., 2004) will be used for the questionnaire. During all follow-up visits, volunteers will undergo a physical examination, including a breast exam; measurements of blood pressure, weight, body mass index (BMI), and hip and waist circumferences; and bioimpedance analysis.
DRUGPENTRAVAN - transdermal gel
Medical consultations for clinical assessment will be conducted, involving the completion of a questionnaire on menopausal symptoms and participant follow-up at baseline (t0) and at 1, 3, and 6 months. The Menopause Rating Scale (MRS) (Heinemann et al., 2004) will be used for the questionnaire. During all follow-up visits, volunteers will undergo a physical examination, including a breast exam; measurements of blood pressure, weight, body mass index (BMI), and hip and waist circumferences; and bioimpedance analysis.
Sponsors
Nutrindo Ideais Research Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Instrument The study will be prospective with cross-sectional analyses involving a sample of volunteers randomized into two groups. Group 1 (G1) will consist of 25 patients who, at baseline (t0), undergo an in-person medical consultation for clinical assessment and laboratory sample collection. Subsequently, a Silastic implant-a minimally invasive procedure-will be inserted under local anesthesia into the patient's right or left gluteal region. Medical consultations for clinical assessment, including the completion of a menopause symptom questionnaire and participant follow-up, will be conducted at baseline (t0) and at 1, 3, and 6 months. The Menopause Rating Scale (MRS) (Heinemann et al., 2004) will be used as the questionnaire. During all follow-up visits, volunteers will undergo a physical examination, including breast examination, measurement of blood pressure, weight, body mass index (BMI), hip and waist circumferences, and bioimpedance analysis.
Eligibility
Sex/Gender
FEMALE
Age
41 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
Women aged 41 to 59 years with climacteric symptoms, weighing 50 to 90 kg, with a BMI of 18.5 to 34.9 kg/m². Hysterectomy (with or without oophorectomy). Hypoestrogenism defined by a total serum estradiol concentration ≤ 50 pg/mL and a serum FSH concentration ≥ 25 mIU/mL. Absence of signs, symptoms, or clinical findings suggestive of breast cancer, as evidenced by a mammography report (for women \> 40 years of age) dated within the last 12 months showing BI-RADS 1 or BI-RADS 2 classification. Agreement not to use other hormones (estrogens, androgens, and/or progestogens) or contraceptives in any pharmaceutical form during the study.
Exclusion criteria
Contraindications to the use of menopausal hormone therapy: vaginal bleeding of unknown cause; personal history of hormone-dependent neoplasia, including breast cancer or breast cancer precursor lesions; liver disease; porphyria; personal history of coronary artery disease, cerebrovascular disease, or venous thromboembolism; systemic lupus erythematosus with high thromboembolic risk; and meningioma. Comorbidities associated with increased cardiovascular risk: smoking, uncontrolled diabetes, dyslipidemia, and uncontrolled hypertension. Severe chronic disorders, including metastatic malignancies, end-stage renal disease (with or without dialysis), clinically unstable heart disease, or any other disorder that, in the investigator's opinion, excludes the participant from the study. Immunocompromise or suspected/confirmed diagnosis of immunodeficiency based on history and/or physical or laboratory examination. Active liver disease or dysfunction. Benign or malignant liver tumors. Clinical diagnosis of polycystic ovary syndrome. Use of other hormones (estrogens, androgens, and/or progestogens) in any pharmaceutical form within the last month. Use of contraceptives. Current use of medications that alter cytochrome P450 activity and estrogen metabolism. Current use of tamoxifen, aromatase inhibitors, or GnRH agonists/antagonists for cancer or any other condition. Current use of phytoestrogens. Participation in another clinical study within 30 days prior to the start of study treatment. Patients who do not complete all study stages, who do not adhere to the intervention, or who experience an intercurrent event that interferes with the study outcome. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| hormonal implant and PENTRAVAN transdermal gel pharmacokinetics | From enrollment to the end of treatment at 168 days | Assessment of total serum estradiol concentration (silastic implant versus transdermal gel). Multiple blood samples will be collected at 0, 2, 4, 6, 8, 10, 12, and 24 hours; and at 7, 14, 21, 28, 56, 84, 112, 140, and 168 days, and will be analyzed using liquid chromatography (LC-MS/MS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| menopausal symptoms | From enrollment to the end of treatment at 168 days | Assessment of menopausal symptoms and participant follow-up at baseline (T0), and after 1, 3, and 6 months. The Menopause Rating Scale (MRS) questionnaire will be used. |
Countries
Brazil
Contacts
PRINCIPAL_INVESTIGATORGuilherme Renke
Department of Endocrinology and Nutrition - Nutrindo Ideais Research Center
Outcome results
None listed