Analysis of the Hormonal Implant and Transdermal Estradiol Gel in Climacteric Women

NCT07754630 | Active Not Recruiting Phase 2

• 1 other identifier: 86424525.3.0000.5257
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Hypoestrogenism; Hormonal Therapy

Keywords

Menopause; Hypoestrogenism; Climacteric; Subdermal implant; Estradiol

Outcome Measures

Primary Outcomes (1)

• hormonal implant and PENTRAVAN transdermal gel pharmacokinetics

  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).

  From enrollment to the end of treatment at 168 days

Secondary Outcomes (1)

• menopausal symptoms

  From enrollment to the end of treatment at 168 days

Study Arms (3)

IMPLANT

EXPERIMENTAL

For the 50 patients, the placement and removal of the gluteal implants will be performed by a single physician from the clinic to ensure study standardization. All patients will receive post-implant instructions, including keeping the dressing in place for 5 days. After this period, the dressing should be removed, and the patient may bathe normally, lathering and rinsing the area and drying it carefully afterward. Following the bath, 70% alcohol should be applied and allowed to air dry. Participants must refrain from physical activity for 3 days after implant placement. Participants will be instructed to apply an ice pack for 15 minutes in the hours following the procedure and to continue this measure over the subsequent days if local swelling occurs. The initial assessment will include medical history, a physical examination, routine screening laboratory tests, mammography, and, when necessary, transvaginal ultrasound.

Drug: implantable estradiol

PENTRAVAN

ACTIVE COMPARATOR

The 25 volunteers in the group will follow the same protocol, except for the use of the 3.0 mg PENTRAVAN compounded estradiol gel, which must be applied daily in the morning to clean skin on the arm or leg after bathing; the gel must not be mixed with other creams or similar products.

Drug: PENTRAVAN - transdermal gel

OESTROGEL

ACTIVE COMPARATOR

The 25 volunteers in the group will follow the same protocol, except for the use of the 3.0 mg OESTROGEL estradiol gel, which must be applied daily in the morning to clean skin on the arm or leg after bathing; the gel must not be mixed with other creams or similar products.

Drug: OESTROGEL - transdermal gel

Interventions

implantable estradiol DRUG

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.

IMPLANT

OESTROGEL - transdermal gel DRUG

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.

OESTROGEL

PENTRAVAN - transdermal gel DRUG

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.

PENTRAVAN

Eligibility Criteria

• Age: 41 Years - 59 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nutrindo Ideais Research Center: lead

Study Sites (1)

Nutrindo Ideais Research Center

Rio de Janeiro, Rio de Janeiro, 22421000, Brazil

Location

Study Officials

• Guilherme Renke

  Department of Endocrinology and Nutrition - Nutrindo Ideais Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 10, 2026
• Study Start: February 25, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)