Estradiol and Testosterone Subdermal Implants for Menopause Treatment (ESTIME)

NCT ID: NCT06343870

Last Updated: 2025-12-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-18
• Study Completion Date: 2027-04-30

Brief Summary

Estrogen and androgen deficiencies negatively impact the quality of life of women at different stages of life, especially after menopause. New modalities and new therapeutic alternatives have been researched. Parenteral administration of estradiol and testosterone could be effective to treat symptoms secondary to estrogen and androgen deficiencies and minimize these adverse events. This study evaluates the efficiency of subdermal implant-bioabsorbable use in women with menopausal symptoms associated with secondary estrogen and androgen deficiencies in women with natural menopause, premature ovarian failure or surgical menopause due to cervical cancer. Pharmacokinetic, biochemical, metabolic, thromboembolic and hormonal data will be evaluated, as well as the effects on quality of life, menopausal symptoms and sexual function after treatment.

Detailed Description

The clinical study will be carried out on 140 women, who will be divided into three groups: (1) postmenopausal women with menopausal and sexual symptoms (n=60); (2) women with premature ovarian failure (n=40); (3) women with cervical cancer undergoing abdominal hysterectomy with bilateral adnexectomy, with menopausal and sexual symptoms (n=40).

All participants will answer questionnaires to assess quality of life, menopausal symptoms and sexual function. All participants will undergo general physical and gynecological examinations, as well as hormonal, biochemical, thromboembolic and imaging tests.

The study will last six months. The included participants will undergo the following visits: inclusion (post-selection) and 1, 3 and 6 months after implant insertion. For the pharmacokinetic study, blood samples will be collected at the following periods: inclusion (before implant placement) and after 1h, 2h, 3h, 6h and 12h; one week, two weeks and one month after placement, and then monthly until six months after implant insertion, to evaluate serum levels of Luteinizing hormone, Follicle stimulating hormone, estradiol, estrone, total testosterone and sex hormone-binding globulin.

Clinical, biochemical, hormonal and therapeutic parameters will be evaluated before placement (inclusion) and after 3 and 6 months. The Mann Whitney test will be applied to evaluate differences between measurements and the chi-square test will be applied to analyze the proportions of improvement between groups before and after treatment.

Conditions

Menopause; Testosterone Deficiency; Estrogen Deficiency

Keywords

menopause; estrogen; testosterone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Testosterone

Subdermal implant-bioabsorbable testosterone pellet (100 mg of testosterone)

Group Type: ACTIVE_COMPARATOR

testosterone pellet (100 mg)

Intervention Type: DRUG

Intervention arm: Subdermal implant-bioabsorbable testosterone pellet (100 mg of testosterone)

Placebo

Subdermal implant-bioabsorbable placebo pellet (cholesterol)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pellet of cholesterol (placebo)

Interventions

testosterone pellet (100 mg)

Intervention arm: Subdermal implant-bioabsorbable testosterone pellet (100 mg of testosterone)

Intervention Type: DRUG

Placebo

Pellet of cholesterol (placebo)

Intervention Type: DRUG

Other Intervention Names

testosterone subdermal implant

Eligibility Criteria

Inclusion Criteria

• menopause time of 2 to 6 years;
• Body Mass Index between 25 and 30 kg/m2;
• women hysterectomized and ovariectomized due to cervical cancer;
• women with premature ovarian failure and under 40 years of age;
• active sex life;
• absence of severe depression and anxiety, confirmed by evaluation using the Beck (specific for depression) and Beck (specific for anxiety) questionnaires.

Exclusion Criteria

• disabling illnesses;
• use of medications that inhibit sexual desire;
• inability to answer the questionnaires;
• altered routine exams and comorbidities:

• Severe hypertension with Blood Pressure measurement > 160 x 90 mmHg in two measurements
• clinical or subclinical thyroid dysfunction with Thyroid-stimulating hormone > 4 mIU/L
• dyslipidemia - fasting triglyceride level > 400 mg/dL
• presence of occult blood in feces
• hyperprolactinemia (>29ng/mL)
• fasting blood glucose > 100 mg/dL
• presence of osteopenia or osteoporosis
• BIRADS classification greater than or equal to 3 on mammography
• presence of endometrial echo > 4mm on transvaginal ultrasound
• presence of changes in oncotic colpocytology
• diagnosis after psychological screening of moderate to severe anxiety/depression.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Edmund Baracat

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Edmund Baracat, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Coracao

Locations

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

André Malavasi, PhD

Role: CONTACT

Phone: 55 11 981348231

Email: drandreluiz@usp.br

Edmund Baracat, PhD

Role: CONTACT

Phone: 55 11 98149-6253

Facility Contacts

André Malavasi, MD, PhD

Role: primary

References

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Reference Type: BACKGROUND

PMID: 26125962 (View on PubMed)

Nelson HD. Menopause. Lancet. 2008 Mar 1;371(9614):760-70. doi: 10.1016/S0140-6736(08)60346-3.

Reference Type: BACKGROUND

PMID: 18313505 (View on PubMed)

Calleja-Agius J, Brincat MP. The urogenital system and the menopause. Climacteric. 2015;18 Suppl 1:18-22. doi: 10.3109/13697137.2015.1078206.

Reference Type: BACKGROUND

PMID: 26366796 (View on PubMed)

The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992. doi: 10.1097/GME.0000000000001609.

Reference Type: BACKGROUND

PMID: 32852449 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 7856686 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 19440781 (View on PubMed)

Brincat M, Magos A, Studd JW, Cardozo LD, O'Dowd T, Wardle PJ, Cooper D. Subcutaneous hormone implants for the control of climacteric symptoms. A prospective study. Lancet. 1984 Jan 7;1(8367):16-8. doi: 10.1016/s0140-6736(84)90183-1.

Reference Type: BACKGROUND

PMID: 6140343 (View on PubMed)

Other Identifiers

ESTIME

Identifier Type: -

Identifier Source: org_study_id