Estradiol and Testosterone Subdermal Implants for Menopause Treatment (ESTIME)

Menopause Clinical Trial

— ESTIME  

Official title:

Pharmacokinetic, Clinical, Hormonal and Therapeutic Effects of the Use of Estradiol and Testosterone Hormonal Subdermal Implants in Women With Natural Menopause, Premature Ovarian Failure or Surgical Menopause Due to Cervical Cancer.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06343870
• Other study ID #: ESTIME
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 31, 2024
• Est. completion date: April 30, 2025

Study information

• Verified date: March 2024
• Source: University of Sao Paulo General Hospital
• Contact: André Malavasi, PhD
• Phone: 55 11 981348231
• Email: drandreluiz[@]usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: April 30, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Estrogen Deficiency
• Menopause
• Testosterone Deficiency

Intervention

Drug:
• testosterone pellet (100 mg)
Intervention arm: Subdermal implant-bioabsorbable testosterone pellet (100 mg of testosterone)
• Placebo
Pellet of cholesterol (placebo)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

References & Publications (7)

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. — View Citation

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

Kingsberg S, Althof SE. Evaluation and treatment of female sexual disorders. Int Urogynecol J Pelvic Floor Dysfunct. 2009 May;20 Suppl 1:S33-43. doi: 10.1007/s00192-009-0833-x. — View Citation

Lev-Sagie A. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations. Clin Obstet Gynecol. 2015 Sep;58(3):476-91. doi: 10.1097/GRF.0000000000000126. — View Citation

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

Suhonen SP, Allonen HO, Lahteenmaki P. Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 1):562-7. doi: 10.1016/0002-9378(95)90573-1. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate hormonal, metabolic thromboembolic and clinical effects on climacteric symptoms	evaluate concentration in serum of luteinizing hormone, follicle stimulating hormone, estradiol, estrone, total testosterone and sex hormone-binding globulin.	6 months
Secondary	Evaluate response in quality of life and sexual function	Evaluate response on vulvovaginal atrophy and genitourinary syndrome of menopause, hormonal and metabolic effects on climacteric symptoms, using the Kupperman Menopausal Index; response in quality of life and sexual function; hormonal and metabolic effects;	6 months