Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women

NCT ID: NCT06136208

Last Updated: 2025-09-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-13

Study Completion Date

2025-07-30

Brief Summary

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A single center, prospective, open-label clinical study will be conducted, to monitor serum concentration and pharmacokinetic profile after subcutaneous implantation of a 25mg-estradiol bioabsorbable implant in postmenopausal women.

Detailed Description

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Assessing serum total estradiol concentration and determination of pharmacokinetic parameters will be performed in participants eligible for the study before and after the insertion of estradiol pellet (25 mg) at different collection times \[in the first 24 hours, weekly in the first month and monthly until 6 months are complete\]. Additionally, the concentration of other hormones influenced by the action of estradiol will be determined (total testosterone, estrone, FSH, LH, SHBG, and prolactin). Medical visits will be carried out for clinical evaluation and follow-up of the participants in the baseline and after 1 month, 3 months, and 6 months. Assessment of the primary outcome will be performed 6 months after estradiol pellet insertion. N=20 participants.

Conditions

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Climacteric Syndrome Menopause Hypoestrogenism

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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s.c 25 mg estradiol pellet

Subcutaneous insertion of 25 mg estradiol pellet.

Intervention Type DRUG

Eligibility Criteria

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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)
* Serum total estradiol concentration ≤ 50 pg/mL and serum FSH concentration ≥ 25 mIU/mL, both determined by immunoassays
* Presence of menopause-associated symptoms
* Absence of signs and symptoms and propedeutics suggestive of breast cancer evidenced by mammography report (woman aged \> 40 years) for less than 12 months = BI-RADS1 or BI-RADS2
* Agreement not to use other hormones (estrogens, androgens and/or progestogens) in any pharmaceutical form during the study

Exclusion Criteria

* Contraindications to the use of menopausal hormone therapy: Bleeding vaginal of unknown cause; personal history of hormone-dependent neoplasm including breast cancer, precursor lesions of breast cancer; liver disease; porphyria; personal history of coronary artery disease, cerebrovascular and venous thromboembolism; systemic lupus erythematosus with high thromboembolic risk and meningioma
* Comorbidities associated with increased cardiovascular risk: smoking, uncontrolled diabetes, dyslipidemia, and uncontrolled hypertension
* Serious chronic disorders, including metastatic malignancies, kidney disease in the end-stage with or without dialysis, clinically unstable heart disease, or any another disorder that, in the opinion of the investigator, excludes the participant from the study
* Immunocompromise or suspected or confirmed diagnosis of immunodeficiency based on history 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 any pharmaceutical 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 for cancer or any other condition
* Current use of phytoestrogens
* Participation in another clinical study within 30 days prior to the start of the Study treatment
Minimum Eligible Age

41 Years

Maximum Eligible Age

59 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Biòs Farmacêutica

UNKNOWN

Sponsor Role collaborator

Science Valley Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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André Luiz Malavasi de Oliveira Longo, MD, PhD

Role: STUDY_CHAIR

Science Valley Research Institute

Locations

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Irmandade Da Santa Casa De Misericórdia De Santos - Science Valley Research Center

Santos, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Casals G, Costa RF, Rull EU, Escobar-Morreale HF, Argente J, Sesmilo G, Biagetti B. Recommendations for the measurement of sexual steroids in clinical practice. A position statement of SEQCML/SEEN/SEEP. Adv Lab Med. 2023 Mar 9;4(1):52-69. doi: 10.1515/almed-2023-0020. eCollection 2023 Apr.

Reference Type BACKGROUND
PMID: 37359897 (View on PubMed)

del Carmen Cravioto M, Larrea F, Delgado NE, Escobar AR, Diaz-Sanchez V, Dominguez J, de Leon RP. Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women. Menopause. 2001 Sep-Oct;8(5):353-60. doi: 10.1097/00042192-200109000-00010.

Reference Type BACKGROUND
PMID: 11528362 (View on PubMed)

Hamoda H, Panay N, Pedder H, Arya R, Savvas M. The British Menopause Society & Women's Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health. 2020 Dec;26(4):181-209. doi: 10.1177/2053369120957514. Epub 2020 Oct 12. No abstract available.

Reference Type BACKGROUND
PMID: 33045914 (View on PubMed)

Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005 Aug;8 Suppl 1:3-63. doi: 10.1080/13697130500148875.

Reference Type BACKGROUND
PMID: 16112947 (View on PubMed)

Lobo RA, March CM, Goebelsmann U, Krauss RM, Mishell DR Jr. Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes. Am J Obstet Gynecol. 1980 Nov 15;138(6):714-9.

Reference Type BACKGROUND
PMID: 6776814 (View on PubMed)

Lobo RA. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol. 2017 Apr;13(4):220-231. doi: 10.1038/nrendo.2016.164. Epub 2016 Oct 7.

Reference Type BACKGROUND
PMID: 27716751 (View on PubMed)

Manson JE, Bassuk SS, Kaunitz AM, Pinkerton JV. The Women's Health Initiative trials of menopausal hormone therapy: lessons learned. Menopause. 2020 Aug;27(8):918-928. doi: 10.1097/GME.0000000000001553.

Reference Type BACKGROUND
PMID: 32345788 (View on PubMed)

Notelovitz M, Johnston M, Smith S, Kitchens C. Metabolic and hormonal effects of 25-mg and 50-mg 17 beta-estradiol implants in surgically menopausal women. Obstet Gynecol. 1987 Nov;70(5):749-54.

Reference Type BACKGROUND
PMID: 3658285 (View on PubMed)

Owen EJ, Siddle NC, McGarrigle HT, Pugh MA. 25 mg oestradiol implants--the dosage of first choice for subcutaneous oestrogen replacement therapy? Br J Obstet Gynaecol. 1992 Aug;99(8):671-5. doi: 10.1111/j.1471-0528.1992.tb13853.x.

Reference Type BACKGROUND
PMID: 1327094 (View on PubMed)

Stanczyk FZ, Shoupe D, Nunez V, Macias-Gonzales P, Vijod MA, Lobo RA. A randomized comparison of nonoral estradiol delivery in postmenopausal women. Am J Obstet Gynecol. 1988 Dec;159(6):1540-6. doi: 10.1016/0002-9378(88)90591-1.

Reference Type BACKGROUND
PMID: 3144919 (View on PubMed)

Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, Santen RJ. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015 Nov;100(11):3975-4011. doi: 10.1210/jc.2015-2236. Epub 2015 Oct 7.

Reference Type BACKGROUND
PMID: 26444994 (View on PubMed)

Suhonen SP, Allonen HO, Lahteenmaki P. Sustained-release subdermal estradiol implants: a new alternative in estrogen replacement therapy. Am J Obstet Gynecol. 1993 Nov;169(5):1248-54. doi: 10.1016/0002-9378(93)90291-p.

Reference Type BACKGROUND
PMID: 8238193 (View on PubMed)

Thom MH, Collins WP, Studd JW. Hormonal profiles in postmenopausal women after therapy with subcutaneous implants. Br J Obstet Gynaecol. 1981 Apr;88(4):426-33. doi: 10.1111/j.1471-0528.1981.tb01008.x.

Reference Type BACKGROUND
PMID: 6784745 (View on PubMed)

Other Identifiers

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CLARA Study

Identifier Type: -

Identifier Source: org_study_id

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