Efficacy, Safety, and Tolerability of Higher Doses Estrogen Therapy in Women With Premature Ovarian Insufficiency

Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Primary Ovarian Insufficiency

Treatments: Drug: Transdermal estradiol gel 0.1% 1.5mg/ day; Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

Study type: Interventional

Funder types: Other

Identifiers

NCT05737329

№2-07/02.2019

Details and patient eligibility

About

The goal of this study is to assess the effects of higher doses versus standard hormone therapy on quality of life (QoL), symptoms due to estrogen deficiency, and bone health in women with premature ovarian insufficiency (POI).

The efficacy of the hormonal treatment will be assessed clinically and also by measuring serum concentrations of Estradiol (E2), Follicle-Stimulating Hormone (FSH), Luteinizing hormone (LH), total Testosterone (T), Estrone (E1), E1 sulfate (E1S), and Sex Hormone Binding Globulin (SHBG). Bone mineral density (BMD) will be measured using dual-energy X-ray absorptiometry. Safety will be assessed by measuring endometrial thickness with Gynecological transvaginal ultrasound (TVS), treatment-related adverse events (AEs) and treatment-emergent AEs monitoring.

Enrollment: 80 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with karyotypically normal spontaneous POI diagnosed before the age of 40. POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea for at least 4 months), elevated serum follicle stimulating hormone (FSH ≥ 25 IU/L with 4 to 6 weeks interval)
• Between 18-45 years of age
• Use of standard-dose estradiol HRT (Estradiol 2 mg+ Dydrogesterone10 mg) for at least the last 12 months
• Signed informed consent before inclusion in the study

Exclusion criteria

• Any contraindication to HRT per the current drug labels. These could include, but are not limited to: history of venous thromboembolism, estrogen-sensitive cancer history, regular cigarette smoking and history of or active liver disease, bleeding from the genital tract of unknown origin, etc.
• POI due to cytotoxic chemotherapy or radiation therapy, surgery
• Diseases that may be associated with hot flashes (such as pheochromocytoma, hyperthyroidism, medullary carcinoma of the thyroid, acromegaly, pancreatic islet-cell tumors, renal cell carcinoma, carcinoid syndrome, systemic mast cell disease, neurological flushing, emotional flushing, spinal cord injury)
• Taking medications that can also cause hot flashes (such as Tamoxifen, Raloxifene, Tricyclic antidepressants, Monoamine oxidase inhibitors, Calcium channel blockers, Depo leuprolide, Clomiphene, Serotonin uptake inhibitors)
• Severe somatic conditions (uncontrolled hypertension, kidney disease, liver disease, etc.)
• Diseases with impaired thyroid and adrenal gland function
• Refusal to participate

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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80 participants in 2 patient groups

Transdermal estradiol gel 0.1% 1.5mg/ day

Other group

Description:

Patient will be given Hormone Replacement Therapy (HRT) in the form of: Transdermal estradiol gel 0.1% 1.5mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.

Treatment:

Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

Drug: Transdermal estradiol gel 0.1% 1.5mg/ day

Transdermal estradiol gel 0.1% 2.0mg/ day

Other group

Description:

Patient with insufficient effect from previous treatment estradiol gel 0.1% 1.5mg will be given HRT in the form of: Transdermal estradiol gel 0.1% 2.0mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.

Treatment:

Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

Drug: Transdermal estradiol gel 0.1% 1.5mg/ day