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

Primary Ovarian Insufficiency Clinical Trial

Official title:

Optimization of Management Tactics for Women With Premature Ovarian Insufficiency, Taking Into Account Their Clinical and Hormonal Profile

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05737329
• Other study ID #: ?2-07/02.2019
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2019
• Est. completion date: April 2023

Study information

• Verified date: February 2023
• Source: Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause, Premature
• Primary Ovarian Insufficiency

Intervention

Drug:
• Transdermal estradiol gel 0.1% 1.5mg/ day
Estradiol gel 0.1% 1.5mg/ daily + Micronized Progesterone 200mg
• Transdermal estradiol gel 0.1% 2.0mg/ day
Estradiol gel 0.1% 2.0mg/ daily + Micronized Progesterone 200mg

Locations

Country	Name	City	State
Russian Federation	Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare	Moscow

Sponsors (1)

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

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the severity of estrogen deficiency symptoms	The Green scale questionnaire was used initially and after 3 months against the background of HRT. The questionnaire includes 21 questions from 0 to 3 points, where a lower score means a better result.	3 months
Primary	Changing the assessment of quality of life using the Short Form Health Survey-36 (SF-36)	The SF-36 is a generic QoL instrument. It consists of 36 items organized into eight domains: Physical Function (AF), Physical Role Function (RF), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Emotional Role Function (RE), and Mental Health (SM) as well as an item on the change of General Health. The scores of each domain have been converted into a scale from 0 to 100. Lower scores are indicative of worse conditions.	3 months
Primary	Changing the assessment of menopause-related quality of life measured using the Menopause-Specific Quality of Life (MENQOL) questionnaire.	The MENQOL questionnaire is a self-administered instrument. This validated questionnaire (range 1-8) assesses four quality of life domains; physical (16 items), vasomotor (3 items), psychosocial (7 items) and sexual (3 items). Scoring generates 4 domain scores and a total score, the mean of the 4 domain scores. Identical scoring for each of the four MENQOL domains is used. A "0" is identical that the woman has not experienced this specific symptom in the previous month; Score "1" demonstrates that the woman experienced the symptom, but it did not bother her; Scores "2" through "7" demonstrate an increasing level of the bothering symptom, so that these scores indicate increasing levels of bother experienced from the symptom and correspond to the ''1'' through ''6'' checkboxes on the MENQOL. With increasing MENQOL scores, levels of bother experienced from the symptom are increased as well.	3 months
Secondary	?hanges in the level of sex hormones after using higher doses estrogen therapy	Assessment of changes in the level of sex hormone in peripheral blood: estradiol (pmol/l). Reference values: 150 - 450 pmol/l. Blood sampling is performed at baseline and after 3 months.	Assessment of changes in the level of sex hormone in peripheral blood: testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.
Secondary	?hanges in the level of sex hormones after using higher doses estrogen therapy	Assessment of changes in the level of sex hormone in peripheral blood: total testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.	3 months
Secondary	?hanges in the level of FSH after using higher doses estrogen therapy		3 months
Secondary	?hanges in the level of E1 after using higher doses estrogen therapy		3 months
Secondary	?hanges in the level of E1S after using higher doses estrogen therapy		3 months
Secondary	?hanges in the level of SHBG after using higher doses estrogen therapy		3 months
Secondary	Bone mineral density (BMD) response to using higher doses estrogen therapy for 12 Months		12 Months