Hormone Replacement for Premature Ovarian Insufficiency

Primary Ovarian Insufficiency Clinical Trial

— HOPE  

Official title:

Optimal Hormone Replacement for Women With Premature Ovarian Insufficiency

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02922348
• Other study ID #: 823553
• Status: Withdrawn
• Phase: Phase 3
• Start date: March 1, 2016
• Est. completion date: December 1, 2018

Study information

• Verified date: July 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators intend to establish feasibility/acceptability of a pilot randomized trial comparing hormone replacement therapy (HRT) and combined oral contraceptives (COCs) in women with premature ovarian insufficiency to estimate differences in quality of life (QOL) and serum hormone assays and markers of bone turnover/cardiovascular risk. At baseline, QOL survey will be administered and serum testing performed. Patients then randomized to HRT or COCs. Repeat testing will be performed after 3 and 6 months.

Description:

Premature ovarian insufficiency (POI) is a term used to describe when a woman's ovaries stop working normally before the natural age of menopause. Early sequelae of POI include vasomotor symptoms, vaginal dryness, mood swings and insomnia due to estrogen deficiency. Long-term sequelae such as loss of bone mineral density and cardiovascular risk carry are considerable concerns. While exogenous estrogen replacement is recommended for the POI patient population, the optimal regimen for replacement is not clear. One approach to hormone replacement therapy (HRT) is to mimic physiologic ovarian function through full replacement doses of estrogen (either orally or transdermally) to reach the typical serum estradiol levels of a menstruating woman (approximately 104 pg/mL per day) with cyclic progestin therapy for endometrial protection. Another approach uses daily combined estrogen-progestin oral contraceptives (COCs), for ease of administration and increased social acceptability. To date, few studies have been performed comparing the two treatment methods in terms of quality of life measures (vasomotor symptoms, bleeding profile, sexual dysfunction, satisfaction with contraception), endocrine function, bone turnover or cardiovascular risk in POI patients. In this proposal, the investigators intend to establish feasibility and acceptability of a pilot randomized controlled trial comparing traditional HRT with COCs in women with POI and to evaluate differences in quality of life measures, hormone assays, bone turnover and cardiovascular risk between treatment arms. The investigators hypothesize that acceptability and feasibility of the pilot trial will be high and that differences will be detected for all measured variables between treatment arms. Demonstration of feasibility and acceptability of this pilot would allow for the pursuit of a larger trial and identification of a superior treatment regimen would have a meaningful impact on the short and long-term care of this patient population.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 14 Years to 45 Years

Eligibility

Inclusion Criteria:

• Female patients,

• Between 14-45 years of age

• Post-menarchal

• Presence of uterus

• POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea), elevated serum serum follicle stimulating hormone (FSH), low serum estradiol concentrations, or estrogen deficiency symptoms.

Exclusion Criteria:

• Pregnancy or lactation within previous 3 months

• Use of hormonal contraception or replacement within previous 3 months

• Any contraindication to oral contraceptive pills or hormone replacement therapy 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, etc.

• Patients will be screened for pregnancy with a urine HCG test at time of screening

Related Conditions & MeSH terms

• Gonadal Dysgenesis
• Menopause, Premature
• Premature Birth
• Primary Ovarian Insufficiency
• Turner Syndrome

Intervention

Drug:
• Hormone Replacement Therapy
Hormone replacement therapy as indicated in Arm 1
• Combined Oral Contraceptives
Combined oral contraceptives as indicated in Arm 2

Locations

Country	Name	City	State
United States	Penn Fertility Care	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment	Patient willingness to participate and be randomized	1 year
Secondary	Vasomotor symptoms - Greene Climacteric Scale	Greene Climacteric Scale	1 year
Secondary	Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey	Menopausal Vasomotor Symptoms (MVS) survey	1 year
Secondary	Bleeding profile - Bleeding questionnaire	Bleeding questionnaire	1 year
Secondary	Bleeding profile - Menstrual diary	Menstrual diary	1 year
Secondary	Sexual dysfunction - Female Sexual Function Index (FSFI)	Female Sexual Function Index (FSFI)	1 year
Secondary	Satisfaction as Contraceptive Method	Birth Control Satisfaction Assessment	1 year
Secondary	Hormone Assays - FSH (mIU/mL)	FSH (mIU/mL)	1 year
Secondary	Hormone Assays - Estradiol (pg/mL)	Estradiol (pg/mL)	1 year
Secondary	Hormone Assays - Sex-hormone binding globulin (nmol/L)	Sex-hormone binding globulin (nmol/L)	1 year
Secondary	Hormone Assays - Total testosterone (ng/dL)	Total testosterone (ng/dL)	1 year
Secondary	Hormone Assays - Free testosterone (ng/dL)	Free testosterone (ng/dL)	1 year
Secondary	Hormone Assays - Anti-mullerian hormone (pmol/l)	Anti-mullerian hormone (pmol/l)	1 year
Secondary	Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)	Dehydroepiandrosterone Sulfate (ng/mL)	1 year
Secondary	Hormone Assays - Thyroid stimulating hormone (U/mL)	Thyroid stimulating hormone (U/mL)	1 year
Secondary	Bone Turnover Markers - Serum osteocalcin (ng/mL)	Serum osteocalcin (ng/mL)	1 year
Secondary	Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)	Serum N-telopeptide of type I collagen (nmol/L)	1 year
Secondary	Cardiovascular Risk Markers - Total cholesterol	Total cholesterol (mg/dL)	1 year
Secondary	Cardiovascular Risk Markers - Triglycerides (mg/dL)	Triglycerides (mg/dL)	1 year
Secondary	Cardiovascular Risk Markers - Lipoprotein a (mg/dL)	Lipoprotein a (mg/dL)	1 year
Secondary	Cardiovascular Risk Markers - Fasting glucose (mg/dL)	Fasting glucose (mg/dL)	1 year
Secondary	Cardiovascular Risk Markers - Fasting insulin (pmol/L)	Fasting insulin (pmol/L)	1 year
Secondary	Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin	Homeostatic model assessment (HOMA) insulin	1 year
Secondary	Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)	Tissue-type plasminogen activator antigen (ng/mL)	1 year
Secondary	Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)	Plasma plasminogen activator inhibitor 1 (ng/mL)	1 year
Secondary	Cardiovascular Risk Markers - Fibrinogen (mg/dL)	Fibrinogen (mg/dL)	1 year
Secondary	Cardiovascular Risk Markers - Factor VII (%)	Factor VII (%)	1 year
Secondary	Cardiovascular Risk Markers - C-reactive protein (mg/L)	C-reactive protein (mg/L)	1 year