Clinical trial NCT02922348: Hormone Replacement for Premature Ovarian Insufficiency
Official title: Optimal Hormone Replacement for Women With Premature Ovarian Insufficiency
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Primary Ovarian Insufficiency
Keywords: premature ovarian failure
hormone replacement
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2016-10-04
Enrollment: 0
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment
timeFrame: 1 year
Secondary outcomes:
measure: Vasomotor symptoms - Greene Climacteric Scale
timeFrame: 1 year
measure: Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
timeFrame: 1 year
measure: Bleeding profile - Bleeding questionnaire
timeFrame: 1 year
measure: Bleeding profile - Menstrual diary
timeFrame: 1 year
measure: Sexual dysfunction - Female Sexual Function Index (FSFI)
timeFrame: 1 year
measure: Satisfaction as Contraceptive Method
timeFrame: 1 year
measure: Hormone Assays - FSH (mIU/mL)
timeFrame: 1 year
measure: Hormone Assays - Estradiol (pg/mL)
timeFrame: 1 year
measure: Hormone Assays - Sex-hormone binding globulin (nmol/L)
timeFrame: 1 year
measure: Hormone Assays - Total testosterone (ng/dL)
timeFrame: 1 year
measure: Hormone Assays - Free testosterone (ng/dL)
timeFrame: 1 year
measure: Hormone Assays - Anti-mullerian hormone (pmol/l)
timeFrame: 1 year
measure: Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
timeFrame: 1 year
measure: Hormone Assays - Thyroid stimulating hormone (U/mL)
timeFrame: 1 year
measure: Bone Turnover Markers - Serum osteocalcin (ng/mL)
timeFrame: 1 year
measure: Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Total cholesterol
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Triglycerides (mg/dL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Fasting glucose (mg/dL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Fasting insulin (pmol/L)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Fibrinogen (mg/dL)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - Factor VII (%)
timeFrame: 1 year
measure: Cardiovascular Risk Markers - C-reactive protein (mg/L)
timeFrame: 1 year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Fertility Care
state: Pennsylvania
Study officials:
References: