Clinical trial NCT01613131: Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression
Official title: Effectiveness of Perimenopausal Hormone Therapy in Suppression of Ovulation, Stabilization of Reproductive Hormones and Symptom Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menopausal and Other Perimenopausal Disorders
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2012-06-06
Enrollment: 39
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hormonal treatment of perimenopausal women has frequently utilized oral contraceptive pills (OCPs). Because of their ability to suppress ovulation and establish cycle control, OCPs have become a popular option, and one that is FDA approved for use until menopause. However, use of OCPs in women in their 40's and 50's carries significant cardiovascular risks. Venous thromboembolism risk is 3-6 fold greater in OCP users, and the risk of myocardial infarction (MI) is approximately doubled in OCP users over the age of 40. This occurs at an age where the background population risk of MI begins to increase, such that the absolute number of cases rises substantially. Women with additional risk factors for cardiovascular disease have a much greater risk for MI (6-40-fold) in association with OCPs. There are also large subgroups of midlife women who are not candidates for OCP use, such a smokers and migraineurs. Moreover, the trend towards lower estrogen dosing with OCPs containing 20 micrograms of ethinyl estradiol has not led to a detectable decrease in thromboembolic risk.

Because of their increased potential risks, it is appropriate to seek alternatives to OCPs and to explore lower doses of hormones to relieve perimenopausal symptoms that occur prior to a woman's final menses. Recent evidence indicates that the hypothalamic-pituitary axis of reproductively aging women is more susceptible to suppression by sex steroids that previously believed. It is possible that hormone doses as low as 50 micrograms of transdermal estradiol (TDE) can suppress the hypothalamic-pituitary axis of midlife women. It is also tempting to speculate that the low but measurable circulating doses of levonorgestrel that are present when a woman uses the Mirena intrauterine system (IUS) can contribute to or even independently suppress the hypothalamic-pituitary axis, and reduce the hormonal fluctuations that result in worsening of perimenopausal symptoms. The combination of low dose TDE plus Mirena may therefore confer superior symptom control as well as contraceptive effectiveness, at far less risk.

Detailed description: The Specific Aims of the present proposal are therefore as follows:

Aim 1: To test the hypothesis that low dose estrogen therapy in concert with the low doses of levonorgestrel that circulate when Mirena is used will suppress ovulation in perimenopausal women.

Aim 2: To examine ovulation rates and symptom control with Mirena alone, and to assess the tolerability of combined estrogen therapy plus the Mirena IUS as a treatment option for symptomatic perimenopausal women.

The proposed pilot study is designed to test the feasibility and tolerability of the proposed regimens: Mirena alone or Mirena plus low-dose TDE in treating symptoms in perimenopausal women and to provide the preliminary data for a larger, comparative effectiveness study of optimal symptom control and provision of long term contraception for midlife women within 5 years of their final menstrual period.

Eligibility criteria: Inclusion Criteria:

* Age 40-52
* History of regular menstrual cycles every 20-35 days in mid-reproductive life (20-35 years of age)
* At least 1 period within the past 3 months
* BMI less than 35 kg/m2
* Presence of at least one of the following perimenopausal symptoms:

  1. Hot flashes (vasomotor symptoms)
  2. Cyclical headache, bloating or adverse mood
  3. Self-reported poor quality of sleep

Exclusion Criteria:

* Age \< 40 years
* Hysterectomy or bilateral oophorectomy
* Cigarette smoking
* Signs or symptoms of restless leg syndrome or sleep apnea
* Any chronic renal or hepatic disease that might interfere with excretion of gonadotropins or sex steroids
* Moderate/vigorous aerobic exercise \> 4 hours per week
* Inability to read/write English
* Pregnant Women
* Prisoners
* Decisionally challenged subjects
* Any medical condition that makes use of Topical estradiol or Mirena contraindicated.
* Sex hormone use within the past 30 days
* History of cancer, blood clots or blood clotting disorder

Primary outcomes:
measure: Hot Flashes
timeFrame: Day 0
measure: Sleep
timeFrame: Day 0
measure: Depression
timeFrame: Day 0
measure: Fatigue
timeFrame: Day 0
measure: Sleep
timeFrame: Day 90
measure: Sleep
timeFrame: Day 140
measure: Hot Flashes
timeFrame: Day 90
measure: Hot Flashes
timeFrame: Day 140
measure: Depression
timeFrame: Day 90
measure: Depression
timeFrame: Day 140
measure: Fatigue
timeFrame: Day 90
measure: Fatigue
timeFrame: Day 140
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: PRINCIPAL_INVESTIGATOR
References: