Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01613131
First received: June 4, 2012
Last updated: January 24, 2014
Last verified: January 2014

June 4, 2012
January 24, 2014
April 2012
June 2014   (final data collection date for primary outcome measure)
Ovulation [ Time Frame: Days 90-140 (daily) ] [ Designated as safety issue: No ]
Daily urinary monitoring for progesterone metabolite excretion, pregnanediol glucuronide
Ovulation Supression [ Time Frame: Day 140 ] [ Designated as safety issue: No ]
Ovulation will be inhibited by use of the Mirena with estradiol, but not with Mirena alone.
Complete list of historical versions of study NCT01613131 on ClinicalTrials.gov Archive Site
  • Hot Flashes [ Time Frame: Day 0, 90 and 140 ] [ Designated as safety issue: No ]
    Ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale, rate during previous week.
  • Sleep [ Time Frame: Day 0, 90, and 140 ] [ Designated as safety issue: No ]
    A short questionnaire designed to measure general sleep disturbances over previous month will be used. This is designed to assess self-reported sleep quality (sleep wake patterns, duration of sleep, sleep latency , impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature. In addition, a 9-item self-report scale assessing fatigue over the past week will be used.
  • Depression [ Time Frame: Day 0, 90, 140 ] [ Designated as safety issue: No ]
    A 20-item scale with 4-level responses indicating frequency of symptoms over past week will be used to assess symptoms.
  • Suppression of Ovulation In Older Reproductive Aged Women [ Time Frame: Day 140 ] [ Designated as safety issue: No ]
    Ovulation will be partially inhibited by Mirena alone in older reproductive aged/perimenopausal women
  • Relief of Perimenopausal Symptoms [ Time Frame: Days 90 and 140 ] [ Designated as safety issue: No ]
    Mirena plus transdermal estradiol will be a well tolerated method for alleviating perimenopausal symptoms by causing relative suppression of the hypothalamic-pituitary-ovarian axis in perimenopausal women and providing symptom control.
Not Provided
Not Provided
 
Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression
Effectiveness of Perimenopausal Hormone Therapy in Suppression of Ovulation, Stabilization of Reproductive Hormones and Symptom Control

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Menopausal and Other Perimenopausal Disorders
  • Drug: Mirena
    Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).
  • Drug: Estradiol
    Topical, .06%, Applied once daily for 50 days.
  • Drug: Placebo Gel
    Topical Gel, Applied once daily for 50 days, Placebo comparator.
  • Active Comparator: Mirena + Estradiol Gel
    Interventions:
    • Drug: Mirena
    • Drug: Estradiol
  • Placebo Comparator: Mirena + Placebo Gel
    Interventions:
    • Drug: Mirena
    • Drug: Placebo Gel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
62
December 2014
June 2014   (final data collection date for primary outcome measure)

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
Female
40 Years to 52 Years
No
Contact: Christina S Gavito, BA 303-724-5559 christina.gavito@ucdenver.edu
United States
 
NCT01613131
11-1711
Yes
University of Colorado, Denver
University of Colorado, Denver
Bayer
Principal Investigator: Nanette Santoro, MD University of Colorado, Denver
University of Colorado, Denver
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP