Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression
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.
Menopausal and Other Perimenopausal Disorders
Drug: Placebo Gel
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effectiveness of Perimenopausal Hormone Therapy in Suppression of Ovulation, Stabilization of Reproductive Hormones and Symptom Control|
- Ovulation [ Time Frame: Days 90-140 (daily) ] [ Designated as safety issue: No ]Daily urinary monitoring for progesterone metabolite excretion, pregnanediol glucuronide
- 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.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Mirena + Estradiol Gel||
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.
|Placebo Comparator: Mirena + Placebo Gel||
Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).Drug: Placebo Gel
Topical Gel, Applied once daily for 50 days, Placebo comparator.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01613131
|Contact: Christina S Gavito, BAfirstname.lastname@example.org|
|United States, Colorado|
|University of Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Principal Investigator: Nanette Santoro, MD|
|Principal Investigator:||Nanette Santoro, MD||University of Colorado, Denver|