Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression
Condition: Menopausal and Other Perimenopausal Disorders
Study type: Interventional

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.
    

Intervention name(s): Mirena; Estradiol; Placebo Gel
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).; Topical, .06%, Applied once daily for 50 days.; Topical Gel, Applied once daily for 50 days, Placebo comparator.
Other intervention name(s): IUD; TDE; placebo
Intervention MeSH terms: Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment