Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression

NCT01613131 | Completed Results DMC

• 1 other identifier: 11-1711
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopausal and Other Perimenopausal Disorders

Outcome Measures

Primary Outcomes (12)

• Hot Flashes

  The Hot Flash Related Daily Interference Scale (HFRDIS) is a 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. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

  Day 0

• Sleep

  The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (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). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

  Day 0

• Depression

  The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores \>16 considered indicative of depressive symptoms.

  Day 0

• Fatigue

  The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

  Day 0

• Sleep

  The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (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). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

  Day 90

• Sleep

  The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (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). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

  Day 140

• Hot Flashes

  The Hot Flash Related Daily Interference Scale (HFRDIS) is a 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. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

  Day 90

• Hot Flashes

  The Hot Flash Related Daily Interference Scale (HFRDIS) is a 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. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

  Day 140

• Depression

  The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores \>16 considered indicative of depressive symptoms.

  Day 90

• Depression

  The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores \>16 considered indicative of depressive symptoms.

  Day 140

• Fatigue

  The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

  Day 90

• Fatigue

  The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

  Day 140

Study Arms (2)

Mirena + Estradiol Gel

ACTIVE COMPARATOR

Subjects will be assigned to use of Estradiol gel for use with Mirena.

Drug: Mirena; Drug: Estradiol

Mirena + Placebo Gel

PLACEBO COMPARATOR

Subjects will be assigned to use of placebo gel for use with Mirena.

Drug: Mirena; Drug: Placebo Gel

Interventions

Mirena DRUG

Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).

Also known as: IUD

Mirena + Estradiol Gel; Mirena + Placebo Gel

Estradiol DRUG

Topical, .06%, Applied once daily for 50 days.

Also known as: TDE

Mirena + Estradiol Gel

Placebo Gel DRUG

Topical Gel, Applied once daily for 50 days, Placebo comparator.

Also known as: placebo

Mirena + Placebo Gel

Eligibility Criteria

• Age: 40 Years - 52 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Hot flashes (vasomotor symptoms)
• Cyclical headache, bloating or adverse mood
• Self-reported poor quality of sleep

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Bayer: collaborator

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Interventions

Levonorgestrel; Estradiol; Dichlorodiphenyldichloroethane

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The main limitation was the sample size, which is consistent with a pilot study, and which can only inform the design of future research.

Results Point of Contact

• Title: Chanel Mansfield
• Organization: University of Colorado Denver

chanel.mansfield@ucdenver.edu

303-724-6501

Study Officials

• Nanette Santoro, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 6, 2012
• Study Start: April 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 2, 2015
• Results First Posted: December 2, 2015

Record last verified: 2015-10

Locations

US (1)