Effect of Estrogen Therapy on Objective Sleep Quality in Postmenopausal Women

Overview

1. Sex hormone including estrogen have synergistic effect to serotonin activity and decrease activity of monoamine oxidase activity so the norepinephrine is not be metabolized, these substance are important to regulate hemostasis and circadian process of sleep 2. Estrogen also regulate gamma-aminobutyric acid (GABA) secretion – GABA substance is in order to initiate sleep and continue sleep 3. According to epidemiologic data, problem of sleep was increasing in postmenopause group compare to premenopause group (aged-match) 4. This research perform to find out the actual effect of estrogen in improving sleep quality.

Full Title of Study: “Effect of Estrogen Therapy on Objective Sleep Quality in Postmenopausal Women at Menopause Clinic, King Chulalongkorn Memorial Hospital, Double- Blind, Randomized, Placebo-controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: January 2012

Detailed Description

1. 40-60 year-old postmenopausal women with insomnia and mild-moderate vasomotor symptom were screened and included in project 2. Block of four randomization was use to categorize participants into 2 groups – Study group (estrogen patch) – Control group (placebo patch) 3. Sleep quality was measured before intervention by subjective and objective sleep quality – Subjective sleep quality (self sleep questionnaire) – Objective sleep quality (wrist actigraphy and sleep diary): wrist actigraph sleep test at home for 1 week 4. Intervention phase : continuous use of weekly patch for 8 weeks – Estrogen patch in study group – Placebo patch in control group 5. Follow up phase – At 4 weeks of use, investigator will telephone call for follow up the participant's compliance and the side effects during patch use. – After completed use of 7th patch, sleep quality was measured again, self sleep quality questionnaire and 1 week-wrist actigraphy and sleep diary test 6. Then the data will be analysed and open label, in nonhysterectomized postmenopausal women in study group will take the medroxyprogesterone acetate for washing out the endometrium for 2 weeks 7. The participants will be counseled, further investigate and proper treatment.

Interventions

  • Drug: Estrogen patch
    • 50 microgram estrogen patch weekly
  • Drug: Placebo
    • Placebo patch for 8 weeks

Arms, Groups and Cohorts

  • Experimental: Estrogen
    • Use estrogen patch for 8 weeks
  • Experimental: Placebo
    • Use placebo patch for 8 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Sleep efficiency (SE)
    • Time Frame: 8 months
    • Sleep efficiency is proportion of sleep in the period potentially filled by sleep-ratio of total sleep time to time in bed.

Secondary Measures

  • Sleep latency (SL)
    • Time Frame: 8 months
    • Sleep latency is the time period measured from “lights out,” or bedtime, to the beginning of sleep.
  • Total sleep time (TST)
    • Time Frame: 8 months
    • TST is amount of actual sleep time in a sleep period.
  • Wake time after sleep onset (WASO)
    • Time Frame: 8 months
    • WASO is the total time of awake occurring between sleep onset and final wake up.
  • Number of awakening
    • Time Frame: 8 months
    • Number of awakening is the number of awakening during onset of sleep and final wake-up.
  • Score of two sleep quality assessment questionnaires.
    • Time Frame: 8 months
    • Insomnia severity index is the 7 topic questionnaire for determine the severity of insomnia problem. Ebworth severity index is the questionnaire to assess daytime sleepiness.

Participating in This Clinical Trial

Inclusion Criteria

  • Postmenopausal women 40-60 years old – Mild to moderate vasomotor symptom – Insomnia – fluent read and write in Thai language – Inform consent Exclusion Criteria:

  • Acute liver and gall bladder disease – undiagnosed abnormal bleeding per vagina – History of BIRADs 3 from mammogram – History or current venous thrombosis, embolism – diagnosis of sleep disorder – use of hypnotic drug or antihistamine in the past month – Diagnosis of psychiatric disorder such as depressive disorder, schizophrenia, anxiety disorder – No past history of malignancy – No history of chronic renal disease, alzheimer's disease, uncontrolled hypertension, uncontrolled diabetes mellitus – history of estrogen use in past 6 months – drug abuse, Alcohol

Gender Eligibility: Female

Minimum Age: 40 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Chulalongkorn University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Pimpika Tansupswatdikul, MD., Principle investigator – Chulalongkorn University
  • Overall Official(s)
    • Pimpika Tansupswatdikul, MD., Principal Investigator, Chulalongkorn University
    • Sukanya Chaikiitisilpa, MD., Study Chair, Chulalongkorn University

References

Kalleinen N, Polo O, Himanen SL, Joutsen A, Polo-Kantola P. The effect of estrogen plus progestin treatment on sleep: a randomized, placebo-controlled, double-blind trial in premenopausal and late postmenopausal women. Climacteric. 2008 Jun;11(3):233-43. doi: 10.1080/13697130802112033.

Huang KE, Baber R; Asia Pacific Tibolone Consensus Group. Updated clinical recommendations for the use of tibolone in Asian women. Climacteric. 2010 Aug;13(4):317-27. doi: 10.3109/13697131003681458.

Halbreich U, Kahn LS. Role of estrogen in the aetiology and treatment of mood disorders. CNS Drugs. 2001;15(10):797-817. doi: 10.2165/00023210-200115100-00005.

Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clin Proc. 2002 Nov;77(11):1207-18. doi: 10.4065/77.11.1207. Erratum In: Mayo Clin Proc. 2004 Aug;79(8):1088.

Sarti CD, Chiantera A, Graziottin A, Ognisanti F, Sidoli C, Mincigrucci M, Parazzini F; Gruppo di Studio IperAOGOI. Hormone therapy and sleep quality in women around menopause. Menopause. 2005 Sep-Oct;12(5):545-51. doi: 10.1097/01.gme.0000172270.70690.5e. Epub 2005 Sep 1.

Wiklund I, Berg G, Hammar M, Karlberg J, Lindgren R, Sandin K. Long-term effect of transdermal hormonal therapy on aspects of quality of life in postmenopausal women. Maturitas. 1992 Mar;14(3):225-36. doi: 10.1016/0378-5122(92)90117-m.

Polo-Kantola P, Erkkola R, Helenius H, Irjala K, Polo O. When does estrogen replacement therapy improve sleep quality? Am J Obstet Gynecol. 1998 May;178(5):1002-9. doi: 10.1016/s0002-9378(98)70539-3.

Saletu B. Sleep, vigilance and cognition in postmenopausal women: placebo-controlled studies with 2 mg estradiol valerate, with and without 3 mg dienogest. Climacteric. 2003 Aug;6 Suppl 2:37-45.

Ensrud KE, Stone KL, Blackwell TL, Sawaya GF, Tagliaferri M, Diem SJ, Grady D. Frequency and severity of hot flashes and sleep disturbance in postmenopausal women with hot flashes. Menopause. 2009 Mar-Apr;16(2):286-92. doi: 10.1097/gme.0b013e31818c0485.

Tranah GJ, Parimi N, Blackwell T, Ancoli-Israel S, Ensrud KE, Cauley JA, Redline S, Lane N, Paudel ML, Hillier TA, Yaffe K, Cummings SR, Stone KL. Postmenopausal hormones and sleep quality in the elderly: a population based study. BMC Womens Health. 2010 May 4;10:15. doi: 10.1186/1472-6874-10-15.

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