Combined Oral Contraceptives and Fluoxetine Versus Combined Oral Contraceptives in Severe Premenstrual Syndrome
Information source: Cairo University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Premenstrual Syndrome
Intervention: Combined oral contraceptives (Drug); Fluoxetine (Drug); Combined oral contraceptives placebo (Drug); Fluoxetine placebo (Drug); Daily record of severity of problems (Procedure)
Phase: Phase 3
Status: Recruiting
Sponsored by: Cairo University
Summary
Three hundred women with severe premenstrual syndrome will be divided into 3 groups using
computer generated random numbers. Group 1 will receive COC containing drospirenone
(drospirenone 3mg+Ethinylestradiol 0. 03mg; Yasmin® ScheringAG, Egypt) daily for 21 days
starting from the 3rd day of menstruation in addition to oral fluoxetine 20 mg daily.
Group 2 will receive COC containing drospirenone daily for 21 days starting from the 3rd day
of menstruation in addition to a daily oral placebo similar in size, color and structure to
fluoxetine . Group 3 will receive oral placebo similar to COC daily for 21 days starting
from the 3rd day of menstruation in addition to a daily oral placebo similar in size, color
and structure to fluoxetine.
Clinical Details
Official title: The Synergistic Use of Combined Oral Contraceptives and Fluoxetine Versus Combined Oral Contraceptives in the Management of Severe Premenstrual Syndrome: A Randomized Double Blind Placebo Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Cured PMS
Detailed description:
Premenstrual syndrome (PMS) manifests with distressing physical, behavioral and
psychological symptoms, in the absence of organic or underlying psychiatric disease, which
regularly recur during luteal phase of each menstrual cycle and disappear or significantly
improve by the end of menstruation. Approximately 85-90 % of women may experience
premenstrual emotional and physical changes in their reproductive age and the prevalence of
severe PMS ranges from 3% to 8%.
The etiology of PMS is unknown but cyclical ovarian activity and the effect of estradiol and
progesterone on serotonin and gamma-amino butyric acid are key factors. Absence of PMS
before puberty, in pregnancy and after the menopause supports a role of cyclical ovarian
activity in PMS etiology. PMS symptoms include psychological symptoms like mood swings,
irritability, depression and feeling out of control; physical symptoms like breast
tenderness, bloating and headaches; and behavioral symptoms like reduced visuospatial and
cognitive ability. To diagnose PMS, symptoms should be recorded prospectively over two
cycles using a symptom diary. Several symptom diaries exist but the Daily Record of Severity
of Problems (DRSP) is reliable, simple for patients and recommended by the Royal College of
Obstetricians and Gynecologists.
Life style modifications like stress reduction, exercise, and low carbohydrate diet have
been suggested for management of PMS but have not been thoroughly investigated.
Pharmacological treatments of PMS include COC, serotonin reuptake inhibitors
gonadotrophin-releasing hormone agonists, anxiolytics, and diuretics. Various other
treatments have also been recommended including acupuncture, dietary supplements, and bright
light therapy, PMS treatment should be based on individual symptoms, concomitant medical
history and the need of contraception.
The objective of the study is to compare the roles of synergistic fluoxetine and combined
oral contraceptives (COC) containing Drospirenone in the management of severe premenstrual
syndrome.
Three hundred women with severe premenstrual syndrome will be divided into 3 groups using
computer generated random numbers. Group 1 will receive COC containing drospirenone
(drospirenone 3mg+Ethinylestradiol 0. 03mg; Yasmin® ScheringAG, Egypt) daily for 21 days
starting from the 3rd day of menstruation in addition to oral fluoxetine 20 mg daily. Group
2 will receive COC containing drospirenone daily for 21 days starting from the 3rd day of
menstruation in addition to a daily oral placebo similar in size, color and structure to
fluoxetine. Group 3 will receive oral placebo similar to COC daily for 21 days starting from
the 3rd day of menstruation in addition to a daily oral placebo similar in size, color and
structure to fluoxetine.
To diagnose PMS women will be asked to document their symptoms daily for 2 months using the
daily record of severity of problems (DRSP). DRSP is a questionnaire comprised of 25
physical and emotional symptoms including impairment of physical and social activities,
women will be asked to give a score of 1 to 6 for each symptom 1 = not at all, 2 = minimal,
3 = mild, 4 = moderate, 5 = severe, 6 = extreme. The investigators will add the symptoms
scores of the first day of menses and PMS will be excluded if the score is< 50. If the total
score is greater than 50, the investigators will recorded two cycles of symptoms. If more
than three items have an average score of more than 3 (mild) during the luteal phase, the
investigators will add the scores of five-day intervals during the luteal and follicular
phases. PMS will be diagnosed when the luteal phase score is 30 percent greater than the
follicular phase score in the 2 months. All women will have a psychiatric review and women
with underlying psychiatric disease will be excluded. Women who are unable to interact
socially or professionally because of the symptoms will be considered to have severe PMS.
All married women will be advised to use barrier contraceptives.
All women will be asked to take the medications for 6 months and record their symptoms using
the DRSP. Women with suboptimal social or professional interaction will be considered having
moderate PMS. Women with no interference with the social or professional activity will be
considered as having mild PMS. Women with day 1 DRSP score <50 and women with average luteal
phase scores <30% more than the average proliferative scores will not be considered having
PMS.
Eligibility
Minimum age: 20 Years.
Maximum age: 40 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Severe PMS
- Regular periods
Exclusion Criteria:
- Underlying psychiatric disease.
- Body mass index > 35.
- Women on combined oral contraceptives.
- History of deep venous thrombosis.
- History of deep venous thrombosis, known liver, kidney or heart disease.
- Allergy to COC or fluoxetine
Locations and Contacts
BeniSuef University hospitals, BeniSuef, Egypt; Recruiting Nesreen AA Shehata, MD, Phone: +2001227866337, Email: nesoomar@yahoo.com Nesreen AA Shehata, MD, Principal Investigator
Cairo University Hospitals, Cairo, Egypt; Recruiting AbdelGany MA Hassan, MRCOG, MD, Phone: 00217801604, Email: abdelgany2@gmail.com AbdelGany MA Hassan, MRCOG, MD, Principal Investigator
Additional Information
Related publications: Lustyk MK, Widman L, Paschane A, Ecker E. Stress, quality of life and physical activity in women with varying degrees of premenstrual symptomatology. Women Health. 2004;39(3):35-44. Endicott J, Nee J, Harrison W. Daily Record of Severity of Problems (DRSP): reliability and validity. Arch Womens Ment Health. 2006 Jan;9(1):41-9. Epub 2005 Sep 20. Smith SS, Gong QH, Hsu FC, Markowitz RS, ffrench-Mullen JM, Li X. GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature. 1998 Apr 30;392(6679):926-30.
Starting date: July 2015
Last updated: July 20, 2015
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