Dienogest Versus Luteal Phase Fluoxetine in the Management of 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: Dienogest (Drug); Fluoxetine (Drug); Placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Cairo University Overall contact: AbdelGany M Hassan, Phone: +201017801604, Email: abdelgany2@gmail.com
Summary
Two hundreds and ten women with premenstrual syndrome will be randomly divided into 3 equal
groups using computer generated random numbers. Group 1 will receive oral dienogest
(visanne® Bayer, Germany) 2mg for 14 days starting from the 15th day of menstruation, Group
2 will receive fluoxetine (Prozac® Lilly, UK) 20mg and group 3 will receive an oral placebo
foe 14 days starting from the 15th day of menstruation.
Clinical Details
Official title: Dienogest Versus Luteal Phase Fluoxetine in the Management of 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, Investigator), Primary Purpose: Treatment
Primary outcome: Improvement of DRSP score
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 and simple for patients.
There is increasing evidence that serotonin may be important in the pathogenesis of PMS. A
number of selective serotonin reuptake inhibitors have been used to treat PMS. Fluoxetine at
was found to significantly reduce symptoms of tension, irritability and dysphoria, as well
as physical symptoms compared with placebo, as measured by visual analogue scales. Luteal
phase sertraline was found effective in the management of severe PMS.
Historically, treatment with progesterone was based on the hypothesis that in PMS sufferers,
the ratio of progesterone and its derivatives to other hormones was lower than is usual in
women. This allowed oestrogens to cause water retention, because there was insufficient
progesterone to oppose them.
Gama amino butyric acid (GABA) produced by inhibitory neurons calms symptoms of anxiety,
irritability and aggression. Part of the receptors, called GABA(A) on the neurone surface,
necessary for GABA to have its effect, cannot be made without the break-down products of
progesterone. The occurrence of severe symptoms has been correlated with falling levels of
progesterone metabolites. Therefore, progesterone could relieve the symptoms of PMS by
preventing falling levels of progesterone metabolites and loss of GABA(A) enhancement.
PMS will be diagnosed prospectively using the 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 was < 50. If the
total score is greater than 50, the patients will record 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. Women with PMS will be asked to take the drugs for 3
months and keep recording their symptoms and symptom scores will compared to those
documented before treatment.
Two hundreds and ten women with premenstrual syndrome will be randomly divided into 3 equal
groups using computer generated random numbers. Group 1 will receive oral dienogest
(visanne® Bayer, Germany) 2mg for 14 days starting from the 15th day of menstruation, Group
2 will receive fluoxetine (Prozac® Lilly, UK) 20mg and group 3 will receive an oral placebo
foe 14 days starting from the 15th day of menstruation.
Eligibility
Minimum age: 20 Years.
Maximum age: 40 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- PMS
- Consents to the procedure
Exclusion Criteria:
- Previous medical treatment for PMS
- Body mass index > 35 kg/m2
- Irregular periods
- Medical disorders like diabetes, hypertension, cardiac, liver, kidney or heart
disease
Locations and Contacts
AbdelGany M Hassan, Phone: +201017801604, Email: abdelgany2@gmail.com
BeniSuef University hospitals, BeniSuef, Egypt; Recruiting Nesreen AA Shehata, MD, Phone: +2001227866337, Email: nesoomar@yahoo.com
Cairo university hospitals, Cairo, Egypt; Recruiting AbdelGany Hassan, MRCOG, MD, Phone: 002 01017801604, 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: April 2015
Last updated: April 29, 2015
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