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Dienogest Versus Luteal Phase Fluoxetine in the Management of Premenstrual Syndrome

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ClinicalTrials.gov Identifier: NCT02427334
Recruitment Status : Recruiting
First Posted : April 28, 2015
Last Update Posted : January 23, 2017
Sponsor:
Information provided by (Responsible Party):
AbdelGany Hassan, Cairo University

Brief 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.

Condition or disease Intervention/treatment Phase
Premenstrual Syndrome Drug: Dienogest Drug: Fluoxetine Drug: Placebo Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Dienogest Versus Luteal Phase Fluoxetine in the Management of Premenstrual Syndrome: A Randomized Double Blind Placebo Controlled Trial
Study Start Date : April 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Dienogest
women will receive oral dienogest 2mg for 14 days starting from the 15th day of menstruation
Drug: Dienogest
women will receive oral dienogest 2mg for 14 days starting from the 15th day of menstruation

Active Comparator: Fluoxetine
women will receive oral fluoxetine 20mg for 14 days starting from the 15th day of menstruation
Drug: Fluoxetine
women will receive oral fluoxetine 20mg for 14 days starting from the 15th day of menstruation

Placebo Comparator: Placebo
women will receive oral placebo for 14 days starting from the 15th day of menstruation
Drug: Placebo
women will receive oral placebo for 14 days starting from the 15th day of menstruation




Primary Outcome Measures :
  1. Improvement of DRSP score [ Time Frame: Monthly, up to 3 months ]
    DRSP scores will be documented in each treatment month, the mean score will be compared with the pretreatment score



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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427334


Contacts
Contact: AbdelGany M Hassan +201017801604 abdelgany2@gmail.com

Locations
Egypt
BeniSuef University hospitals Recruiting
BeniSuef, Egypt
Contact: Nesreen AA Shehata, MD    +2001227866337    nesoomar@yahoo.com   
Cairo university hospitals Recruiting
Cairo, Egypt
Contact: AbdelGany Hassan, MRCOG, MD    002 01017801604    abdelgany2@gmail.com   
Principal Investigator: AbdelGany MA Hassan, MRCOG, MD         
Sponsors and Collaborators
Cairo University

Publications:
Responsible Party: AbdelGany Hassan, Lecturer of Gynecology and Obstetrics, Cairo University
ClinicalTrials.gov Identifier: NCT02427334     History of Changes
Other Study ID Numbers: PMS
First Posted: April 28, 2015    Key Record Dates
Last Update Posted: January 23, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Syndrome
Premenstrual Syndrome
Disease
Pathologic Processes
Menstruation Disturbances
Fluoxetine
Dienogest
Nandrolone
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Contraceptives, Oral
Contraceptive Agents, Female
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents