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.