Slide 1

Hippocrates works (370 BC)

The blood of females is subject to intermittentagitations and as a result the agitated bloodmakes its way from the head to the uterus whenceit is expelled.3

four landmark stages parallelour understanding of the premenstrual disorders.From the agitations of Hippocrates (370 BC) topremenstrual tension (PMT);1 recognition and description of symptoms

From PMT to PMS;2 in this period, the link betweenthe ovarian hormone cycles and symptoms wasrecognized.recognition and description of symptomsattempt to define andquantify premenstrual disorders and the theory ofprogesterone deficiency was explored and refuted.From PMDD to the present day; in this period therehas been the realization that women are sensitive tonormal levels of ovulatory progesterone, that thispossibly has a neuroendocrine explanation, and thattherapy can be achieved by altering neuroendocrinestatus with psychotropic drugs (notably selectiveserotonin reuptake inhibitors [SSRIs]) or by eliminationof ovulation.

The diagnosis of PMS/PMDD the currentdebate

Current diagnostic criteria for PMS/PMDDICD-10 ACOG DSM-IV

ACOG

Occur 5 days before mensesRemit within 4 days of onset of before mensesNo recurrence at least untilday 13 of cycle

PMS can be diagnosed after the patient prospectivelydocuments at least one of the affective or somaticsymptoms during the 5 days prior to menses for threemenstrual cycles. Symptoms should be of such severityas to impact social or economic performance. Thereshould be no concomitant pharmacological therapy,hormone ingestion, or drug or alcohol abuse.Otherpsychiatric and medical disorders must have beenexcluded as a potential cause of the symptoms

DSM-IV

Occur during the last week Remit within few days afterNo recurrence at least until onset of follicular phase

At least five symptoms, with atleast one of: depression,anxiety, or tension, anger orirritability, and monthly swingsOther qualifying symptoms are:decreased interest, difficultyconcentrating, lack of energy,changed sleep, overwhelmed,out of control, change inappetite

Other physical symptoms suchas breast tenderness, bloatingheadaches, painMarkedly interferes with work,social activities, relationshipsMost menstrual cycles duringpast yearAt least two consecutive cyclesNot merely an exacerbation ofanother disorderNot associated withpharmacological, hormone,alcohol or drug use or abuse

UNSOLVED ISSUES WITH CURRENTDIAGNOSTIC CRITERIA

lack of universal agreement on the nature of thePMS as well as lack of universal acceptance of the criteriaper se.definition of PMDD asa diagnostic entity, independent of PMS.

Any mood, behavioral or physical symptom(s), orcluster(s) of symptoms that occur recurrently and cyclicallyduring the luteal phase of the menstrual cycle. The symptom(s) remit(s) shortly following thebeginning of menses and consistently do not existfor at least 1 week of the follicular phase of mostmenstrual cycles. The symptom(s) cause emotional or physical distressand/or suffering and/or impairment in dailyfunctioning, and/or impairment in relationships. The recurrence, cyclicity, and timing of the cycle,and severity of the symptoms as well as existence ofa menstrually related symptom-free period are documentedby daily monitoring and/or reports.

Proposed or researched PMS treatments

Non-pharmacological treatments: Counseling Relaxation therapy Psychotherapy Cognitive behavioral therapy (CBT) Stress management Homeopathy Intravaginal electrical stimulation Rest Isolation Yoga Aromatherapy Exercise Music therapy Hypnosis Dietary manipulation Salt restriction Self-help groups Agnus castus Irradiation of ovaries

Non-hormonal pharmacological treatments: Tranquilizers Antidepressants Lithium SSRIs initial studies Vitamin B6 Beta-blockers Evening primrose oil Diuretics, spironolactone Magnesium, zinc, and calcium

Hormonal treatments: Progesterone (pessaries, injections, vaginal gel) Progestogens (norethisterone, dydrogesterone,medroxyprogesterone acetate, Depo-Provera) COC pill: cyclical/continuous Testosterone Bromocriptine Mifepristone, RU-486 Cyproterone acetate Tibolone Danazol, gestrinone Estradiol (oral, patch, implant) GnRH agonist analogs Non-steroidal anti-inflammatory drugs

Surgical treatments: Hysterectomy Hysterectomy and bilateral oophorectomy Endometrial ablation techniques

SHOULD PMS BE REGARDED ANENDOCRINE CONDITION OR ASA BRAIN DISORDER?

women with premenstrualcomplaints differ from controls not with respectto ovarian function, but with respect to how responsivethe target organs are to the influence of gonadal steroids.One important target organ for sex steroids is thecentral nervous system. Receptorsin many brain regions including theamygdala and the hypothalamus.

IS PMS DUE TO SEROTONERGICDYSFUNCTION?

manystudies however do lend support to the notion thatwomen with PMS/PMDD differ from controls withrespect to various indices of serotonergic activity, indicatingthat serotonin in fact may play a significant partin the pathophysiology of this condition

recent pilot studies suggesting that symptomatic women differ from non-symptomatic controls with respect to uptake of a serotonin precursor and density of serotonergic 5HT1A receptors, respectively.Eriksson O, Wall A, Marteinsdottir I et al. Psychiatry Res 2006; 146:10716. Jovanovic H, Cerin , Karlsson P et al. Psychiatry Res 2006; 148:18593.