Hippocrates’ works (370 BC)

2. Hippocrates’ works (370 BC) The blood of females is subject to intermittent ‘agitations’ and as a result the ‘agitated blood’ makes its way from the head to the uterus whence it is expelled.3

3. four landmark stages parallel • our understanding of the premenstrual disorders. • From the ‘agitations’ of Hippocrates (370 BC) to • premenstrual tension (PMT);1 recognition and description of symptoms • From PMT to PMS;2 in this period, the link between • the ovarian hormone cycles and symptoms was • recognized. • recognition and description of symptoms • attempt to define and • quantify premenstrual disorders and the theory of • progesterone deficiency was explored and refuted. • From PMDD to the present day; in this period there • has been the realization that women are sensitive to • normal levels of ovulatory progesterone, that this • possibly has a neuroendocrine explanation, and that • therapy can be achieved by altering neuroendocrine • status with psychotropic drugs (notably selective • serotonin reuptake inhibitors [SSRIs]) or by elimination • of ovulation.

4. The diagnosis of PMS/PMDD – the current • debate

5. Current diagnostic criteria for PMS/PMDD • ICD-10 • ACOG • DSM-IV

6. ACOG Occur 5 days before menses Remit within 4 days of onset of before menses No recurrence at least until day 13 of cycle

7. PMS can be diagnosed after the patient prospectively • documents at least one of the affective or somatic • symptoms during the 5 days prior to menses for three • menstrual cycles. Symptoms should be of such severity • as to impact social or economic performance. There • should be no concomitant pharmacological therapy, • hormone ingestion, or drug or alcohol abuse. • Other • psychiatric and medical disorders must have been • excluded as a potential cause of the symptoms

9. DSM-IV Occur during the last week Remit within few days after No recurrence at least until onset of follicular phase

10. At least five symptoms, with at • least one of: depression, • anxiety, or tension, anger or • irritability, and monthly swings • Other qualifying symptoms are: • decreased interest, difficulty • concentrating, lack of energy, • changed sleep, overwhelmed, • out of control, change in • appetite

12. Other physical symptoms such • as breast tenderness, bloating • headaches, pain • Markedly interferes with work, • social activities, relationships • Most menstrual cycles during • past year • At least two consecutive cycles • Not merely an exacerbation of • another disorder • Not associated with • pharmacological, hormone, • alcohol or drug use or abuse

13. UNSOLVED ISSUES WITH CURRENTDIAGNOSTIC CRITERIA lack of universal agreement on the nature of the PMS as well as lack of universal acceptance of the criteria per se. definition of PMDD as a diagnostic entity, independent of PMS.

14. Any mood, behavioral or physical symptom(s), or • cluster(s) of symptoms that occur recurrently and cyclically • during the luteal phase of the menstrual cycle. • ● The symptom(s) remit(s) shortly following the • beginning of menses and consistently do not exist • for at least 1 week of the follicular phase of most • menstrual cycles. • ● The symptom(s) cause emotional or physical distress • and/or suffering and/or impairment in daily • functioning, and/or impairment in relationships. • ● The recurrence, cyclicity, and timing of the cycle, • and severity of the symptoms as well as existence of • a menstrually related symptom-free period are documented • by daily monitoring and/or reports.

17. 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 ● Agnuscastus ● Irradiation of ovaries

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

19. 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

20. Surgical treatments: • ● Hysterectomy • ● Hysterectomy and bilateral oophorectomy • ● Endometrial ablation techniques

22. SHOULD PMS BE REGARDED AN • ENDOCRINE CONDITION OR AS • A BRAIN DISORDER?

23. women with premenstrual • complaints differ from controls not with respect • to ovarian function, but with respect to how responsive • the target organs are to the influence of gonadal steroids. • One important target organ for sex steroids is the • central nervous system. Receptors • in many brain regions including the • amygdala and the hypothalamus.

24. IS PMS DUE TO SEROTONERGIC • DYSFUNCTION?

25. many • studies however do lend support to the notion that • women with PMS/PMDD differ from controls with • respect to various indices of serotonergic activity, indicating • that serotonin in fact may play a significant part • in the pathophysiology of this condition

26. 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; 146:107–16. • Jovanovic H, Cerin Å, Karlsson P et al. Psychiatry Res 2006; 148:185–93.