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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
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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.
 The diagnosis of PMS/PMDD – the current
 debate
 Current diagnostic criteria for PMS/PMDD
 ICD-10
 ACOG
 DSM-IV
ACOG
Occur 5 days before menses
Remit within 4 days of onset of before menses
No recurrence at least until
day 13 of cycle
 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
DSM-IV
Occur during the last week
Remit within few days after
No recurrence at least until onset of follicular phase
 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
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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
UNSOLVED ISSUES WITH CURRENT
DIAGNOSTIC 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.
 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.
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● 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.
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)
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● 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 AN
 ENDOCRINE CONDITION OR AS
 A BRAIN DISORDER?
 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.
 IS PMS DUE TO SEROTONERGIC
 DYSFUNCTION?
 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
 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.