Premenstrual Syndrome (PMS) /Premenstrual Dysphoric Disorder (PMDD)

Question 1

Hormones and Mood

Answer 1

Ø Estrogen effects on neurotransmitters:

Positive effect on serotonin:
* Increase synthesis of serotonin
* Up regulation of 5-HT1 receptors
* Modulation of binding affinity of 5-HT receptors

Also effect of other neurotransmitter systems (ie noradrenalin,
dopamine)

Progesterone
l Progesterone can increase 5-HT uptake in several regions,
increase 5-HT turnover

Question 2

PMS/PMDD: Introduction

Answer 2

Ø Cyclic recurrence of symptoms during luteal phase of
menstrual cycle.
l Often symptoms dissipate with onset of menses
l Mixture of mood, physical and cognitive symptoms
Ø Symptoms usually begin 25 – 35 years of age. may begin earlier
Ø PMDD – could be categorized as severe PMS

Question 3

PMS/PMDD: Pathophysiology

Answer 3

Many theories exist:
Ø Correlation of hormones and + central neurotransmitters
l Serotonin (5-HT) – major central neurotransmitter involved
Ø Possible effects: greater susceptibility to
l normal cyclic changes in hormones or
l ratio of estrogen to progesterone
Ø Other theory: progesterone key mediator of PMS/PMDD
l GABA receptors (metabolite of progesterone –
allopregnanolone is an agonist)

Question 4

Risk Factors

Answer 4

Ø Genetics
Ø Traumatic or major life events/stressors
Ø Comorbidity with depression/anxiety
Ø Psychosocial factors (ie fewer social support etc
very common

up to 75% indivudals who have a uterus and ovaries

Question 5

Risk Factors

Answer 5

Ø Genetics
Ø Traumatic or major life events/stressors
Ø Comorbidity with depression/anxiety
Ø Psychosocial factors (ie fewer social support etc
very common

up to 75% indivudals who have a uterus and ovaries

Question 6

PMS Signs and Symptoms

Answer 6

emotinal symptoms

physical symptoms

see slide 7

Question 7

Diagnosis

Answer 7

Ø To establish diagnosis of PMS/PMDD, symptoms must be:
l Characteristic of PMS/PMDD
l Limited to luteal phase
* Often worse few days before menses
l Impacting daily life
l Symptoms present for at least 2 previous cycles
l Not explained by some other diagnosis

Question 8

PMDD: DSM-5 criteria

Answer 8

Ø 5 symptoms must occur during the final week before menses and starts to improve
within a few days after menses.

Ø B: one or more of the following with symptoms
1. Markedly depressed mood
2. Marked anxiety
3. Marked affective lability (feeling suddenly sad or increased sensitivity to
rejection)
4. Marked anger or irritability or increased personal conflicts

Ø C: One (or more) of the following symptoms must additionally be present, to reach a
total of five symptoms when combined with symptoms from Criterion B above
1. Decreased interest in usual activities (ie work, school, etc)
2. Subjective difficulty in concentration
3. Lethargy, easy fatigability, or marked lack of energy
4. Marked change in appetite, overeating or specific foods
5. Hypersomnia or insomnia
6. A subjective sense of being overwhelmed or out of control
7. Other physical symptoms (ie those listed for PMS)
Ø Interferes with daily life
Ø The disturbance is not another affective disorder
Ø Confirmed with 2 consecutive cycles

Question 9

Assessment of Patient for PMS or PMDD

Answer 9

Have the patient keep a daily
symptom diary for 2 – 3 months

Are the symptoms
consistent with PMS?
yes

no Evaluate for other disorders

Are the symptoms
in luteal phase?
yes

Do the symptoms interfere
with daily functioning?
yes
PMS PMDD

no
Mild premenstrual
symptoms

Question 10

Non-pharmacological Options

Answer 10

Patient education
l Biologic basis of PMS – may help give patient sense of
control
l Education to establish patient expectations
Ø Daily charting of symptoms – symptom diary
l Greater awareness of symptoms by patient
Ø Exercise
l regular, aerobic
l reduces severity of symptoms

Ø Adequate rest and relaxation
l Relaxation courses
Ø Stress reduction
l Cognitive behavioral treatment – technique, helps controls
thoughts, behaviors and emotions
Ø Dietary:
l Sodium restriction – if fluid retention, bloating, breast swelling
l Caffeine restriction – if irritability or insomnia
l Complex carbohydrate diets
l Some foods but not as clear ie bananas

Question 11

Natural Health Products for
PMS/PMDD

VITAMINS AND MINERALS

Answer 11

Vitamins and minerals:
Ø Calcium – 1200 mg daily
l RCTs have shown improvement for mood and physical
symptoms (specifically fluid retention)
Ø Magnesium – 200 – 400 mg daily
l shown to reduce fluid retention/bloating
Ø Vitamin B6 – 100 mg daily
l mild symptoms (mood and physical symptoms)
Ø Vitamin E - 400 IU daily
l mild symptoms (breast tenderness, mood)
Note: most evidence is with calcium for PMS symptoms, other minerals/vitamins data is more limited

Question 12

Natural Health Products for
PMS/PMDD
Natural Health Products:

Answer 12

Chasteberry fruit (Vitex) – 20 mg daily
l RCTs have shown benefit in PMS symptoms (breast tenderness, mood)
Ø Evening primrose oil (EPO)
l Prostaglandin precursor
l Systematic review showed no better than placebo
Ø St Johns wort
l Open label trial showed benefit (mood), no RCTs
Ø Gingko – one RCT, administered 40 mg leaf extract tid through
luteal phase, helped both physical and mood

Question 13

Pharmacological

Answer 13

Ø NSAID
s – ibuprofen, naproxen
l May help with the physical symptoms of PMS
l Can start in luteal phase, often stopped 1 – 2 days after
menses starts
Ø Diuretics – spironolactone
l 25 – 100 mg per day during luteal phase
l Most helpful for fluid retention, bloating, and breast
tenderness
- start for 2 wks durign that time or just before arohnd the time they start having symptoms

Question 14

Non-prescription combination products (ie Midol®)

Answer 14

l pamabrom (a mild diuretic), pyrilamine (an antihistamine) +
analgesics (ie acetaminophen)
l No added benefit to the addition of these compounds\

OTC
mild diuretic may help a bit ame with analgesic
hard to know if there’s added beenfit

caffeine in some pdt for ppl w headahces, migraines during time of PMS

Question 15

Combined Hormonal Contraceptives (CHC):

Answer 15

l Mixed results with CHC
* 50% of patients will see no change, 25% will see
improvements, and 25% will get worse (sensitive to progestin with mood effects)
l Use continuous, so not having fluations during the time
l ?consider drospirenone containing CHC for those patients with
fluid retention, anti mineralcorticoid effects

Question 16

Ø Progesterone

Answer 16

l Historically used during the luteal phase to help with
symptoms
l Micronized progesterone, usually
l Systematic review of progesterone in PMS found no
benefit\

progesterone (micronized and natural) gets metabolized into allopregnolone which has effects on GABA receptors and can help with anxiety and possibly mood

used for 14 days in luteal phase , mixed evidence

Question 17

SSRI
s

Answer 17

l SSRIs are drugs of choice for PMDD
l Effective for helping with PMS/PMDD symptoms
l Intermittent as effective as continuous:
* Intermittent:
l Luteal phase or symptom day
l Drug discontinued on the first day of menses or 1 – 3
days later
l Symptoms often improve within 24 – 48 hours for PMS/PMDD
– but it may take 3 menstrual cycles to see full benefit
l Intermittent not associated with SSRI discontinuation
symptoms.
l If intermittent not effective then switch to continuous.
l Symptom-onset dosing has also been trialed, however has
shown modest benefit over placebo.
1

effect on estrogen and prog were on serotonin , they have a quick effect
works quickly enough that you can use SSRI intermittently
last 14 days of menstrual cycle or symptom day, as soonn as someone feels mood start to get affected
luteal is seen more common

Question 18

SNRI’s
anxiolytics

Answer 18

Ø SNRI’s are also an option
most evidence for PMDD is fluoxetine, sertraline, paroxetine (dont need to memorize)
- paroxetine has indication for PMDD not others but can still use
Ø Anxiolytics
l Benzodiazepines (ie alprazolam) during the luteal phase
has been shown to be effective for PMS/PMDD especially
for anxiety.
Usually reserved for women who do not respond or used in
conjunction with antidepressants
prn for anxiety during those few days

Question 19

If nothing else effective then ovulation suppression may be
considered including:

Answer 19

agents that stop ovulation completely, cause basically a menopause

l GnRH agonists: leuprolide, buserelin, etc
* Have been successful in relieving symptoms
l Danazol
* May be limited by androgenic side effects
Ø Note: bilateral oophorectomy is the final line of treatment for
severe PMS/PMDD

Question 20

Therapeutic Approach

Answer 20

Individualize therapy to target most troublesome symptoms.
Ø Non-pharmacological and symptom diaries should be considered.
Ø Benefit usually seen in 2 – 3 menstrual cycles. Try one agent for
~3 cycles before switching to the next therapy

Question 21

CPS mild to mod PMS symptoms

Answer 21

non-pharm for PMS: caffeine reducation, salt redution, exercise, good sleep hyfein/e, relaxation, small carb rich meals (complex carbs so insulin doesnt spike

2-3 mont trial for each
if no benefit, can use calcium, Vit B6, magensium, NSAIDS

Next options if nonpharmacologic not effective:
Mild to moderate :
Ø Breast tenderness/water retention - spironolactone
Ø CHC – consider continuous

Question 22

Treatment of Severe
PMS/PMDD

Answer 22

Severe PMS/PMDD (or when mood primary
problem):
Ø SSRI
s – continuous or intermittent
Ø If initial SSRI ineffective or not tolerated:
l try 2 additional SSRI agents before
abandoning this type of class.
(can then try SNRI)
l Switch to continuous if on intermittent

withdrawal effects not seen