PMS & PMDD

J. Christopher Lynch, Pharm.D., BCACP

Professor of Pharmacy Practice
SIUE School of Pharmacy
 Definitions: PMS & PMDD
 Premenstrual molimina:
 Normally occurring premenstrual symptoms without
significant impact on patient’s function or QOL.
 PMS: (~45-50% of ovulating women)
 Premenstrual Syndrome
 PMDD: (~6-8% of ovulating women)
 Premenstrual Dysphoric Disorder
 More severe than PMS with significantly greater
psychological symptoms.

Braverman PK. Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

J Pediatr Adolesc Gynecol (2007) 20:3-12.
 Definitions: PMS & PMDD
 PMS:
 An array of predictable physical, cognitive,
affective and behavioral symptoms that occur
cyclically during the luteal phase of the menstrual
cycle and resolve quickly at or within a few days
of the onset of menstruation.
 There are no universally accepted diagnostic
criteria for PMS.

Braverman PK. Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

J Pediatr Adolesc Gynecol (2007) 20:3-12.
 Definitions: PMS & PMDD
 A single ICD-9 Code (625.4), Premenstrual
Tension Disorder, covers both PMS &
PMDD.

Braverman PK. Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

J Pediatr Adolesc Gynecol (2007) 20:3-12.
PMS Diagnosis: ACOG
 A patient must have at least one of the affective
symptoms and one of the somatic symptoms
beginning at least 5 days prior to the onset of
menses in 3 consecutive cycles and cease
within 4 days of the onset of menses.

 The symptoms must adversely affect social or

work-related activities.
Diagnostic Symptoms: PMS
 Affective Symptoms
Somatic Symptoms
 Breast tenderness
Depression
 Angry outbursts
Abdominal bloating
 Irritability
Headache
 Anxiety of extremities
Swelling
 Confusion
 Social withdrawal
Other symptoms of PMS
 Relationship issues
Insomnia
 Hypersomnia
Worsening of underlying disorders:
 Criminal behavior
 Mastalgia
 Suicidal ideations
 Bloatedness
 Absenteeism
 Weight gain
 Joint pain
 Generalized pain
PMDD diagnosis criteria
 See table 3 from the reading assignment.
 Symptoms must persist for a year prior to
reaching diagnosis of PMDD.
 Must clearly differentiate from a catamenial
trigger of other underlying disorders.
Differential diagnosis
 Most of the symptoms of PMS & PMDD can
be attributed to other diseases.
 The central point of diagnosis of PMS &
PMDD is the relationship of the symptoms
to the menstrual cycle.
 The symptoms do not appear at all during other
portions of the menstrual cycle.
Diagnosis of PMS & PMDD
 Premenstrual experience diary.
 Women typically seek a diagnosis from 3.7
physicians for 5.2 years prior to reaching a
diagnosis and being treated.
Mishell D. Premenstrual disorders: epidemiology and
disease burden. Am J Manag Care. 2005;11:S473-S479.
Differential Diagnosis
 Thyroid Disease
 Irritable Bowel Disease
 Urinary Tract Infection
 Cystitis (bladder cyst)
Risk Factors for PMS & PMDD
 Age > 30 years
 Family history (mother and sisters)
 Stress (?) or response to stress
 History of traumatic events:
 Childhood sexual abuse
 Severe accidents
 Severe physical threat history (rape, physical
abuse).
Physiology & Etiology
 PMS & PMDD only occur in ovulating
women.
 Both appear to be mediated by a sensitivity
to the progesterone levels in the luteal
phase.
 Women with PMS & PMDD do NOT have
higher progesterone levels than the general
population.
embryology.med.unsw.edu.au/.../images/Mcycle.GIF
Physiology & Etiology
 Women who suffer from severe PMS &
PMDD have been shown to have lower
platelet concentrations of serotonin during
he last 10 days of the cycle than the
general population.
 Serotonin deficiency may lead to increased
sensitivity to the effects of progesterone.
Catamenial diseases
These are not PMS or PMDD
 Any disease that is worsened during the premenstrual period.
 Often responsive to hormonal manipulation (OCP).
 Common examples:
 Seizures
 Migraines
 Irritable bowel disease
 Diabetes
 Asthma
 Rheumatoid arthritis
Treatment of PMS
& PMDD
Non-drug therapy
 Education of expectations
 Aerobic exercise:
 30-60 mins per day has significant reduction of
mood symptoms.
 Stress management:
 Biofeedback
 Meditation
 Therapeutic Massage
Non-drug therapy
 Accupressure & accupuncture
 Chiropractic adjustment (?)
 Phototherapy
 Cognitive Behavioral Therapy:
 Focusing on changing dysfunction thoughts,
emotions and behaviors.
 Equivacal results.
Dietary Modifications for PMS
 Increasing carbohydrates helps with:
 Mood, memory, carbohydrate craving.
 Complex carbs are less likely to be craved, but may
satisfy cravings with less weight gain.
 Decrease sodium, alcohol and caffeine.
 Helps with water retention and mood.
 May be related to magnesium deficiency.
 Low-fat high-fiber diet throughout the month:
 May lessen excursions of estrogen and progesterone
through the cycle.
Vitamin supplementation
 Vitamin B6:
 Serves as cofactor in the synthesis of serotonin.
 Equivocal results show some benefit.
 Dose 50-100mg per day
 >100mg per day may lead to neuropathies
 Calcium:
 Shows benefit in the reduction of water retention, food
cravings and generalized pain.
 1200-1500mg per day (divided) of calcium carbonate was
used in most clinical trials.
Herbal & Natural Products
 Chasteberry (vitus agnus-castus):
 May reduce irritability, mood alteration, anger, headache
and breast tenderness.
 May alter estroegen & progesterone production by corpus
luteum.
 Perhaps similar response as fluoxetine (1 small study).
 Should not be used during pregnancy or lactation.
 20 mg per day is maximum recommended dose.
 Poorly studied in comparison to legend drugs.
Herbal & Natural Products
 Ginkgo biloba (ginkgo leaf extract):
 Improves breast tenderness, fluid retention and mood.
 Dose: 80mg BID from day 16 through day 5 of cycle.
 May increase bleeding risk, and has multiple CYP450
interactions.
 St. John’s Wort:
 Similar but lesser effects as SSRI’s
 More drug interactions than SSRI’s.
 Should not generally be recommended.
 Evening Primrose Oil:
 Used to treat PMS symptoms for centuries.
 Not effective in clinical trials, except for the reduction of breast
pain & tenderness.
 Drug Therapy for
Somatic Symptoms
NSAIDS
 NSAIDS may help reduce generalized pain and
breast tenderness.
 Dose starting on day 15 through 5 of the cycle.
 Dose around the clock rather than prn.
 Prevention is slightly better than treatment.

 Naproxen is moderately superior to ibuprofen in 2

small trials.
Spironolactone
 May help treat the symptoms of breast
tenderness, bloating and fluid weight gain.
 Dose: 100mg per day on days 15-28.
 Some sources suggest using only in
women with regular weight gain > 3 lbs
during luteal phase of cycle.
Bromocriptine
 Dopamine agonist & reduces prolactin levels.
 Useful only to treat breast symptoms (pain,
tenderness, fullness).
 Dose: 2.5mg BID-TID on days 10-28.
 Cautious use in those with HTN.
 Should not use in those with seizure disorders.
 Drug Therapy for
Psychological Aspects of
PMS & PMDD
SSRI’s
 SSRI’s are the drugs of first-choice for severe
PMS & PMDD.
 SSRI’s improve all psychological and many
physical manifestations of the disease.
 PMS symptoms respond much quicker than does
depression to SSRI therapy (1-2 days is not
uncommon).
 The use of intermittent SSRI’s (days 14-28) is
typically as effective with fewer toxicities.
Fluoxetine
 Fluoxetine is the most widely studied of the
SSRI’s for PMS & PMDD.
 20mg per day is as effective as higher
doses with fewer toxicities.
 There is no reason to use Sarafem rather
than generic fluoxetine.
Other meds for psychological
symptoms
 Clomipramine may be used.
 Less effective than SSRI’s
 Fewer sexual side-effects than SSRI’s.
 Benzodiazepines may be added for the
treatment of anxiety.
Hormonal Therapy to
Treat PMS & PMDD
Contraception
 Anything that leads to total suppression of
ovulation will treat PMS & PMDD.
 Typical oral contraception does not totally
suppress ovulation.
 COP containing drospirenone (YAZ) is superior to
those containing other progestins in the short
term.
 Anti-mineralocorticoid and pro-estrogenic effects.
 Depo-provera has some benefit, but oral
progestin-only pills are not effective.
Drosperinone vs. other COC’s
 YAZ is the only COC with an FDA approved
indication for ADHD
 Cochrane analysis shows little or no benefit of
drosperinone vs other COCs in efficacy or
toxicity after 3 months of use.
Non-responders
 A Cochrane review showed that more
women (~50%) did not respond to SSRI,
than women who did respond (~40%).

 Addition of a COC did not significantly alter

percentage of responders (but responder
improvement may be better with combo).
GnRH agonists
 Leuprolide, Danazol.
 Result in initial surge of LH & FSH, but within 1-4
weeks, result in suppression of LH & FSH.
 Result in “chemical oopherectomy”.
 Used for no more than 6 months typically.
 Will cause hot flashes, may cause osteoporosis.
 May identify women who would benefit from
surgical oopherectomy.
Surgical treatment of PMS & PMDD
 Bilateral oopherectomy with or without
hysterectomy will cure PMS & PMDD.
 The risks of these procedures generally
outweigh the benefits.
 Surgery should never be performed without a
prior trial of a GnRH agonist.
Ineffective Therapies
 Lithium
 Tricyclic antidepressants
 MAO-Inhibitors
Cases
 OP is a 45-year-old Caucasian woman who presents to the Family
Medicine clinic where you are the clinical pharmacist. This is her third
visit in 6 months seeking care for her premenstrual symptoms.

 She has complained of anxiety, irritability, breast tenderness, joint pain,

and generalized pain during the last 10 days of her menstrual cycle.
These problems have created problems in her relationship with her
husband, and have been getting worse over the past 7 months (prior to
that time her premenstrual symptoms were rare and mild). Her
physician has had her complete a symptom log for the last 2 months.

 It shows that these problems are relatively severe during the

premenstrual phase of her cycle, and do not exist at all during other
days of the month. Prior to this visit you had recommended that she
start following appropriate lifestyle and dietary modifications, which
you believe she has done.
References
 Braverman PK. Premenstrual Syndrome and Premenstrual
Dysphoric Disorder. J Pediatr Adolesc Gynecol (2007) 20:3-
12.
 Steiner M, et al. Expert Guidelines for the Treatment of
Severe PMS, PMDD, and Comorbidities: The role of SSRIs.
Journ Women’s Health (2006) 15: 57-69.
 Indusekhar R. Psychological aspects of premenstrual
syndrome. Best pract & research clin obstet and gyn (2007)
21: 207-220.
 Reissman D, et al. The Pharmacist’s Role in Breaking the
Cycle of PMDD. Pharmacy Times CE. ACPE Program ID:
290-000-07-006-H01.