Sindrome Premenstrual

Table of Contents
1. Prevention: Not applicable to this module. ...................................... 2

2. 8creening: 8creen all menstruating women during routine
exams for symptoms of premenstrual syndrome. ............................... 2
2.1 Screen all menstruating women routinely for emotional, behavioral, or
physical symptoms that fluctuate with their menstrual cycle. ............................ 3
3. Diagnosis: Diagnose PM8 and PMDD when emotional,
behavioral, and physical symptoms that are distressing to the
patient appear in the second half of the menstrual cycle and
resolve post-menses. .................................................................................... 3
3.1 Diagnose PMS or PMDD by history and careful charting of symptoms. ......3
3.2 Use a validated questionnaire to do a prospective symptom inventory and
consider laboratory testing to exclude other diagnoses. ....................................4
3.3 Consider other psychiatric or medical disorders in patients with the
diagnosis of PMS or PMDD. .............................................................................. 5
4. Consultation for Diagnosis: Obtain appropriate consultation if
severe psychiatric or medical symptoms are present. ..................... 5
4.1 Consider consultation with a psychiatrist or medical specialist if severe
psychiatric or medical premenstrual symptoms are present. .............................6
5. Hospitalization: Hospitalize patients in whom outpatient
treatment is ineffective who are at risk of harming themselves or
others. ................................................................................................................ 6
5.1 Consider inpatient or partial hospitalization if premenstrual symptoms lead
to compromised safety for the patient or others. ................................................6
6. Non-drug Therapy: Consider dietary regimens, calcium
supplementation, exercise, and cognitive therapy in patients with
PM8 and PMDD. ............................................................................................... 7
6.1 Consider dietary recommendations to increase complex carbohydrate
consumption and to make other dietary changes. ............................................. 7
6.2 Consider recommending calcium supplements. .......................................... 7
6.3 Consider vitamins and multinutrients. .......................................................... 8
6.4 Consider recommending regular exercise. .................................................. 8
6.5 Consider cognitive therapy to reduce premenstrual symptoms. .................. 9
6.6 Recognize the uncertain role of complementary/alternative therapies in the
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Page: 1 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
The preponderance of data
supporting this statement
is derived from level 1
studies, which meet all of
the evidence criteria for
that study type
studies, which meet at
least one of the evidence
criteria for that study type
studies, which do meet
none of the evidence
criteria for that study type
or are derived from expert
opinion, commentary or
consensus
Study types and evidence
criteria are defined at
http://pier.acponline.org/
criteria.html
The information included herein
should never be used as a
substitute for clinical judgment
and does not represent an
official position of ACP.
Because all PER modules are
updated regularly, printed web
pages or PDFs may rapidly
become obsolete. Therefore,
PER users should compare the
date of the last update on the
website with any printout to
ensure that the information
being referred to is the most
current available.
treatment of PMS. .............................................................................................. 9
6.7 Recognize that there is some preliminary research suggesting the use of
other non-drug treatments for PMS. ................................................................ 10
7. Drug Therapy: Consider the use of antidepressant medication
as first-line treatment for PMDD and ovulation suppression as
second-line treatment. ............................................................................... 10
7.1 Consider SSRs as first-line treatment for severe PMS and PMDD. ......... 10
7.2 Consider luteal phase SSR treatment as an alternative to continuous
treatment for severe PMS and PMDD. ............................................................ 12
7.3 Consider GnRH agonists as second-line treatment for PMS or PMDD. .... 12
7.4 Do not use oral contraceptives as a first-line treatment for PMS or PMDD.
.......................................................................................................................... 13
7.5 Do not recommend luteal phase progesterone for treatment of PMS or
PMDD. ............................................................................................................. 14
7.6 Consider anxiolytics, either alone or as adjunctive treatment, for decreasing
premenstrual tension and irritability. ................................................................ 15
7.7 Consider other pharmacologic treatments for specific premenstrual
symptoms. ........................................................................................................15
8. Patient Education: Provide information to patients with PM8 or
PMDD about lifestyle modifications, self-management techniques,
peer support, and overall management. ............................................... 16
8.1 Encourage patients to adopt lifestyle modification and self-management
techniques as an alternative or adjunct to drug therapy. ................................. 16
9. Consultation for Management: Consider consulting appropriate
specialists for help in managing patients with severe
premenstrual emotional or physical symptoms that do not
respond to conventional treatments. .................................................... 17
9.1 Obtain psychiatric or gynecologic consultation if SSRs, anxiolytics, or
hormonal treatments do not significantly reduce premenstrual symptoms. .....17
10. Follow-up: Follow patients through several menstrual cycles
to determine treatment effectiveness and need for ad]ustment to
therapy. ............................................................................................................ 17
10.1 After initiating drug therapy and non-drug therapy, maintain contact with
patients with severe PMS or PMDD after each menses to determine response
to treatment. ..................................................................................................... 17
1. Prevention: Not applicable to this module.
2. 8creening: 8creen all menstruating women during
routine exams for symptoms of premenstrual
syndrome.
Page: 2 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
2.1 Screen all menstruating women routinely for emotional,
behavioral, or physical symptoms that fluctuate with their menstrual
cycle.
Specific recommendation:
f a woman complains of symptoms such as mood swings, irritability, or
physical symptoms before her menstrual periods, ask:
Do the symptoms resolve after the period?
To what degree is functioning or quality of life impaired?
Recognize that women whose symptoms do not resolve after menses
may have an exacerbation of an underlying psychiatric or medical
disorder.
Recognize that women with a previous history of major depressive
disorder or postpartum depression, as well as a family history of PMS,
may be at increased risk for having severe PMS.
RationaIe:
Premenstrual emotional, behavioral, and physical symptoms appear in
most women between menarche and menopause.
Many women with moderate to severe PMS may benefit from treatment,
but if they are not screened during routine exams, they may not
volunteer their symptoms.
Women may be more likely to seek treatment for the emotional
symptoms of PMS rather than the physical symptoms, particularly for
irritability, which is the most frequent premenstrual complaint.
Evidence:
Premenstrual symptoms are problematic for 20% to 50% of women with
PMS (1).
Approximately 4% of women have multiple, severe premenstrual
symptoms that interfere with daily functioning and quality of life, and may
have premenstrual dysphoric disorder (PMDD), which has a specific set
of diagnostic criteria (1).
Comments:
None.
3. Diagnosis: Diagnose PM8 and PMDD when
emotional, behavioral, and physical symptoms that are
distressing to the patient appear in the second half of
the menstrual cycle and resolve post-menses.
3.1 Diagnose PMS or PMDD by history and careful charting of
symptoms.
nstruct women to prospectively chart their emotional, behavioral, and
physical symptoms daily for two menstrual cycles by:
Using an existent daily rating form to confirm the diagnosis of PMS or
PMDD
Page: 3 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
Selecting her own most problematic premenstrual symptoms and
rating them daily; for example, from 1 = "none to 4 = "severe
Diagnose PMDD if at least 5 of 11 symptoms required for the PMDD
diagnosis as well as functional impairment and decreased quality of life
are present.
Diagnose PMS if symptoms are present and there is associated
functional impairment and decreased quality of life.
See table History and Physical Examination Elements for Premenstrual
Syndrome/Premenstrual Dysphoric Disorder.
See table Diagnostic Criteria for Premenstrual Dysphoric Disorder.
See table Diagnostic Criteria for Premenstrual Syndrome.
RationaIe:
Up to 60% of women who retrospectively identify premenstrual
symptoms do not have PMS after prospective charting.
Often what is perceived by the patient to be PMS is an exacerbation of
an underlying psychiatric or medical disorder, or a disorder whose
symptoms are not related to menstrual cycle phases.
Charting confirms the nature and timing of the symptoms (presence of
symptoms in the luteal, or premenstrual, phase; and absence of
symptoms in the follicular, or postmenstrual phase), the regularity of
menses, and the absence of an underlying disorder.
Evidence:
Diagnostic criteria are specified in the Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition (1).
Several diagnostic criteria exist for PMS, and most require prospective
symptom charting and the resolution of symptoms after menses (2).
Comments:
None.
3.2 Use a validated questionnaire to do a prospective symptom
inventory and consider laboratory testing to exclude other
diagnoses.
Use a reliable and valid instrument to prospectively document symptoms
compatible with PMDD, such as:
Daily Record of Severity of Problems (DRSP)
(http://www.pmdd.factsforhealth.org/drsp/drsp_month.pdf)
Daily Symptom Report (DSR)
Daily Rating Form (DRF)
Prospective Record of mpact of Menstrual Symptoms (PRSM)
See figure Visual Analogue Scale (VAS)
Obtain at least two cycles of daily ratings (Likert scales or visual analog
scales) to establish absence of follicular phase symptoms and
appearance of premenstrual symptoms.
Be aware that a three-point Likert scale daily rating form, which includes
all PMDD symptoms, is available with illustrative examples of "PMS,
Page: 4 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
"PMDD, and "depression to aid the clinician in differential diagnosis
from the daily ratings.
Perform laboratory tests to exclude other diagnoses, such as
hypothyroidism or hyperthyroidism.
See figure Premenstrual Daily Symptom Chart.
See figure Example of Premenstrual Syndrome on Daily Symptom Chart.
See figure Example of Premenstrual Dysphoric Disorder on Daily
Symptom Chart.
See figure Example of Depression on Daily Symptom Chart.
RationaIe:
nstruments (questionnaires such as DRSP, DSR, DRF, COPE, PRSM,
VAS) have been utilized in studies to confirm the diagnosis of PMS or
PMDD.
Evidence:
Research studies have used multiple daily rating questionnaires to
differentiate women with severe PMS or PMDD from women with other
depressive or anxiety disorders, such as the DRSP (3), DSR (4), DRF
(5), COPE (6), PRSM (7) VAS (8; 9).
A fast, retrospective screening tool provides an important starting point
(10).
Comments:
None.
3.3 Consider other psychiatric or medical disorders in patients with
the diagnosis of PMS or PMDD.
Ask about:
Chronic low mood, such as current or previous major depression, or
manic-depressive illness, or anxiety symptoms that may be
exacerbated premenstrually
Chronic medical disorders that may be exacerbated premenstrually,
such as headaches, asthma, or other conditions
See table Differential Diagnosis of Premenstrual Syndrome or
Premenstrual Dysphoric Disorder.
RationaIe:
Many women with chronic diseases that are exacerbated premenstrually
perceive their increase in symptoms as PMS.
Evidence:
When women prospectively chart their symptoms on a daily basis, a
large proportion will have another disorder whose symptoms are
increased premenstrually, or a disorder whose symptoms do not, in fact,
fluctuate with the menstrual cycle (9).
Comments:
None.
4. Consultation for Diagnosis: Obtain appropriate
Page: 5 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
consultation if severe psychiatric or medical
symptoms are present.
4.1 Consider consultation with a psychiatrist or medical specialist if
severe psychiatric or medical premenstrual symptoms are present.
Recommend referral to a psychiatrist in women with:
Severe premenstrual depressive symptoms and impaired functioning
Premenstrual suicidal ideation
Recommend consultation with a psychiatrist for diagnosis or treatment of
premenstrual exacerbation of another underlying mood and anxiety.
Recommend consultation with a gynecologist for changes in menstrual
pattern or galactorrhea.
Recommend consultation with an internist for premenstrual exacerbation
of a medical condition.
RationaIe:
Psychiatrists and gynecologists are most likely to have the greatest
experience with diagnosis of the disorder.
Evidence:
Consensus.
Comments:
None.
5. Hospitalization: Hospitalize patients in whom
outpatient treatment is ineffective who are at risk of
harming themselves or others.
5.1 Consider inpatient or partial hospitalization if premenstrual
symptoms lead to compromised safety for the patient or others.
Hospitalize all patients in whom there is risk of suicide or assault in an
unsupervised setting.
RationaIe:
Premenstrual suicidal, self-injurious, or assaultive behavior is rare in
women with severe PMS or PMDD, but it can occur.
Even though suicidal and assaultive ideation may be transitory during
the premenstrual phase, women need to be in a setting in which such
impulses can be controlled and treatment instituted.
Evidence:
Suicidal ideation and attempts are elevated during the premenstrual
phase in women with PMS (11), and psychiatric admission rates are
elevated in the premenstrual phase (12).
Comments:
Page: 6 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
None.
6. Non-drug Therapy: Consider dietary regimens,
calcium supplementation, exercise, and cognitive
therapy in patients with PM8 and PMDD.
6.1 Consider dietary recommendations to increase complex
carbohydrate consumption and to make other dietary changes.
nstruct patients to:
ncrease consumption of complex carbohydrates
Decrease consumption of refined sugar and artificial sweeteners
Eliminate caffeine and alcohol
Eat three to six small meals per day
RationaIe:
t has been proposed that premenstrual increased appetite and
carbohydrate cravings are a homeostatic mechanism to increase the
ingestion of tryptophan, a precursor for serotonin synthesis, leading to
increased serotonin availability.
Caffeine anecdotally may exacerbate anxiety and tension.
The rationale for eating small, frequent meals is to maintain a fairly
constant glucose level, but this theory has yet to be studied in PMS.
Evidence:
One controlled, double-blind crossover study of a drink containing simple
and complex carbohydrates indicated efficacy in reducing premenstrual
dysphoria and other symptoms (13; 14).
L-tryptophan, 6 g/d, was superior to placebo in reducing symptoms of
PMDD (15).
Comments:
No other controlled trials of a single dietary regimen have been
conducted in women with PMS or PMDD.
6.2 Consider recommending calcium supplements.
Recommend oral calcium supplementation, 1200 mg/d, to reduce
premenstrual emotional and physical symptoms.
RationaIe:
Researchers have proposed that PMS may involve a cyclical, transient,
secondary hyperparathyroidism with peri-ovulatory decrease in calcium
and increase in parathyroid hormone levels following the pre-ovulatory
estrogen peak.
Evidence:
t has been suggested that normalizing calcium levels may normalize
calcium effects on monoamine neurotransmitter synthesis and release,
thus decreasing affective and anxiety symptoms (16).
Page: 7 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
The largest randomized, controlled treatment trial conducted to date in
women with PMS involved the daily administration of calcium, 600 mg
bid, or placebo in 466 subjects. Premenstrual emotional symptoms and
physical symptoms improved with a 48% efficacy rate, with the exception
of insomnia and fatigue. Patients receiving oral contraceptives, however,
had somewhat lower response rates. Patients receiving other treatments
were not excluded, and concurrent psychiatric illness was not rigorously
excluded (17).
Comments:
None.
6.3 Consider vitamins and multinutrients.
Recognize that the effectiveness of vitamin B6, vitamin E, magnesium,
and multinutrients in treating PMS and PMDD is uncertain.
RationaIe:
There are studies suggesting that there is a luteal phase decrease in
magnesium, which could affect neuronal stability, leading to
premenstrual mood and anxiety symptoms.
Evidence:
Studies of vitamin B6 (100 mg/d) have been extensively reviewed, and
there is minimal efficacy compared to placebo (18; 19). Neurotoxicity is
possible in doses above 200 mg/d.
Magnesium supplementation may offset lowered premenstrual phase
magnesium (20; 21; 22).
One older study suggested that vitamin E reduced premenstrual
symptoms (23).
Comments:
None.
6.4 Consider recommending regular exercise.
Consider recommending aerobic exercise for 30 minutes, three to five
times per week.
RationaIe:
Exercise may reduce premenstrual symptoms by its effect on the
endorphin system, the serotonin system, or through an increase in
feelings of self-efficacy.
Exercise is helpful in improving mood in women and men with major
depression.
Evidence:
There are no controlled trials of exercise in women with PMS or PMDD
published to date, but premenstrual emotional and physical symptoms
are decreased with regular exercise in women in general (24; 25).
Comments:
Page: 8 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
t is unclear if aerobic exercise is superior to nonaerobic exercise.
Exercise may decrease premenstrual symptoms in women in general,
but it has not been studied in a population of women with PMS or PMDD.
6.5 Consider cognitive therapy to reduce premenstrual symptoms.
Recommend individual or group cognitive therapy as an efficacious
treatment for PMS.
RationaIe:
Components of cognitive therapy that may be helpful include alteration of
dysfunctional attitudes, cognitive restructuring, and increasing coping
strategies, such as assertiveness training.
Evidence:
A randomized, controlled trial in women with prospectively confirmed
PMS have reported improvement in psychological and social functioning
with individual cognitive therapy (26), and another controlled trial
demonstrated a decrease in anxiety, depression, negative thoughts, and
physical changes with group cognitive-behavioral therapy (27).
A recent randomized, controlled trial suggested that cognitive therapy
had different treatment effects on PMDD than fluoxetine. Fluoxetine had
a more rapid effect and greater impact on anxiety, and cognitive therapy
was more helpful in adopting behavioral coping strategies (28).
Comments:
None.
6.6 Recognize the uncertain role of complementary/alternative
therapies in the treatment of PMS.
Note that there is some evidence that the agnus castus fruit
(chasteberry) may reduce premenstrual symptoms.
RationaIe:
t is possible that chasteberry may reduce some emotional and physical
symptoms of PMS.
Other herbs and homeopathic medications have been studied in women
with PMS, but there is no current compelling evidence to recommend
any single treatment.
Evidence:
Chasteberry reduced emotional and physical symptoms in 170 women
with PMS, but how the diagnosis was confirmed in the sample was not
stated in the manuscript (29).
Chasteberry did not differ from fluoxetine in overall treatment response in
a preliminary study but reduced more physical than mood symptoms
(30).
Open and controlled studies with several herbal treatments, including
Page: 9 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
hypericum and gingko biloba, have been reviewed, and several may
deserve further study (31; 32; 33).
A controlled clinical trial of oral homeopathic medicine was recently
reported to be beneficial in improving scores on a daily menstrual
distress questionnaire by more than 30% in 90% of the study group as
compared to 37.5% of those patients receiving placebo (34).
n a meta-analysis of seven trials, lack of homogeneity and inconsistent
quality made pooling of data impossible, but the two most well-controlled
trials failed to show beneficial effects of evening primrose oil (35).
n another systematic review of randomized, controlled trials of
complementary/alternative therapies, there was insufficient evidence
among the 27 trials to recommend any of the therapies in the treatment
of PMS (31).
Comments:
None.
6.7 Recognize that there is some preliminary research suggesting
the use of other non-drug treatments for PMS.
Consider discussing preliminary data on:
Light therapy
Sleep deprivation
Relaxation techniques
Massage
Chiropractic manipulation
Biofeedback
Reflexology
Acupuncture
RationaIe:
There is some preliminary research data to suggest efficacy of light
therapy, sleep deprivation, relaxation techniques, massage or
chiropractic manipulation, biofeedback, and reflexology.
Evidence:
There is some positive preliminary research support for light therapy
(36), sleep deprivation (37), relaxation (38), reflexology (39), massage
(40), biofeedback (41), acupuncture (42) and chiropractic manipulation
(43).
Comments:
These treatments require further study.
7. Drug Therapy: Consider the use of antidepressant
medication as first-line treatment for PMDD and
ovulation suppression as second-line treatment.
7.1 Consider SSRs as first-line treatment for severe PMS and
PMDD.
Page: 10 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
Consider:
Fluoxetine, 20 mg/d, or during the luteal phase only, for the treatment
of the emotional and physical symptoms of PMDD
Sertraline, 50 to 100 mg/d, or during the luteal phase only
Paroxetine CR, 12.5 mg/d or 25 mg/d, or during the luteal phase only
Prescribe the same SSR doses for PMS or PMDD as for major
depression.
n women with premenstrual exacerbation of chronic mood and anxiety
disorders, consider increasing the SSR dose during the premenstrual
weeks, and returning to the lower dose at menses.
Recognize that there are no evidence-based recommendations for
length of treatment with SSRs, but premenstrual symptoms recur in
many women when treatment is stopped.
Be aware that the FDA has recommended a black box warning for
antidepressant drugs for pediatric and adolescent patients under age 18.
See table Drug Treatment for Premenstrual Syndrome or Premenstrual
Dysphoric Disorder.
RationaIe:
Multiple studies have reported that SSRs reduce premenstrual mood,
anxiety, behavioral, and physical symptoms.
The efficacy rate averages 65% for SSRs vs. 30% for placebo in most
studies.
The action of SSRs in enhancing serotonin is unique in PMDD
compared to depression, due to the rapid onset of action and the
selective superiority of serotonergic antidepressants compared to
non-serotonergic antidepressants.
Evidence:
Superior efficacy of daily dosing of SSRs compared to placebo for the
reduction of premenstrual emotional and physical symptoms have been
reported in 12 randomized, controlled trials with fluoxetine (44; 45; 46;
47; 48; 49; 50), sertraline (51; 52), paroxetine (53; 54), and citalopram
(55), as recently reviewed (56; 57).
Two large, multisite, randomized, controlled trials have confirmed
efficacy for fluoxetine (44) and sertraline (51).
A Cochrane review concluded that very good evidence supports the use
of SSRs for PMS (58).
Multiple serotonin abnormalities have been reported in women with
PMDD (59; 60), and it is presumed that SSRs are effective by their
enhancement of serotonin (61).
A consensus panel of experts reported that SSRs are the treatment of
choice for prominent premenstrual mood and anxiety symptoms (62).
A multisite trial reported that daily venlafaxine was superior to placebo in
reducing PMDD symptoms (63).
A recent small trial reported that nefazodone was not superior to placebo
for PMS (64).
Serotonergic antidepressants are selectively effective in PMDD. Three
randomized, controlled trials comparing SSRs to non-serotonergic
Page: 11 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
antidepressants have reported that the non-serotonergic antidepressants
are not significantly superior to placebo (45; 52; 53).
t has been proposed that the rapid relief of symptoms achieved with
SSRs may possibly involve an alteration in allopregnanolone levels, an
anxiolytic metabolite of progesterone that acts at the GABA receptor (60;
65).
Comments:
Fluoxetine, sertraline, and paroxetine are FDA-approved for the
treatment of PMDD.
7.2 Consider luteal phase SSR treatment as an alternative to
continuous treatment for severe PMS and PMDD.
Consider luteal phase (or intermittent) dosing of an SSR, administering
from ovulation to menses only.
Before initiating luteal phase dosing, review the symptom chart to rule
out a chronic mood or anxiety disorder, to confirm PMS or PMDD, and to
avoid inadequate antidepressant therapy.
Dysphoric Disorder.
RationaIe:
Due to the quick onset of action of SSRs for the alleviation of
premenstrual symptoms, it may not be necessary to administer the SSR
daily.
t has been proposed that the rapid relief of symptoms achieved with
SSRs may possibly involve an increase in allopregnanolone, an
anxiolytic metabolite of progesterone that acts at the y-aminobutyric acid
receptor.
Evidence:
Four randomized, controlled trials of intermittent dosing with sertraline
(66; 67; 68) and citalopram (55) and a comparison of intermittent vs.
continuous dosing with sertraline (69) indicate efficacy rates comparable
to daily dosing (56; 57).
Three large multisite studies have indicated that fluoxetine, 20 mg/d,
from ovulation to menses (70); fluoxetine, 90 mg/wk, 14 days and 7 days
before next expected menses (71); and sertraline, 50 to 100 mg/d, from
ovulation to menses (72) are beneficial for PMDD.
There are currently no published studies of the efficacy of
"symptom-onset SSR dosing, such as administration of the SSR from
the first day of symptoms until menses or of weekly fluoxetine
administration in PMDD.
Comments:
None.
7.3 Consider GnRH agonists as second-line treatment for PMS or
PMDD.
Page: 12 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
Consider ovulation suppression with GnRH agonists, such as leuprolide
or goserelin.
Note that GnRH agonists can have hypoestrogenic effects, and that
adding back estrogen and progesterone may induce mood and anxiety
symptoms.
Dysphoric Disorder.
RationaIe:
Suppression of ovulation may be effective for PMS due to the elimination
of the interaction of gonadal hormone fluctuation at ovulation with
neurotransmitter and neuroendocrine parameters. The use of GnRH
agonists may, however, be limited by their hypoestrogenic effects.
Evidence:
Eight randomized, controlled trials of GnRH agonists report efficacy
compared to placebo (73; 74; 75; 76; 77; 78; 79; 80); two do not report
efficacy compared to placebo (81; 82).
Attempts to decrease hypoestrogenic effects of prolonged anovulation
with add-back estrogen and progesterone has led to the induction of low
mood and anxiety symptoms (76; 77), limiting the long-term usefulness
of GnRH agonists for PMS or PMDD.
A meta-analysis indicates that GnRH analogs appear to be an effective
treatment for PMS/PMDD. The addition of hormonal add-back therapy
did not reduce the efficacy of GnRH analogs (83).
GnRH agonists may be less useful for premenstrual exacerbation of
chronic depression (74) or severe premenstrual depression (75).
The addition of a synthetic compound, tibolone, to a GnRH agonist
reduced hot flashes compared to placebo in women with PMS, without
compromising the symptomatic relief obtained from the GnRH agonist
(84).
Comments:
None.
7.4 Do not use oral contraceptives as a first-line treatment for PMS
or PMDD.
Note that:
The effect of long-term oral contraceptive use on PMS, such as for 3
months followed by a placebo week, is an unstudied option
Hormone replacement regimens administered for perimenopausal
physical and emotional symptoms, such as hot flushes, insomnia, poor
concentration, and irritability, may improve or worsen premenstrual
symptoms
Dysphoric Disorder.
RationaIe:
Page: 13 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
Although oral contraceptives are widely used, their efficacy is not
substantiated by currently available research studies.
Women anecdotally report improvement, worsening, and no change in
their premenstrual symptoms with oral contraceptives.
There are currently no predictors of the influence of oral contraceptives
on premenstrual symptoms.
Evidence:
A recent study of 82 women with PMDD reported that a new oral
contraceptive containing ethinyl estradiol, 30 g, and drospirenone, 3
mg, was superior to placebo for alleviating the premenstrual symptoms
of increased appetite, food cravings, and acne only (85). This study
reported a placebo response rate of 43%, and was not originally
powered to detect a significant difference from placebo.
As reviewed, early studies of women with confirmed PMS have not
reported improvement of PMS with monophasic or triphasic oral
contraceptives, although monophasic may be better tolerated than
triphasic oral contraceptives for low mood symptoms (86). These authors
suggest that the influence of oral contraceptives on premenstrual
symptoms may involve the type of progestin, the androgenic properties
of the progestin component, and the estrogen/progesterone ratio.
Women receiving oral contraceptives may have PMS or PMDD, and oral
contraceptives were recently reported to not alter the response to
sertraline in women with PMDD (87).
Oral contraceptives are not recommended as a first-line treatment (2;
62).
Comments:
None.
7.5 Do not recommend luteal phase progesterone for treatment of
PMS or PMDD.
Be aware that luteal phase progesterone, administered as vaginal
suppositories or oral micronized tablets, and progestogens are not
clinically indicated for the treatment of PMS or PMDD.
Dysphoric Disorder.
RationaIe:
Although multiple trials have failed to correlate premenstrual symptoms
with abnormal fluctuations of gonadal hormone levels, the administration
of luteal phase progesterone is one of the oldest treatments of PMS. t
has been theorized that oral micronized progesterone might be beneficial
due to its conversion to allopregnanolone, which may be beneficial for
premenstrual anxiety due to its action at the GABA receptor in the brain.
Evidence:
A recent systematic review of published, randomized, placebo-controlled
trials of progesterone and progestogens reported that neither treatment
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leads to clinically significant, superior efficacy compared to placebo (88).
This review did report a slight, statistically significant, but not clinically
significant, advantage of progesterone over placebo.
Oral micronized progesterone was slightly more effective than vaginal
suppositories or progestogens (88).
Comments:
None.
7.6 Consider anxiolytics, either alone or as adjunctive treatment, for
decreasing premenstrual tension and irritability.
Consider one of the following anxiolytic drugs:
Alprazolam, 0.25 mg bid, administered from ovulation to menses with a
taper at menses:
Do not administer alprazolam to women with previous substance
abuse problems
Note that sedation may be an unwelcome adverse effect of
alprazolam
Buspirone, up to 25 mg/d, either in the luteal phase or continually
Dysphoric Disorder.
RationaIe:
Alprazolam may reduce premenstrual anxiety, irritability, and tension
through its action as a benzodiazepine; however, it is less effective than
SSRs and does not improve the same range of symptoms, such as food
cravings.
Evidence:
Alprazolam has been reported to have positive efficacy with luteal phase
dosing in four randomized, controlled trials (89; 90; 91; 92); another
randomized, controlled trial reported no improvement (93).
Buspirone was recently reported to reduce premenstrual irritability with
daily dosing (64), and an older study reported efficacy for several
premenstrual symptoms with luteal phase dosing (94).
Comments:
None.
7.7 Consider other pharmacologic treatments for specific
premenstrual symptoms.
Consider the use of bromocriptine or danazol for mastalgia.
Consider the use of prostaglandin inhibitors to treat premenstrual pain
and emotional and physical symptoms.
Consider the use of spironolactone to reduce premenstrual bloat and
some emotional symptoms.
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Dysphoric Disorder.
RationaIe:
Mastalgia, bloating, and some emotional symptoms may respond to
nonhormonal and non-psychopharmacotherapy.
Evidence:
Premenstrual mastalgia may be reduced by bromocriptine (95), danazol
(96), or lisuride maleate, a dopamine agonist (97).
Prostaglandin inhibitors have been reported to treat both pain (98) and
emotional or other physical symptoms (99).
Spironolactone may reduce premenstrual bloat and some emotional
symptoms (100).
Comments:
None.
8. Patient Education: Provide information to patients
with PM8 or PMDD about lifestyle modifications,
self-management techniques, peer support, and overall
management.
8.1 Encourage patients to adopt lifestyle modification and
self-management techniques as an alternative or adjunct to drug
therapy.
Provide patients with access to the recommended lifestyle modifications
found in self-help literature and patient education pamphlets or make
recommendations in an individual or group format.
Advise patients that PMS symptoms generally:
Recur with cessation of treatment
May increase with age or after childbirth
Are absent during pregnancy and after menopause
Advise patients who may conceive while receiving drug therapy to
choose a treatment option with lower risk to the pregnancy (e.g.,
medication with short half-life that will be eliminated sooner upon
discontinuation after pregnancy confirmed).
RationaIe:
Women may receive validation of their PMS by participating in peer
support groups.
Professionally administered individual or group patient education usually
encompasses multimodalities, including diet and exercise
recommendations, cognitive techniques, relaxation, and other
self-management techniques.
Evidence:
Minimal research has been conducted on the components of
multimodality patient education, lifestyle changes, and self-monitoring
that is helpful, except for a small amount of literature indicating that
cognitive therapy is helpful. A four-session group treatment
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encompassing diet, exercise, self-monitoring, self-regulation, relaxation,
and cognitive techniques was superior to wait-list control (104). Women
randomly assigned to the wait-list control had their symptoms monitored
while "waiting for group treatment.
A four-session group treatment encompassing diet, exercise, and
positive reframing of menstrual cycle experiences was superior to
wait-list control (105).
Comments:
Many women with PMS anecdotally report that peer support groups are
helpful.
9. Management Consultation: Consider consulting
appropriate specialists for help in managing patients
with severe premenstrual emotional or physical
symptoms that do not respond to conventional
treatments.
9.1 Obtain psychiatric or gynecologic consultation if SSRs,
anxiolytics, or hormonal treatments do not significantly reduce
premenstrual symptoms.
Recommend psychiatric consultation for assessment of acute risks,
adjustment of antidepressant treatment, or treatment of an underlying
disorder in women with:
Severe premenstrual depressive symptoms and impaired functioning
Premenstrual suicidal ideation
Premenstrual exacerbation of underlying mood and anxiety disorders
Recommend consultation with an internist when patients have
premenstrual exacerbation of underlying medical disorders.
Recommend consultation with a gynecologist when hormonal therapy is
contemplated.
RationaIe:
There may be a need for further expertise in difficult cases.
Evidence:
Consensus.
Comments:
None.
10. Follow-up ssues: Follow patients through several
menstrual cycles to determine treatment effectiveness
and need for ad]ustment to therapy.
10.1 After initiating drug therapy and non-drug therapy, maintain
contact with patients with severe PMS or PMDD after each menses
to determine response to treatment.
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current available.
nstruct patients who start drug therapy for severe PMS or PMDD to
contact their physician after each menses for medication adjustment until
symptom remission is achieved.
Consider changing from daily dosing to luteal phase dosing if side effects
are problematic.
Consider adding one or more non-drug measures as adjunctive therapy.
Recognize that drug therapy may need to be altered if the patient is
planning to conceive.
Taper or discontinue drug therapy if the patient has already conceived.
See table Elements of Follow-up for Premenstrual Disorder or
Premenstrual Dysphoric Disorder.
RationaIe:
n general, women have recurrence of premenstrual symptoms after
treatment is discontinued.
Women do not have PMS or PMDD when pregnant or after menopause.
Evidence:
There are no current guidelines as to optimal length of treatment. After 3
months of fluoxetine luteal phase therapy was discontinued, recurrence
of premenstrual symptoms was immediate (106).
Comments:
Drug therapy is generally long-term due to the recurrence of PMS or
PMDD following discontinuation of treatment.
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PremenstruaI DaiIy Symptom Chart
This image cannot be displayed. See the online version of PIER
to view this figure
Copyright 2000 Eli Lilly and Company. All rights reserved. Used with
permission.
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current available.
ExampIe of PremenstruaI Syndrome on DaiIy Symptom Chart
to view this figure
permission.
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current available.
ExampIe of PremenstruaI Dysphoric Disorder on DaiIy Symptom
Chart
to view this figure
permission.
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current available.
ExampIe of Depression on DaiIy Symptom Chart
to view this figure
permission.
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current available.
VisuaI AnaIogue ScaIe
to view this figure
Reprinted from 107. Copyright 1987, with permission from Elsevier
Science.
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http://pier.acponline.org/
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(PMD: 9435325)
77 Leather AT, Studd JW, Watson NR, Holland EF. The treatment of
severe premenstrual syndrome with goserelin with and without
'add-back' estrogen therapy: a placebo-controlled study. Gynecol
Endocrinol. 1999;13:48-55. (PMD: 10368798)
78 Hammarback S, Backstrom T. nduced anovulation as treatment of
premenstrual tension syndrome. A double-blind cross-over study with
GnRH-agonist versus placebo. Acta Obstet Gynecol Scand.
1988;67:159-66. (PMD: 3140572)
79 Hussain SY, Massil JH, Matta WH, Shaw RW, O'Brien PM. Buserelin in
premenstrual syndrome. Gynecol Endocrinol. 1992;6:57-64. (PMD:
1580169)
80 Sundstrom , Nyberg S, Bixo M, Hammarback S, Backstrom T.
Treatment of premenstrual syndrome with gonadotropin-releasing
hormone agonist in a low dose regimen. Acta Obstet Gynecol Scand.
1999;78:891-9. (PMD: 10577620)
81 West CP, Hillier H. Ovarian suppression with the
gonadotrophin-releasing hormone agonist goserelin (Zoladex) in
management of the premenstrual tension syndrome. Hum Reprod.
1994;9:1058-63. (PMD: 7962376)
Page: 28 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
82 Helvacioglu A, Yeoman RR, Hazelton JM, Aksel S. Premenstrual
syndrome and related hormonal changes. Long-acting gonadotropin
releasing hormone agonist treatment. J Reprod Med. 1993;38:864-70.
(PMD: 8277482)
83 Wyatt KM, Dimmock PW, smail KM, Jones PW, O'Brien PM. The
effectiveness of GnRHa with and without 'add-back' therapy in treating
premenstrual syndrome: a meta analysis. BJOG. 2004;111:585-93.
(PMD: 15198787)
84 Di Carlo C, Palomba S, Tommaselli GA, Guida M, Di Spiezio Sardo A,
Nappi C. Use of leuprolide acetate plus tibolone in the treatment of
severe premenstrual syndrome. Fertil Steril. 2001;75:380-4. (PMD:
11172843)
85 Freeman EW, Kroll R, Rapkin A, Pearlstein T, Brown C, Parsey K, et al.
Evaluation of a unique oral contraceptive in the treatment of
premenstrual dysphoria. J Womens Health Gend Based Med.
2001;10:561-9. (PMD: 11559453)
86 Kahn LS, Halbreich U. Oral contraceptives and mood. Expert Opin
Pharmacother. 2001;2:1367-82. (PMD: 11585017)
87 Freeman EW, Rickels K, Sondheimer SJ, Polansky M. Concurrent use
of oral contraceptives with antidepressants for premenstrual syndromes.
J Clin Psychopharmacol. 2001;21:540-2. (PMD: 11593086)
88 Wyatt K, Dimmock P, Jones P, Obhrai M, O'Brien S. Efficacy of
progesterone and progestogens in management of premenstrual
syndrome: systematic review. BMJ. 2001;323:776-80. (PMD:
11588078)
89 Freeman EW, Rickels K, Sondheimer SJ, Polansky M. A double-blind
trial of oral progesterone, alprazolam, and placebo in treatment of
severe premenstrual syndrome. JAMA. 1995;274:51-7. (PMD:
7791258)
90 Berger CP, Presser B. Alprazolam in the treatment of two subsamples
of patients with late luteal phase dysphoric disorder: a double-blind,
placebo-controlled crossover study. Obstet Gynecol. 1994;84:379-85.
(PMD: 8058235)
91 Smith S, Rinehart JS, Ruddock VE, Schiff . Treatment of premenstrual
syndrome with alprazolam: results of a double-blind, placebo-controlled,
randomized crossover clinical trial. Obstet Gynecol. 1987;70:37-43.
(PMD: 3299178)
92 Harrison WM, Endicott J, Nee J. Treatment of premenstrual dysphoria
with alprazolam. A controlled study. Arch Gen Psychiatry.
1990;47:270-5. (PMD: 2407209)
93 Schmidt PM, Grover GN, Rubinow DR. Alprazolam in the treatment of
premenstrual syndrome. A double-blind, placebo-controlled trial. Arch
Gen Psychiatry. 1993;50:467-73. (PMD: 8498881)
94 Rickels K, Freeman E, Sondheimer S. Buspirone in treatment of
premenstrual syndrome. Lancet. 1989;1:777. (PMD: 2564578)
95 Andersch B. Bromocriptine and premenstrual symptoms: a survey of
double blind trials. Obstet Gynecol Surv. 1983;38:643-6. (PMD:
6358978)
96 O'Brien PM, Abukhalil E. Randomized controlled trial of the
management of premenstrual syndrome and premenstrual mastalgia
using luteal phase-only danazol. Am J Obstet Gynecol. 1999;180(1 Pt
1):18-23. (PMD: 9914571)
97 Kaleli S, Aydin Y, Erel CT, Colgar U. Symptomatic treatment of
premenstrual mastalgia in premenopausal women with lisuride maleate:
a double-blind placebo-controlled randomized study. Fertil Steril.
2001;75:718-23. (PMD: 11287025)
Page: 29 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
98 Facchinetti F, Fioroni L, Sances G, Romano G, Nappi G, Genazzani
AR. Naproxen sodium in the treatment of premenstrual symptoms. A
placebo-controlled study. Gynecol Obstet nvest. 1989;28:205-8. (PMD:
2695413)
99 Mira M, McNeil D, Fraser S, Vizzard J, Abraham S. Mefenamic acid in
the treatment of premenstrual syndrome. Obstet Gynecol.
1986;68:395-8. (PMD: 3526218)
100 Wang M, Hammarback S, Lindhe BA, Backstrom T. Treatment of
premenstrual syndrome by spironolactone: a double-blind,
placebo-controlled study. Acta Obstet Gynecol Scand. 1995;74:803-8.
(PMD: 8533564)
101 Sundblad C, Modigh K, Andersch B, Eriksson E. Clomipramine
effectively reduces premenstrual irritability and dysphoria: a
placebo-controlled trial. Acta Psychiatr Scand. 1992;85:39-47. (PMD:
1546547)
102 Sundblad C, Hedberg MA, Eriksson E. Clomipramine administered
during the luteal phase reduces the symptoms of premenstrual
syndrome: a placebo-controlled trial. Neuropsychopharmacology.
1993;9:133-45. (PMD: 8216696)
103 Hahn PM, Van Vugt DA, Reid RL. A randomized, placebo-controlled,
crossover trial of danazol for the treatment of premenstrual syndrome.
Psychoneuroendocrinology. 1995;20:193-209. (PMD: 7899538)
104 Taylor D. Effectiveness of professional--peer group treatment: symptom
management for women with PMS. Res Nurs Health. 1999;22:496-511.
(PMD: 10625865)
105 Morse G. Positively reframing perceptions of the menstrual cycle among
women with premenstrual syndrome. J Obstet Gynecol Neonatal Nurs.
1999;28:165-74. (PMD: 10102544)
106 Pearlstein T, Miner CM, Brown EB, Joliat MJ. Recurrence of symptoms
of premenstrual dysphoric disorder (PMDD) after cessation of luteal
phase fluoxetine treatment. Am J Obstet Gynecol. [n press].
107 Melzack R. The short-form McGill Pain Questionnaire. Pain.
1987;30:191-7. (PMD: 3670870)
New References of Interest
108 Johnson SR. Premenstrual syndrome, premenstrual dysphoric disorder,
and beyond: a clinical primer for practitioners. Obstet Gynecol.
2004;104:845-59. (PMD: 15458909)
Page: 30 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
Glossary
COPE Calendar of Premenstrual Experience
DRF Daily Rating Form
DRSP Daily Record of Severity of Problems
DSR Daily Symptom Report
GABA y-aminobutyric acid
GnRH gonadotropin-releasing hormone
PMDD premenstrual dysphoric disorder
PMS premenstrual syndrome
PRSM Prospective Record of mpact of Menstrual Symptoms
SSR selective serotonin reuptake inhibitor
TSH thyrotropin
VAS Visual Analogue Scale
Terms
Catamenial headaches Headaches associated with menstruation
Page: 31 of 41
Premenstrual
8yndrome
Author(s):
Teri Pearlstein, MD
Status:
Module updated
2005-02-01
current available.
History and Physical Examination Elements for Premenstrual 8yndrome or Premenstrual
Dysphoric Disorder
Category Element Notes
History Anger or irritability May be 1 of 11 symptoms present in at least two menstrual
cycles, occurs during luteal phase, and resolves post-menses
History Depressed mood, feelings of hopelessness, or self-deprecating
thoughts
May be 1 of 11 symptoms present in at least two menstrual
History Feelings of tension, anxiety, or being keyed up May be 1 of 11 symptoms present in at least two menstrual
History Abdominal or generalized sensation of bloating May be 1 of 11 symptoms present in at least two menstrual
History Breast tenderness or swelling May be 1 of 11 symptoms present in at least two menstrual
History Headaches May be 1 of 11 symptoms present in at least two menstrual
History nterference with usual activities May be 1 of 11 symptoms present in at least two menstrual
History Labile mood, suddenly sad or tearful, increased sensitivity to
rejection
May be 1 of 11 symptoms present in at least two menstrual
History Marked change in appetite, overeating, or specific food cravings May be 1 of 11 symptoms present in at least two menstrual
History Forgetfulness and difficulty concentrating May be 1 of 11 symptoms present in at least two menstrual
History Lethargy, easily fatigued, or marked lack of energy May be 1 of 11 symptoms present in at least two menstrual
Physical exam General medical and gynecologic exam for underlying medical
illness or hormonal imbalance
Underlying medical illness or hormonal imbalance may contribute
to emotional and/or physical symptoms
Author:
Status:
Teri Pearlstein, MD
Module updated - 2005-02-01
Premenstrual 8yndrome
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of
ACP. Because all PER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete. Therefore, PER
users should compare the date of the last update on the website with any printout to ensure that the information being referred to is the
most current available.
PER is copyrighted (c) 2004 by the American College of
Physicians. 190 N. ndependence Mall West,
Page: 32 of 41
Laboratory table not applicable to this module
Author:
Status:
Teri Pearlstein, MD
Page: 33 of 41
Differential Diagnosis of Premenstrual 8yndrome or Premenstrual Dysphoric Disorder
Disease Characteristics Notes
Major depression Pervasive low mood, sadness, low energy, lack of pleasure, etc.
space
Present at least 2 weeks
Usually mood does not fluctuate with the menstrual cycle;
however, mood may be exacerbated in the premenstrual phase
Dysthymia Chronic low mood, less severe than major depression
space
Present at least 2 years
Usually mood does not fluctuate with the menstrual cycle;
however, mood may be exacerbated in the premenstrual phase
Generalized anxiety disorder Pervasive anxiety and worries
space
Present at least 3 months
Usually anxiety does not fluctuate with the menstrual cycle;
however, anxiety may be exacerbated in the premenstrual phase
Panic disorder Panic attacks, may or may not be accompanied by agoraphobia Usually panic attacks do not fluctuate with the menstrual cycle;
however, panic attacks may be exacerbated in the premenstrual
phase
Bipolar disorder Persistently elevated or irritable mood, often with grandiosity
space
Present for at least 1 week
Usually manic symptoms do not fluctuate with the menstrual cycle
Alcohol or drug abuse Persistent use of alcohol and/or drug use, despite negative
consequences
Can have anger and/or irritability, usually symptoms do not
fluctuate with the menstrual cycle
Bulimia nervosa Binge eating and purging Usually binge eating does not fluctuate with the menstrual cycle;
however, binge eating may be exacerbated in the premenstrual
phase
Migraine Severe headache Catamenial headaches or premenstrual exacerbation of migraines
may not be associated with emotional or other physical symptoms
of PMS
Chronic fatigue Consistent throughout the month, possible history of antecedent
illness
Less likely to consistently occur only in the luteal phase but may
be exacerbated premenstrually
rritable bowel syndrome Characterized by abdominal pain, chronic diarrhea, possible
weight loss
May flare premenstrually, not usually associated with emotional or
other physical symptoms of PMS
Endometriosis ncreased pain and symptoms with menses Not present during luteal phase; emotional symptoms of PMS
often not present
Seizure disorder Epileptic attacks Catamenial seizures or premenstrual exacerbation of seizures,
not usually associated with emotional or other physical symptoms
of PMS
Author:
Status:
Teri Pearlstein, MD
Table Continued...
Page: 34 of 41
Differential Diagnosis of Premenstrual 8yndrome or Premenstrual Dysphoric Disorder
Disease Characteristics Notes
Hyperthyroidism/hypothyroidism May present with mood alterations Exclude with TSH test
space
Mood alterations of hyperthyroidism or hypothyroidism generally
do not fluctuate with the menstrual cycle
Asthma Lung disorder May flare premenstrually, not generally associated with emotional
or physical symptoms of PMS
Allergies Hypersensitivity to allergen May flare premenstrually, not generally associated with emotional
or physical symptoms of PMS
PMS = premenstrual syndrome; TSH = thyrotropin.
Author:
Status:
Teri Pearlstein, MD
Page: 35 of 41
Drug Treatment for Premenstrual 8yndrome
or Premenstrual Dysphoric Disorder
Agent Mechanism of Action Dosage Benefits 8ide Effects Notes
Fluoxetine SSR; blocks presynaptic
serotonin transporter
20 mg/d or from ovulation to
menses
Absence of discontinuation
symptoms when used luteal
phase only
Long-term side effects of
weight gain and sexual
dysfunction
f sexual dysfunction occurs,
consider adjunctive bupropion,
150 mg bid.*
space
Daily dosing: 44; 45; 46; 47; 48;
49; 50
space
Luteal phase dosing: 70; 71
Sertraline SSR; blocks presynaptic
50-100 mg/d or from ovulation
to menses
Short half-life, absence of side
effects when used luteal phase
only
dysfunction
150 mg bid.*
space
Daily dosing: 51; 52
space
Luteal phase dosing: 66; 67;
68; 72
space
Comparison of luteal phase
dosing and continuous dosing:
69
Paroxetine
Paroxetine CR
SSR; blocks presynaptic
Paroxetine: 10-30 mg/d
space
Paroxetine CR: 12.5 mg/d or 25
mg/d or from ovulation to
menses
Short half-life Long-term side effects of
dysfunction possible, and may
be most likely with this
particular SSR
f used during luteal phase only,
unclear if there are
discontinuation symptoms if
abruptly stopped at menses.*
space
150 mg bid (53)
Citalopram SSR; blocks presynaptic
20-40 mg/d or from ovulation to
menses
Short half-life, decrease of side
effects when used luteal phase
only
dysfunction possible
150 mg bid (55)*
Venlafaxine Serotonin and norepinephrine
reuptake inhibitor
130 mg/d, average of
immediate-release venlafaxine
Dual-action antidepressant Long-term side effects of
dysfunction possible
150 mg bid (63)*
Author:
Status:
Teri Pearlstein, MD
Table Continued...
Page: 36 of 41
Clomipramine Tricyclic antidepressant with
predominant inhibition of
serotonergic reuptake
25-75 mg/d or from ovulation to
menses
Largely serotonergic tricyclic
antidepressant
Sedation, weight gain, dry
mouth, constipation, orthostatic
hypotension
Effective dose is less than
usual effective dose for major
depression.*
space
Daily dosing: 101
space
Luteal phase dosing: 102
Leuprolide GnRH agonist causes
anovulation by abolishing FSH
and LH surge at ovulation
3.75-7.5 mg im monthly Effective for emotional and
physical premenstrual
symptoms
Hypoestrogenic symptoms
such as hot flushes
Less effective for severe or
exacerbated premenstrual
depression (74; 75)
space
Adding back estrogen or
progesterone led to induction of
mood and anxiety symptoms
(76)
Goserelin GnRH agonist causes
anovulation by abolishing FSH
and LH surge at ovulation
3.6 mg sc monthly Effective for emotional and
physical symptoms
such as hot flushes
Adding back estrogen and
progesterone led to induction of
mood and anxiety symptoms
(77)
Buserelin GnRH agonist causes
anovulation by suppressing
FSH and LH surge at ovulation
100-900 g intranasally daily Effective for emotional and
physical symptoms
such as hot flushes
Not available in the United
States (78; 79; 80)
Danazol Synthetic steroid that
suppresses FSH and LH surge
at ovulation
200-400 mg/d Effective for emotional and
physical symptoms
Weight gain, hirsutism, acne,
nausea, decreased
high-density lipoprotein
Anovulation necessary for
efficacy for emotional and
physical symptoms.
space
Side effects limit its use.
space
Daily dosing: 103
space
Luteal phase dosing only
effective for mastalgia: 96
Author:
Status:
Teri Pearlstein, MD
Table Continued...
Page: 37 of 41
Ethinyl estradiol/drospirenone Oral contraceptive,
drosperinone has unique
antiandrogenic and
antimineralocorticoid action
One combination pill daily
(ethinyl estradiol, 30 g, and
drospirenone, 3 mg)
Effective for acne, food
cravings and increased appetite
Nausea, headache,
breakthrough bleeding
Not significantly effective for
most premenstrual symptoms
due to high placebo response
in study (85)
Alprazolam Benzodiazepine that increases
GABA neurotransmission at
GABAA receptor
0.25 mg bid or tid from
ovulation to menses
Beneficial adjunct for
premenstrual anxiety symptoms
Sedation, risk of tolerance, and
dependence
Efficacy rate ~40%.
space
Taper over first few days of
menses.
space
Contraindicated if prior drug
abuse or dependence (89; 90;
91; 92)
Buspirone Partial 5-HT1A receptor agonist 25 mg/d Anxiolytic Dizziness, nervousness Daily dosing: 64
space
Luteal phase dosing: 94
Spironolactone Aldosterone receptor
antagonist
100 mg/d from ovulation to
menses
Reduced premenstrual
irritability, depression, and
bloating
Gastritis, diarrhea 100
* The FDA has recommended a black box warning for antidepressant medications for use in children and adolescents under age 18.
FSH = follicle-stimulating hormone; GABA = y-aminobutyric acid; GnRH = gonadotropin-releasing hormone; LH = luteinizing hormone; SSR = selective serotonin reuptake inhibitor.
Author:
Status:
Teri Pearlstein, MD
Page: 38 of 41
Elements of Follow-up for Premenstrual Disorder or
Premenstrual Dysphoric Disorder
Category ssue How? How Often? Notes
History Response to treatment Ask about status of symptoms,
functioning, quality of life
Each visit Treatment efficacy is determined by
amelioration of symptoms
Physical exam General health status Routine annual exam by primary care
physician or gynecologist
Annually
Laboratory testing General health status, comorbid
disorders
Pap smear and other tests depending
on comorbid disorders
Annually or as needed
Non-drug therapy Response to therapy nitiate discussion of adjunctive
non-drug therapies
Every 3-6 months or as needed See Non-drug Therapy
Drug therapy Medication effectiveness and side
effects
Consider need for second-line
hormonal therapy.
space
Consider changing from daily dosing
to luteal phase dosing if side effects
are problematic, or consider
adjunctive bupropion, 150 mg bid, for
sexual dysfunction in patients
receiving SSR
Monthly for first 2-3 months, then
every 3-6 months, or as needed
Patient education Overall management Discuss lifestyle modifications
including diet and exercise
Each visit
SSR = selective serotonin-reuptake inhibitor.
Author:
Status:
Teri Pearlstein, MD
Page: 39 of 41
Diagnostic Criteria for Premenstrual Dysphoric Disorder
Research Criteria for Premenstrual Dysphoric Disorder
A. n most menstrual cycles during the past year, five (or more) of the following symptoms were present for most of the time during the last week of the luteal phase, began to remit within a few days after
the onset of the follicular phase, and were absent in the week post-menses, with at least one of the symptoms being either (1), (2), (3), or (4):
(1) markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts
(2) marked anxiety, tension, feelings of being "keyed up, or "on edge
(3) marked affective lability (e.g., feeling suddenly sad or tearful or increased sensitivity to rejection)
(4) persistent and marked anger or irritability or increased interpersonal conflicts
(5) decreased interest in usual activities (e.g., work, school, friends, hobbies)
(6) subjective sense of difficulty in concentrating
(7) lethargy, easy fatigability, or marked lack of energy
(8) marked change in appetite, overeating, or specific food cravings
(9) hypersomnia or insomnia
(10) a subjective sense of being overwhelmed or out of control
(11) other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of "bloating, weight gain
B. The disturbance markedly interferes with work or school or with usual social activities and relationships (e.g., avoidance of social activities, decreased productivity and efficiency at work or school).
C. The disturbance is not merely an exacerbation of the symptoms of another disorder, such as Major Depressive Disorder, Panic Disorder, Dysthymic Disorder, or a Personality Disorder (although it may
be superimposed on any of these disorders).
D. Criteria A, B, and C must be confirmed by prospective daily ratings during at least two consecutive symptomatic cycles. (The diagnosis may be made provisionally before this confirmation).
Reprinted with permission from 1. Copyright 1994 American Psychiatric Association.
Author:
Status:
Teri Pearlstein, MD
Page: 40 of 41
Diagnostic Criteria for Premenstrual 8yndrome
Premenstrual syndrome can be diagnosed in the patient reports at least one of the following affective and somatic symptoms during the 5 days before menses in each of the three prior menstrual cycles*:
Affective
Depression
Angry outbursts
rritability
Anxiety
Confusion
Social withdrawal
Somatic
Breast tenderness
Abdominal bloating
Headache
Swelling of extremities
*These symptoms are relieved within 4 days of the onset of menses, without recurrence until at least cycle day 13. The symptoms are present in the absence of any pharmacologic therapy, hormone
ingestion, or drug or alcohol use. The symptoms occur reproducibly during two cycles of prospective recording. The patient suffers from identifiable dysfunction in social or economic performance.
Adapted from Mortola JF, Girton L, Yen SC. Depressive episodes in premenstrual syndrome. Am J Obstet Gynecol 1989;161:1682-7. Reprinted from 2.
Author:
Status:
Teri Pearlstein, MD
Page: 41 of 41

Sindrome Premenstrual

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