Download Premenstrual syndrome DynaMed http://web.a.ebscohost.com

DynaMed
1 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
Premenstrual syndrome
Updated 2013 Aug 14 05:00:00 PM: SSRIs may be effective for reducing PMS symptoms (Cochrane Database Syst Rev 2013
Jun 7) view update Show more updates
General Information
Description:
group of physical or affective symptoms during luteal phase relieved with onset or within 2-3 days of menses
symptom-free at least 1 week
present at least 3 months
patient ovulatory (symptoms do not occur if anovulatory)
Also called:
PMS
premenstrual tension syndrome
premenstrual dysphoric disorder (PMDD)
premenstrual dysphoric disorder (PMDD) has more specific diagnostic criteria (DSM-IV), is more severe, and has primarily
psychiatric symptoms
term "premenstrual dysphoric disorder" dropped from fluoxetine (Prozac) labeling after European drug regulator found it is
not a well-established disease entity (BMJ 2004 Feb 14;328(7436):365 full-text)
late luteal phase dysphoric disorder
Who is most affected:
reproductive age women, aged 30-50 years
Incidence/Prevalence:
10%-90% depending on definition, only 2%-3% severe
2.5% prevalence using strict diagnostic criteria (editorial in N Engl J Med 1998 Jan 22;338(4):256)
30% prevalence in cohort of 697 women who kept daily symptom ratings, but only 388 (56%) completed 2 cycles of daily ratings
(Obstet Gynecol 2007 May;109(5):1068)
Causes and Risk Factors
Causes:
unknown
Pathogenesis:
theories include increased estrogen, decreased B6, increased prolactin, decreased glucose, fluid retention, prostaglandin
abnormalities, endorphin withdrawal, hypothyroidism, decreased serotonin (5HT), increased monoamine oxidase (MAO),
hormone allergy, cyclic manifestations of underlying psychopathology
abnormal response to normal hormonal changes suggested in recent study
PMS defined as at least 30% increase in mean self-ratings of negative moods (depression, anxiety, irritability) in 7 days
before menses compared to 7 days after menses in 2 of 3 baseline cycles
20 women with and 20 women without PMS given leuprolide 3.75 mg/month vs. placebo for 3 months
no differences in women without PMS, but 10 of 18 women with PMS given leuprolide during double-blind or open-label
period had significant decrease in symptoms (sadness, anxiety, bloating, breast pain, food cravings, impaired function,
irritability)
leuprolide responders then given estradiol and progesterone in cross-over fashion, both of which were associated with return
of symptoms; no symptoms when estradiol or progesterone given to women without PMS
Reference - N Engl J Med 1998 Jan 22;338(4):209, editorial commentary can be found in N Engl J Med 1998 Jan
22;338(4):256
Likely risk factors:
postpartum depression, other affective disorders
Possible risk factors:
serotonin receptor 1A C(-1019)G polymorphism associated with premenstrual dysphoric disorder
22/03/2014 05:17 p.m.
DynaMed
2 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
based on case-control study with 53 women with premenstrual dysphoric disorder and 51 healthy controls
Reference - Obstet Gynecol 2007 Oct;110(4):788
Complications and Associated Conditions
Complications:
possibility that recurrent perimenstrual mood changes may increase risk of chronic depression (Psychol Med 1993;Suppl 24:1)
premenstrual phase of cycle may be period of increased vulnerability for onset or worsening of depression (J Affect Disord 1993
Oct;29(2-3):193)
increasing signs and symptoms (elevated blood sugars) in patients with diabetes mellitus
increasing seizures in patients with epilepsy
increased headaches in patients with migraine
Associated conditions:
magnesium deficiency (Acta Obstet Gynecol Scand 1994 Jul;73(6):452)
PMS associated with perceived stress, alcohol intake and being physically active in telephone interviews of 874 women 18-44
years old, 8.3% of whom experienced PMS (Arch Fam Med 1999 Mar-Apr;8(2):122 full-text)
may be associated with somatization disorder, somatoform pain disorder, or other functional somatic syndromes including
irritable bowel syndrome, non-ulcer dyspepsia, chronic pelvic pain, fibromyalgia, atypical or non-cardiac chest pain,
hyperventilation syndrome, chronic fatigue syndrome, tension headache, temporomandibular joint dysfunction, atypical facial
pain, globus syndrome, multiple chemical sensitivity (Lancet 1999 Sep 11;354(9182):936), commentary can be found in Lancet
1999 Dec 11;354(9195):2078
EBSCOhost Full Text (correction can be found in Lancet 2000 Feb 12;355(9203):580)
History and Physical
History:
Chief concern (CC):
psychological symptoms
fatigue
irritability
labile mood
depression
oversensitivity
crying
social withdrawal
forgetfulness
difficulty concentrating
physical symptoms
abdominal bloating
breast tenderness
acne
appetite changes or food cravings
swelling of extremities
headache
gastrointestinal upset
History of present illness (HPI):
symptom diary for 2-3 months
basal body temperature chart with menstrual calendar, or other method of natural family planning with reliable identification of
ovulation
recent history of hormonal contraceptive use
Physical:
General physical:
exam is normal in PMS, but may be useful to rule out organic pathology
Diagnosis
Making the diagnosis:
at least 5 of the following symptoms, including at least 1 of the first 4, present in most menstrual cycles in the past year;
symptoms should be isolated to late luteal phase and remit within days of onset of menses (this corresponds to the week before
and a few days after the start of menstruation)
22/03/2014 05:17 p.m.
DynaMed
3 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
depressed, feelings of hopelessness, self-deprecating thoughts
anxiety, tension, feeling "keyed up" or "on edge"
affective lability
persistent irritability or anger and increased interpersonal conflicts
decreased interest in usual activities
difficulty in concentrating
fatigue, lethargy
changes in appetite
change in sleep pattern
feeling overwhelmed or out-of-control
physical symptoms such as breast tenderness, headaches, weight gain, joint or muscle pain
symptoms cause interference with work, school, usual social activities, or relationships
symptoms are not an exacerbation of symptoms of a chronic condition (for example, major depressive disorder)
above criteria must be confirmed by prospective daily ratings during at least 3 consecutive symptomatic cycles to confirm
provisional diagnosis
Differential diagnosis:
depression, bipolar disorder, anxiety disorder, personality disorder, life circumstance, substance abuse, somatoform disorder,
eating disorder, thyroid disease, endocrinopathies, anemia
Testing overview:
symptom diary - prospective daily ratings of symptoms to establish premenstrual pattern
consider complete blood count (CBC), thyroid stimulating hormone (TSH), fasting blood sugar
consider timed hormonal profile with midluteal progesterone and estradiol
Treatment
Treatment overview:
ACOG guidelines
first step
supportive therapy
lifestyle modifications
complex carbohydrate diet - can improve mood and reduce food cravings
aerobic exercise - can improve mood and reduce fluid retention
reducing salt intake - can reduce symptoms of bloating, weight gain, breast tenderness
caffeine restriction reduces irritability and insomnia
improving sleep habits
nutritional supplements
calcium 1,200 mg/day can reduce pain, cramping, mood swings
magnesium 200-400 mg/day can reduce headache, fluid retention, mood changes
vitamin E 400 units/day (especially for mastalgia)
spironolactone 100 mg/day for 2 weeks before menses may reduce water retention, breast tenderness, weight gain
second step
SSRIs (fluoxetine or sertraline as initial choice), especially for more severe mood changes
for women who do not respond, consider an anxiolytic for specific symptoms, such as, alprazolam (Xanax)
third step - hormonal ovulation suppression
oral contraceptives
useful for physical symptoms (such as headache or breast tenderness) but may initially worsen symptoms
monophasic pills may be less likely to cause mood changes
GnRH agonists (leuprolide, goserelin) for severe cases unresponsive to other therapies
evidence does not support use of natural progesterone
Reference - Prescriber's Letter 2000 Aug;7(8):46
evidence for medications (based on randomized trials)
vitamin B6 50-100 mg/day and elemental calcium 1,200 mg/day are effective, safe, and inexpensive
SSRIs are more effective, more expensive, may cause side effects (dosing for 2 weeks preceding menses may be more
tolerable)
alprazolam 0.25-0.5 mg 3-4 times daily for 2 weeks preceding menses may reduce mood or anxiety symptoms
no convincing evidence of benefit for hormonal therapies (oral contraceptives, GnRH agonists, danazol, estrogen), diuretics,
magnesium, beta blockers, or lithium
Reference - J Fam Pract 2002 Oct;51(10):894
EBSCOhost Full Text
22/03/2014 05:17 p.m.
DynaMed
4 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
acupuncture might improve symptoms in women with premenstrualsyndrome (PMS) (level 2 [mid-level] evidence)
chaste tree berry (fruit extract) may improve symptoms in women with PMS (level 2 [mid-level] evidence)
Diet:
recommendations have included
frequent small meals to avoid hypoglycemia
fresh more than processed foods
diet high in protein, vitamins and complex carbohydrates
diet low in fat, linoleic acid (omega-6) and linolenic acid (omega-3)
no refined sugars, limit salt
avoid alcohol, tobacco, caffeine
low-fat vegetarian diet associated with decreased symptoms in 4-month randomized trial (2 months on intervention diet, 2
months on placebo supplement) of 51 women, only 33 women completed the study; unclear if benefit related to diet, group
support or study participation (Obstet Gynecol 2000 Feb;95(2):245 in Am Fam Physician 2000 May 1;61(9):2860)
Activity:
aerobic exercise (for example, 30 minutes daily) may increase endorphins
Counseling:
education for understanding
stress management
Medications:
Estrogen or combination oral contraceptive:
drospirenone 3 mg plus ethinyl estradiol 20 mcg (Yaz)
Yaz is first oral contraceptive FDA approved for premenstrual dysphoric disorder (Prescriber's Letter 2006 Nov;13(11):64)
drospirenone plus ethinyl estradiol 20 mcg may improve premenstrual symptoms in women with premenstrual
dysphoric disorder (level 2 [mid-level] evidence)
based on Cochrane review of trials with high dropout rates
systematic review of 5 randomized trials evaluating combined oral contraceptives containing drospirenone for effect on
premenstrual symptoms in 1,600 women
dropout rates ranged from 27% to 64%, only 1 trial had dropout rate < 20%
comparing drospirenone plus ethinyl estradiol 20 mcg vs. placebo in 2 trials of patients with premenstrual dysphoric disorder
drospirenone associated with less severe premenstrual symptoms at 3 months
drospirenone associated with greater decreases in impairment of productivity, social activities, and relationships
drospirenone plus more estrogen had little effect on less severe symptoms when compared to another combination oral
contraceptive
side effects more common with combination oral contraceptives were nausea, intermenstrual bleeding, and breast pain
drospirenone associated with fewer symptoms in 1 trial lasting 6 months, no differences found in 1 trial lasting 2 years
Reference - Cochrane Database Syst Rev 2012 Feb 15;(2):CD006586
evidence does not support use of progesterone or progestogens in management of premenstrualsyndrome
insufficient evidence to evaluate progesterone for premenstrualsyndrome
based on Cochrane review
systematic review of 2 randomized trials evaluating progesterone in 180 women with premenstrualsyndrome; exclusion
criteria were
exclusion criteria included women with psychiatric disorder and/or use of hormonal preparations or other treatments for
premenstrualsyndrome during trial period
< 70% analyzed in both trials
neither trial found progesterone (oral or vaginal) provided significant symptom relief compared to placebo but large
number of exclusions limited analyses
Reference - Cochrane Database Syst Rev 2012 Mar 14;(3):CD003415
systematic review of 10 trials of progesterone therapy (531 women) and 4 trials of progestogen therapy (378 women)
progesterone and progestogens were both statistically superior to placebo, but amount of improvement was not
clinically significant
review found that perhaps 20% patients can expect improvement in physical symptoms attributed to progestin use
(NNT 5) but asserted that magnitude of effect size for physical symptoms is not considered clinically significant
results not reported in such a way to determine the proportion of patients achieving clinically significant improvement
Reference - BMJ 2001 Oct 6;323(7316):776 full-text, commentary can be found in J Fam Pract 2002 Feb;51(2):109
EBSCOhost Full Text
DynaMed commentary -- trials included in this meta-analysis were limited in that evaluation did not include midluteal
22/03/2014 05:17 p.m.
DynaMed
5 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
progesterone levels, and therapy was not reliably given in luteal phase (after ovulation had occurred)
to cause anovulation
medroxyprogesterone acetate
oral contraceptives
transdermal estrogen and cyclic oral progesterone
"medical oophorectomy" - GnRH agonist (goserelin, leuprolide), danazol
American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 110 on noncontraceptive uses of hormonal
contraceptives can be found in Obstet Gynecol 2010 Jan;115(1):206 (reaffirmed 2012 Aug) or at National Guideline
Clearinghouse 2010 Jul 5:15428, commentary can be found in ACOG News Release 2009 Dec 21
Selective serotonin reuptake inhibitors (SSRIs):
see antidepressants for general information
SSRIs may be effective for reducing PMS symptoms (level 2 [mid-level] evidence)
based on Cochrane review of trials with methodologic limitations
systematic review of 31 randomized trials comparing SSRIs vs. placebo in 4,372 women with premenstrualsyndrome (PMS)
all trials had unclear allocation concealment, unclear blinding, and/or lack of intention-to-treat analysis
SSRIs included fluoxetine, paroxetine, sertraline, escitalopram, and citalopram
comparing low-dose SSRIs to placebo, low-dose SSRIs associated with
increased treatment response in analysis of 6 trials with 1,243 women
odds ratio (OR) 1.78 (95% CI 1.41-2.25)
NNT 5-12 with treatment response in 43% of placebo group
increased withdrawal due to adverse effects in analysis of 7 trials with 1,301 women
OR 1.76 (95% CI 1.13-2.75)
NNH 13-163 with withdrawal due to adverse effects in 5% of placebo group
comparing moderate-dose SSRIs to placebo, moderate-dose SSRIs associated with
increased treatment response in analysis of 19 trials with 2,647 women
OR 2.75 (95% CI 2.2-3.44)
NNT 4-6 with treatment response in 37% of placebo group
increase withdrawal due to adverse effects in analysis of 15 trials with 2,447 women
OR 2.55 (95% CI 1.84-3.53)
NNH 10-28 with withdrawal due to adverse effects in 4.5% of placebo group
comparing high-dose SSRIs vs. placebo in 1 trial with 211 women
treatment response in 46.2% vs. 20% (p < 0.0001, NNT 4)
withdrawal due to adverse effects in 33% vs. 7.2% (p < 0.0001, NNH 3)
SSRIs associated with improved psychological, physical, and functional symptoms, similar effect whether taken continuously
or only in luteal phase
Reference - Cochrane Database Syst Rev 2013 Jun 7;(6):CD001396
SSRIs associated with improved premenstrual symptoms (level 2 [mid-level] evidence)
based on systematic review with heterogeneity
systematic review of 29 randomized trials evaluating effects of SSRIs vs. placebo on symptoms related to
premenstrualsyndrome and premenstrual dysphoric disorder in 2,964 women
decreased premenstrual symptoms with SSRIs compared to placebo (OR 0.40, p < 0.05)
treatment effect size greater with continuous (OR 0.28) vs. intermittent (OR 0.55)
no SSRI significantly superior to others
Reference - Obstet Gynecol 2008 May;111(5):1175 full-text
Fluoxetine (Prozac, Sarafem):
fluoxetine 20 mg or 60 mg once daily through 6 menstrual cycles more effective than placebo in trial of 313 women with 53% vs.
28% cycles showing improved mood symptoms (N Engl J Med 1995 Jun 8;332(23):1529)
fluoxetine 20 mg once daily through 2 menstrual cycles more effective than bupropion or placebo (J Clin Psychopharmacol 1997
Aug;17(4):261)
fluoxetine FDA approved for premenstrual dysphoric disorder under brand name Sarafem, not studied with oral contraceptives
(FDA Talk Paper 2000 Jul 6), both 10 mg and 20 mg strengths approved (Monthly Prescribing Reference 2000 Aug:A-22)
premenstrual 2-week use of fluoxetine
premenstrualfluoxetine 20 mg effective; 260 women 18-45 years old with PMDD were randomized to fluoxetine 10 mg vs. 20
mg vs. placebo orally once daily starting 14 days before expected menses and ending on first day of menses for 3 cycles; 20
mg but not 10 mg associated with significant reduction in total symptom scores compared with placebo, both doses
improved mood-related symptoms, 20 mg dose improved physical symptoms; study funded by drug manufacturer (Obstet
Gynecol 2002 Sep;100(3):435 in J Watch Online 2002 Sep 17)
22/03/2014 05:17 p.m.
DynaMed
6 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
fluoxetine 20 mg once daily for 2 weeks before menses appeared as effective as throughout cycle in non-randomized trial of
48 women (Psychopharmacol Bull 1997;33(4):771)
Sarafem FDA approved for use during 14 days prior to anticipated menses (Monthly Prescribing Reference 2002 Aug:A-8)
fluoxetine lengthened or shortened menstrual cycle by at least 4 days in 21-28% women with PMS (Obstet Gynecol 1997
Oct;90(4):590 in Am Fam Physician 1998 May 15;57(10):2514)
symptoms recur after stopping fluoxetine; retrospective study of 517 women with PMDD randomized to fluoxetine vs. placebo for
3 menstrual cycles in 2 trials, all women given single-blind placebo in fourth menstrual cycle; symptoms improved in both groups
during first 3 months, with greater improvement with fluoxetine; symptoms worsened during placebo cycle in fluoxetine group,
becoming similar to placebo group, but still better than baseline (Am J Obstet Gynecol 2003 Apr;188(4):887 in J Watch Online
2003 May 27)
Sertraline (Zoloft):
sertraline (Zoloft) FDA approved for premenstrual dysphoric disorder with either continuous daily dosing or intermittent dosing
during last 2 weeks of luteal phase (Prescriber's Letter 2002 Jun;9(6):35)
sertraline showed efficacy in randomized trial, 62% vs. 34% much improved compared with placebo (JAMA 1997 Sep
24;278(12):983 in J Watch 1997 Oct 15;17(20):164), commentary can be found in JAMA 1998 Feb 4;279;357 (for which
commentary can be found in JAMA 1998 Jun 17;279(23);1873)
luteal phase sertraline reduces psychologic symptoms of PMDD; study of 281 women 24-45 years old with severe PMDD for at
least 2 years (excluding women using oral contraceptives or having high scores on depression screening), all had previously
responded adequately to treatment of PMDD with antidepressants; 142 women whose symptoms continued after compliance with
1 cycle of placebo treatment were randomized to sertraline (50 mg with potential for increased to 100 mg) vs. placebo orally
daily for 14 days before anticipated onset of bleeding for 3 cycles; sertraline associated with significant improvement in all
measures of depression and anxiety compared to placebo in all 3 cycles; no significant differences in physical symptoms such as
headache, breast tenderness or bloating; significant side effects included headache, nausea, dry mouth, insomnia and diarrhea;
8% discontinued sertraline due to side effects (Obstet Gynecol 2002 Dec;100(6):1219 in Am Fam Physician 2003 Mar
1;67(5):1077)
luteal phase treatment with sertraline safe and effective for moderate-to-severe premenstrual dysphoric disorder in small trial; 57
women 19-49 years with DSM-IV diagnosis of premenstrual dysphoric disorder at large outpatient multispecialty clinic in central
Texas first had 2-menstrual cycle drug-free period then randomized to late-luteal phase treatment with sertraline 50 mg/day
(cycle 1) then 100 mg/day (cycle 2) vs. placebo in crossover fashion; 22-item calendar of premenstrual experiences completed
daily, statistical analysis found significant beneficial effect from sertraline in improving calendar of premenstrual experiences total
(p < 0.01), behavioral factor (p < 0.01) and physical factor (p < 0.04) scores; study not reported in fashion amenable to NNT
reporting but 70% had at least 30% reduction in luteal phase total score after first cycle of sertraline vs. 50% after first cycle of
placebo (p < 0.05, NNT 5); most women improved when taking sertraline 50 mg but 25% had further improvement with 100 mg,
only adverse event reported by > 10% was 14% had insomnia (Arch Fam Med 1999 Jul-Aug;8(4):328 full-text)
sertraline 50-150 mg/day for 2 weeks before menses more effective than placebo in unpublished trial (Int J
Neuropsychopharmacol 2000 Jul;3(suppl 1):S248 in The Medical Letter 2001 Jan 22;43(1096):5)
intermittent luteal-phase (premenstrual) sertraline and continuous (full-cycle) sertraline have similar efficacy
(level 1 [likely reliable] evidence); randomized placebo-controlled trial of 167 women with PMS treated with sertraline
50-100 mg daily for 3 cycles; both sertraline groups had similar improvement in first cycle (NNT 6-7) and second cycle compared
to placebo, but placebo group had similar improvement by third cycle (Am J Psychiatry 2004 Feb;161(2):343 in J Watch Online
2004 Mar 9)
long-term sertraline treatment associated with lower relapse risk than short-term treatment for severe
premenstrualsyndrome (level 2 [mid-level] evidence)
based on randomized trial without intention-to-treat analysis
174 women with premenstrualsyndrome or premenstrual dysphoric disorder randomized to sertraline for 12 months vs. 4
months, then switched to placebo and followed to 18 months
relapse rate 41% in 12-month group vs. 60% in 4-month group (p = 0.04, NNT 6)
women with severe symptoms at baseline had higher relapse risk compared to women with lower symptom severity group
(hazard ratio, 2.02, 95% CI 1.18-3.41)
no difference in relapse rates between long-term and short-term treatments in subgroup analysis of women with lower
symptom severity
Reference - Arch Gen Psychiatry 2009 May;66(5):537 full-text
Other serotonergic antidepressants:
paroxetine (Paxil), citalopram (Celexa), and clomipramine (Anafranil) each reported to be effective (Int Clin Psychopharmacol 1999
May;14 Suppl 2:S27 in The Medical Letter 2001 Jan 22;43(1096):5)
FDA changes pregnancy category for paroxetine from C to D; 2 studies suggest increased risk of congenital heart defects
(1.5% to 2% vs. 1% in controls) in infants of women taking paroxetine during first 3 months of pregnancy (FDA Press Release
22/03/2014 05:17 p.m.
DynaMed
7 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
2005 Dec 8)
citalopram (Celexa) may be effective in treating premenstrual dysphoria, intermittent dosing in luteal phase
effective (level 2 [mid-level] evidence)
based on small randomized trial
78 women with increase in irritability or depressed mood 5 days preceding menstruation (late luteal phase) compared to
days 6-10 after menstruation for 2 consecutive cycles were randomized to 1 of 4 treatment groups
continuous citalopram
low-dose citalopram in follicular phase and higher dose in luteal phase
citalopram in luteal phase and placebo in follicular phase
continuous placebo
all women given 3 capsules (citalopram 10 mg or placebo) per day and told that recommended dose was 2 pills
69 women (88%) completed study of 3 menstrual cycles
significant improvement in global impression of symptoms with continuous citalopram and luteal phase citalopram compared
with placebo, but no significant improvement with variable low then high dose citalopram
no correlation between dose or serum drug concentration and clinical effect
Reference - J Clin Psychopharmacol 1998 Oct;18(5):390 in Psychiatric Medicine in Primary Care 1999 Premiere Issue;1(1):5
venlafaxine (Effexor)
venlafaxine effective for premenstrual dysphoric disorder (PMDD); after 3 screening cycles including single-blind placebo
cycle, 164 women were randomized to venlafaxine (50-200 mg/day) vs. placebo for 4 menstrual cycles, venlafaxine
significantly more effective than placebo in reducing PMDD symptoms as assessed by daily symptom report scores, 60% vs.
35% of improved > 50% (p = 0.003, NNT 4), 43% vs. 25% had symptom remission defined as reduction of symptom scores
to postmenstrual level (p = 0.034, NNT 5.6), 80% symptom reduction occurred in first treatment cycle; adverse events
included nausea, insomnia, and dizziness (Obstet Gynecol 2001 Nov;98(5 Pt 1):737)
venlafaxine more effective than placebo in unpublished trial (Int J Neuropsychopharmacol 2000 Jul;3(suppl 1):S241 in The
Medical Letter 2001 Jan 22;43(1096):5)
escitalopram during late luteal phase may improve symptoms in patients with premenstrual dysphoric disorder
(PMDD) (level 2 [mid-level] evidence)
based on randomized trial without intention-to-treat analysis
158 patients with PMDD randomized to escitalopram 10 mg vs. escitalopram 20 mg/day during luteal phase vs. placebo for 3
consecutive menstrual cycles
151 patients (96%) analyzed
for primary outcome of sum of symptom scores for irritability, depressed mood, tension or anxiety and affective lability
escitalopram 10 mg and 20 mg each more effective than placebo (p < 0.01)
escitalopram 20 mg more effective than 10 mg (p < 0.001)
≥ 80% reduction in rating of irritability (cardinal symptom of PMDD) in 80% with escitalopram 20 mg vs. 30% with placebo
no significant differences between groups for outcomes of breast tenderness, food craving or lack of energy
adverse effects associated with escitalopram included nausea and reduced libido, but no significant differences between
10-mg and 20-mg doses
Reference - J Clin Psychopharmacol 2008 Apr;28(2):195
medications with modest efficacy were fluoxetine 10 mg/day, alprazolam 0.75 mg/day and propranolol 20-40
mg/day (level 2 [mid-level] evidence) in 5-way randomized placebo-controlled trial in 120 women with severe
premenstrualsyndrome (Int J Gynaecol Obstet 1998 Jul;62(1):63)
Supplements and over-the-counter medications:
calcium supplementation may be modestly beneficial in some women
479 women ages 18-45 years with PMS randomized to calcium carbonate (elemental calcium 1,200 mg/day) vs. placebo for
3 menstrual cycles
466 women included in intent-to-treat analysis
primary outcome was average of 17 daily symptom ratings covering negative affect, water retention, food cravings and pain
calcium group had lower symptom scores during luteal phase of second and third treatment cycles, 48% vs. 30% reduction
in total symptom scores in third cycle
55% calcium vs. 36% placebo group reported > 50% improvement in symptoms
Reference - Am J Obstet Gynecol 1998 Aug;179(2):444
see also Calcium intake and supplementation
vitamin B6 may be helpful but trials of poor quality (level 2 [mid-level] evidence)
vitamin B6 up to 100 mg/day likely to be of benefit in treating premenstrual symptoms and premenstrual depression, but
conclusions limited by low quality of trials
systematic review of 10 randomized placebo-controlled trials, trials had poor quality and 1 trial excluded due to statistical
heterogeneity
22/03/2014 05:17 p.m.
DynaMed
8 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
vitamin B6 was more effective than placebo for improvement in overall premenstrual symptoms with odds ratio 2.32 (95%
CI 1.95-2.54) in meta-analysis of 9 trials with 940 patients
vitamin B6 improved depressive symptoms with odds ratio 1.69 (95% CI 1.39-2.06) in meta-analysis of 4 trials with 541
patients
only 1 patient had any side effects that could be attributed to neuropathy associated with pyridoxine toxicity, but assessment
of side effects was limited
Reference - BMJ 1999 May 22;318(7195):1375 full-text, commentary can be found in West J Med 2000
Apr;172(4):245 full-text in Am Fam Physician 2000 Oct 15;62(8):1912
pyridoxine 300 mg/day for 3 months no more effective than placebo (level 2 [mid-level] evidence) in 5-way
randomized trial in 120 women with severe premenstrualsyndrome (Int J Gynaecol Obstet 1998 Jul;62(1):63)
vitamin E 400 units/day reduced physical and emotional symptoms in 3-month placebo-controlled trial (J Reprod Med 1987
Jun;32(6):400)
magnesium supplementation may alleviate fluid retention but evidence limited (level 2 [mid-level] evidence)
38 women randomized to magnesium oxide (200 mg magnesium) vs. placebo for two menstrual cycles
no significant differences across 6 symptom categories in first menstrual cycle
hydration symptoms (weight gain, swelling of extremities, breast tenderness and abdominal bloating) was the only 1 of
6 symptom categories significantly reduced with magnesium in the second menstrual cycle
Reference - J Womens Health 1998 Nov;7(9):1157
EBSCOhost Full Text
32 women aged 24-29 years randomized to magnesium pyrrolidone carboxylic acid (360 mg magnesium) vs. placebo 3
times/day from 15th day of menstrual cycle to onset of menstrual flow for two menstrual cycles
both groups had reduced pain but no difference comparing magnesium with placebo
symptoms relating to mood changes and fluid retention improved in magnesium group
Reference - Obstet Gynecol 1991 Aug;78(2):177 in Prescriber's Letter 2005 Aug;12(8):46
Women's Tylenol Menstrual Relief caplets (acetaminophen 500 mg plus the diuretic pamabrom 25 mg) FDA approved for relief of
some symptoms of menstrual periods (for example, cramps, headache, and bloating) (Monthly Prescribing Reference 2000
Dec:A-19)
chaste tree berry
also called chasteberry, monk's pepper, Vitex agnus-castus L. (VAC) tree fruit,
approved in Germany for premenstrualsyndrome and mastodynia
contains many bioactive compounds including progestins and androgens, active ingredients unknown
chaste tree berry may improve symptoms in women with PMS (level 2 [mid-level] evidence)
based on 2 randomized trials with allocation concealment not stated
178 women who met Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) criteria for
premenstrualsyndrome (PMS) randomized to fruit extract Ze 440 (standardized to casticin 20 mg tablet) vs. placebo
orally once daily for 3 consecutive cycles
main efficacy variable was change from baseline to endpoint in combined scores (total 0-600) of 6 self-assessment
items (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast
fullness)
170 women had at least 1 follow-up measure and were analyzed
baseline scores 263 vs. 256, change in scores -128.5 vs. -78.1 (p = 0.001)
significantly greater improvement with agnus castus fruit extract over placebo found for 5 of the 6 individual
items
52% vs. 24% had > 50% improvement in composite score (NNT 4)
13% of subjects were taking oral contraceptives, but excluding these subjects did not alter results
5% both treatment and placebo groups reported adverse effects, but adverse effects differed between treatment
(acne, multiple abscesses, intermenstrual bleeding, urticaria) and placebo (acne, early menstrual period, gastric
upset)
study funded by drug manufacturer
Reference - BMJ 2001 Jan 20;322(7279):134 full-text, commentary can be found in J Fam Pract 2001
Apr;50(4):298
EBSCOhost Full Text
162 women aged 18-45 years with PMS randomized to Vitex agnus-castus L. (VAC) extract Ze 440 8, 20, or 30 mg
orally once daily vs. placebo over 3 menstrual cycles
PMS total symptom score assessed by visual analog scales for the symptoms of irritability, mood alteration, anger,
headache, bloating, and breast fullness
≥ 50% reduction in total symptom score in
11% with placebo
14% with 8 mg VAC extract Ze 440 (not significant vs. placebo)
81% with 20 mg VAC extract Ze 440 (p < 0.001 vs. placebo, p < 0.05 vs. 8 mg VAC extract Ze 440, NNT 2 for
22/03/2014 05:17 p.m.
DynaMed
9 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
both)
61% with 30 mg VAC extract Ze 440 (p < 0.001 vs. placebo, NNT 2, not significant vs. 20 mg VAC extract Ze
440)
Reference - Phytomedicine 2012 Nov 15;19(14):1325
other clinical studies did not have appropriate controls
175 women 18-45 with premenstrual tension randomized to Agnolyt (vitex capsule formulation 3.5-4.3 mg once daily)
vs. pyridoxine (vitamin B6 100 mg twice daily on days 16-35 of menstrual cycle) for 3 cycles; only 127 women (72.6%)
completed study, necessary sample size of 200 calculated a priori, baseline differences between groups; similar -47.7%
vs. -48% reductions in premenstrual tension syndrome scores, 77.1% vs. 60.6% reported improvement in clinical global
impression scale, 36% vs. 21.1% had no complaints, 12 vs. 5 women had adverse effects (Phytomedicine 1997;4:183)
vitex 600 mg 3 times daily reduced jitters and restlessness compared to soya-based placebo in 3-month double-blind
trial (Complement Ther Med 1993;1:73)
chasteberry may be effective in patients with cyclical breast discomfort (level 2 [mid-level] evidence), based
on 2 randomized trials with limited quality (Complement Ther Med 1993;1:73, Ceska Gynekol 1998 Oct;63(5):388 in Am Fam
Physician 2005 Sep 1;72(5):821)
adverse effects may include gastrointestinal and lower abdominal complaints, allergic skin reactions, headache, increased
menstrual flow; long-term effects unknown
contraindications - pregnancy, lactation, women receiving hormone replacement therapy
dosages and preparations vary widely (since dietary supplement in US), no data for specific recommendation, common
formulation provides 20-40 mg of dried berry extract standardized to contain 0.5% agnuside
theoretical drug interactions with antipsychotics, metoclopramide (Reglan), dopamine agonists, oral contraceptives and
hormone replacement therapy
Reference - Alternative Medicine Alert 2004 Jan;7(1):4, Alternative Medicine Alert 1999 Jun;2(6):64
review of chasteberry can be found in Am Fam Physician 2005 Sep 1;72(5):821
Ginkgo biloba L. may reduce severity of PMS symptoms (level 2 [mid-level] evidence)
based on randomized trial with unclear blinding
90 university students with verified PMS diagnosis randomized to Ginkgo biloba L. tablet (containing 40 mg leaf extracts) vs.
placebo 3 times daily from day 16 of menstrual cycle to following cycle day 5
mean decrease in severity of overall PMS symptoms after second cycle of treatment was 23.7% with ginkgo vs. 8.7% with
placebo (p < 0.001)
Reference - J Altern Complement Med 2009 Aug;15(8):845
EBSCOhost Full Text
saffron may reduce symptoms of premenstrualsyndrome (level 2 [mid-level] evidence)
based on small randomized trial
50 women aged 20-45 years with regular menstrual cycles and premenstrualsyndrome for ≥ 6 months were randomized to
saffron (Crocus sativus L.) 15 mg vs. placebo twice daily for 2 menstrual cycles
comparing saffron vs. placebo
at least 50% reduction in total premenstrual daily symptoms in 76% vs. 8% (p < 0.001, NNT 2)
at least 50% reduction in Hamilton Depression Rating Scale in 60% vs. 4% (NNT 2)
Reference - BJOG 2008 Mar;115(4):515
EBSCOhost Full Text
evening primrose oil
insufficient evidence to support use of evening primrose oil; systematic review found 5 randomized controlled trials with
multiple methodologic flaws, 2 higher quality trials found no benefit for evening primrose oil for premenstrualsyndrome
(Control Clin Trials 1996 Feb;17(1):60)
use of evening primrose oil in PMS appears to be solely a placebo effect (Med J Aust 1990 Aug 20;153(4):189)
review of evening primrose oil can be found in Am Fam Physician 2009 Dec 15;80(12):1405
EBSCOhost Full
Text full-text
insufficient evidence to evaluate Chinese herbal medicines for treatment of premenstrualsyndrome
based on Cochrane review
systematic review of 2 randomized trials evaluating Chinese herbal medicines for treatment of premenstrualsyndrome in 549
women
both trials had methodologic limitations
Jingqianping granule 15 g orally 3 times daily demonstrated therapeutic effectiveness compared to Xiaoyaowan 9 g orally
twice daily in 1 trial with 303 women, but unclear method of randomization and drug (Jingqianping) made at study author's
university
Cipher decoction associated with higher rate of recovery than co-vitamin B6 capsules in 1 trial with 246 women, but unclear
methods of randomization, allocation concealment and blinding
Reference - Cochrane Database Syst Rev 2009 Jul 8;(3):CD006414
Other management:
22/03/2014 05:17 p.m.
DynaMed
10 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
acupuncture might improve symptoms in women with premenstrualsyndrome (PMS) (level 2 [mid-level]
evidence)
based on 2 systematic reviews
systematic review of 10 trials with methodologic limitations comparing acupuncture vs. sham acupuncture, medication or no
treatment for PMS
methodologic limitations included
unclear methods of randomization
unclear allocation concealment
unclear blinding of outcome assessors
acupuncture associated with improved symptoms
compared to any control in analysis of 8 trials with 429 patients
risk ratio (RR) 1.55 (95% CI 1.33-1.8)
NNT 3-6 assuming improved symptoms in 55% of controls
compared to medications (progestin 4-6 mg daily with or without anxiolytics) in analysis of 4 trials with 232
patients
RR 1.49 (95% CI 1.27-1.74)
NNT 3-7 assuming improved symptoms in 60.7% of controls
compared with sham acupuncture in analysis of 2 trials with 95 patients
RR 5.99 (95% CI 2.84-12.66)
NNT 1-5 assuming improved symptoms in 12.8% of controls
Reference - BJOG 2011 Jul;118(8):899
EBSCOhost Full Text
systematic review of 9 mostly poor-quality randomized trials evaluating acupuncture for PMS
based on systematic review of 9 mostly poor-quality randomized trials evaluating acupuncture for PMS
PMS symptoms significantly reduced with acupuncture vs. pharmacological treatment in analysis of 4 trials
1 case of small subcutaneous hematoma in analysis of 2 trials reporting adverse events
Reference - Complement Ther Med 2010 Apr;18(2):104
insufficient evidence to recommend complementary or alternative therapy for premenstrualsyndrome
based on systematic review of 27 randomized controlled trials evaluating herbal medicine (7 trials), homeopathy (1), dietary
supplements (13), relaxation (1), massage (1), reflexology (1) chiropractic (1), and biofeedback (2)
some positive findings but no compelling evidence for any of these therapies
Reference - Am J Obstet Gynecol 2001 Jul;185(1):227
relaxation response elicitation (repeat word, sound, prayer, phrase or muscular activity, and ignore everyday thoughts to return
to repetition) more effective than symptom-charting in reducing physical pain and emotional symptoms in women with
premenstrualsyndrome, greatest difference in women with most severe symptoms (Obstet Gynecol 1990 Apr;75(4):649 in
Alternative Medicine Alert 1998 Feb;1(2):13)
Prognosis
PMS appears stable over time based on small study; 27 women with PMS and 21 controls were followed for 5-12 years, increased
risk for depressive episodes with PMS disappeared after accounting for increased history of major depression in women with PMS
(J Clin Psychiatry 1999 Nov;60(11):763)
Prevention and Screening
Prevention:
high intake of calcium and vitamin D, and high intake of skim or low-fat milk, associated with lower risk of developing PMS (level
2 [mid-level] evidence); nested case-control study compared 1,057 women who developed PMS with 1,968 women who did
not from cohort of women aged 27-44 years with no PMS at baseline and followed 10 years in Nurses' Health Study II (Arch
Intern Med 2005 Jun 13;165(11):1246); study does not establish that higher intakes are preventive, higher intakes of foods
considered healthier are likely to be associated with other healthy behaviors (DynaMed commentary)
Guidelines and Resources
Guidelines:
International guidelines:
International Society for Premenstrual Disorders (ISPMD) Montreal consensus on diagnostic criteria, measurement, and trial
design of premenstrual disorders can be found in Arch Womens Ment Health 2011 Feb;14(1):13
EBSCOhost Full Text
United States guidelines:
American College of Obstetricians and Gynecologists (ACOG)
Practice Bulletin 110 on noncontraceptive uses of hormonal contraceptives can be found in Obstet Gynecol 2010
22/03/2014 05:17 p.m.
DynaMed
11 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
Jan;115(1):206 (reaffirmed 2012 Aug) or at National Guideline Clearinghouse 2010 Jul 5:15428, commentary can be found
in ACOG News Release 2009 Dec 21
Review articles:
review can be found in Lancet 2008 Apr 5;371(9619):1200 full-text, commentary can be found in Lancet 2008 Aug
9;372(9637):446
review can be found in Am Fam Physician 2003 Apr 15;67(8):1743
EBSCOhost Full Text full-text
review of premenstrualsyndrome and premenstrual dysphoric disorder can be found in Am Fam Physician 2011 Oct 15;84(8):918
EBSCOhost Full Text full-text
review of perimenstrual symptoms and syndromes can be found in Adv Stud Med 2005 May;5(5):228 PDF
review of premenstrual dysphoric disorder can be found in Am Fam Physician 2002 Oct 1;66(7):1239
EBSCOhost Full
Text full-text
review of premenstrual dysphoric disorder can be found in N Engl J Med 2003 Jan 30;348(5):433
review of diagnosis and management of premenstrual disorders can be found in BMJ 2011 Jun 3;342:d2994
review of "integrative treatments" for premenstrualsyndrome can be found in Altern Ther Health Med 2001 Sep-Oct;7(5):32
review of diagnostic criteria, measurement and trial design of premenstrual disorders can be found in Arch Womens Ment Health
2011 Feb;14(1):13
EBSCOhost Full Text
review of management of functional somatic syndromes can be found in Lancet 2007 Mar 17;369(9565):946
MEDLINE search:
to search MEDLINE for (Premenstrualsyndrome) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis
Patient Information
Web brochure from American Academy of Family Physicians
handout on premenstrual dysphoric disorder can be found in Am Fam Physician 2002 Oct 1;66(7):1253
handout from Patient UK
ICD-9/ICD-10 Codes
ICD-9 codes:
625.4 premenstrual tension syndromes
ICD-10 codes:
N94.3 premenstrual tension syndrome
N94.8 other specified conditions associated with female genital organs and menstrual cycle
References
General references used:
Am Fam Physician 1998 Jul;58(1):183
Postgrad Med 2000 May 1;107(5):151
American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 15 on premenstrualsyndrome, reaffirmed 2010 Jun,
withdrawn 2012 Aug
DynaMed editorial process:
DynaMed topics are created and maintained by the DynaMed Editorial Team.
Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step
evidence-based method for systematic literature surveillance. DynaMed topics are updated daily as newly discovered best
available evidence is identified.
The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing interests
related to this topic.
The participating reviewers have declared that they have no financial or other competing interests related to this topic, unless
otherwise indicated.
McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates. Over 1,000 practicing
physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your
practice.
F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates. Over 2,000 practicing clinicians from
20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice.
How to cite:
For attribution in other publications see How to Cite Information from DynaMed.
Está viendo un resumen de DynaMed. El uso de DynaMed indica la aceptación de las DynaMed Condiciones de uso. Las limitaciones de
22/03/2014 05:17 p.m.
DynaMed
12 de 13
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
DynaMed se encuentran en las Condiciones de uso de DynaMed.
Haga sus comentarios enviando un correo electrónico para DynaMed a: [email protected]
22/03/2014 05:17 p.m.
DynaMed
http://web.a.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delive...
Parte superior de la página
Sitio de asistencia de EBSCO
Cláusula de confidencialidad
Términos de uso
Copyright
© 2014 EBSCO Industries, Inc. Todos los derechos reservados.
13 de 13
22/03/2014 05:17 p.m.