1 de 13 22/03/ :17 p.m.

Transcription

1 1 de 13 22/03/ :17 p.m. 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 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

2 2 de 13 22/03/ :17 p.m. 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 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)

3 3 de 13 22/03/ :17 p.m. 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 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 B 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 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

4 4 de 13 22/03/ :17 p.m. 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):CD 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):CD 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

5 5 de 13 22/03/ :17 p.m. 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 ) 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 ) NNH 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 ) 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 ) NNH 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 < , NNT 4) withdrawal due to adverse effects in 33% vs. 7.2% (p < , 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):CD 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 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)

6 6 de 13 22/03/ :17 p.m. 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 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 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 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 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 ) 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

7 7 de 13 22/03/ :17 p.m 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 ( 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 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 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

8 8 de 13 22/03/ :17 p.m. vitamin B6 was more effective than placebo for improvement in overall premenstrual symptoms with odds ratio 2.32 (95% CI ) in meta-analysis of 9 trials with 940 patients vitamin B6 improved depressive symptoms with odds ratio 1.69 (95% CI ) 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 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 vs (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 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 < vs. placebo, p < 0.05 vs. 8 mg VAC extract Ze 440, NNT 2 for

9 9 de 13 22/03/ :17 p.m. both) 61% with 30 mg VAC extract Ze 440 (p < 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 with premenstrual tension randomized to Agnolyt (vitex capsule formulation mg once daily) vs. pyridoxine (vitamin B6 100 mg twice daily on days 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 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 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):CD Other management:

10 10 de 13 22/03/ :17 p.m. 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 ) 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 ) 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 ) 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 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

11 11 de 13 22/03/ :17 p.m. 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: 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

12 12 de 13 22/03/ :17 p.m. DynaMed se encuentran en las Condiciones de uso de DynaMed. Haga sus comentarios enviando un correo electrónico para DynaMed a:

13 13 de 13 22/03/ :17 p.m. 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.