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Premenstrual Syndrome (PMS) is now officially called Premenstrual Dysphoric Disorder (PMDD) in its more severe form, but I doubt  anyone other than researcher bother to use this awkward term.  Some PMS symptoms are experienced by 95% of women but only 5% having severe symptoms. 

In the treatment of PMS, SSRI medication has done best, although vitamin B-6 (pyridoxine), calcium, vitamin D, and magnesium have been found of value.  Reduced sodium (salt) intake is probably also helpful.  These supplements are far cheaper with essentially no side-effects and have other health benefits.  Common sense suggests that they should be tried first.  Chasteberry extract may also be of value, especially for physical symptoms.  Fish oil may help painful periods.  Unfortunately, it appears that these non-medication approaches are infrequently recommended by physicians, although many women have tried various alternative treatments on their own.  Of course, those benefiting for alternative treatment don't seek medical treatment for PMS.  

Women who do seek and receive conventional medical treatment have often not found benefit with complementary therapies and are very often satisfied for standard medical treatment (Gynecol Endocrinol. 2003 Feb;17(1):13-8).  Birth control pills may help some women.  The birth control pills Yasmin may also have better than average beneficial effects compared to other birth control pills.

Using intermittent sertraline (Zoloft) may be the best initial PMS medication strategy after non-medications strategies have proven inadequate.  If this fails, switching to fluoxetine (generic Prozac) for continuous treatment is more economical.  Fluoxetine is not good for the intermittent strategy since it is very long acting and thus requires more time to build up to a full dose and stays in the system for a long time after the last dose.  By contrast, paroxetine (Paxil) is too short-acting and Paxil-CR offers no advantage over sertraline and will be covered by patent much longer.

No Relation to Suicide: Although 71 suicide attempters with normal periods had a high rate of PMS symptoms, there was no relationship between the symptoms and the attempts. Baca-Garcia, Madrid, APA 5/17/99

Birth Control Pill Yasmin Helps: DB 700 women, 72% with PMS symptoms. PMS affecting general well-being moderately to extremely dropped from 35% to 21%. PMS affecting daily activities moderately, quite a bit or extremely cut from 30% to 16%. 46% had been on another BCP before study. UCLA. Funded by manufacturer. J Reprod Med. 2003 Feb;48(2):79-85

Birth Control Pills Don't Help Most: In a study of 976 premenopausal women in the 658 women who were using oral contraceptive pills, 16.3% of the women reported oral contraceptive pill-related premenstrual mood deterioration, and 12.3% of the women reported premenstrual mood improvement. Previous depression was the only significant predictor of mood deterioration on BCPs (odds ratio, 2.0), while early-onset premenstrual mood disturbance and dysmenorrhea were significant predictors of oral contraceptive pill-related mood improvement (OR 3.1 and OR 2.3, respectively). Harvard-MGH. Impact of oral contraceptive pill use on premenstrual mood: predictors of improvement and deterioration. Joffe H, Cohen LS, Harlow BL. Am J Obstet Gynecol. 2003 Dec;189(6):1523-30

B-1 Thiamine Claimed Curative of Menstrual Pain in Teens:  In a DB PC study of 556 girls 12-21 in Indian with painful periods, those given 100 mg/day (1.6 mg/day = 100% of the Daily Value) for 90 days had dramatic relief in 95% with 87% "completely cured." Two months after stopping thiamine, improvement persisted. Curative treatment of primary (spasmodic) dysmenorrhoea. Gokhale LB. Indian J Med Res. 1996 Apr;103:227-31. Ed: This sounds too good to be true.

B-6 & Magnesium in DB: 200 mg of magnesium and 50 mg of vitamin B-6 a day helped a little in a DB PC study of 30 days. The author said 200 mg of magnesium is not enough to replenish deficient stores. Ed: Two 250 mg tablets a day seems more reasonable.  This is still a modest dose and I like the research on magnesium in general.  For more, see Magnesium.

Buspirone Helped Irritability, Nefazodone No Benefit: In a DB PC study for four cycles, buspirone 20-40 mg/day was superior to placebo on irritability and global assessment. Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo. Landen M, Eriksson O, Sundblad C, Andersch B, Naessen T, Eriksson E. Sahlgrenska University. Psychopharmacology (Berl). 2001 May;155(3):292-8

Calcium Helps Mood & Pain: In a DB PC study of 644 women, improvement was noted in the 2nd month. By the 3rd month, there was a 48% decrease in symptoms of water retention, negative affect, food craving, and pain. St Luke-Roosevelt in NYC, Thys-Jacobs, Columbia, Am J ObGyn 179:444

Calcium & Manganese Help: DB study with 1337 mg vs. 600 mg/day of calcium and 5.6 mg vs. 1 mg/day of manganese helpful for both mood and pain. Am J Obstet Gynecol 1993 May;168(5):1417-23

Calcium, Chasteberries, B-6 May Help PMS: Calcium 1200 mg/day helped in a DB study of 466 with PMS using Tums with 52% decrease in symptoms vs. 35% for placebo (Am J Ob Gyn 179:444 ’98). BMJ 322:134 ’01 for 52% improved vs. 24% of placebo takers in 170 Germans studied. B-6 may help, but studies called flawed. (BMJ 318:1375 ’99).

Chasteberry Extract Common Herbal Treatment: Extracts of the fruits of chaste tree (Vitex agnus castus) are widely used to treat PMS. DB PC studies in Germany show that premenstrual breast pain is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to hyperprolactinemia. Univ Gottingen. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlova-Wuttke D. Phytomedicine. 2003 May;10(4):348-57. Ed: While the research is inadequate, there is enough to suggest that it is reasonable to try chasteberry extract if calcium, magnesium, and B-6 haven't worked before using an SSRI.

Chasteberry Extract did as well as Fluoxetine: In a small 41-patient 2-month Turkish study comparing chasteberry extract to fluoxetine, both groups showed similar improvement (57% vs. 68%). Chasteberry extract tended to do better for physical symptoms and fluoxetine for emotional ones. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Atmaca M, Kumru S, Tezcan E. Hum Psychopharmacol. 2003 Apr;18(3):191-5

Essential Fatty Acids Not Help: This was a DB PC study. Acta ObGyn Scand ’93;72:337

Fish Oil Helped Teenagers with Painful Periods: 21 teenagers given placebos for two months then half were given 1080 mgday EPA and 720 mg/day DHA (6 standard fish oil capsules) and Vit E 1.5 mg for two months. There was a marked decrease in symptoms in the treatment groups from score of 69 to 44 and no change in controls. Harel, Cincinnati, Am J Ob Gyn 4/96;174:1335-8; Dysmenorrhea Correlates with Low Intake n-3: Deutsch, Eur J Clin Nutr 95;49:508

Fluoxetine (Prozac) Helps Work Capacity: In a large 320-patient Canadian DB PC study for 6 months, fluoxetine 20 mg/day was found as good as 60 mg/day and better than placebo in improving work capacity. Benefits appeared in the first cycle on fluoxetine. Fluoxetine improves functional work capacity in women with premenstrual dysphoric disorder. Steiner M, Brown E, Trzepacz P, Dillon J, Berger C, Carter D, Reid R, Stewart D. Arch Women Ment Health. 2003 Feb;6(1):71-7; Another study found that patients improving on fluoxetine tended to deteriorate back to PMS during with first cycle off fluoxetine. Am J Obstet Gynecol. 2003 Apr;188(4):887-95

Fluoxetine (Prozac), Propranolol Better Than B6: In a DB PC study of fluoxetine 10 mg/day or propranolol 20 mg/day with 40 mg/day during menses, or placebo, or vitamin B6. 65% did better fluoxetine, 59% with propranolol, 45% with B6, and 39% with placebo. Int J Gynaecol Obstet 1998 Jul;62(1):63-7

Fluoxetine Better than Bupropion (Wellbutrin) in DB: Small 34 pt DB PC 1 month placebo then 2 month DB PC study. Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder. Brown Univ: Pearlstein TB, Stone AB, Lund SA, Scheft H, Zlotnick C, Brown WA. J Clin Psychopharmacol 1997 Aug;17(4):261-6

Inositol No Help: Myo-inositol has no beneficial effect on premenstrual dysphoric disorder. Nemets B, Talesnick B, Belmaker RH, Levine J. World J Biol Psychiatry 2002 Jul;3(3):147-9

Magnesium Helps: 200 mg/day of supplemental magnesium was used in a DB PC study for two months with no benefit first month but the second month showed a decrease in bloating, breast tenderness, weight gain, and swelling. Walker, UK, J Womens Health 11/98;7:1157

Neptune Krill Oil Claimed Better than Fish Oil: A DB study of 70 women with PMS reports that those taking a brand-named oil extract from a type of ocean shrimp, Neptune Krill Oil, took fewer pain pills and had fewer emotional symptoms during the three month study than women randomized to fish oil. Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea. Univ Montreal. Sampalis F, Bunea R, Pelland MF, Kowalski O, Duguet N, Dupuis S. Altern Med Rev. 2003 May;8(2):171-9. Ed: The manufacturer claims that the anti-oxidant value and phospholipid content of NKA adds to the benefit for the omega-3 fatty acids.  I have a hard time accepting this.  I suspect the study was funded by the manufacturer.

PMDD Diagnosis Controversial in Europe: In June 2003, as part of European harmonization of product information, the Committee for Proprietary Medicinal Products found that "PMDD is not a well-established disease entity across Europe." It said that the disorder was not listed in the international classification of diseases and was listed only as a research diagnosis in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. The committee strongly criticized two key trials of fluoxetine for premenstrual dysphoric disorder, noting that in one study almost half of the participants dropped out and that in the other little attempt was made to distinguish between mild and severe health problems. Fluoxetine was first approved for PMDD by the US Food and Drug Administration in 2000, after an influential 1998 "round table discussion" of experts supported by Lilly and attended by at least four Lilly representatives. The disorder was characterized by anger, irritability, and tension triggered by the menstrual cycle.  An aggressive promotional campaign quickly followed, including television advertisements featuring a frustrated woman with a shopping trolley outside a shop and accompanied by the line, "Think its PMS? It could be PMDD." The campaign was criticized by some women's groups and was found by the Food and Drug Administration to be unbalanced and misleading because it "broadens the indication" and played down side effects. BMJ  2/14/2004;328:365 

Primrose, Magnesium No Help PMS: Two DB studies of 65 women using 4-6 g/day of primrose oil for 3-4 months found no benefit vs. placebo. Ob & Gyn 81:93 ’93, M J Australia 153:189 ’90. Two studies with magnesium found no benefit. J Women’s Health 7:1157 ’98, 9:131 ’00.

Sertraline (Zoloft) Better than Desipramine in DB: 167 women ages 18-45 with at least a 6-month history of PMS interfering with their lives were all given 1 month of a placebo pill. The 167 not responding while on the placebo were divided into 3 groups. A Daily Symptom Report used a decrease of 50% as a response cut off. 65% responsed while on sertraline(50-150mg/d), 36% while on desipramine (50-150mg/d), and 29% on placebo. There were more dropouts on desipramine. (47% v 24%). Freeman, U Penn, Arch Gen Psychiatry 99;56:932

Sertraline Intermittent as Good as Continuous: In a 3-month DB PC study of women with severe PMS, researchers found sertraline 50-100 mg/day did better than placebo and that taking the sertraline only during luteal phase periods did as well as taking it all month long. A history of major depression was not associated with treatment response. More sertraline-treated subjects reported improved family relationships, social activities, and sexual activity. Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder. Freeman EW, Rickels K, Sondheimer SJ, Polansky M, Xiao S. Am J Psychiatry. 2004 Feb;161(2):343-51. Ed: While fluoxetine is cheaper, it long half-life means that it would not be ideal for intermittent dosing.  Thus, using sertraline just from a few days before the usual onset of symptoms until the first day of menstruation when symptoms usually disappear, would allow the least medication exposure.

Venlafaxine (Effexor) Helps in DB: In a 146-patient DB PC study for 4 months, venlafaxine 50-200 mg/day had 43% remission while on venlafaxine vs. 25% on placebo. Venlafaxine in the treatment of premenstrual dysphoric disorder. Freeman EW, Rickels K, Yonkers KA, Kunz NR, McPherson M, Upton GV. Obstet Gynecol 2001 Nov;98(5 Pt 1):737-44

Vitamin D: PMS: Lower in Women with Higher Vitamin D and Calcium Intake: In a case-control study within the prospective Nurses' Health Study II cohort of women aged 27 to 44 years and free from PMS at baseline, 1057 women developed PMS over 10 years of follow-up and 1968 women reporting no diagnosis of PMS and no or minimal menstrual symptoms. After adjustment for age, parity, smoking status, and other risk factors, women in the highest quintile of total vitamin D intake (median, 706 IU/d) had a relative risk of 0.59 compared with those in the lowest quintile (median, 112 IU/d) (P = .01). The intake of calcium from food sources was also inversely related to PMS; compared with women with a low intake (median, 529 mg/d), participants with the highest intake (median, 1283 mg/d) had a relative risk of 0.70 (P = .02 for trend). The intake of skim or low-fat milk was also associated with a lower risk (P<.001). Calcium and vitamin D intake and risk of incident premenstrual syndrome. Bertone-Johnson FR, et al. University of Massachusetts, Amherst. Arch Intern Med. 2005 Jun 13;165(11):1246-52.