Premenstrual Syndrome (PMS)
Chasteberry (Vitex agnus-castus)
Chasteberry (Vitex agnus-castus) is a shrub found on riverbanks and shores of the Mediterranean region, Southern Europe, and Central Asia (Rani 2013). A rigorous review of published clinical trials found that seven out of eight trials deemed chasteberry superior to placebo for PMS treatment (van Die 2013). Results from a randomized, controlled trial showed that 91 women who took 20 mg chasteberry extract daily had more improvements in psychological and physical PMS symptoms than 87 women who took placebo. Symptoms of irritability, mood, anger, headaches, and breast fullness were reduced (Schellenberg 2001). A follow-up study found that women who took 20 mg chasteberry had greater improvements in symptoms than women who took 8 mg chasteberry extract. However, symptom improvement peaked at 20 mg, and no additional benefit was observed by increasing the dose to 30 mg (Schellenberg 2012).
Three randomized studies comparing chasteberry extract to placebo, and two open-label trials have shown similar benefits with 20–40 mg chasteberry extract or 40 drops of crude chasteberry extract. Marked improvement in aches and pains, anger and short temper, anxiety and nervousness, appetite and food cravings, backache, bloating, breast swelling or pain, crying spells, depression, extremity swelling, fatigue, irritability, lower abdominal cramping, mood, and restlessness were observed (Momoeda 2014; Zamani 2012; Ambrosini 2013; Ma, Lin, Chen, Wang 2010; Ma, Lin, Chen, Zhang 2010).
A trial of chasteberry extract for PMS in nursing students found a significant benefit, with nearly 70% of participants reporting complete resolution of their PMS symptoms by the end of the trial. The authors called chasteberry extract “one of the most effective therapeutic options for PMS” (Ibrahim 2012). A comparison of chasteberry extract with the SSRI fluoxetine in PMDD found that a similar percentage of participants responded to each, with chasteberry more effective for physical symptoms and fluoxetine more effective for psychological symptoms (Atmaca 2003).
Calcium and Vitamin D
Levels of calcium and vitamin D fluctuate throughout the menstrual cycle in all women, most likely because calcium and vitamin D metabolism are influenced by ovarian sex hormones (Thys-Jacobs 2000). However, one study found that compared with women who do not have PMDD, women with PMDD had lower ionized calcium levels during menstruation, lower urinary excretion of calcium during the late follicular phase and early luteal phase, and lower vitamin D levels during the luteal phase (Thys-Jacobs 2007).
A randomized controlled trial compared 1000 mg calcium carbonate daily for three months to placebo. During the calcium treatment, PMS symptom scores were significantly lower during both the luteal and menstrual phases. Seventy-three percent of women reported fewer symptoms during calcium treatment. Negative mood, bloating, and menstrual pain were all significantly relieved by calcium (Thys-Jacobs 1989).
A large, multi-center trial compared treatment with 1200 mg calcium carbonate daily to placebo for moderate-to-severe PMS. The women in this study took calcium or placebo for three menstrual cycles. The women who took calcium had significantly lower average PMS symptom scores in the second and third months of treatment. They also had an overall 48% reduction in total symptom score by the third cycle. Negative mood, bloating, food cravings, and pain were all significantly reduced by the third menstrual cycle in the calcium group (Thys-Jacobs 1998). A more recent double-blind trial of 1000 mg calcium carbonate daily for three months found that calcium treatment effectively relieved PMS-related fatigue, appetite changes, and depression (Ghanbari 2009). A literature review of pharmaceutical and integrative treatments for PMS recommended calcium supplementation as first-line treatment for mild-to-moderate PMS symptoms (Douglas 2002).
Women with lower dietary intake and blood levels of vitamin D may have an increased risk of PMS. An analysis was performed in 401 women who were free of PMS at baseline but later developed PMS. It was found that among those whose vitamin D levels were measured before they were diagnosed with PMS, lower vitamin D levels were related to a significantly higher risk of developing premenstrual breast tenderness, fatigue, depression, and constipation or diarrhea (Bertone-Johnson 2014). A case-control study compared 1057 women who developed PMS with 1968 controls; researchers found that women in the highest 20% total vitamin D intake group had a 41% lower risk of PMS compared to women in the lowest 20% total vitamin D intake group. In this study, those who consumed the most calcium had a 30% reduced risk of developing PMS (Bertone-Johnson 2005).
St. John’s wort (Hypericum perforatum)
Hypericum perforatum, more commonly known as St. John’s wort, is frequently used to treat depression in Europe (NCCAM 2014). A randomized controlled trial in women with mild PMS used 900 mg per day of a St. John’s wort extract, standardized to hypericin and hyperforin, or placebo, for two menstrual cycles. St. John’s wort significantly improved a range of physical and behavioral PMS symptoms such as food cravings, swelling, poor coordination, insomnia, confusion, headaches, crying, and fatigue compared with placebo. St. John’s wort also appeared to improve pain and mood symptoms towards the end of the trial (Canning 2010).
Another randomized, controlled trial used a similar dosage of St. John’s wort extract in women with PMS over two menstrual cycles and found that it markedly improved PMS scores compared to placebo. Overall, symptoms were reduced by 40%. The symptoms most strongly impacted were tearfulness, which improved 71%, and depression, which improved 52%. The side effect profile of St. John’s wort in this trial was similar to placebo (Ghazanfarpour 2011).
In an open-label trial, St. John’s wort extract was administered for two menstrual cycles to 19 women with PMS. The treatment resulted in an average reduction in symptom scores of 51% by the end of the trial. Over two-thirds of the participants experienced a 50% reduction in symptom severity. The treatment was well-tolerated (Stevinson 2000).
A case report told of a woman with PMDD who discontinued SSRIs due to intolerable gastrointestinal side effects. St John’s wort extract at a dosage of 900 mg per day was substituted, and her symptoms improved over five months of follow up. The authors proposed that St. John’s wort extract be considered an alternative treatment option for PMDD, particularly in those who experienced undesirable side effects from SSRIs (Huang 2003).
It is important to note that St. John’s wort interacts with some prescription and over-the-counter medications, including OCPs and antidepressants, so women taking such medications should consult with their physicians before taking St. John’s wort (NCCAM 2014).
Two separate analyses, including data from 9 and 13 randomized controlled trials, found that 100 mg vitamin B6 may be more effective than placebo for the treatment of PMS symptoms. One of these reviews found that, among 541 women from four of the studies, those taking vitamin B6 had 2.3 times greater likelihood of an improvement in their overall PMS symptoms compared to those taking placebo, and 1.7 times greater likelihood of an improvement in depressive symptoms (Nevatte 2013; Whelan 2009; Wyatt 1999). Vitamin B6 has been shown to improve symptoms of bloating, headache, breast pain, depression, and irritability (Gaby 2011).
A large 10-year study found that women with the highest dietary intake of vitamins B1 (thiamin) and B2 (riboflavin) had a lower incidence of PMS. Women whose dietary intake of riboflavin was in the highest one-fifth of the distribution had a 35% lower risk of developing PMS compared to those in the lowest one-fifth (Chocano-Bedoya 2011).
Magnesium may play an important role in the treatment of PMS (Higdon 2013; UMMC 2013a). Some studies have found that women with PMS have lower blood levels of magnesium than women without PMS (Posaci 1994; Rosenstein 1994). Several successful trials have used magnesium to treat symptoms of PMS. A randomized, placebo-controlled trial found that supplementation with 200 mg of magnesium daily significantly reduced weight gain, bloating, and breast tenderness in women with PMS (Walker 1998). Results from two additional randomized, placebo-controlled trials demonstrated that supplementation with 360 mg magnesium daily significantly improved symptoms related to mood, and the incidence of migraines (Facchinetti, Borella 1991; Facchinetti, Sances 1991). Women may also benefit from the combination of magnesium and vitamin B6. Two randomized controlled trials showed that magnesium (200–250 mg) combined with vitamin B6 (40–50 mg) reduced general symptoms of PMS and anxiety more than either supplement alone or placebo (Fathizadeh 2010; De Souza 2000).
Saffron, derived from the plant Crocus sativus, has historically been a part of traditional Persian medicine. Saffron has been shown to modulate serotonin neurotransmitter signaling, and has been investigated for treatment of depression and PMDD (Agha-Hosseini 2008). In fact, several clinical trials have found that saffron effectively relieves depression, with efficacy comparable to that of some antidepressant medications (Noorbala 2005; Akhondzadeh 2004; Akhondzadeh 2005).
A randomized, controlled trial enrolled 50 women between the ages of 20 and 45 who had been experiencing PMS symptoms for six months or more. For two menstrual cycles, 25 of the women received 30 mg of saffron extract daily and 25 received placebo. In the saffron group, 76% of women experienced a 50% or greater reduction in overall premenstrual symptom severity, while in the placebo group only 8% of the women did. In the saffron group, 60% of women experienced a 50% or greater reduction in depression symptoms, while in the placebo group only 4% did. In the saffron extract group, there was a significant improvement from the first to the second month in depression score and overall premenstrual symptom scores. Women in the saffron group had significantly greater reductions in depression and overall premenstrual symptom scores compared with those who received a placebo (Agha-Hosseini 2008).
Omega-3 Fatty Acids
Omega-3 fatty acids are found in fish and some plant foods such as flaxseeds and walnuts. Omega-3 fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA) (UMMC 2013b; Huang 2010). Within the body, omega-3 fatty acids help suppress inflammation and are important structural components of cells (Calder 2015).
A randomized, controlled trial assessed the ability of omega-3 fatty acids to decrease symptoms of PMS. Compared with placebo, 90 days of treatment with 2 g omega-3 fatty acids daily led to significant reductions in depression, anxiety, lack of concentration, bloating, nervousness, headaches, and breast tenderness (Sohrabi 2013). A controlled trial found that krill oil or fish oil were both effective for the treatment of PMS, but krill oil was more effective than fish oil (Sampalis 2003).
In a randomized controlled trial in 85 women with PMS, Ginkgo biloba extract, 40 mg three times daily, taken from the 16th day of the menstrual cycle to the 5th day of the next cycle, was compared with placebo. Ginkgo extract resulted in a significantly greater average decrease in severity of physical and psychological symptoms than placebo (Ozgoli 2009). A controlled study in 143 women with PMS also administered ginkgo extract from the 16th day of one menstrual cycle to the 5th day of the next, for two cycles. Ginkgo extract was significantly more effective than placebo for breast pain symptoms, and also improved psychological symptoms (Tamborini 1993).
Gamma-linolenic acid (GLA) is a fatty acid derived from seeds of plants such as evening primrose, borage, and black currant (EBSCO 2014). One of these, evening primrose oil, has been used to treat symptoms of PMS, but studies have been inconclusive (UMMC 2013c). However, one randomized controlled trial in 120 women with PMS or PMDD compared a GLA-containing formula with placebo. Subjects received one or two capsules per day containing 210 mg each of GLA along with other fatty acids, or placebo. This trial followed these women over six months, evaluating the results at three and six months. Both dosages significantly reduced PMS symptoms, with the two capsule dosage resulting in greater improvement than one capsule (Rocha Filho 2011).
Tryptophan is an amino acid that can be metabolized into serotonin, and altered serotonin activity is thought to contribute to premenstrual symptoms (Higdon 2014; Rapkin 2012). In a randomized controlled trial, women with PMDD who received 2 g of L-tryptophan three times daily reported 34.5% reductions in mood, tension, and irritability symptoms, compared with 10.4% reductions in women who took placebo (Steinberg 1999).
Ginger, which contains anti-inflammatory compounds, has been used for a variety of ailments, including menstrual pain and cramping (Shimoda 2010). A randomized, placebo-controlled trial of ginger in 66 women used 250 mg ginger tablets twice daily, beginning seven days before menstrual bleeding started and continuing until three days after the onset of bleeding. The ginger treatment produced significant improvements in mood, physical, and behavioral symptoms of PMS, and in overall PMS symptom scores. This symptom reduction was significantly greater after one, two, and three months in the ginger group, compared with placebo (Khayat 2014).
A randomized trial in 90 women with PMS compared 100 mg of chamomile extract three times daily to 250 mg of the NSAID mefenamic acid three times daily. Women who received chamomile extract had greater improvement in emotional symptoms than women who took mefenamic acid, and mefenamic acid was not significantly superior to chamomile extract in providing relief from physical symptoms (Sharifi 2014).
Acupuncture is frequently used to treat symptoms of PMS in Asian countries. Two separate analyses of 8 and 10 randomized, controlled trials found that acupuncture may be an effective treatment option for the physical symptoms of PMS. In all the trials, acupuncture was more effective than no treatment; sham acupuncture; or a progestin, anxiolytic, or both for reducing PMS symptoms. In four trials symptoms were reduced more than 50% from baseline (Kim 2011; Jang 2014). Women reported symptom improvements in as few as two sessions, and efficacy was observed when treatment was performed in both the luteal and follicular phases (Jang 2014). However, it is important to note that many of these trials were poorly designed, with small numbers of subjects (Kim 2011; Jang 2014). Larger, well-designed trials are needed to confirm these findings.
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