Wednesday, December 16, 2009

PMS: Natural Approaches

PMS always worsens this time of year - so I thought I'd post the latest data from a favorite database: Natural Medicines Comprehensive Database. Short version of what is proven to be helpful:
  • calcium 1200 mg/day
  • Chasteberry
  • Ginkgo
  • Magnesium
  • Pyridoxine
  • Vitamin E
While I agree with what they say about the glories of calcium, magnesium and chastetree, I disagree with their comments on natural progesterone. Here's what they say....

The cluster of symptoms called "premenstrual syndrome" got its official name in 1931, but it has been recognized since antiquity. Up to 85% of women are affected by PMS to varying degrees. It often starts with development of menstruation in young women and tends to follow a consistent pattern until menopause.

Over 150 symptoms associated with PMS have been catalogued. The most common are irritability, agitation, headache, depression, breast tenderness, fluid retention, and weight gain. These symptoms typically show up in the second half of the menstrual cycle, about 7-10 days before the start of the next period.

Minerals / Vitamins

ACOG guidelines suggest that several nutrition supplements are worth trying as a first step in treating PMS.

Calcium is one of the more interesting minerals used for PMS. Researchers began to suspect a calcium-PMS connection when they noticed that calcium deficiency and PMS share similar symptoms. In addition, women who have PMS tend to have abnormally low levels of calcium at the time of ovulation, compared to women without PMS.13776 Low calcium levels stimulate overproduction of parathyroid hormone. Too much parathyroid hormone can affect mood, possibly by interacting with serotonin.13777,13778

Some evidence suggests that women who consume an average of 1283 mg/day of calcium from the diet have about a 30% lower risk of developing PMS, compared to women who consume 529 mg/day.13094

What really makes the case for calcium is that clinical trials show giving 1000-1200 mg of elemental calcium daily for a few months to women with PMS significantly improves mood and decreases bloating, food cravings, and pain.1822,1823,1824

Calcium makes sense for most women with PMS...especially if they don't already get enough calcium in their diet.

Magnesium deficiency might be another factor that contributes to symptoms of PMS. Women with PMS tend to have lower magnesium levels than other women.6847 Women with PMS who take 360 mg/day of magnesium supplements seem to have improved mood and less fluid retention.1187,1188,6847 Taking magnesium might also reduce premenstrual migraine.1186,6847

Magnesium might be beneficial because it is involved in the activity of serotonin and other neurotransmitters. Magnesium also has a role in vascular contraction and cell membrane stability.

There is less evidence for magnesium than calcium. It's too soon to recommend magnesium for most women, but it might be worth considering for women with premenstrual migraine, fluid retention, and poor mood, despite other treatments.
Vitamin E is sometimes suggested for PMS. There is some evidence that women with PMS who take vitamin E 400 IU/day for three cycles have improved mood, reduced PMS-related anxiety and food cravings.4719,4720 Women with PMS do NOT seem to have reduced vitamin E levels. It is not known how vitamin E might work to improve symptoms of PMS. The evidence isn't strong enough to recommend vitamin E for most patients just yet.

Practice Pearl - Advise women with diabetes or heart disease NOT to use vitamin E supplements in doses of 400 IU/day or more. There is some concern that these doses of vitamin E could increase the risk of heart failure in patients with diabetes or heart disease. More evidence is needed to verify this potential risk. In the meantime, explain to these patients that the potential benefit of using vitamin E doesn't outweigh the potential risks.
Vitamin D is now being studied for prevention of PMS. There is some evidence that increasing total or dietary intake of vitamin D is associated with a decreased risk of developing PMS. Women with an average vitamin D intake of 706 mg/day seem to have about a 40% lower risk of developing PMS compared to women with an average vitamin D intake of 112 mg/day;13094 however, taking vitamin D supplements does not appear to reduce the risk of developing PMS. And there is no evidence that vitamin D can decrease symptoms in women with existing PMS. Advise patients to make sure they get adequate amounts of vitamin D in their diet.

Pyridoxine (vitamin B6) is another vitamin that is recommended for PMS. One theory is that PMS might be related to low dopamine levels. Pyridoxine is a co-factor needed for dopamine production. Another theory is that pyridoxine and other B vitamins might prevent fat accumulation in the liver. This could improve estrogen metabolism and potentially affect PMS symptoms.
There is not much scientific support for these theories. But there is some evidence from clinical studies that pyridoxine might help. Taking 100 mg/day of pyridoxine supplements seems to decrease overall symptoms of PMS as well as depression.3093

Practice Pearl: Advise patients to be careful with pyridoxine. High doses can cause peripheral neuropathy. Recommend not using doses over 100 mg/day. This is generally there's no evidence that doses over 100 mg/day are any more effective.
Manganese is a lesser known mineral. It's in most multivitamins, but in very small amounts. Low intake of dietary manganese has been linked with increased symptoms of PMS.7135 There is some evidence that taking manganese in combination with calcium might improve symptoms of PMS...irritability, depression, anxiety, tension, restlessness, etc.2004 But its not known if this benefit is due to the calcium or the manganese. For now, don't recommend manganese for PMS. Instead, let patients know that if they take a multivitamin, they're probably getting enough manganese.

Supportive Treatment: Analgesics, NSAIDs, Diuretics

Supportive treatment is also recommended as a first step in treating PMS. These treatments generally target specific symptoms.

For relief of headache, backache, or cramping, acetaminophen (Tylenol) or NSAIDs (ibuprofen, naproxen, etc) are typically used. For bloating and fluid retention, spironolactone (Aldactone) is often used. It works as a diuretic to decrease fluid retention, and it has the added benefit of having an antiandrogen effect. This might further contribute to symptom relief in women with PMS.

Women with PMS also often turn to natural products for supportive treatment.
Ginkgo (Ginkgo biloba) is sometimes tried. We don't usually think of it as a traditional "woman's herb," but there is some evidence ginkgo leaf extract can relieve PMS fluid retention and its consequences...breast swelling and tenderness, pelvic pain and swelling, and swollen hands and feet.6229 Investigators started looking into ginkgo because women who were taking it for memory reported relief from fluid retention associated with PMS. No one is quite sure why ginkgo seems to work for this indication, but one theory is that it INHIBITS platelet activating factor (PAF).5719,9760 PAF normally triggers inflammation, leading to vascular congestion, edema, and breast swelling. Therefore, it is thought that ginkgo might have an anti-inflammatory effect.
Evening primrose oil (Oenothera biennis) is often recommended for PMS. Evening primrose oil contains the omega-6 fatty acid, gamma-linolenic acid (GLA). It is thought that some women with PMS are deficient in gamma-linolenic acid, possibly due to a defect in their ability to convert linoleic acid to gamma-linolenic acid.6034 This could be important because GLA and its metabolites are precursors to the anti-inflammatory prostaglandin E1.6036,12470

In theory, by taking evening primrose oil, women could boost GLA levels, decrease inflammation, and possibly relieve some symptoms of PMS. But the clinical evidence says otherwise. Several small-scale studies suggest that evening primrose does NOT relieve symptoms of PMS.1105,1106,6847,8219 Don't recommend it.

Selective serotonin reuptake inhibitors (SSRIs) are now being used more for PMS. In fact, fluoxetine, under a different brand name Sarafem (to distinguish it from Prozac), and sertraline (Zoloft) are approved for the more severe symptoms of premenstrual dysphoric disorder (PMDD). Fluoxetine and sertraline primarily help severe mood changes, including depression and anxiety, but can also improve breast tenderness, bloating, irritability, and headache.12337,13779,13780

The ACOG guidelines suggest considering antidepressants in Step 2, for women who don't respond to supportive treatment and lifestyle changes. Fluoxetine or sertraline are considered the first line antidepressants for PMS or PMDD.12337,12349

Some women are reluctant to use conventional antidepressants. Many turn to "natural" alternatives.

St. John's wort (Hypericum perforatum) is the most popular herbal antidepressant...and the best studied. Numerous studies show that it can be beneficial for mild to moderate depression. But there is only very preliminary evidence that it can help for PMS symptoms.6429
Before patients try St. John's wort, remind them of its downside...St. John's wort causes LOTS of drug interactions. It is a potent INDUCER of cytochrome P450 3A4. It can decrease levels and the effectiveness of lots of drugs. Some of these include the HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors, oral contraceptives, cyclosporin, some statins, and many others.

Practice Pearl - Tell women who take St. John's wort that if they use oral contraceptives for birth control they should use a back up method of contraception. St. John's wort can decrease the effectiveness of oral contraceptives, which could result in unexpected pregnancy.11886,11887

SAMe (S-adenosyl-L-methionine) is another well-known natural antidepressant. SAMe works by donating methyl groups to various physiological processes, including synthesis of neurotransmitters. SAMe increases levels of serotonin, norepinephrine, and dopamine.5196,5231,5232,9110 It does seem to help for depression and seems to be safe. But there is no reliable evidence that it works for symptoms of PMS. Don't recommend it.

Advise patients to avoid supplements containing L-tryptophan or 5-HTP. These products are precursors to serotonin. They are often marketed for depression, anxiety, and sometimes for PMS. There's actually some evidence that L-tryptophan might improve some symptoms of PMS.6246 But there are lots of questions about the safety of these products. Years ago these products were linked to several cases of eosinophilia myalgia syndrome (EMS).902,919,7067,8053,10084,10085,11474,11478 Until more is known about the safety of 5-HTP and L-tryptophan, tell patients not to use them.

Practice Pearl - Tell women who take St. John's wort that if they use oral contraceptives for birth control they should use a back up method of contraception. St. John's wort can decrease the effectiveness of oral contraceptives, which could result in unexpected pregnancy.11886,11887
SAMe (S-adenosyl-L-methionine) is another well-known natural antidepressant. SAMe works by donating methyl groups to various physiological processes, including synthesis of neurotransmitters. SAMe increases levels of serotonin, norepinephrine, and dopamine.5196,5231,5232,9110 It does seem to help for depression and seems to be safe. But there is no reliable evidence that it works for symptoms of PMS. Don't recommend it.

Advise patients to avoid supplements containing L-tryptophan or 5-HTP. These products are precursors to serotonin. They are often marketed for depression, anxiety, and sometimes for PMS. There's actually some evidence that L-tryptophan might improve some symptoms of PMS.6246 But there are lots of questions about the safety of these products. Years ago these products were linked to several cases of eosinophilia myalgia syndrome (EMS).902,919,7067,8053,10084,10085,11474,11478 Until more is known about the safety of 5-HTP and L-tryptophan, tell patients not to use them.

Hormonal Agents

Lots of theories about PMS are based on hormone imbalances. Some investigators attribute PMS anxiety and depression to high estrogen and low progesterone. They think food cravings, headache, fatigue, and palpitations might be related to increased insulin resistance, low anti-inflammatory prostaglandin E1, and high levels of pro-inflammatory prostaglandin 2. And they attribute PMS fluid retention to high aldosterone levels.
Some clinicians try to adjust a woman's hormonal balance in an effort to address this potential underlying cause. Hormone therapy is usually directed toward suppressing ovulation. Oral contraceptives or gonadotropin-releasing hormones (leuprolide, goserelin) are tried. Oral contraceptives are most popular and make sense if the symptoms are mainly physical...breast tenderness, headache, etc. But when they are initiated, they can sometimes make these symptoms worse. And they're usually not helpful for mood changes. Many clinicians are reluctant to use gonadotropin-releasing hormone because they produce a "chemical menopause" that can lead to bone loss.

ACOG guidelines consider these hormonal options as the third step in treating PMS symptoms.

Lots of natural products are promoted for their hormone-like effects. Many women turn to these products with the hope of symptom relief, without the downside of conventional drugs.

Chasteberry (Vitex agnus-castus) is a very popular "woman's herb" evaluated in several studies for PMS. Chasteberry seems to be best for physical symptoms such as breast tenderness, edema, and constipation. It also seems to improve irritability, mood, anger, and headache.7055,7076,7078,7079 In some women, chasteberry improves symptoms by as much as 50%.7055 But chasteberry does not appear to be very helpful for symptoms of bloating.7055

There is also some evidence that chasteberry might help for the more severe symptoms of PMDD. One study found chasteberry to be comparable to fluoxetine 20-40 mg/day; however, chasteberry tended to be more effective for physical symptoms, while fluoxetine was more effective for psychological symptoms.12207

Exactly how chasteberry works for PMS is not known. But chasteberry has a variety of pharmacological effects that might be beneficial. Chasteberry might affect dopamine, acetylcholine and opioid receptors.7014,7015,10122 Chasteberry might also have estrogen and progestin activity.10979,11456

Chasteberry is very promising based on the evidence so far. But the evidence is somewhat limited due small sample sizes or inadequate study designs. Due to these limitations, chasteberry shouldn't be recommended just yet to most patients.

Natural progesterone is another product that is promoted for PMS...often over the Internet. But it doesn't work any better than placebo.1220,10332 Urge your patients to save their money and steer clear.

Black cohosh (Actaea racemosa), red clover (Trifolium pratense), and soy (Glycine max) are widely known as "women's herbs." They may be helpful for menopausal symptoms, but there isn't much evidence they work for PMS symptoms. Don't recommend them.
Also, steer patients away from dong quai (Angelica sinensis) for PMS. There is no reliable evidence that it is effective...and not enough is known about its safety.

The Bottom Line

If your patient wants to take a natural approach to relieving PMS symptoms, suggest 1200 mg of calcium daily. Be sure she understands that benefits would not appear for at least a few months. Even if she doesn't see an improvement in PMS symptoms, she will at least be getting some protection against osteoporosis.
Other minerals and vitamins might be helpful...magnesium, vitamin E, and pyridoxine. But there is not as much evidence for these as there is for calcium. If patients want to try pyridoxine, remind them not to exceed 100 mg/day due to risk of neuropathy.

Chasteberry is the herb with the most evidence in support of efficacy for PMS. But it is still not enough to recommend to most women.

A few other natural products have some preliminary evidence, but more research is needed before these can be recommended...ginkgo, St. John's wort, and manganese.

Tell women that using evening primrose oil, progesterone, black cohosh, red clover, soy, or dong quai is unlikely to improve PMS symptoms.

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6429 Stevinson C, Ernst E. A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome. BJOG 2000;107:870-6.

6847 Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutrition 2000;19:3-12.

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7078 Berger D. Schaffner W, Schrader E, et al. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with premenstrual syndrome (PMS). Arch Gynecol Obstet 2000;264:150-3.

7079 Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med 2000;9:315-20.

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I'm an organic gynecologist, yoga teacher + writer. I earn a living partnering with women to get them vital and self-realized again. We're born that way, but often fall off the path. Let's take your lousy mood and fatigue, and transform it into something sacred and useful.