Woman with symptoms of PMS curled up on the couch

Premenstrual Syndrome (PMS)

Last Section Update: 02/2015

Table of Contents

1 Overview

Summary and Quick Facts for Premenstrual Syndrome (PMS)

Many women experience troublesome physical, emotional and cognitive symptoms during the two weeks before menstruation. These symptoms are called premenstrual syndrome, or PMS. A severe condition closely related to PMS, called premenstrual dysphoric disorder (PMDD), can dramatically reduce a woman’s quality of life.
This protocol will help you understand the monthly hormonal changes that contribute to PMS. Learn about medical treatments that may reduce PMS symptoms, several dietary and lifestyle changes and supplements that can support a healthy cycle.
Clinical trials have shown that chasteberry (Vitex agnus-castus) extract helped improve several PMS-related symptoms.

Millions of women experience troublesome physical, emotional, and cognitive symptoms during the two weeks before menstruation. These symptoms are called premenstrual syndrome, or PMS, and can interfere with day-to-day activities. A severe premenstrual condition closely related to PMS, called premenstrual dysphoric disorder (PMDD), can impact a woman’s life as much as major depressive disorder. Vitamin B6 and saffron, among other integrative interventions, can greatly help reduce these irritating and debilitating symptoms.

Common Signs and Symptoms of PMS

Physical:

Bloating, weight gain
Acne
Breast tenderness

Psychological:

Irritability
Mood swings
Fatigue

Behavioral:

Food cravings
Angry outbursts
Decreased motivation

Possible Causes of PMS/PMDD

Estrogen and progesterone are high when PMS occurs
Deregulation of the hypothalamic-pituitary-adrenal axis
Altered serotonin levels

Risk Factors for PMS/PMDD

Smoking and alcohol consumption
Obesity
High-fat, high-sugar diet
Traumatic stress or having post-traumatic stress disorder

Conventional Medical Treatments

Medications for symptoms: Non-steroidal anti-inflammatory drugs (ibuprofen, naproxen), mefenamic acid, and spironolactone
Medications to regulate mood: SSRIs, drugs to treat anxiety
Medications to suppress ovulation and regulate hormones: oral contraceptive pills, gonadotropin-releasing hormone agonists

Note: Some newer contraceptive formulations contain the progestin drospirenone, which may increase the risk of life-threatening blood clots known as venous thromboembolism.

Bioidentical hormones for hormone regulation

Dietary and Lifestyle Considerations

Avoid high-sugar and high-salt foods, caffeine, and alcohol
Exercise improved physical and psychological symptoms in women with PMS
Stress management

Integrative Interventions

Chasteberry: This has been found through many research studies to be “one of the most effective therapeutic options for PMS.”
Vitamin B6: Vitamin B6 has been shown to improve symptoms of bloating, headache, breast pain, depression, and irritability.
Magnesium: Research has found that supplementation with magnesium significantly reduced weight gain, bloating, and breast tenderness in women with PMS.
Saffron: Supplementation with saffron reduces symptoms of depression and overall premenstrual symptom severity.
Fish Oil: Compared with placebo, daily treatment with omega-3 fatty acids led to significant reductions in depression, anxiety, lack of concentration, bloating, nervousness, headaches, and breast tenderness.

2 Premenstrual Syndrome (PMS)

Millions of women, at some point in their lives, experience troublesome physical, emotional, and cognitive symptoms during the two weeks leading up to menstruation (Bhatia 2002; MGH 2013). When these symptoms interfere with day-to-day life, this is called premenstrual syndrome or PMS (Marjoribanks 2013; O'Brien 2011; Rapkin 2012; Alvero 2014). It is estimated that 8–20% of reproductive-aged women experience moderate-to-severe PMS (Rapkin 2009).

Premenstrual dysphoric disorder or PMDD is a premenstrual condition closely related to PMS that affects an estimated 3–8% of women (Rees 2014; Marjoribanks 2013; Steiner 2006). PMDD is usually characterized by severe psychological symptoms such as depression, anxiety, or persistent anger. PMDD is much more severe than PMS and can impact a woman’s life as much as major depressive disorder (Pearlstein 2008; Rapkin 2009; Epperson 2012).

Both PMS and PMDD occur in cycles. During the luteal phase of the menstrual cycle, which lasts from ovulation to the onset of menstruation, levels of the hormones estrogen and progesterone in a woman’s body change (Justice 1999; Ounis-Skali 2006). These hormonal fluctuations coincide with the onset of PMS symptoms. It is thought that changing hormone levels affect brain chemicals called neurotransmitters and neuropeptides, which help regulate mood (Freeman 2002). Direct actions of hormones, coupled with their effects on neurotransmitters, are believed to contribute to PMS and PMDD. The symptoms of PMS and PMDD usually go away when, or soon after, menstruation begins and return again during the next luteal phase (Rapkin 2012; Rees 2014; Rapkin 2014).

Dietary and lifestyle changes may be sufficient to resolve symptoms in mild cases of PMS. These include exercising; eating a healthy diet rich in vegetables, whole grains, and fruits; avoiding excess salt, sugar, alcohol, and caffeine; getting adequate sleep; managing stress; and not smoking. Over-the-counter pain relievers can help address physical symptoms such as cramps, pain, and headaches, but are not without side effects, especially if used long-term (OWH 2012; Alvero 2014). Cognitive behavioral therapy and other behavioral and self-help modalities may also reduce PMS and PMDD symptoms (Pearlstein 2008; Willacy 2012).

For women whose symptoms are not relieved by dietary and lifestyle modifications alone, several drugs are available to treat PMS and PMDD, though many women find several of them to be only partially effective or experience unwanted side effects (Kleinstauber 2012; Rapkin 2009; Marjoribanks 2013). These medications include oral contraceptives and gonadotropin-releasing hormone agonists, which block ovulation; and serotonin reuptake inhibitors and anxiolytics, which modify brain neurochemical metabolism (Mayo Clinic 2012).

Women who suffer from PMS or PMDD are not limited to conventional treatments, however. Many integrative interventions, including calcium and vitamin D, chasteberry extract, magnesium, St. John’s wort, and vitamin B6 have been shown to reduce symptoms of PMS in clinical studies (Bertone-Johnson 2005; Canning 2010; Yonkers 2008; Alvero 2014; OWH 2012). Moreover, given the hormonal basis of PMS and PMDD symptoms, women who experience either of these conditions should undergo a blood test to evaluate their sex hormone levels. Hormonal imbalance, which can be revealed by blood testing, may be an important underlying factor in PMS and PMDD for some women. Once a hormonal imbalance has been identified, some women may benefit from using bioidentical hormone replacement therapy to restore balance among their hormones (Dennerstein 1985; Fugh-Berman 2007; Holtorf 2009; Hudson 2013).

In this protocol you will learn about the possible causes of PMS and PMDD, and how to differentiate these two conditions. You will also learn how PMS and PMDD are typically treated and common side effects of conventional treatments. Emerging treatment modalities will be examined and a number of integrative interventions that may help relieve symptoms of PMS and PMDD will be described.

3 Background

The Menstrual Cycle

During the menstrual cycle, fluctuations in sex hormone levels prepare a woman’s reproductive system for pregnancy. A normal cycle generally ranges from 25–36 days. The first day of menstruation is considered day one of the cycle and is part of the follicular phase (Brzyski 2013). Key hormones involved in the menstrual cycle are luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and progesterone. The fluctuation pattern of these hormones over the course of the menstrual cycle is depicted in Figure 1.

Follicular phase. The follicular phase, which begins on the first day of menstrual bleeding, usually lasts 13–14 days (Hawkins 2008; Brzyski 2013).
Ovulatory phase. The ovulatory phase usually lasts for 16–32 hours and occurs at approximately day 14 of the menstrual cycle (Hawkins 2008; Brzyski 2013; Ajala 2013).
Luteal phase. The luteal phase usually lasts for approximately 14 days (Hawkins 2008; Brzyski 2013).
Menstruation. The entire menstrual cycle resets itself on the first day of menstruation, and the process is repeated (Hawkins 2008; Brzyski 2013).

In order for a woman to be diagnosed with PMS, troublesome symptoms must occur during the luteal phase of the menstrual cycle, end soon after menstruation, and not recur until the next luteal phase.

4 Signs and Symptoms

The specific PMS or PMDD symptoms each woman experiences may differ. However, a woman will typically experience the same symptoms from one cycle to the next. Symptoms occur during the luteal phase of the menstrual cycle, usually peak approximately two days before menstruation, and are typically relieved by the start of menstruation or a few days thereafter. In some women, symptoms linger into the next cycle, but there must be a symptom-free period of time before the next ovulatory phase in order for the condition to qualify as PMS. PMS, by definition, cannot occur after menopause. Nevertheless, symptoms similar to those caused by PMS can occur during perimenopause or after the reproductive years, particularly if a woman is receiving combined estrogen-progestogen hormone replacement (Rapkin 2014; Yonkers 2008).

It has been reported that there are over 150 symptoms associated with PMS or PMDD (Alvero 2014). However, irritability, anxiety, depression, mood swings, bloating, abdominal discomfort, breast tenderness, headache, and fatigue are the most common symptoms. Many of these symptoms can be further aggravated by stress, alcohol or caffeine consumption, and smoking (Rapkin 2014; Alvero 2014).

Table 1: Common Physical, Psychological, and Behavioral Symptoms of PMS or PMDD*

Physical Symptoms	Abdominal bloating Acne Breast engorgement and tenderness Constipation or diarrhea Headache Joint or muscle pain Poor coordination Swelling of feet and legs Weight gain
Psychological Symptoms	Anxiety Change in libido Depression Fatigue Irritability Mood swings Panic attacks Reduced concentration Reduced confidence Sleep disturbance (insomnia or excessive sleeping)
Behavioral Symptoms	Angry outbursts Decreased motivation Food cravings Hostility Increased appetite Paranoia Withdrawal from others

*Derived from (Alvero 2014; Yonkers 2008; Rapkin 2014)

5 Possible Causes

The exact cause of PMS and PMDD is unclear, but it is generally agreed that PMS and PMDD develop through a combination of cyclical changes in hormone levels and dysregulation of brain neurochemical activity. Interestingly, the relationship between hormones and neurochemicals appears to be bidirectional. Hormones activate brain neurochemical pathways, directly or indirectly, and are involved in the regulation of many essential brain functions; in turn, these neurochemicals appear to impact hormones (Rasgon 2001; Andreen 2009; Kuhl 2002; Finocchi 2011). Hormones also interact with the hypothalamic-pituitary-adrenal axis, which then impacts the stress hormone cortisol, another interaction that may contribute to premenstrual symptoms (Segebladh 2013; Girdler 2001).

Estrogen and Progesterone

Young women who have not started menstruation do not have a menstrual cycle, and thus do not experience PMS. Women who have undergone menopause also do not have a menstrual cycle or a luteal phase and thus do not experience PMS. This provides evidence that the hormones progesterone and estrogen contribute to PMS and PMDD. Furthermore, PMS and PMDD occur during the luteal phase of the menstrual cycle, when progesterone and estrogen levels are high (Rapkin 2014; Brzyski 2013). However, PMS symptoms do not appear to solely relate to hormone levels, as researchers have been unable to detect differences in hormone levels or patterns in women with PMS compared with control women (Rubinow 1988; Backstrom 1983; Rapkin 2012).

Another possibility that has received some attention from researchers is that hormone metabolites, or derivatives, may underlie some aspects of PMS and PMDD. For example, several studies have suggested that allopregnanolone, a progesterone metabolite, may be involved in PMS and PMDD (Reddy 2010; Andreen 2006; Backstrom 2011; Nillni 2011; Rapkin 1997; Monteleone 2000; Lombardi 2004; Bernardi 2004; Engin 2007; Klatzkin 2006).

Additionally, the relationship or “balance” between sex hormones in a woman’s body may play a discrete but influential role in PMS and PMDD. For example, the fluctuating balance between sex hormones during a woman’s menstrual cycle influences neurotransmitter systems in the brain, which in turn modulate mood and cognition. This is intriguing because altered activity or signaling of certain neurotransmitter systems is thought to contribute to some PMS symptoms (Steiner 2003; Studd 2011; Hudson 2013). Thus, helping establish balance between sex hormones may relieve PMS symptoms for some women (Studd 2011; Hudson 2013).

Hypothalamic-Pituitary-Adrenal Axis

The hypothalamic-pituitary-adrenal (HPA) axis comprises two brain regions—the hypothalamus and the pituitary gland—and the adrenal glands, which are found on top of each kidney. These three structures work in concert to regulate neurochemical and hormonal signals passed between the brain and adrenal glands, helping manage the response to stress through regulation of cortisol. This functional group is called the HPA axis (Smith 2006). Deregulation of the HPA axis in women with PMS or PMDD can affect cortisol and allopregnanolone levels, resulting in changes in mood and altered responses to stress (Klatzkin 2010; Segebladh 2013; Girdler 2007; Mortola 1989). A more detailed discussion about the HPA axis is available in the Stress Management protocol.

Serotonin

Serotonin, a neurotransmitter, is involved in the regulation of mood and response to stress, eating behavior, and circadian rhythm (sleep-wake cycle) (Caspi 2003; Parsey 2006; Hainer 2006; Monti 2011). Serotonin activity is partly controlled by ovarian sex hormone levels. Therefore, fluctuations in hormone levels during the menstrual cycle can alter serotonin levels and lead to changes in mood (Benmansour 2012; Rapkin 2012; Yonkers 2008). Some but not all studies have found evidence of a relationship between serotonin signaling and sex steroids in the context of premenstrual symptoms (Clayton 2006; Yen 2013; Dhingra 2007; Gingnell 2010; Magnay 2010; Magnay 2006; Yonkers 2008).

Other Potential Mechanisms

Prolactin is a hormone released by the pituitary gland to stimulate breast development and lactation (Liou 2012), while beta-endorphins are neurochemicals that control pain, reward, and addictive behaviors (Sprouse-Blum 2010; Roth-Deri 2008). Both may play a role in premenstrual symptoms. Women who have PMS may have high prolactin levels or low beta-endorphin levels, and this may contribute to some of the psychological and physical symptoms of PMS (van Die 2013; Cunningham 2009). There is also limited evidence to suggest that thyroid dysfunction may be more common in women who experience PMS (Girdler 1995; Schmidt 1993). Women who suffer from PMS should consider having blood testing to determine whether they have a thyroid hormone imbalance. More information about thyroid hormone testing and correcting thyroid hormone levels is available in the Hyperthyroidism and Hypothyroidism protocols.

6 Risk Factors

Smoking and Alcohol Consumption

A population study in over 3 000 women found that those who smoke had a more than two-fold higher risk of developing PMS, while those who began smoking before age 15 had a greater than 2.5-fold risk, compared with women who never smoked. Former smokers who smoked 25 or more cigarettes per day had a 1.8-fold higher risk of developing PMS relative to women who never smoked. Smoking more cigarettes over a longer period of time also increased PMS risk (Bertone-Johnson 2008).

A study in over 200 women found that those with PMS drank significantly more servings of alcohol per week, both pre- and postmenstrually, than did those without PMS. This same study found that women who had 10 or more alcoholic drinks per week in their postmenstrual phase were significantly more likely to have moderate to severe PMS. Other studies have also found a relationship between alcohol consumption and PMS (Rossignol 1991; Bryant 2006).

Obesity

Increasing body mass index (BMI) is associated with PMS. In one study, a BMI > 27.5 conferred a significantly higher risk of PMS than a BMI < 20. Higher BMI was significantly associated with symptoms of backache, swelling of extremities, and abdominal cramping (Bertone-Johnson 2010). A survey of 874 women found that those who were obese had a 2.8-fold higher risk of PMS (Masho 2005). Higher BMI has also been associated with PMDD (Yen 2010).

Diet

Two surveys found that a diet high in fat is associated with worse PMS symptoms (Goker 2014; Nagata 2004). There is also evidence that women with PMDD have an increased desire for high-fat and high-calorie foods during the luteal phase compared to the follicular phase (Reed 2008). Another survey found that consumption of foods and beverages high in sugar was associated with PMS (Rossignol 1991).

Psychological Risk Factors

Multiple studies have found that traumatic stress or having post-traumatic stress disorder increases a woman’s odds of developing PMDD (Pilver, Levy 2011; Wittchen 2003; Perkonigg 2004). There is also evidence that women who perceive discrimination during their lifetimes, including gender and race discrimination, are more likely to experience PMDD (Pilver, Desai 2011). One study found that women with PMS were more than three times as likely to report significant trauma in childhood compared with those without PMS (Bertone-Johnson 2014).

Lastly, it is important to note that women with psychiatric illnesses may experience exacerbation of their condition during the luteal phase of their menstrual cycle (Nillni 2011; Kim 2004; Miyaoka 2011; Cirillo 2012; Rees 2014). You can learn more about psychiatric conditions that are sometimes mistaken for PMS and PMDD in Life Extension’s Anxiety and Depression protocols.

7 Diagnosis

PMS and PMDD are diagnosed on the basis of a woman’s symptoms and medical history (Pinkerton 2013; Nillni 2011; Rees 2014). It is important that other gynecological conditions that may cause similar symptoms be distinguished from PMS and PMDD. Menopausal symptoms, endometriosis, dysmenorrhea (painful cramping during the menstrual period), and several other conditions may be mistaken for PMS or PMDD (Yonkers 2008; Rapkin 2014).

PMS and PMDD symptoms must be cyclical, in that a symptom-free interval occurs during the follicular phase. Patients with symptoms that do not remit during the follicular phase may have another disorder or condition with similar symptoms (Rees 2014; Alvero 2014). Practice guidelines recommend that women record their symptoms in a daily diary for at least two consecutive menstrual cycles to help establish a diagnosis (Nevatte 2013; Endicott 2006).

Tests may be performed to rule out other diseases or conditions that cause symptoms similar to those caused by PMS. For instance, thyroid function tests can rule out the possibility of thyroid disease (Rees 2014). Questionnaires may be used to screen for depression and generalized anxiety disorder (Alvero 2014). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels can help determine if symptoms may be related to menopause (BreastCancer.org 2013).

Physicians can diagnose PMS on the basis of standardized criteria from sources such as the International Statistical Classification of Diseases and Related Health Problems 10th edition (ICD-10), which uses the term “premenstrual tension syndrome,” or the American Congress of Obstetricians and Gynecologists (ACOG) guidelines. PMDD is diagnosed based on the guidelines from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) (Rees 2014). The requirements and possible symptoms for each diagnostic tool are listed in Table 2.

Table 2: Symptoms and Symptom Requirements for the ICD-10, ACOG, and DSM-5 Diagnostic Tools for PMS and PMDD*

Diagnostic Tool	Requirements	Symptoms
ICD-10 — PMS	One distressing physical or behavioral symptom	feeling sad, hopeless, or self-deprecating tension, anxiety, tearfulness, persistent irritability, or easily changing moods anger decreased interest in usual activities difficulty concentrating fatigue changes in appetite hypersomnia or insomnia feeling overwhelmed or out of control physical symptoms such as headaches, breast tenderness or swelling, joint or muscle pain, bloating or weight gain
ACOG — PMS	At least one of the affective and physical symptoms Symptoms occur during five days before menses in each of three previous cycles, and occur in two cycles of recording symptoms Symptoms relieved within four days of menstruation Symptoms do not recur until day 13 or later of cycle Patient suffers from social and economic performance dysfunction Symptoms present in the absence of pharmacologic or hormonal therapy, drugs or alcohol	Affective symptoms: anxiety confusion depression irritability angry outbursts social withdrawal Physical symptoms: headaches breast tenderness abdominal bloating lower-extremity swelling
DSM-5 for PMDD	At least 5 of 11 symptoms during the luteal phase Symptoms must resolve soon after menstruation begins Symptoms must include at least 1 of the first 4 listed symptoms Symptoms must be present in the absence of medical drug or hormone use, and not be associated with another psychiatric disorder Symptoms must interfere with usual activities and relationships Symptoms must have occurred during most of the previous 12 months Symptoms must occur during two months of recording symptoms	depressed mood significant anxiety easily changing moods persistent anger/irritability decreased interest in usual activities difficulty concentrating lethargy change in eating habits insomnia or hypersomnia feeling of being overwhelmed physical symptoms such as breast tenderness, headaches, bloating, or weight gain

*Derived from (Rees 2014; ACOG 2001)

8 Conventional Treatment

Treatment of PMS or PMDD depends in part on the type and severity of symptoms. Most mild cases of PMS can be treated with lifestyle changes (as described in the Dietary and Lifestyle Considerations section) or over-the-counter drugs to manage physical symptoms (Rapkin 2014), though lifestyle changes are recommended for all patients (Rees 2014). Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Midol) and naproxen (Aleve), are commonly used to treat physical symptoms such as cramping and breast tenderness.

Mefenamic acid (Ponstel), a prescription NSAID commonly prescribed for menstrual pain, is also sometimes used in PMS. A small randomized controlled trial of mefenamic acid found it significantly reduced premenstrual physical symptoms and mood swings (Mira 1986; NLM 2012). Diuretics, such as spironolactone (Aldactone), may be prescribed to treat premenstrual swelling and bloating (Mayo Clinic 2012).

Standard conventional treatment of PMS or PMDD primarily relies on medications that modulate mood; synthetic hormones that interrupt ovulation; referral for cognitive behavioral therapy; or in rare and extremely severe cases, surgical removal of a woman’s ovaries.

Psychiatric Medications

Selective serotonin reuptake inhibitors. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat mood disorders influenced by serotonin, such as anxiety and depression. SSRIs are considered the first-line pharmacologic treatment option for psychological and behavioral symptoms of PMS/PMDD, with improvements observed in 60–80% of women (Marjoribanks 2013). Among women with PMDD who respond to SSRI treatment, there is generally a greater than 50% improvement in symptoms. SSRIs may be effective when taken either continuously, or only during the luteal phase. Currently, fluoxetine (Prozac or Sarafem), sertraline (Zoloft), and paroxetine (Paxil) are the only SSRIs approved by the US Food and Drug Administration (FDA) for the treatment of PMDD (Rapkin 2013).

Side effects of SSRIs are fairly common, with those most frequently reported being nausea, fatigue or weakness, sleepiness, reduced libido, and sweating. These adverse effects have been shown to be dose-related (Marjoribanks 2013). Sexual dysfunction is another relatively common side effect of SSRIs, occurring in 80% of those who take these medications continuously over long periods of time (ARHP 2008). Another potential problem is SSRI discontinuation syndrome, in which patients experience withdrawal symptoms when stopping the medications. These include sensory and gastrointestinal symptoms, dizziness, lethargy, sleep disturbances, and psychological symptoms (Renoir 2013). Gradual withdrawal of SSRI medication appears to prevent some of these problems (Haddad 1998).

Anxiolytic drugs. Anxiolytic drugs are used to treat anxiety. Anxiolytics prescribed for PMS or PMDD include the benzodiazepine alprazolam (Xanax), buspirone (Buspar), and clonidine (Catapres) (Alvero 2014; Rees 2014; Rapkin 2014). Benzodiazepines such as alprazolam have potential to cause significant side effects including physical dependency, as well as withdrawal symptoms upon abrupt discontinuation. Therefore, alprazolam is only used if a patient fails to respond to other treatments, such as SSRI therapy (Freeman 2003).

Suppression of Ovulation

Since PMS/PMDD symptoms are attributed, at least in part, to fluctuations in sex hormones, some treatments work by interrupting ovulation:

Oral contraceptive pills. Oral contraceptive pills (OCPs) that contain a synthetic progesterone-like drug (a progestin) and an estrogen are commonly prescribed to treat symptoms of PMS; however, their effect may depend on the formulation (Rapkin 2012; Lopez 2012; ARHP 2008). Oral contraceptives work by inhibiting ovulation and preventing the changes in hormone levels that occur during the luteal phase (Nevatte 2013). Certain OCPs with 21 days of hormone tablets and 7 days of pills that contain no hormones appear to reduce the physical symptoms of PMS; however, they have limited impact on psychological symptoms (Rapkin 2012). Additionally, some of these OCPs still allow for normal hormonal fluctuations during the hormone-free week, and many women experience PMS-like symptoms during this period (Sulak 2000). Some relatively newer OCPs offer either a continuous hormone dosage without a drug-free interval or a reduced drug-free period, thus reducing the incidence of PMS-like symptoms during the drug-free period (ARHP 2008). An analysis of four studies that evaluated continuous hormone use with levonorgestrel (a progestin) and ethinyl estradiol tablets revealed overall improved symptoms in 30–81% of women (Freeman 2012).

Newer hormone formulations containing 24-day drospirenone (a progestin) and ethinyl estradiol with only a four-day drug-free interval significantly improve PMDD symptoms and are approved by the FDA to treat PMDD (Lopez 2012; ARHP 2008). It is uncertain if these formulations have any effect in women with less severe symptoms (Lopez 2012).

Potential Risks From Newer Hormone Preparations

Recent studies suggest some of the newer hormone formulations containing the progestin drospirenone, which is often combined with ethinyl estradiol, may increase the risk of life-threatening blood clots known as venous thromboembolism (FDA 2013). Venous thromboembolism includes deep vein thrombosis and pulmonary embolism (Rodriguez 2012). In approximately 6–32% of deep vein thrombosis cases, a clot can travel from the extremities to the lungs, forming a pulmonary embolism. It is estimated that approximately 300 000 people die from pulmonary embolism each year in the United States (Ozaki 2012).

All OCPs are associated with a slightly increased risk of blood clot formation (Tchaikovski 2010; Stegeman 2013). However, some studies have demonstrated that contraceptives containing drospirenone and newer progestogens are associated with up to a 3.3-fold greater risk of venous thromboembolism compared with older formulations (Wu 2013; Parkin 2011; Jick 2011; Tricotel 2014).

The FDA issued a position statement on April 4th, 2012 stating that OCPs containing drospirenone may be associated with a higher risk of blood clot formation than other progestin-containing pills (FDA 2013). It is important for patients to discuss their complete medical history with their physicians to determine if drospirenone-containing OCPs pose any unnecessary risks. Common brand names of drospirenone-containing OCPs are Beyaz, Gianvi, Loryna, Ocella, Safyral, Syeda, Yasmin, Yaz, and Zarah (FDA 2013).

Gonadotropin-releasing hormone agonists. Gonadotropin-releasing hormone (GnRH) agonists interrupt the hormonal cycle and ovulation. This creates a state of medically-induced menopause, which, if continued long-term, carries a risk of osteoporosis and heart disease similar to that of natural menopause. Thus, the use of GnRH agonists for PMS or PMDD is limited to 3–6 month courses, and GnRH agonists are typically only used when other treatments such as SSRIs or OCPs have failed (Rees 2014; Kumar 2014; Magon 2011).

The low levels of circulating sex hormones caused by GnRH agonists can also cause menopausal symptoms such as hot flashes, vaginal dryness, and headaches. To alleviate their undesired effects and allow longer treatment periods, estrogen, progesterone, or both are commonly prescribed as “add back therapy”; however, this can reintroduce symptoms of PMS (Nevatte 2013). To minimize serious complications, hormone replacement therapy is recommended when GnRH treatment lasts longer than six months (Rees 2014; Rapkin 2013). Commonly prescribed GnRH agonists include leuprolide (Eligard, Lupron), buserelin (Suprefact), goserelin (Zoladex), and nafarelin (Synarel) (Freeman 2003).

Estradiol. High doses of estradiol in the form of a patch, gel, or intrauterine implant are sometimes used to suppress ovulation in order to treat PMS/PMDD (Nevatte 2013; Watson 1989; Smith 1995). A side effect of estradiol administration is increased risk of endometrial hyperplasia, which is non-cancerous overgrowth of cells lining the inside of the uterus (CRUK 2014). Endometrial hyperplasia may lead to endometrial cancer in some cases (Goncharenko 2013; Boruban 2008). Bioidentical progesterone may be used to reduce the risk of endometrial hyperplasia in women being treated with transdermal estradiol (PEPI Trial Writing Group 1996).

Bioidentical Hormones and PMS

Some evidence suggests that hormonal imbalance may contribute to PMS symptoms (Studd 2011). Since sex hormones exert broad influence throughout the body, a relative excess or deficiency of one or more hormones may give rise to a wide spectrum of symptoms, such as those associated with PMS. Thus, ensuring hormonal balance may ease PMS symptoms for some women (Steiner 2003; Studd 2011). Diligent use of bioidentical hormone replacement therapy is a natural way to accomplish this.

Bioidentical hormones are hormones that have the identical chemical structure as hormones produced by the human body. These include hormones approved by the FDA for treatment of menopausal symptoms, or hormones sold over-the-counter or compounded by a compounding pharmacy. Bioidentical estrogens include estriol, estradiol, and estrone. Bioidentical progesterones include oral micronized progesterone and progesterones sold over-the-counter or compounded in the form of gels and creams (Files 2011; Fugh-Berman 2007; Marsden 2010). FDA-approved bioidentical hormones have also been used to treat PMS and PMDD (Fugh-Berman 2007; Files 2011).

Achieving hormonal balance through the use of bioidentical hormones may require different protocols for different women, since each woman’s body may not respond exactly the same way to specific hormone levels. A reasonable approach is for a woman who experiences bothersome PMS symptoms to undergo hormone blood testing about seven days before the cycle starts, which corresponds to day 21 of a typical 28 day cycle. (Day number 1 is the day that bleeding begins). This will allow an innovative physician to discern the levels of hormones in the woman’s body during her luteal phase, when PMS symptoms occur. If, for example, a woman is found to have a low level of progesterone relative to her level of estrogen, then her progesterone levels can be bolstered using transdermal bioidentical micronized progesterone. If this results in waning of the woman’s symptoms, the woman could then work with her doctor to continue progesterone therapy and follow up with a blood test on the 21st day of her next menstrual cycle to monitor the impact of the bioidentical progesterone on her hormone levels and PMS symptoms. Likewise, a similar approach could be undertaken with bioidentical estradiol, or possibly even testosterone, depending on blood test results.

This approach is difficult to study in organized clinical trials involving many women, because each woman may require a different dose of bioidentical hormones or different hormones altogether. Unfortunately, this means that published scientific evidence in favor of treating PMS with bioidentical hormone therapy has been slow to accumulate. However, some evidence has been published. For example, a randomized controlled trial showed that oral bioidentical progesterone therapy resulted in an improvement in mood and some physical symptoms of PMS after one and two months of treatment (Dennerstein 1985; Fugh-Berman 2007). Also, several integrative physicians have reported clinical success using bioidentical hormones (Hudson 2013).

Women interested in learning more about bioidentical hormones can refer to the Life Extension magazine article Bioidentical Hormones: Why are They Still Controversial? and to the Female Hormone Restoration protocol.

Cognitive Behavioral Therapy

Cognitive behavioral therapy (CBT) may be an effective treatment for the psychological and behavioral symptoms of PMS (Busse 2009). CBT is commonly used to treat mood disorders, anxiety, and depression (Duckworth 2012). A review of randomized, controlled trials found that CBT significantly reduced anxiety and depression, with possible benefit for behavioral changes, in women with PMS (Busse 2009).

Bilateral Oophorectomy

For women with severe PMDD that does not respond to any other treatment, bilateral oophorectomy (surgical removal of the ovaries) with or without hysterectomy (surgical removal of the uterus) may be considered (Rapkin 2014; Rees 2014). Bilateral oophorectomy removes PMDD hormone-related symptomatology; however, due to the highly invasive nature of this procedure, it should only be considered when all other treatment options have failed (Alvero 2014). Removal of the ovaries induces menopause by eliminating the source of most sex steroid hormones (Cunningham 2009; AMS 2013).

9 Dietary and Lifestyle Considerations

Diet

Foods containing high amounts of simple sugars or salt may promote bloating and weight gain, and should be avoided (Alvero 2014). Some authors have theorized that consuming more complex carbohydrates during the luteal phase may increase serotonin levels and improve symptoms of PMS (Nevatte 2013). Women suffering from PMS should avoid caffeine and alcohol because they may exacerbate PMS (Rossignol 1990; Alvero 2014).

Exercise

Four small studies examined the impact of exercise on PMS signs and symptoms; all of them found benefit. Breast tenderness, fluid retention, stress, anxiety, depression, muscle stiffness, cramps, tension, and restlessness improved in these trials (Dennerstein 1985). In a study comparing aerobic exercise (60 minutes, 3 times a week for 8 weeks) to no exercise in women with PMS, women who exercised had significant reductions in physical and psychological symptoms of PMS (Samadi 2013).

Stress Management

Managing stress may help reduce PMS symptoms (Alvero 2014). Speaking with friends or writing in a journal may help some women cope with stress. Additionally, yoga, massage, or relaxation therapy may be useful (OWH 2012; ACOG 2001). Adequate rest and sleep may improve response to treatment (Alvero 2014; NIH 2007). A more thorough discussion about strategies to manage stress is available in the Stress Management protocol.

Acupuncture

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.

10 Nutrients

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).

B Vitamins

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

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

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).

Ginkgo Extract

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

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

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

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).

Chamomile Extract

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).

2015

Feb: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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Premenstrual Syndrome (PMS)

Premenstrual Syndrome (PMS)

1 Overview

Summary and Quick Facts for Premenstrual Syndrome (PMS)

Common Signs and Symptoms of PMS

Possible Causes of PMS/PMDD

Risk Factors for PMS/PMDD

Conventional Medical Treatments

Dietary and Lifestyle Considerations

Integrative Interventions

2 Premenstrual Syndrome (PMS)

3 Background

The Menstrual Cycle

4 Signs and Symptoms

5 Possible Causes

Estrogen and Progesterone

Hypothalamic-Pituitary-Adrenal Axis

Serotonin

Other Potential Mechanisms

6 Risk Factors

Smoking and Alcohol Consumption

Obesity

Diet

Psychological Risk Factors

7 Diagnosis

8 Conventional Treatment

Psychiatric Medications

Suppression of Ovulation

Potential Risks From Newer Hormone Preparations

Bioidentical Hormones and PMS

Cognitive Behavioral Therapy

Bilateral Oophorectomy

9 Dietary and Lifestyle Considerations

Diet

Exercise

Stress Management

Acupuncture

10 Nutrients

Chasteberry (Vitex agnus-castus)

Calcium and Vitamin D

St. John’s wort (Hypericum perforatum)

B Vitamins

Magnesium

Saffron

Omega-3 Fatty Acids

Ginkgo Extract

Gamma-Linolenic Acid

Tryptophan

Ginger

Chamomile Extract

Update History

2015

Disclaimer and Safety Information

References

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