Mass General Hospital

Harvard Medical School

PMS & PMDD

pms

Premenstrual Mood Changes

Many women in their reproductive years experience transient physical and emotional changes around the time of their period. In fact, at least 75% of women with regular menstrual cycles report unpleasant physical or psychological symptoms premenstrually. For the majority of women, these symptoms are mild and tolerable. However, for a certain group of women, these symptoms can be disabling and may cause significant disruption in their lives.

Premenstrual Syndrome (PMS)

Premenstrual Syndrome, commonly referred to as ‘PMS,’ is a broader term that typically refers to a general pattern of physical, emotional and behavioral symptoms occurring 1-2 weeks before menses and remitting with the onset of menses. PMS is common, affecting from 30-80% of women of reproductive age.

Psychological Symptoms

• Anger
• Anxiety
• Depression
• Irritability
• Sense of feeling overwhelmed
• Sensitivity to rejection
• Social withdrawal

Physical Symptoms

• Abdominal bloating
• Appetite disturbance (usually increased)
• Breast tenderness
• Headaches
• Lethargy or fatigue
• Muscle aches and/or joint pain
• Sleep disturbance (usually hypersomnia)
• Swelling of extremities

Behavioral Symptoms

• Fatigue
• Forgetfulness
• Poor Concentration

Premenstrual Dysphoric Disorder (PMDD)

Premenstrual Dysphoric Disorder (PMDD) is a more severe form of premenstrual syndrome characterized by significant premenstrual mood disturbance with a major prevalence of irritability. Symptoms of PMDD can emerge 1-2 weeks preceding menses and resolve completely with the onset of menses. By definition, this mood disturbance results in marked social or occupational impairment, with its most prominent effects in interpersonal functioning.
PMDD effects 3-8% of women in their reproductive years with typical symptom emergence during a woman’s 20’s. These symptoms may worsen over time; for example, it has been observed that some women may experience worsening premenstrual symptoms as they enter into menopause. Less commonly, PMDD may begin during adolescence, with case reports suggesting that successful treatment options mimic those for adult women with PMDD. The major risk factors for PMDD include psychiatric history of a mood or anxiety disorder, family history of premenstrual mood dysregulation, stress and age in the late 20’s to mid-30’s.

Psychological Symptoms

• Anxiety
• Feeling overwhelmed or out of control
• Increased depressed mood
• Irritability
• Mood Swings
• Sense of feeling overwhelmed
• Sensitivity to rejection
• Social withdrawal
• Sudden sadness or tearfulness

Physical Symptoms

• Abdominal bloating
• Appetite disturbance (usually increased)
• Breast tenderness
• Headaches
• Lethargy or fatigue
• Muscle aches and/or joint pain
• Sleep disturbance (usually hypersomnia)
• Swelling of extremities

Behavioral Symptoms

• Fatigue
• Forgetfulness
• Poor Concentration

Diagnosis

It is important for clinicians to distinguish between PMDD and other medical and psychiatric conditions. Medical illnesses such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome and migraine disorder can have features that overlap with PMDD. Additionally, psychiatric illnesses such as depression or anxiety disorders can worsen during the premenstrual period and thus may imitate PMDD.

Ruling Out Other Psychiatric Illnesses

Mood disorders, such as major depression or bipolar disorder, can worsen during the premenstrual period and thus may mimic PMDD. When this occurs, the term PME (premenstrual exacerbation) is used to refer to the mood worsening in the premenstrual phase. An estimated 40% of women who seek treatment for PMDD actually have a PME of an underlying mood disorder.
PMDD can be distinguished from other mood disorders primarily by the cyclical nature of the mood disturbance. PMDD mood symptoms are only present for a specific period of time, while other mood disorders are variable or constant over time. The specific time for mood symptoms to occur with PMDD is only during the luteal phase of the menstrual cycle. In addition, PMDD mood symptoms are not present in the absence of a menstrual cycle, including pregnancy and menopause, unlike other mood disorders which may continue over all reproductive life events.

Confirming the Diagnosis of PMDD

The best way to confirm the diagnosis of PMDD is by prospective daily charting of symptoms. Women with PMDD will experience a symptom-free interval between menses and ovulation (luteal phase). Although there is no consensus about the best instrument by which to confirm the diagnosis of PMDD, two well-validated scales for the recording of premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE) and the Prospective Record of the Severity of Menstruation (PRISM).

What Causes PMS and PMDD?

Although the etiology of PMS and PMDD remains uncertain at present, researchers now concur that these disorders represent biological phenomena rather than purely psychological events. Recent research indicates that women who are vulnerable to premenstrual mood changes do not have abnormal levels of hormones or some type of hormonal dysregulation, but rather a particular sensitivity to normal cyclical hormonal changes.

Fluctuations in circulating estrogen and progesterone cause marked effects on central neurotransmission, specifically serotonergic, noradrenergic and dopaminergic pathways. In particular, accumulating evidence implicates the serotonergic system in the pathogenesis of PMS and PMDD. Recent data suggest that women with premenstrual mood disorders have abnormal serotonin neurotransmission, which is thought to be associated with symptoms such as irritability, depressed mood and carbohydrate craving.

There may also be some role for gamma amino-butyric acid (GABA), the main inhibitory neurotransmitter, in the pathogenesis of PMS/PMDD, however this remains to be defined. Likewise, the potential involvement of the opioid and adrenergic systems in these disorders has yet to be elucidated.

Non-Pharmacologic Treatment for PMS and PMDD

Monthly Mood Chart

Keeping a monthly mood chart can be informative and even therapeutic for many women. In addition to helping with the diagnosis, many women feel better if they can identify the relationship between their cycles and mood changes, and also anticipate days that they may be at risk for mood worsening.

Life Style Changes

Lifestyle changes can help to ameliorate the symptoms of PMS and PMDD. For women with mild symptoms, these interventions should be tried before pharmacological treatment. Although solid evidence is lacking, clinicians generally recommend that patients with PMS or PMDD decrease or eliminate the intake of caffeine, sugar and sodium. Other helpful lifestyle modifications include decreasing alcohol and nicotine use and ensuring adequate sleep. Also, regular aerobic exercise has been demonstrated to have beneficial effects on both the emotional and physical symptoms of PMS/PMDD.

Nutritional Supplements

Certain nutritional supplements have also been shown to improve premenstrual symptomatology. A large, multicenter trial of calcium supplementation found that 1200 mg calcium a day significantly reduced both the physical and emotional symptoms of PMS.

Other studies have demonstrated that Vitamin B6 in doses of 50-100 mg a day can have beneficial effects in women with PMS; however, patients must be cautioned that doses above 100 mg a day can cause peripheral neuropathy.

Limited evidence suggests that magnesium (200-360 mg a day) and Vitamin E (400 IU a day) can provide modest relief of symptoms.

Herbal Remedies

Herbal remedies may have some role in the treatment of premenstrual symptoms. One recent double-blind, placebo-controlled trial concluded that agnus castus fruit extract (1 tab a day), also known as chasteberry, significantly decreased premenstrual symptoms of irritability, anger, headache and breast fullness when compared to placebo.

In another study, gingko biloba was found to improve PMS symptoms, particularly breast tenderness and fluid retention.

Though early evidence suggested that evening primrose oil was a useful treatment of PMS, a recent review of studies found that it was no more effective than placebo.

Other botanical remedies include black cohash, St. John’s Wort and Kava Kava.

Light Therapy

Light therapy has also been explored as a possible treatment for PMDD. Effect size appears to be modest for this modality, although further exploration is warranted to determine whether this may be an effective and well-tolerated option for some women.

Psychotherapy or Cognitive-Behavioral Therapy

Psychotherapy and Cognitive-Behavioral Therapy (CBT) also offer a non-pharmacologic approach to the treatment of PMS and PMDD. A recent study found that cognitive-behavioral therapy (CBT) was as effective as fluoxetine (20 mg daily), in the treatment of women with PMDD. Other limited studies suggest that cognitive approaches can be useful in helping to reduce premenstrual symptoms.

Pharmacologic Treatment for PMS and PMDD

Psychotropic Medications

For women who are ultimately diagnosed with a premenstrual exacerbation of a mood disorder, there are several treatment options. These women require treatment throughout the menstrual cycle and typically do not respond well to intermittent dosing. It may also be helpful to raise the dose of antidepressant in the luteal phase and return to a lower level at the onset of menses.

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological agents for the treatment of premenstrual mood symptoms. A significant body of evidence, including numerous double-blind, randomized studies, supports the effectiveness of SSRIs in reducing both the emotional, as well as physical symptoms, of PMS and PMDD. In general, women respond to low doses of SSRIs, and this treatment response usually occurs rapidly, often within several days.

Women with bipolar disorder who have mood worsening premenstrually should consider antidepressant use carefully, as switching to mania/hypomania is an associated risk with antidepressant use or increased antidepressant dosing. SSRIs may be prescribed continuously throughout the menstrual cycle, or may be given in intermittent fashion during the luteal phase of the cycle. Studies have also begun to examine whether beginning medication at the onset of symptoms may be effective for some women. Discontinuation of SSRI treatment after symptom remission should be considered in conjunction with individual symptom severity.
Other antidepressants have evidence to endorse their use in the treatment of premenstrual symptoms including clomipramine (a tricyclic antidepressant), venlafaxine (Effexor) and duloxetine (Cymbalta).

Benzodiazepines

Among other psychotropic medications used in the treatment of PMS and PMDD, benzodiazepine alprazolam (Xanax) has been shown to have benefit in reducing premenstrual symptomatology, in particular premenstrual anxiety. However, this medication should be prescribed cautiously, given its potential for addiction.

Hormonal Interventions

Oral Contraceptives

Hormonal treatments of PMS and PMDD are based on the principle that suppression of ovulation eliminates premenstrual symptomatology. Results from studies using oral contraceptives (OCPs) to treat PMS and PMDD have been mixed. Weighing the risks and benefits of starting a hormonal intervention is important. Preliminary research suggests that continuous treatment with oral contraceptives may have efficacy for treating PMS symptoms. A past study also found that adding oral contraceptives to the antidepressant regimen in women with PMS and PMDD can improve residual mood symptoms that occur prior to menstruation. Still, some women need to need to avoid OCPs, especially if there is a history of blood clots, strokes, and migraines. Women who are 35 years of age or older and who smoke should not use OCPs. Additionally, women with a history of depression should speak with their doctor before taking an OCP and should remain vigilant to any mood changes that occur once they are started on an OCP treatment regime.

Leuprolide and Danazol

Gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide, which suppress ovarian function, have been found to reduce premenstrual symptoms in most studies. These medications, however, cause estrogen to fall to menopausal levels and are thus associated with side effects such as hot flashes and vaginal dryness, as well as increased risk of osteoporosis. These side effects may be mitigated by “add-back” therapy with estrogen and progesterone. Similarly, danazol, a synthetic androgen, is an effective therapy for PMS/PMDD when given in doses high enough to inhibit ovulation. However, this medication is associated with significant androgenic side effects, including acne, hirsutism and weight gain.

Treatment Approach

After the diagnosis of PMS or PMDD has been made through exclusion of other medical and psychiatric conditions, as well as by prospective daily ratings of symptoms, treatment can be initiated. For all women, simple lifestyle changes in diet, exercise and stress management are encouraged. These modifications have no associated risks and may provide significant benefits. Additionally, all women should be advised to continue daily charting of their premenstrual symptoms after diagnosis, as this can help both to determine treatment effectiveness and to give women a sense of control over their symptoms. For patients with mild physical and emotional symptoms of PMS, a trial of nutritional supplements, including calcium, magnesium, and vitamin B6 may also be considered.

In determining whether or not to start medication therapy, the patient’s preference, the severity of the patient’s symptoms, as well as the associated medication side effects must be thoroughly considered. For patients with severe symptoms of PMS or with a diagnosis of PMDD, SSRIs are the first-line treatment. These medications can be dosed on a continuous or intermittent schedule depending on the patient’s preference and on the severity of her symptoms. If a woman does not show improvement in symptoms after 3 menstrual cycles, a trial with a different SSRI should be initiated. Additionally, if a patient has severely troubling side effects with one SSRI, she should be switched to a different medication.

For severe symptoms that fail to respond to any of the above strategies, medications that suppress ovulation, such as GnRH, may be considered. Because these medications induce a chemical menopause associated with troubling side effects and possible long-term consequences, they are not first-line agents for treatment of PMS or PMDD and should be used cautiously.

How do I get an appointment?

Our clinical program offers pharmacologic and non-pharmacologic therapies for women with both premenstrual depression and/or anxiety.

Consultations regarding treatment options can be scheduled with all of our physicians by calling our intake coordinator at (617) 724-7792.

PMS and PMDD Research at the CWMH

At this time the Center does not have any active studies investigating PMS and PMDD. New studies may become active in the near future. In order to remain informed about any studies for which you may be eligible, click here.