PMS & PMDD

womensmentalhealth.org/specialty-clinics/pms-and-pmdd/

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

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Premenstrual Dysphoric Disorder (PMDD)
Premenstrual Dysphoric Disorder (PMDD) is a more severe form of premenstrual syndrome
characterized by significant premenstrual mood disturbance, often with prominent mood
reactivity and irritability. Symptoms of PMDD can emerge 1-2 weeks preceding menses and
typically resolve 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 affects 3-8% of women in their reproductive years symptoms usually emerging
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 in adolescents with PMDD are similar
to those used for adult women.

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

It is important for clinicians to distinguish between PMDD and other medical and psychiatric
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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. With PMDD, mood
symptoms are present only during the luteal phase (the last two weeks) of the menstrual
cycle. The best way to distinguish PMDD from an underlying mood disorder is by using
daily charting of symptoms.

In addition, PMDD mood symptoms are not present in the absence of a menstrual cycle.
Thus, PMDD resolves during pregnancy and after menopause, whereas other mood
disorders typically persist across 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, several well-validated scales for the recording of
premenstrual symptoms include:

Calendar of Premenstrual Experiences (COPE)

Daily Record of Severity of Problems (DRSP)
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

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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.

Continue Reading: The Etiology of Premenstral Dysphoric Disorder by Dr. Edwin

Raffi & Dr. Marlene Freeman

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.

Lifestyle Modifications

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.
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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: SSRI 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.

Other antidepressants with serotonergic activity have evidence to endorse their use in the
treatment of premenstrual symptoms including clomipramine (a tricyclic antidepressant),
venlafaxine (Effexor) and duloxetine (Cymbalta).

Several dosing strategies for SSRIs may be used — continuous dosing (daily throughout
the month), intermittent (luteal phase only) dosing, and semi-intermittent dosing
(continuous with increased dose in the luteal phase). While women with PMDD and no
mood disorder may do well with luteal phase dosing, women who are ultimately diagnosed
with a premenstrual exacerbation of a mood disorder 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. Studies have also begun to examine whether beginning medication
at the onset of symptoms may be effective for some women.

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
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continuously throughout the menstrual cycle, or may be given in intermittent fashion during
the luteal phase of the cycle.

A definitive recommendation about how long to continue SSRI treatment in a patient with
PMS or PMDD cannot be made because of the limited research in this area. After
discontinuation of SSRI, relapse rates are relatively high. Patients who had more severe
symptoms appear to have a greater chance of relapse compared to those with lower
symptom severity. Thus symptom severity and degree of functional impairment should be
considered when making decisions regarding the duration SSRI treatment in women with
PMS and PMDD. For the majority of women, this is a chronic condition, requiring long-term
treatment.

Psychotropic Medications: Benzodiazepines

The 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 abuse and dependence.

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. Oral contraceptive
showing greater efficacy may be related to the addition of the novel progestin,
drospirenone. Drospirenone is distinct from the progestins used in other oral
contraceptives and is chemically related to spironolactone, a diuretic that is sometimes
used to treat fluid retention in women with premenstrual symptoms.

While oral contraceptives are typically given in a cyclic manner with 21 days of active pills
followed by 7 days of placebo, preliminary research suggests that continuous treatment
with oral contraceptives may have greater efficacy for treating PMS symptoms. One 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.

Weighing the risks and benefits of starting a hormonal intervention is important. Some
women are not good candidates for treatment with OCPs, especially if there is a history
of blood clot, stroke, or migraine. 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.

Hormonal Interventions: 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

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risk of osteoporosis. These side effects may be mitigated by “add-back” therapy with
estrogen and progesterone; however, some women may experience recurrent PMDD
symptoms with the addition of these hormones.

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 a GnRH agonist, 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.

PMS and PMDD in Teens

Epidemiologic studies have shown that premenstrual disorders may begin during the teen
years. It has been reported that at least 20% of adolescents experience moderate to severe
premenstrual symptoms. How common The prevalence of PMDD appears to be as
common in teens as in older women, with various studies estimating that about 2%-6% of
girls between the ages of 14 and 16 meet criteria for PMDD. Randomized controlled trials
of pharmacologic treatments have not been conducted in teens with PMS and PMDD;
however, clinical experience indicates that the same treatments that are effective for adults
may be used in adolescents.

Teens may want to take a look at our Guide for Teens with PMS and PMDD.

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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.

Research at the Center for Women’s Mental Health

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, please visit our research page.

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