• PMS & PMDD2019-01-28T18:19:48-04:00

    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 90% of women with regular menstrual cycles report unpleasant physical or psychological symptoms premenstrually.1 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 broad term that typically refers to a general pattern of physical, emotional and behavioral symptoms occurring 1-2 weeks before and remitting with the onset of menses. PMS is common, affecting from 30-80% of women of reproductive age, though clinically significant PMS symptoms have been reported in 3-8% of patients.2

    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, 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. This mood disturbance results in marked social or occupational impairment, with its most prominent effects in interpersonal functioning. In fact, a recent study found that women with untreated PMDD were likely to experience a loss of three quality-adjusted life years during their lifetime as a result of their premenstrual symptoms. This did not include menstruation-free periods, such as pregnancy, breastfeeding and menopause.3

    PMDD affects 3-8% of women in their reproductive years, with symptoms usually emerging during a woman’s twenties.2 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.4 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 personal 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 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 mimic PMDD.

    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. 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.

    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 premenstrual exacerbation or PME is used to refer to the mood worsening which occurs during the premenstrual phase. An estimated 40% of women who seek treatment for PMDD actually have a PME of an underlying mood disorder.5

    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, during the luteal phase (the last two weeks) of the menstrual cycle. Conversely, other mood disorders are variable or constant over time. Therefore, the best way to distinguish PMDD from an underlying mood disorder is through 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 (the proliferative 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:

    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.  When ovarian cycling is suppressed, for example, using a gonadotropin releasing hormone (GnRH) agonist, such as leuprolide (Lupron), women with PMDD experience resolution of their premenstrual symptoms.  However, women whose PMDD symptoms remit with ovarian suppression experience recurrent symptoms when they begin estradiol/progesterone add-back. Symptoms are typically not reported when women with PMDD initiate ovarian hormone suppression, nor with steady-state suppression, suggesting that increasing levels of estradiol and/or progesterone may trigger the onset of the negative affective symptoms characteristic of PMDD.6

    Fluctuations in circulating estrogen and progesterone cause marked effects on central neurotransmission, specifically serotonergic, noradrenergic and dopaminergic pathways. Accumulating evidence particularly implicates the serotonergic system in the pathogenesis of PMS and PMDD. Recent data suggest that women with premenstrual mood disorders have abnormal serotonin neurotransmission, along with a lower density of serotonin transporter receptors, 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. Allopregnanolone is a metabolite of progesterone and a positive modulator of the GABAA receptor, enhancing the effects of GABA. meaning that women who are sensitive to ovarian hormones may also be sensitive to their metabolites. In a randomized, double-blind, placebo-controlled study, women with PMDD were treated with a steroid antagonist of allopregnanolone (UC1010) during the luteal phase. This drug significantly reduced PMDD scores on the DRSP by 75%, compared with 47% following treatment with placebo (p=0.006).7

    Further supporting the role of GABA in the etiology of PMDD is the finding that women with PMDD may have a deficiency of GABAergic inhibition in their cerebellum. A study using positron emission tomography (PET) scans to assess cerebral glucose metabolism and mood in women with and without PMDD. Plasma levels of ovarian hormones did not differ between the two groups, but women with PMDD showed an increase in cerebellar activity, though those in the control group did not. This increase in activity occurred during the luteal phase and was positively correlated with worsening of mood (p = 0.018).8

    Continue Reading: The Etiology of Premenstral Dysphoric Disorder by Dr. Edwin Raffi & Dr. Marlene Freeman

    Non-Pharmacologic Treatment for PMS and PMDD

    Monthly Mood Charting

    Keeping a monthly mood chart can be informative and even therapeutic for many women. In addition to confirming the diagnosis, many women feel better if they can identify the relationship between their cycles and mood changes and can thus anticipate times at which 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.9  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.10

    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.11

    Limited evidence suggests that magnesium (200-360 mg a day) and Vitamin E (400 IU a day) can provide modest relief of symptoms. However, there is not yet enough research to recommend these as effective treatments for PMDD.

    Herbal Remedies

    Herbal remedies may have some role in the treatment of premenstrual symptoms.  A recent systemic review of all randomized controlled trials using vitex agnus castus fruit extract, also known as chasteberry, concluded that it is a safe, efficacious treatment for PMS/PMDD symptoms. Though the RCTs examined had slightly different modes of chasteberry administration and outcome measures, the review found that chasteberry should be considered particularly for the alleviation of somatic PMS symptoms.12  However, another systemic review and meta-analysis suggested that there was considerable room for bias in these studies, and further research was needed in this area.13

    In another study, gingko biloba was found to improve PMS symptoms, particularly breast tenderness and fluid retention.14 Though early evidence suggested that evening primrose oil may be a useful treatment of PMS, a recent review of studies found that it was no more effective than placebo.15

    Other botanical remedies, including black cohosh, St. John’s Wort and Kava Kava, have been explored but the results have been mixed.  In women with PMS and PMDD, it appears that St. John’s Wort was superior to placebo for the treatment of physical symptoms but did not have a significant impact on depressive symptoms, anxiety or irritability.

    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.16

    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.17 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),18 venlafaxine (Effexor),19 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 entire menstrual cycle and typically do not respond well to intermittent dosing.20 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 in women who experience breakthrough symptoms during the luteal phase. 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 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 have 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 of 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.21,22

    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 (OCP) may have greater efficacy for treating PMS symptoms.23,24 However, in women with depressive disorders who suffer from premenstrual exacerbation of mood symptoms (breakthrough depressive symptoms during the premenstrual period), OCP augmentation of antidepressants was not found to be effective against these symptoms. The data did suggest a trend toward improvement in premenstrual DRSP scores for women with fewer lifetime depressive episodes, necessitating further studies of women with hormonal sensitivity and mood symptoms.25

    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. A recent study found that women on OCP were twice as likely to attempt or complete suicide compared to women who were not on OCP.26

    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 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.27

    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, unwanted hair growth (hirsutism) and weight gain.

    Surgical Intervention

    Women who have tried all of the above treatments and still suffer from severe PMDD symptoms may consider surgery. A Canadian review examined several studies in which women opted for hysterectomy and bilateral salpingo-oopherectomy (removal of the uterus, fallopian tubes and ovaries) with hormone add-back therapy. Satisfaction was very high with the procedure, which the author attributed to matching the right patient with the right treatment. Surgery was recommended for women who have completed their families and who found the side effects of antidepressants to be intolerable. If a 3 to 6 month trial of pharmacological ovarian suppression plus estrogen add-back dramatically improves PMDD symptoms, surgery may be considered if the woman is more than five years away from natural menopause. Though radical, surgery may be the best option for patients who see improvement with medical ovarian suppression but for whom the cost or inconvenience of monthly injections is prohibitive to continuing treatment. However, these women should continue receiving estrogen replacement therapy to prevent complications of menopause such as osteoporosis and heart disease.28

    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. Surgical removal of the uterus, fallopian tubes and ovaries may also be considered. Because these approaches induce 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.


    With link to a new page

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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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