Premenstrual Syndrome

Women's Health & Education Center Contribution

The definition of Premenstrual Syndrome (PMS) has been elusive because this condition is characterized by a wide variety of symptoms, most of which are immeasurable by objective standards. Any combinations of emotional or physical signs or symptoms that occur cyclically prior to menstruation and then regress or disappear during or after menstruation. Description of PMS can be traced at least as far back as the writings of Hippocrates. Modern investigation of PMS began in 1931 when the entity of "premenstrual tension'' was described. Premenstrual emotional changes and physical changes occur in up to 80% of women of reproductive age. Estimates regarding the incidence of PMS generally agree that 20-40% of these women experience some difficulty as a result of these changes during the premenstrual interval, and 2.5-5% report a significant impact on work, lifestyle, or relationships.

Etiology:
A single cause for PMS has not been identified. Multiple factors have been proposed, but 50 years of investigation have failed to provide a uniform hypothesis for the pathophysiology of PMS. Since the symptoms occur prior to menses and resolve following menstrual bleeding, PMS has been blamed on alterations in luteal estrogen or progesterone levels. No convincing association has been demonstrated between androgens and prolactin levels.

Since PMS is often associated with complaints of bloating and fluid retention, mineralocorticoid changes have been suspected as a potential cause. Other theories are, hypoglycemia, endorphin hypothesis, prostaglandin hypothesis and vitamin and mineral deficiencies.

Psychologic Hypothesis: Because many of the significant changes of PMS strongly suggest an affective disorder, an underlying psychological abnormality has been sought as the primary problem in PMS. Approximately 60% of women with a major affective disorder have been diagnosed as having a premenstrual affective syndrome. At least 30% of women with primary recurrent depression experience their first depressive episode during a time of significant hormonal change. In a psychological review of women with PMS, between 57% and 100% of women were found to have a prior major depressive episode at least once in their lives in contrast to only 0% to 20% of women without PMS.

Symptoms Associated With PMS:
Since the original description of PMS by Frank (1931), approximately 150 symptoms have been included in the list of possible premenstrual syndrome. It is any combination of emotional and physical signs or symptoms that occur cyclically prior to menstruation and then regress or disappear during or after menstruation.

Affective Symptoms: Sadness, Anxiety, Anger, Irritability, Labile mood
Cognitive Symptoms: Decreased concentration, Indecision, Paranoia, Rejection-sensitive, Suicidal ideation
Pain: Headache, Breast Tenderness, Joint and muscle pain
Neurological Symptoms: Insomnia, Hypersomnia, Anorexia, Food craving, Fatigue, Lethargy, Agitation, Libido change
G.I. Symptoms: Nausea, Diarrhea, Palpitations, and Sweating
Central Nervous System: Clumsiness, Seizures, Dizziness, Vertigo, Paresthesia, and Tremors
Fluid/Electrolyte: Bloating, Weight Gain, Oliguria, Edema
Dermatological: Acne, Oily skin, Greasy hair, and Dry hair, Hirsutism

Diagnosis:
Making the diagnosis of PMS has been problematic, since its specific etiology is unknown and there is no objective marker which can quantitate the existence or the severity of symptomatology or even the objective response to therapy.

A Practical Approach to PMS:

  • History and Physical Examination
  • Endocrine tests: Thyroid Function Test, Thyroxine, Prolactin
  • Tests to rule out Dysmenorrhea and Endometriosis
  • Daily symptom questionnaire, prospective symptoms
  • Exercise and dietary counseling
  • Psychologic counseling

Treatment:
The cornerstone of treatment for PMS remains a careful evaluation of symptoms and their chronicity. Since the placebo-response rate in women with PMS is high in virtually all studies, conservative supportive therapy may be effective in many patients.

  1. Exercise: Clinical studies of exercise demonstrate reduction in anger and depression in women who exercise. It has a profound effect on the hormones like cortisone, testosterone, prolactin, estrogens, and growth hormones.
  2. Nutrition: It is unclear whether dietary changes offer a medicinal effect or placebo effect. Some studies show tea consumption and high carbohydrate diet during premenstrual phase is helpful. Some recommend vitamins as part of the treatment, especially vitamin B6. Doses in excess of 100 mg/d may cause medical harm, including peripheral neuropathy. One large multicenter well-designed trial of 466 women with PMS reported that 1,200 mg/d of calcium carbonate was efficacious in reducing total symptom scores. Two small trials have found that 200-400 mg of magnesium may be somewhat effective.
  3. Pharmacology Therapy: The Pharmacological approach to PMS remains both empiric and controversial. The following medications have been tried: GnRH-agonist (Lupron), Danazol, Oral Contraceptives, and Progestins. When the psychological symptoms predominate, specific anxiolytics or antidepressants are indicated. Recent anecdotal success with fluoxetine (Prozac) is encouraging. Other medications used are lithium, alprazolam (Xanax) sertraline (Zoloft), and buspirone (Buspar).
    Selective Serotonin Reuptake Inhibitors (SSRIs): The SSRIs are the initial drugs of choice for severe PMS. Fluoxetine is the most studied drug of this group and dosages of 20-60 mg/d are recommended to relieve the symptoms. Another SSRI drug that has a beneficial effect is sertraline (Zoloft) and it is usually given in doses ranged between 50 to 150 mg/d. Intermittent therapy with an SSRI is given only during the symptomatic phase is also efficacious. The drug is started between 7 and 14 days before the next menstrual period, with the start day individualized to begin the medication at or just before the expected onset of symptoms. Side effects associated with fluoxetine include headaches, nausea, and jitteriness. Insomnia often can be avoided by early morning dosing or if appropriate by lowering the dosage. Decreased libido also is problematic in some patients. In cases in which improvement of libido is not seen after dosage changes, alternative therapies may be considered.
    Oral Contraceptives: Although oral contraceptives are widely prescribed for the treatment of PMS, few data support their effectiveness. The evidence suggests that oral contraceptives should be considered if symptoms are physical, but may not be effective if mood symptoms are more prevalent.
    Gonadotropin-Releasing Hormone Agonists (GnRH): The hypoestrogenic side effects and cost of GnRH agonists limit the usefulness of this method except in severe cases of PMS unresponsive to other treatment. If this therapy is to be used for more than a few months, bone loss becomes a concern. Add-back therapy also may result in the return of the symptoms.
  4. Surgical Therapy: In severe cases of PMS, surgical oophorectomy or hysterectomy with removal of ovaries has been used successfully in women who no longer desire preservation of fertility.

Summary:
The following recommendations are based on good and consistent scientific evidence:

  • Women in whom PMS has been diagnosed should meet standard diagnostic criteria and should have the timing of their symptoms confirmed using a prospective symptom calendar.
  • Risk factors such as increased imposed stress and specific personality profiles are not helpful in differentiating women with PMS from those without PMS.
  • The SSRIs, particularly fluoxetine and sertraline, have shown to be effective in treating PMS. The bulk of scientific evidence does not support the usefulness of natural progesterone or primrose oil in the treatment on PMS.

The following recommendations are based primarily on consensus and expert opinion:

  • Supportive therapy is central to the management of all PMS patients.
  • Aerobic exercise should be recommended to PMS patients.
  • As an overall clinical approach, treatments should be employed in increasing orders of complexity. Using this principle, in most cases, the therapies should be used in the following order:

    Step 1. Supportive therapy, complex carbohydrate diet, aerobic exercise, nutritional supplements (calcium, magnesium, vitamin E), spironolactone.

    Step 2. The SSRIs (fluoxetine or sertraline) as the initial choice; for women who do not respond, consider an anxiolytic for specific symptoms.

    Step 3. Hormonal ovulation suppression (oral contraceptives or GnRH agonists).

Women's Health & Education Center
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Springfield, MA 01104
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