Pathophysiology: Incorrect older theories about the causes of PMS include an estrogen excess, estrogen withdrawal, progesterone deficiency, pyridoxine (vitamin B-6) deficiency, alteration of glucose metabolism, and fluid-electrolyte imbalances. Current research provides some evidence supporting the following etiologies:

• Serotonin deficiency is postulated because patients who are most affected by PMS have differences in serotonin levels. The symptoms of PMS can respond to selective serotonin reuptake inhibitors (SSRIs), ie, medications that increase the amount of circulating serotonin.
• Magnesium and calcium deficiencies are postulated as nutritional causes of PMS. Studies evaluating supplementation show improvement in physical and emotional symptoms.
• Women with PMS often have an exaggerated response to normal hormonal changes. Although their levels of estrogen and progesterone are similar to women without PMS, rapid shifts in levels of these hormones promote pronounced emotional and physical responses.
• Other theories under investigation include increased endorphins and hypoprolactinemia.

Frequency:

• In the US: Nearly 30% of women experience PMS. Approximately 10% are affected severely. Recent studies indicate that 14-88% of adolescent girls have moderate-to-severe symptoms. Another 3-5% of women meet criteria for premenstrual dysphoric disorder (PDD).

Mortality/Morbidity: Inability to maintain normal activities is part of the definition of this disease; hence, morbidity is related to loss of function.

Sex: By definition, females are affected.

Age: PMS affects women with ovulatory cycles. Older adolescents tend to have more severe symptoms than younger adolescents. Women in their fourth decade of life tend to be affected most severely. PMS resolves completely at menopause.

History:

• Elicit from the patient a description of cyclic symptoms occurring before the menstrual period that resolve with menses.

  To establish the diagnosis, instruct patients to chart symptoms daily for 2 cycles. This usually demonstrates symptoms clustering around the luteal phase of ovulation, with resolution when menses begins.

  Advise the patient to use a numeric scoring system (1 for mild, 2 for moderate, 3 for severe) when recording symptoms (Table 1). Ask the patient bring her lists to the next appointment.

  Table 1. PMS Symptoms Grouped by Type (Instruct the patient to rate the symptoms in each category on a chart (1 for mild, 2 for moderate, 3 for severe.)

  Category	Symptoms
  PMS-A, anxiety	Difficulty sleeping, tense feelings, irritability, clumsiness, mood swings
  PMS-C, craving	Headache, cravings for sweet foods, cravings for salty foods, cravings for other types of food
  PMS-D, depression	Depression, angry feelings for no reason, feelings that are easily upset, poor concentration or memory, feelings of low self-worth, violent feelings
  PMS-H, hydration	Weight gain, abdominal bloating, breast tenderness, swelling of extremities
  PMS-O, other	Dysmenorrhea, change in bowel habits, frequent urination, hot flashes or cold sweats, general aches or pains, nausea, acne, allergic reactions, upper respiratory infections

Physical:

• Usually, no physical findings are specifically helpful in establishing the diagnosis of PMS. If the adolescent presents during the luteal phase, she may have mastalgia or edema of the breasts or legs.

Causes:

• The definitive cause of PMS is unknown.

Other Problems to be Considered:

Depression
Premenstrual dysphoric disorder

Lab Studies:

• No laboratory studies currently exist to reliably assist in the diagnosis of PMS.

Imaging Studies:
 

• Imaging studies are not needed to make the diagnosis, but they may be helpful to exclude other etiologies.

Medical Care: Medical care is primarily pharmacological and behavioral, with an emphasis on relief of symptoms.

Surgical Care: In women who are affected severely, a total hysterectomy with bilateral oophorectomy has been effective to alleviate symptoms. For obvious reasons, this therapy is not recommended for adolescents and young women.

Diet: Avoidance of salt, caffeine, alcohol, and/or simple carbohydrates may improve symptoms.

No single treatment is universally effective, and studies with all therapies have produced conflicting results. Ineffective therapies include pyridoxine (vitamin B-6) supplementation, progesterone suppositories, and oral contraceptives. Many health care providers continue to use oral contraceptives in their patients with PMS, with little benefit. Some women's symptoms have even worsened with oral contraceptive use.
Drug Category: Gonadotropin-releasing hormone (GnRH) agonists -- These drugs act as potent inhibitors of gonadotropin secretion by binding competitively on GnRH receptors. They cause suppression, or down-regulation, of gonadotropins and, consequently, suppress ovarian and testicular steroidogenesis. This results in a hypoestrogenic state. The effects are reversible with discontinuation of drug therapy. GnRH agonists are not recommended for use in adolescents.

Drug Category: Pituitary-ovarian axis suppressants -- These synthetic steroids probably work by a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and the interaction of the drug with sex hormone receptors. Depresses the output of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Not recommended for use in adolescents.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Useful for managing the general aches, pains, and dysmenorrhea associated with PMS.

Drug Category: Cyclooxygenase-2 (COX-2) inhibitors -- These drugs are alternatives to standard NSAIDS and work by inhibiting prostaglandin synthesis via inhibition of COX-2.

Drug Category: Diuretics -- Used for edema, bloating, weight fluctuations, and mastalgia of PMS.

Drug Category: Dopamine agonists -- Bromocriptine may be helpful in the treatment of severe mastalgia not responsive to NSAIDs.

Drug Category: Antidepressants -- The SSRIs, fluoxetine (Prozac) and sertraline (Zoloft), are the first-line drugs for severe emotional symptoms. They work best when taken throughout the month. Clomipramine (Anafranil) given for the full cycle or half-cycle has been effective in treatment of emotional symptoms. Nefazodone, an antidepressant that blocks serotonergic and noradrenergic uptake, recently was shown to be effective in relieving symptoms.

Drug Category: Antianxiety agents -- Alprazolam (Xanax) and buspirone (BuSpar) have been effective in helping the anxiety-related symptoms of PMS.

Drug Category: Nutritional supplements -- Recent studies have shown that calcium and magnesium deficiency may play a role in PMS; therefore, supplementation is suggested.

Further Outpatient Care:
 

• Outpatient management primarily involves monitoring, a 2-month symptom diary and instituting further therapy as the symptoms warrant. PMS is a very difficult condition to treat and cannot be completely eradicated by any single therapy. It is hoped that continued research in this area will lead to better treatment.

Prognosis:

• Most PMS symptoms worsen with the patient’s age until menopause; thus, little good news can be given to severely affected adolescents.

Patient Education:

• Because PMS may cause major morbidity for the adolescent, it is important to provide patient education regarding alternative therapies that may alleviate some symptoms.

• Behavioral counseling and stress management may help the patients regain control during times of high emotionalism. Relaxation techniques also may help. Patients should be counseled to avoid salt, caffeine, alcohol, and simple carbohydrates.

• Regular exercise often decreases the symptoms of PMS.