eMedicine Specialties > Pediatrics: Surgery > Gynecology
Premenstrual Syndrome
Updated: Apr 13, 2009
Introduction
Background
Premenstrual syndrome (PMS) is a recurrent luteal phase condition characterized by physical, psychological, and behavioral changes of sufficient severity to result in deterioration of interpersonal relationships and normal activity. Premenstrual dysphoric disorder (PMDD) is considered a severe form of PMS.1,2
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), which are 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, alterations in the gamma-aminobutyric system (GABA), and hypoprolactinemia.3,4,5
Frequency
United States
Symptoms of PMS have been reported to affect as many as 90% of women of reproductive age sometime during their lives. Nearly 20% of women experience PMS; approximately 10% are affected severely. Studies indicate that 14-88% of adolescent girls have moderate-to-severe symptoms. Another 3-5% of women meet the criteria for PMDD. PMDD is reported to affect 3-8% of women of reproductive age.
Two risk factors for PMS are obesity and smoking. Research reveals that women with a body mass index (BMI) of 30 or above are nearly 3 times as likely to have PMS than women who are not obese. Women who smoke cigarettes are more than twice as likely to have more severe PMS symptoms.6,7,8,9
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 completely resolves at menopause.10
Clinical
History
Elicit a description of cyclic symptoms that occur before the menstrual period and resolve with menses from patients with suspected premenstrual syndrome (PMS).
- 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. Ask the patient to bring her lists to the next appointment.
- Instruct the patient to rate their symptoms according to severity (1 for mild, 2 for moderate, and 3 for severe). The categories of PMS symptoms are as follows:11,12,9,13
- 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
- PMS-A (anxiety)
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.12
Causes
- The definitive cause of PMS is unknown.
Differential Diagnoses
Somatoform Disorder: Pain
Other Problems to Be Considered
Depression
Premenstrual dysphoric disorder (PMDD)
Dysmenorrhea12,14
Workup
Laboratory Studies
- No laboratory studies currently reliably assist in the diagnosis of premenstrual syndrome (PMS).
Imaging Studies
- Imaging studies are not needed to make the diagnosis, but they may be helpful to exclude other etiologies.
Other Tests
- If depression is a concern, consider using a depression inventory to assess the patient.
Treatment
Medical Care
Medical care of premenstrual syndrome (PMS) is primarily pharmacological and behavioral, with an emphasis on relief of symptoms.
Surgical Care
In women who are severely affected, bilateral oophorectomy has been effective to alleviate symptoms because it renders the patient postmenopausal. A hysterectomy is not needed to gain the symptomatic relief. For obvious reasons, this therapy is not recommended for adolescents and young women.
Diet
Despite a lack of evidence that diet changes can definitively change PMS symptoms, healthy lifestyle recommendations benefit the patient overall, as well as give her a sense of control.
- Eating 4-6 smaller meals per day during the premenstrual period may be of benefit to reduce symptoms or food cravings.
- One study has shown that women with PMS typically consume more dairy products, refined sugar, and high-sodium foods than women without PMS. Therefore, many clinicians recommend reducing or eliminating these foods from the diet. Avoidance of salt, caffeine, alcohol, chocolate, and/or simple carbohydrates may improve symptoms.
- A written sheet with foods to avoid (cola, coffee, hot dogs, potato chips, canned goods) and foods to encourage (fruits, vegetables, milk, complex carbohydrates, high-fiber foods, low-fat meats) may help assist patients in food choices.15,16,17
Activity
Benefits of exercise include physical improvements as well as stress reduction.
- Regular aerobic exercise has been shown to decrease symptoms in some adolescents and young women.
- Preliminary studies suggest that yoga may also alleviate symptoms in some women.18
Medication
No single treatment is universally effective, and studies with all therapies have not produced consistent results. Current recommendations in the literature regarding oral contraceptive pills are conflicting.19,20,21,22,23,24,25,14,26,27,28,29,30,31,32,33,34,35,36,37,38,17,13,39,2,40
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 because of unknown effects on adolescent bone density.19
Leuprolide (Lupron), nafarelin (Synarel)
GnRH agonists. Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Dosing
Adult
Leuprolide acetate: 3.75 mg IM qmo or 11.25 mg IM q3mo for up to 6 mo
Nafarelin acetate: 1 spray (200 mcg) into 1 nostril every am and 1 spray into other nostril every pm; initiate treatment between days 2 and 4 of menstrual cycle for 6 mo
Pediatric
Not recommended for adolescents
Interactions
None reported
Contraindications
Documented hypersensitivity to GnRH or related products; pregnancy; pernicious anemia; undiagnosed abnormal vaginal bleeding
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May develop ovarian cysts; not for use if breastfeeding
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.
Danazol (Danocrine)
Synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action.
Dosing
Adult
200-400 mg PO qd
Pediatric
Not recommended for adolescents
Interactions
Decreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine or cyclosporine levels
Contraindications
Documented hypersensitivity; porphyria; pregnancy; lactating patients; undiagnosed abnormal vaginal bleeding
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Adverse effects include weight gain and androgenic activity, which limit its use; use with caution in those with migraine headaches, liver dysfunction, hemophilia, congestive heart failure, or seizure disorder
Nonsteroidal anti-inflammatory drugs (NSAIDs)
These agents are useful for managing the general aches, pains, and dysmenorrhea associated with PMS. The US Food and Drug Administration (FDA) has issued a warning regarding the increased risk of serious cardiovascular thrombotic events, myocardial infarction, and cerebrovascular events associated with cyclooxygenase-2 (COX-2) selective NSAIDs (eg, celecoxib, valdecoxib, and rofecoxib). Valdecoxib (Bextra) and rofecoxib (Vioxx) are no longer marketed. Nonselective NSAIDs (eg, ibuprofen, naproxen) also carry this risk. For more information, see the FDA Drug Information Page on COX-2 Selective and Nonselective NSAIDs.
Tolmetin (Tolectin), sulindac (Clinoril), diclofenac (Cataflam)
Acetic and salicylic acids NSAID derivatives. Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors.
Dosing
Adult
Tolmetin (Tolectin) 400 mg PO tid
Sulindac (Clinoril) 200 mg PO bid
Diclofenac (Cataflam) initial: 100 mg PO once, then 50 mg PO tid
Pediatric
Adolescents: Administer as in adults
Interactions
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE
Concomitant administration of low-dose aspirin with NSAIDs may result in an increased rate of GI ulceration or other complications, compared to use of NSAIDs alone
Clinical studies and postmarketing observations show that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients; this response has been attributed to inhibition of renal prostaglandin synthesis
May elevate lithium levels and reduce renal lithium clearance
May increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding) may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Contraindications
Documented hypersensitivity (eg, swelling, asthma, hives, urticaria or any form of angioedema); active GI bleed or active ulcer; cross allergenicity to aspirin
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts rarely occur and usually return to normal with ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia occurs
Ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), ketoprofen (Orudis)
Propionic acid NSAID derivatives. Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors.
Dosing
Adult
Ibuprofen (Motrin): 400 mg PO q6-8h
Naproxen (Naprosyn): 500 mg PO once, then 250 mg PO q6-8h
Naproxen sodium (Anaprox): 550 mg PO once, then 275 mg PO q 6-8h
Ketoprofen (Orudis): 75 mg PO tid
Pediatric
Ibuprofen (Motrin): 5-10 mg/kg/d PO divided q6-8h
Naproxen: 2.5-10 mg/kg/dose PO q8-12h
Ketoprofen (Orudis): 0.5-1 mg/kg PO q6-8h
Adolescents: Administer as in adults
Interactions
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors
Concomitant administration of low-dose aspirin with NSAIDs may result in an increased rate of GI ulceration or other complications, compared to use of NSAIDs alone
Clinical studies and postmarketing observations show that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients; this response has been attributed to inhibition of renal prostaglandin synthesis
May elevate lithium levels and reduce renal lithium clearance
May increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding) may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Contraindications
Documented hypersensitivity (eg, swelling, asthma, hives, urticaria or any forms of angioedema); active GI bleed or active ulcer; cross allergenicity to aspirin
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts rarely occur and usually return to normal with ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia is present
Mefenamic acid (Ponstel), meclofenamate (Meclomen)
Fenamate NSAID derivatives. Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors.
Dosing
Adult
Mefenamic acid (Ponstel): 500 mg PO once, then 250 mg PO q4-6h; alternatively, start with 250 mg PO q8h on day 16 of cycle, increase to 500 mg PO on day 19 of the cycle
Meclofenamate (Meclomen): 100 mg PO once, then 50-100 mg PO q6h
Pediatric
Adolescents: Administer as in adults
Interactions
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors
Concomitant administration of low-dose aspirin with NSAIDs may result in an increased rate of GI ulceration or other complications, compared to use of NSAIDs alone
Clinical studies and postmarketing observations show that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients; this response has been attributed to inhibition of renal prostaglandin synthesis
May elevate lithium levels and reduce renal lithium clearance
May increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding) may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Contraindications
Documented hypersensitivity (eg, swelling, asthma, hives, urticaria or any forms of angioedema); active GI bleed or active ulcer; cross allergenicity to aspirin
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts rarely occur and usually return to normal with ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia occurs
COX-2 Inhibitors
These drugs are alternatives to standard NSAIDS and work by inhibiting prostaglandin synthesis via inhibition of COX-2. The FDA has issued a warning regarding the increased risk of serious cardiovascular thrombotic events, myocardial infarction, and cerebrovascular events associated with COX-2 selective NSAIDs (eg, celecoxib, valdecoxib, and rofecoxib). Valdecoxib (Bextra) and rofecoxib (Vioxx) are no longer marketed. Nonselective NSAIDs (eg, ibuprofen, naproxen) also carry this risk. For more information, see the FDA Drug Information Page on COX-2 Selective and Nonselective NSAIDs.
Celecoxib (Celebrex)
Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus GI toxicity may be decreased.
Dosing
Adult
100 mg PO qd or bid
Pediatric
Adolescents: Administer as adults
Interactions
Coadministration with CYP2C9 inhibitors (eg, fluconazole) may cause increase in rofecoxib plasma concentrations because of inhibition of rofecoxib metabolism; coadministration of rofecoxib with rifampin may decrease rofecoxib plasma concentrations; antacids decrease bioavailability; coadministration may increase lithium levels; may decrease effect of loop diuretics; coadministration with warfarin may increase PT, INR, or bleeding episodes
Contraindications
Documented hypersensitivity (eg, swelling, asthma, hives, urticaria or any forms of angioedema); active GI bleed or active ulcer; cross allergenicity to sulfonamides (celecoxib) or aspirin
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention; caution in severe heart failure and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction, or in abnormal liver lab results; GI bleeding may occur
Diuretics
These agents are used for edema, bloating, weight fluctuations, and mastalgia of PMS.
Spironolactone (Aldactone)
Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Dosing
Adult
25 mg PO qd/qid for 2-3 d before the onset of symptoms
Pediatric
Not established
Interactions
May decrease effect of anticoagulants; potassium and potassium-sparing drugs (eg, triamterene, ACE inhibitors, amphetamines) may increase risk of hyperkalemia
Coadministration with alcohol, barbiturates, opioid analgesics, or benzodiazepines may increase risk of orthostatic hypotension
Spironolactone reduces the vascular responsiveness to pressor amines (norepinephrine); may increased responsiveness to nondepolarizing muscle relaxants (eg, tubocurarine)
Lithium should not be given with diuretics because of reduced renal clearance, thus increasing the risk of lithium toxicity
NSAIDs can reduce the diuretic, natriuretic, and antihypertensive effect
Contraindications
Documented hypersensitivity; anuria; renal failure; hyperkalemia
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for evidence of fluid or electrolyte imbalance, including hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia; caution in renal and hepatic impairment
Hydrochlorothiazide (HydroDiuril)
May be beneficial in reducing edema. Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.
Dosing
Adult
25 mg PO qd at onset and during menses; if needed, may increase to 50 mg/d
Pediatric
Adolescents: Administer as in adults
Interactions
Thiazides may decrease effects of anticoagulants, antigout agents, and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants
Contraindications
Documented hypersensitivity; anuria or renal decompensation
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal disease, hepatic disease, gout, diabetes mellitus, and erythematosus
Antidepressants
The selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac)13,39 and sertraline (Zoloft)23,35,40 are the first-line drugs for severe emotional symptoms.37 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.
SSRIs are greatly preferred over the other classes of antidepressants. Because the adverse effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.
Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
However, a study of more than 65,000 children and adults treated for depression between 1992 and 2002 by the Group Health Cooperative in Seattle found that suicide risk declines, not rises, with the use of antidepressants.27 This is the largest study to date to address this issue.
Currently, evidence does not associate obsessive compulsive disorder (OCD) and other anxiety disorders treated with SSRIs with an increased risk of suicide. For more information, see the FDA Web site on Antidepressant Use in Children, Adolescents, and Adults.
In July 2006 the FDA issued a Public Health Advisory highlighting the dangers of taking SSRIs and triptans (eg, sumatriptan) concurrently. As both of these drug classes increase levels of serotonin, simultaneous use of them may lead to serotonin syndrome. The FDA recommends that those who are taking both medications speak with their physician before stopping either medication.
Fluoxetine (Sarafem), sertraline (Zoloft)
SSRIs are used to treat premenstrual dysphoric disorder.
Dosing
Adult
Fluoxetine: 20-40 mg PO qd
Sertraline: 50-150 mg PO qd
Pediatric
Not established
Interactions
Inhibits CYP1A2, CYP2C9, CYP2C19, and CYP3A4 isoenzymes; increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAOIs, and highly protein-bound drugs; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan, 5-HT1 agonists [eg, sumatriptan]), discontinue other serotonergic agents at least 2 wk before SSRIs
Contraindications
Documented hypersensitivity; use of MAOIs within 14 d of initiating treatment
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Newborn infants exposed to SSRIs during the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding
Anxiety and insomnia; weight loss; caution in hepatic impairment and history of seizures; caution with known or suspected history of mania or hypomania (may precipitate mania)
Clomipramine (Anafranil)
A tricyclic antidepressant. Affects serotonin uptake whereas its metabolite desmethylclomipramine affects norepinephrine uptake.
Dosing
Adult
25-75 mg PO qd, given for the full cycle or half-cycle
Pediatric
Not established
Interactions
Barbiturates, phenytoin, and carbamazepine, decrease effects of clomipramine; clomipramine increases effects of anticholinergics, neuroleptic agents, sympathomimetics, alcohol and CNS depressants; toxicity of MAOIs increases with clomipramine; may partially depend on CYP3A4 for metabolism, caution with coadministration of inhibitors or inducers of this pathway
Contraindications
Documented hypersensitivity; recent myocardial infarction; use of MAOIs within 14 d of initiating treatment
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Myocardial infarction; nonspecific ECG changes and changes in AV conduction; heart block; arrhythmia; hypotension, particularly orthostatic hypotension; syncope; hypertension; tachycardia; palpitation have been reported
Caution in severe cardiopulmonary or renal impairment and inability to metabolize sorbitol
Nefazodone (Serzone)
Antidepressant unrelated to the other antidepressant classes. Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors.
Dosing
Adult
100-150 mg PO bid
Pediatric
Not established
Interactions
Coadministration with buspirone resulted in marked increases in plasma buspirone concentrations, thus, a low dose of buspirone (ie, 2.5 mg bid) is recommended; decreases effects of anticoagulants, oral hypoglycemics, diuretics, clonidine, methyldopa; increases effects of digoxin, carbamazepine, and MAOIs
Contraindications
Documented hypersensitivity; use of MAOIs within 14 d of initiating treatment
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cardiac disease, cerebrovascular disease or seizures; discontinue therapy and reevaluate if priapism occurs; liver failure resulting in transplantation or death have occurred rarely
Antianxiety agents
Alprazolam (Xanax) and buspirone (BuSpar) have been effective in helping the anxiety-related symptoms of PMS.
Alprazolam (Xanax)
A benzodiazepine antianxiety agent. Binds receptors at several sites within the central nervous system, including the limbic system and reticular formation. Effects may be mediated through GABA receptor system.
Dosing
Adult
0.25 mg PO bid/tid
Pediatric
Not established
Interactions
Carbamazepine and disulfiram decrease effects; toxicity increases with cimetidine, lithium, oral contraceptives, and CNS depressants (including alcohol)
Contraindications
Documented hypersensitivity; severe respiratory depression; narrow-angle glaucoma; preexisting hypotension
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Withdrawal symptoms, including seizures, have occurred 18 h to 3 d following abrupt discontinuation
Buspirone (BuSpar)
An antianxiety agent not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative or anxiolytic drugs. A 5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in CNS. Has anxiolytic effect but may take up to 2-3 wk for full efficacy.
Dosing
Adult
7.5 mg PO bid
Pediatric
Not established
Interactions
Coadministration with nefazodone, erythromycin, or itraconazole increase serum levels of buspirone (use low dose not exceeding 2.5 mg bid)
May cause hypertensive crisis with coadministration of MAOIs; toxicity increased with phenothiazines and CNS depressants; increases toxicity of digoxin and haloperidol
Contraindications
Documented hypersensitivity; use of MAOIs within 14 d of initiating treatment
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Interferes with motor performance; caution in hepatic or renal impairment
Nutritional supplements
Studies have shown that calcium and magnesium deficiency may play a role in PMS; therefore, supplementation is suggested.31,32,33
Calcium carbonate (Caltrate, Os-Cal)
Calcium moderates nerve and muscle-performance by regulating action potential excitation threshold.
Dosing
Adult
1200 mg PO qd
Pediatric
Adolescents: Administer as adults
Interactions
May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; large intakes of dietary fiber may decrease calcium absorption and levels
Contraindications
Renal calculi; hypercalcemia; hypophosphatemia; renal or cardiac disease; patients with digitalis toxicity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hypercalcemia or hypercalcuria may occur when therapeutic amounts are given
Magnesium (Almora, Magonate)
Selectively causes a depletion of brain dopamine, which may alter mood. The most common adverse effect is diarrhea. May use other PO supplements, including magnesium oxide or magnesium hydroxide.
Dosing
Adult
27 mg (as elemental magnesium) PO qd
Pediatric
Adolescents: Administer as adults
Interactions
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; also may worsen neuromuscular blockade observed with aminoglycosides, tubocurarine, vecuronium, and succinylcholine; magnesium may increase CNS effects and toxicity of CNS depressants, betamethasone, and ritodrine
Contraindications
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
May alter cardiac conduction, leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when administered parenterally; caution when administering magnesium dose because may produce significant hypotension or asystole
Contraceptive, Oral
Combination oral contraceptive agents have been pursued as treatment for PMS due to their ovulation suppression effects. However, studies have suggested that treatment with combination oral contraceptive agents does not significantly improve symptoms compared to treatment with placebo.38,18,24,2
Combination oral contraceptives (estrogen and progesterone)
Reduces secretion of LH and FSH from pituitary by decreasing amount of gonadotropin-releasing hormones.
Dysmenorrhea can be prevented altogether in some patients by use of OCs, although these agents are not approved by the FDA for this indication. OCs may be an appropriate treatment choice in patients who do not wish to conceive. The combination OCs suppress the hypothalamic-pituitary-ovarian axis and thereby inhibit ovulation and prevent PG production in the late luteal phase. This generally significantly reduces the amount of menstrual flow and effectively alleviates primary dysmenorrhea in most patients.
Combination OCs and depot medroxyprogesterone acetate provide effective pain relief and are associated with a reduced menstrual flow. The use of NSAIDs in combination with an OC may be necessary, especially during the first few cycles after initiation of the OC. The dose of ethinyl estradiol generally should be less than 50 mcg. A monophasic OC containing 30 mcg of ethinyl estradiol is a reasonable choice. To date, studies comparing the efficacy of various OC formulations in the management of dysmenorrhea have not been performed.
Dosing
Adult
Schedule 1 (Sunday starter): Begin dose on first Sunday after onset of menstruation; start that Sunday if menstrual period starts on Sunday
21-tab package: 1 tab qd for 21 d followed by 7 d off medication; new course begins on eighth d after taking last tab
28-tab package: 1 tab qd without interruption
Schedule 2 (Day 1 starter): Start dose on day 1 of menstrual cycle
21-tab package: 1 tab qd for 21 d followed by 7 d off medication; begin new course on day 8 after taking last tab
Continue dosing cycle if 1 period missed; pregnancy test required if 2 periods missed
Pediatric
Not established
Interactions
Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce enzymes that decrease levels of contraceptive steroids; PO anticoagulants may increase thromboembolic potential; antibiotics may alter GI flora and cause a reduction in absorption of oral contraceptives, which may reduce efficacy
Contraindications
Documented hypersensitivity, endometrial, and hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; smokers >35 y; cardiovascular disease
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in patients diagnosed with hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease
Follow-up
Further Outpatient Care
- Outpatient management primarily involves monitoring, a 2-month symptom diary and instituting further therapy as the symptoms warrant. Premenstrual syndrome (PMS) is a very difficult condition to treat and cannot be completely eradicated by any single therapy. Continued research in this area will hopefully lead to better treatment.
- Because of the difficulty in treating PMS and the variations in response to treatments experienced by patients, complementary and alternative strategies have been explored for patients with PMS. These include the following:
- Relaxation response: This technique consists of quiet sitting, progressive muscle relaxation, and the repetition of a constant stimulus, such as the word "one" during each inhale and exhale. Patients are recommended to practice for 10-20 minutes daily.
- Biofeedback and guided imagery
- Cognitive behavioral therapy and group therapy
- Light therapy: Bright-light therapy uses 10,000 lx cool-white fluorescent light daily for 30 minutes.
- Massage
- Chiropractic therapy
- Homeopathy and herbal medicines: Studies have examined the efficacy of various homeopathic and herbal medicines, including Crocus sativus L (saffron) and Chinese herbal medications. One study found that 90% of patients experienced improvement in symptoms following a homeopathic treatment regiment compared with 37.% of patients receiving placebo. Studies have concluded that these methods may be beneficial in symptom alleviation and that further research is warranted.41,42,43,39,36
Complications
- School absence
- Behavior problems
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, providing patient education regarding alternative therapies that may alleviate some symptoms is important.
- Behavioral counseling and stress management may help the patients regain control during times of high emotionalism.
- Relaxation techniques may also help. Areas of stress should be identified. Relaxation techniques such as yoga, biofeedback, and self-hypnosis may be beneficial.
- Regular exercise often decreases the symptoms of PMS.
- Patients should be counseled to avoid salt, caffeine, alcohol, and simple carbohydrates.
- For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Premenstrual Syndrome (PMS).
Miscellaneous
Medicolegal Pitfalls
- It is important to rule out other conditions that cause erratic or dysphoric behavior before diagnosing premenstrual syndrome (PMS). Rare conditions, such as temporal lobe epilepsy, may cause behavioral changes consistent with PMS. However, these behaviors should not cluster during the luteal phase.
- Some parents view their daughter's dysphoria as PMS instead of recognizing a more serious depression and suicidal ideation. In this situation, the parent often is looking for a way to avoid recognizing the possibility that their child is experiencing mental health symptoms. If the physician accepts this history uncritically, a serious depressive disorder may be misdiagnosed as PMS.
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Keywords
premenstrual syndrome, PMS, menstrual molimina, premenstrual tension, menses, period, menstrual period, menstruation, premenstrual dysphoric disorder, PMDD, PDD, hypoprolactinemia, obesity, smoking, mastalgia, edema, difficulty sleeping, tense feelings, irritability, clumsiness, mood swings, headaches, cravings, depression, weight gain, abdominal bloating, breast tenderness, dysmenorrhea, hot flashes, frequent urination, upper respiratory infection
Contributor Information and Disclosures
Author
Megan A Moreno, MD, MEd, MPH, Assistant Professor, Department of Pediatrics, Section of Adolescent Medicine, University of Wisconsin-Madison School of Medicine and Public Health
Megan A Moreno, MD, MEd, MPH is a member of the following medical societies: Society for Adolescent Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Ann E Giesel, MD, Clinical Associate Professor, Division of General Pediatrics, Section on Adolescent Medicine, University of Washington
Ann E Giesel, MD is a member of the following medical societies: Society for Adolescent Medicine and Washington State Medical Association
Disclosure: Nothing to disclose.
Cara Beth Rogers, University of Rochester
Disclosure: Nothing to disclose.
Liana Roxanne Clark, MD, Assistant Professor, Department of Pediatrics, Craig-Dalsimer Division of Adolescent Medicine, The Children's Hospital of Philadelphia
Liana Roxanne Clark, MD is a member of the following medical societies: American Academy of Pediatrics and Society for Adolescent Medicine
Disclosure: Nothing to disclose.
Medical Editor
Elizabeth Alderman, MD, Director of Fellowship Training Program, Director, Adolescent Ambulatory Service, Clinical Professor, Department of Pediatrics, Division of Adolescent Medicine, Albert Einstein College of Medicine and Montefiore Medical Center
Elizabeth Alderman, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, North American Society for Pediatric and Adolescent Gynecology, and Society for Adolescent Medicine
Disclosure: Nothing to disclose.
Pharmacy Editor
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Managing Editor
Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati
Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
CME Editor
Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting
Chief Editor
Andrea L Zuckerman, MD, Assistant Professor of Obstetrics/Gynecology and Pediatrics, Tufts University School of Medicine; Division Director, Pediatric and Adolescent Gynecology, Tufts Medical Center
Andrea L Zuckerman, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, North American Society for Pediatric and Adolescent Gynecology, and Society for Adolescent Medicine
Disclosure: Nothing to disclose.
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