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Premenstrual Syndrome
Susan Johnson, MD, MS

he symptoms of premenstrual syndrome may be mild and merely annoying or severe enough to cause impairment. They fall into two broad categories: psychological/emotional (e.g., irritability) and physical (e.g., breast
tenderness). Most women who seek treatment have mood symptoms; however, some patients present with physical symptoms as their primary complaint. Every primary care physician who cares for women should be familiar
with the diagnostic approach to this complaint, as well as the most common
differential diagnoses and the most effective approaches to therapy.

Terminology
Most women who ovulate experience one or more potentially adverse symptoms that recur in the late luteal (premenstrual) phase of the cycle. The most
common symptoms are irritability, mood lability, breast tenderness, food
cravings, sleep disturbance, fatigue, headache, and bloating. The majority of
women experience three or four mild symptoms for a only few days, and there
is no great effect on their life; these common, nonproblematic symptoms are
referred to as the molimina. The clinically relevant luteal phase syndromes
discussed in this chapter, on the other hand, are typically characterized by a
larger number of symptoms that last longer and are more intense.
A variety of diagnostic labels have been used for these clinically relevant
luteal phase symptoms over the past century (1). In the early part of the 20th
century, a syndrome called premenstrual tension was first described, and that
label was most often used in the United States until the 1970s, when premenstrual syndrome emerged as the more common term. In the 1980s the American Psychiatric Association added to the appendix of DSM-III diagnostic
125

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criteria for severe luteal phase symptoms, labeling this condition late luteal
phase dysphoric disorder. In DSM-IV-R, these criteria were slightly revised,
and the name was changed to premenstrual dysphoric disorder (PMDD) (2).
Although the existence of a less severe syndrome, premenstrual syndrome
(PMS), is mentioned in the discussion section for PMDD, specific diagnostic
criteria were not defined except to say that in PMDD the salient symptoms are
the mood problems, whereas in PMS physical symptoms play a larger role.
For the clinician, the distinction between PMS and PMDD (if there is one!)
is not particularly important. The PMDD label is used to describe severe luteal
phase symptoms that lead to impairment, but many women with less severe
symptoms, who are merely annoyed but not impaired, also seek treatment.
The diagnostic approach is the same for all levels of problematic symptoms,
and the same range of treatments should be considered (3). Thus, in this chapter, PMS/PMDD is used when the discussion is relevant to all levels of severity.

Clinical Criteria
Women with PMS/PMDD experience a cluster of symptoms that recur in the
luteal phase and remit in the follicular phase of the menstrual cycle; these
symptoms cannot be explained by another psychiatric or medical disorder (4).
PMS/PMDD are distinguished from molimina by the fact that the woman experiences some level of discomfort (1 week) (PMS) and/or impairment
(PMDD) as a result. Thus the key diagnostic criteria are the presence of symptoms
that are typical for this syndrome, the prospective verification that symptoms
are confined to the luteal phase, and the presence of impairment or discomfort.
The symptoms associated with PMS/PMDD are affective (irritability, mood
swings, depression, and hostility), somatic (bloating, mastalgia, appetite
changes, hot flashes, insomnia, headache, and fatigue), cognitive (confusion
and poor concentration), and behavioral (social withdrawal, hyperphagia, and
arguing). Ovulation, which is the event that initiates the luteal phase, typically occurs 2 weeks before the onset of menstrual flow, and symptoms typically begin 1 to 2 weeks before menses. Because the symptoms are not unique
to PMS/PMDD, psychiatric disorders (e.g., depression, anxiety) or medical disorders (e.g., migraine, irritable bowel syndrome, hypothyroidism) must be
differentiated from it.
The timing of symptoms should be confirmed with a prospective symptom
record (charting) kept by the patient for at least two menstrual cycles. In the
classic pattern, symptoms begin at or after ovulation and begin to resolve with
the onset of menstrual flow. Charting is required by the DSM-IV criteria for
PMDD because of data suggesting that more than half of the women who present
with a specific complaint of PMS are found not to have a pure luteal phase

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pattern based on prospective charting and thus have some other explanation for
all or some of their symptoms. In addition, the charting period is an excellent
time to introduce self-help strategies independently of other therapy. Because as
many as 30% of women will respond to these approaches, deferring the decision
about pharmacological therapy for two months is acceptable to most patients.
There is no standardized method of measuring symptom severity. For the
diagnosis of either PMS or PMDD to be plausible, there must be at least a 30%
increase in severity of symptoms during the luteal phase as compared with
the follicular phase. Problems with relationships at home and at work, parenting, and work performance can be assessed to determine the extent to
which the patients life is disrupted. The sole fact that a woman seeks treatment implies a certain level of severity.

Epidemiology
Prevalence
Symptoms that occur repetitively during the luteal (premenstrual) phase of
the cycle are nearly universal among women who ovulate. The number, severity, and duration of these symptoms determine whether an individual woman
has a clinically definable syndrome (PMS or PMDD) for which she may seek
treatment or has symptoms that she simply considers part of her normal
menstrual experience.
Based on several large cross-sectional epidemiological studies, it appears that
80% or more of ovulating women experience some level of adverse luteal phase
symptoms. For the majority, the symptoms are mild, last only a few days, and
are not bothersome; as mentioned previously, these symptoms are sometimes
referred to as the molimina (5). At the other end of the spectrum, for 5%-10%
of ovulating women the symptoms are numerous, severe, and last nearly the
entire luteal phase of approximately 2 weeks per cycle; this group would now be
characterized as having premenstrual dysphoric disorder (PDD) as defined in
the DSM-IV appendices. The third group, in the middle, might best be described
as having a week or more of the same sort of symptoms, annoying but not the
cause of significant disruption of relationships, work, or other life activities;
this group would now be described as having premenstrual syndrome (PMS).

Risk Factors
Luteal phase symptoms are found among women of all ages, but in clinical
practice the majority of women who seek care are over 30 years of age. Usually
they describe having had symptoms for several years, so it is not clear if

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PMS/PMDD worsen with age or if older women are simply more likely to ask
for help for this kind of problem.
No difference in prevalence has been found based on racial/ethnic, socioeconomic, or marital status. Women in developing cultures and women in developed countries have similar rates of severe symptoms.

Comorbidity
There is a higher rate of major depressive disorder and, probably, of postpartum depression among women with PMDD. These syndromes have not
been associated with any other reproductive history characteristics, such as
menstrual cycle length, amount of flow, presence or absence of dysmenorrhea, previous use of oral contraceptives, or tubal sterilization.

Pathophysiology
Based on studies of the effect of ovulation suppression, ovulation is a prerequisite for the occurrence of PMS/PMDD. The exact sequence of events from
ovulation to the emergence of symptoms is not known. The practical implication of this finding is that women who are post-menopausal, amenorrheic or
anovulatory, or who have had their ovaries removed by definition cannot have
PMS/PMDD.
Substantial evidence suggests that many women with PMDD experience a
decline in serotonin during the luteal phase; this is supported by the effectiveness of the SSRI drugs in treating these syndromes (6). Other central transmitters may be involved as well, such as MSH and endorphins.
Some investigators have speculated that PMS/PMDD is simply a variant of
major depressive disorder, but this view is not the prevalent theory based on the
fact that there are several important differences between these syndromes (7).

Differential Diagnosis
The symptoms of PMS/PMDD are not unique, and clinicians must be familiar
with the differential diagnoses in the woman who presents with a constellation of complaints that may be PMS/PMDD.

Menstrual Magnification of a Mood Disorder

Of women who seek treatment in specialty clinics for premenstrual disorders, the
majority are found to have some other mood disorder, predominately depression.
The confusion is caused by the fact that many women with a mood disorder

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(major depressive disorder, dysphoric disorder, bipolar disorder, and depression not otherwise specified; or an anxiety disorder) commonly experience a
worsening of symptoms just before or during menses, a phenomenon often
referred to as menstrual magnification (8). The key to identifying this problem is the presence of symptoms in the follicular phase of the cycle (i.e., in
the week after menses). Another common clinical presentation is a woman
who is being treated with serotonin reuptake inhibitors for a diagnosis of depression and is doing well except during the late luteal/menstrual phase,
when her symptoms re-emerge each month.

Medical Conditions
Many medical conditions can become entrained in the menstrual cycle,
such that the symptoms specific to these conditions are manifested exclusively or more commonly in the late luteal or menstrual phase. The most
common example is migraine headaches; 5% of women with migraines experience them exclusively in the late luteal phase (so-called menstrual migraines), and many more women report that their migraines increase in
frequency or severity at that time. Many other conditions have been reported
during the late luteal phase, including herpes, diabetes, asthma, and even
coronary heart disease.
The key to diagnosis in these cases is to recognize that the symptoms are
characteristic of the specific condition, not of PMS/PMDD. The initial treatment approach should be whatever is usual for the condition. For example,
for menstrual migraine, the usual abortive therapies are the first step, with
the usual prophylactic medications as needed (9). If, however, the usual therapies are not sufficient to eliminate late luteal phase symptoms, ovulation
suppression may need to be considered (10).

Diagnosis
Making a diagnosis and devising a treatment plan for most women with probable PMS/PMDD is usually straightforward (11,12). The diagnostic evaluation
should involve two clinic appointments separated by two menstrual cycles
(Table 6-1). At the first visit, the presenting symptoms (Table 6-2) are evaluated and a differential diagnosis is developed. During the next two cycles, the
woman is asked to keep a daily symptom record (charting), and the physician
obtains any indicated referrals or diagnostic test results. At the second visit,
all information is reviewed, and a management plan is formulated.
As mentioned earlier, because PMS/PMDD symptoms are not unique to this
syndrome, other disorders must be considered. Charting should demonstrate

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Table 6-1

Diagnostic Evaluation of PMS/PMDD

At the first visit:

1. Determine the range of symptoms and decide if consistent with PMS.
2. Based on the history and physical examination, decide if some other diagnosis should also
be considered.
3. Obtain any laboratory tests or consultations needed to assess additional diagnoses under
consideration.
Refer: Severe mood symptoms (vegetative symptoms, suicidal ideation, unable to function)
Between the first and second visit:
4. Have the patient, over a two-month period, record daily the presence or absence of the
relevant symptoms, as well as the dates of her menstrual periods.
5. Recommend that the patient try lifestyle and nutritional interventions.
At the second visit:
6. Assess the symptoms pattern on the menstrual calendar and determine if consistent with
PMS. If not, pursue other diagnoses. If consistent with PMS, and nonpharmacological
therapy has not been effective, proceed to drug therapy.
Refer: Failure to respond to Level 1 and 2 therapies (Fig. 6-1) or if hysterectomy is being
considered

Table 6-2

Common Symptoms of PMS/PMDD

Irritability
Mood lability
Anxiety
Depression
Unprovoked crying
Hostility

Breast tenderness
Fatigue
Food cravings
Difficulty concentrating
Headaches
Mental fuzziness
Bloating
Aches and pains
Sleep disturbance (middle-of-night awakening)

that symptoms occur during the luteal phase only; another symptom pattern
would suggest a different cause for the symptoms. Another diagnosis should be
entertained in women who are postmenopausal, anovulatory, or amenorrheic.
There are no laboratory tests that confirm the diagnosis of PMS/PMDDit is
a clinical diagnosis. Specifically, there is no value in obtaining levels of any of the
reproductive hormones (estradiol, progesterone, FSH, LH, testosterone, etc.),
because these levels do not vary between women with and without PMS/PMDD.
If the clinical picture suggests that a medical condition may explain the cyclic
symptoms in an individual woman, appropriate tests should be performed.

Treatment
In the last decade, the pharmacological treatment of PMS has undergone a revolution because of the development of uniform operational diagnostic criteria
and the use of placebo-controlled randomized clinical trials. Commonly used

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therapies, such as natural progesterone, vitamin B6, vitamin E, evening primrose oil, and diuretics, have been shown to be ineffective, and oral contraceptives have been shown primarily helpful for physical symptoms. The remainder
of this chapter describes therapeutic strategies that have been found effective.
Once an accurate diagnosis is made, appropriate interventions should be based
on two principles. First, PMS is a chronic problem that typically does not resolve
until menopause, making both cost and side effects important components of
the treatment choice. Second, women experience different degrees of symptom
severity, and the intensity of the treatment approach should be matched to the
symptoms. For example, for women with mild symptoms, lifestyle and nutritional
supplement therapies are a more appropriate starting place than SSRI therapy.
An overview of the treatment approach to PMS is shown in Figure 6-1.
Most women seek treatment as a result of problems with mood (irritability,
mood lability, etc.), and the following treatment approaches are targeted primarily at these symptoms. For most of these treatments, however, there is a
concomitant improvement in physical symptoms as well. The problem of isolated (or remaining) physical symptoms is addressed later in this chapter.

LEVEL 1 Lifestyle and over-the-counter drugs

1. Exercise, nutritional changes, mineral supplements

2. Herbal agents (St. Johns wort, chasteberry fruit)

LEVEL 2 (When mood symptoms are the prominent feature)

1. Symptom day only selective serotonin reuptake inhibitor (SSRI)

2. Daily SSRI

3. If the initial SSRI is ineffective or not tolerated, move to a trial of at least 2

additional SSRI agents before abandoning this approach

Buspirone in the luteal phase

LEVEL 2 (When physical symptoms are the prominent feature, add to above or give
alone)
Spironolactone daily (especially for breast tenderness and bloating)

Oral contraceptives (especially for breast pain, abdominal pain)

NSAIDs in the luteal phase (all physical symptoms except breast pain)

LEVEL 3 Ovulation suppression (refer)

Figure 6-1 Hierarchical treatment approach to premenstrual syndrome. Move to the next
level, or the next method within a level, if the current approach is ineffective over 2 to 3 cycles.

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For most women it is reasonable to recommend exercise, dietary changes,

and nutritional supplements as initial therapy. With this approach, approximately one third of women seeking treatment improve enough to not need
prescription drug therapy.

Exercise
Regular moderate aerobic exercise has been shown in epidemiological studies
to be associated with less severe premenstrual symptoms. In the single randomized trial, a group of sedentary women with PMS were randomly assigned to
regular walking or continuation of usual activity for 6 months (13). The active
group reported fewer symptoms at the end of the trial. A reasonable initial regimen for sedentary women is 30 minutes of brisk walking five times a week.

Diet
An increase in complex carbohydrate intake during the luteal phase has been
shown in two randomized trials to reduce the severity of premenstrual mood
symptoms (14). The commonly given advice to avoid sugar is the inverse of
this advice, but there are no data to support it.
The role of caffeine in premenstrual symptoms is unclear. Observational
studies have found that women who report the most severe premenstrual
symptoms also report the highest caffeine intake, but it is unclear whether the
caffeine is causative, aggravates existing symptoms, or is actually being used as
self-treatment for the common symptoms of fatigue and reduced concentration. A trial of reducing or eliminating caffeine for several cycles is reasonable.
The role of sodium is purely anecdotal and probably derives from the belief
that the symptoms of bloating and weight gain are due to salt or at least can
be improved by reducing its intake. As with caffeine, it may be reasonable to
have women experiment with reducing dietary salt, but to continue this practice only if improvement is noted.

Nutritional Supplements
Mineral Supplements

Calcium and magnesium supplements have each been shown to reduce emotional and luteal phase symptoms. Most of the data are with calcium. In the
largest randomized trial, 497 symptomatic women were randomized to either
placebo or 1200 mg of calcium carbonate taken daily (15). Forty percent of
the women were taking oral contraceptives. After 3 months, there was an
overall 48% reduction in total symptom scores from baseline in the active
therapy group compared with a 30% reduction in the placebo group. Calcium
has never been compared directly to SSRI therapy, but most experts believe

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that calcium supplements are probably most effective in women with mild-tomoderate symptoms.
Magnesium (as magnesium pyrrolidine carboxylic acid 360 mg) has been
studied in one small randomized trial with similar results (16). Calcium is the
preferred choice because of the concomitant bone benefit, but for women who
do not tolerate calcium, daily magnesium 400 mg is an alternative.
Herbal Remedies and Other Supplements

Girman et al. have written an excellent review of all the herbal preparations
that have been used for premenstrual symptoms (17), to which interested
readers are referred. To summarize their findings, based on an extensive literature review these authors conclude that evening primrose oil and vitamin B6
are unlikely to be of significant benefit for luteal phase symptoms. Black
cohosh, ginko, and kava may be of benefit, but they have not been adequately
tested in placebo-controlled trials. Of these, kava (hepatotoxicity), St. Johns
wort (drug-drug interaction), and ginko (drug-drug interaction) can be associated with potentially severe side effects.
St. Johns wort (SJW), whose active ingredient is thought to be hyperceium,
is a logical therapeutic candidate because of its SSRI-like effects, and it is used
by many women for PMS. However, it has been evaluated in only one open,
uncontrolled, observational study (18). Thirty women with well-documented
luteal phase symptoms were randomized to either placebo or SJW 80 mg bid for
3 months. Women on the active regimen reported a 50% reduction in symptoms after 2 months, which is on the same order of magnitude as calcium.
However, until a placebo-controlled trial verifies these results, this therapy
cannot be considered proven.
Chasteberry fruit (Vitex agnus-castus) has been shown in two randomized
trials to be superior to placebo (19,20). In each trial, participants who met
DSM-III criteria for luteal phase syndrome were randomized to chasteberry
20 mg or placebo. At the end of three cycles, the active therapy groups reported 50%-60% reductions in luteal phase symptoms as compared with a
25%-35% reduction among placebo users. Chasteberry fruit has few side effects and can be found in health food stores.

SSRI Therapy
For women who do not have an adequate response to exercise, dietary change,
or nutritional supplements after two or three cycles, SSRI therapy is indicated
(21). Numerous randomized placebo-controlled trials of fluoxetine (22), sertraline
(23), paroxetine (24), and citalopram (25) have shown clear benefit compared
with placebo for women with PMDD. The effect is not a general antidepressant
effect; agents with different mechanisms of action are not effective (26-28).

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Because there is no evidence to suggest that any specific agent is clearly superior, drug choice can be based on cost, patient preference, and the womans
response and side effect experience. It appears that lack of response to one SSRI
does not predict response to other agents in this class, so trying at least three different drugs before moving to a different form of therapy has been suggested (25).
The effect of SSRIseven fluoxetine, with its long half-lifeon PMS/PMDD
is usually immediate, with symptom improvement seen in 24 to 28 hours. This
is quite different than when using these drugs for the treatment of depression or
anxiety, where the full effect may take 4 to 6 weeks. This feature of SSRI response
allows many women to use SSRIs intermittently rather than continuously.
Several randomized trials of luteal phase only or symptom day only treatment (approximately the 14 days before the onset of menses) have shown that
this regimen is clearly superior to placebo (29-35). In a trial of citalopram,
luteal phase therapy was found to be equivalent to daily therapy (36). A weekly
dose of fluoxetine has been shown to be superior to placebo but does not
appear to be as effective as luteal phase or continuous therapy (37).
Intermittent therapy has clear advantages, including lesser cost and fewer
days at risk for side effects (including sexual symptoms). Thus women with
PMS/PMDD and no evidence of co-existing mood disorder may begin with
symptom day therapy. The initial dose for fluoxetine is 20 mg (usual range,
10-40 mg); for sertraline, 50 mg (usual range, 25-150 mg). Treatment should
begin as soon as typical symptoms start. The drug should be discontinued
either on the first day of menses or 1 to 3 days later, depending on the usual
day that symptoms spontaneously resolve.
If intermittent therapy is insufficient, a trial of a daily SSRI therapy for at
least 2 months is appropriate. At least three different agents should be tried
before SSRI therapy is abandoned, since the side effect profile may differ, and,
women may respond to one but not all agents in the class (25).
If the SSRI class of agents is not tolerated or not effective, an anxiolytic
can be considered. Luteal phase alprazolam was found in several small trials
to be superior to placebo. Luteal phase buspirone has been reported in one
small clinical trial to be also superior to placebo. Because buspirone has less
addictive potential and fewer side effects than alprazolam (38), the former is
preferred when an anxiolytic is desirable.

Isolated Physical Symptoms

The majority of women who seek treatment for luteal phase symptoms have
mood symptoms (irritability, mood lability, depressive symptoms). However,
some women present with a physical symptom as their primary complaint, or,
continue to have problems with a physical symptom after successful therapy with
another approach (12). Spironolactone (50 to 200 mg as a single daily dose) may

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offer benefit for breast tenderness, bloating, luteal phase weight gain, and, possibly, mood symptoms. Oral contraceptives have been shown to reduce luteal
phase physical symptoms, but they do not appear to improve, and may even
worsen, mood symptoms. Nonsteroidal anti-inflammatory agents, given in a
modestly high dose in the luteal phase (e.g., naproxen sodium 600 mg three times
daily), have been shown in several small randomized trials to improve all physical
symptoms except breast tenderness, and they may also modify mood symptoms.

Ovulation Suppression Therapy

Patients who do not respond to any of the above regimens are candidates for a
trial of ovulation suppression. Oral contraceptives would seem to be a logical
choice for this purpose. However, there are only two randomized clinical
trials, and the results have either found no benefit for mood symptoms (39) or
a insignificant improvement (40). Thus women should be referred to a specialist (ideally to a gynecologist, or possibly a psychiatrist, with a special interest in PMDD) for this form of therapy.
The gold standard is gonadotropin-releasing hormone agonist. The problems with long-term use of this agent are high cost and the need for add back
estrogen therapy to prevent or minimize bone loss. Danazol, a synthetic androgen, is also effectively in suppressed ovulation and PMDD symptoms. However,
because of significant side effects (weight gain, androgen side effects, and, of
most concern, predictable suppression of HDL), danazol can only be used short
term and is thus rarely prescribed. An inexpensive, relatively safe, and side effect
free alternative is continuous medroxyprogesterone acetate given orally (20-40
mg daily) or as the depot injection (typical dose, 150 mg every three months).
Bilateral oophorectomy has been studied in two nonrandomized trials and
appears to be beneficial (41,42). However, it should rarely be necessary to
resort to this method given the array of effective pharmacological options. A
reasonable approach is to restrict consideration of oophorectomy to women
who have benefited only from gonadotropin-releasing hormone agonist therapy and who are likely to need several more years of therapy. These women
should be referred to a specialist with expertise in this issue.

Summary
Our understanding of the diagnosis and treatment of PMS/PMDD has progressed greatly over the last two decades. The diagnosis is generally straightforward, with the diagnostic evaluation typically accomplished after two office
visits. Therapy is based on the symptom severity of the individual patient. Because of the progress made in the understanding of PMS/PMDD treatment,

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most women with premenstrual symptoms, whether mild and merely bothersome or severe and disabling, can be offered effective therapy.

REFERENCES
1. Endicott J. History, evolution, and diagnosis of premenstrual dysphoric disorder. J Clin
Psychiatry. 2000;61(Suppl):12:5-8.
2. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.
3. Clinical management guidelines for obstetricians-gynecologists: premenstrual syndrome. American College of Obstetricians and Gynecologists Practice Bulletin. April
2000; No. 15.
4. Freeman EW. Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis. Psychoneuroendocrinology. 2003;28(Suppl 3):25-37.
5. Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact,
and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003;28(Suppl 3):1-23.
6. Steiner M, Pearlstein T. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J Clin Psychiatry. 2000;61(Suppl 12):17-21.
7. Endicott J, Amsterdam J, Eriksson E, et al. Is premenstrual dysphoric disorder a distinct clinical entity? J Womens Health Gend Based Med. 1999;8:663-79.
8. Hartlage SA, Brandenburg DL, Kravitz HM. Premenstrual exacerbation of depressive
disorders in a community-based sample in the United States. Psychosom Med. 2004;
66:698-706.
9. Kornstein SG, Parker AJ. Menstrual migraines: etiology, treatment, and relationship to
premenstrual syndrome. Curr Opin Obstet Gynecol. 1997;9:154-9.
10. Murray SC, Muse KN. Effective treatment of severe menstrual migraine headaches with
gonadotropin-releasing hormone agonist and add-back therapy. Fertil Steril.
1997;67:390-3.
11. Kessel B. Premenstrual syndrome: advances in diagnosis and treatment. Obstet Gynecol Clin North Am. 2000;27:625-39.
12. Johnson SR. Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a
clinical primer for practitioners. Obstet Gynecol. 2004;104:845-59.
13. Prior JC, Vigna Y, Sciarretta D, et al. Conditioning exercise decreases premenstrual
symptoms: a prospective, controlled 6-month trial. Fertil Steril. 1987;47:402-8.
14. Freeman EW, Stout AL, Endicott J, Spiers P. Treatment of premenstrual syndrome with
a carbohydrate-rich beverage. Int J Gynaecol Obstet. 2002;77:253-4.
15. Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual
syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome
Study Group.[Summary for patients in Can Fam Physician. 2002;48:705-7.] Am J
Obstet Gynecol. 1998;179:444-52.
16. Facchinetti F, Borella P, Sances G, et al. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991;78:177-81.
17. Girman A, Lee R, Kligler B. An integrative medicine approach to premenstrual syndrome. Am J Obstet Gynecol. 2003;188(5 Suppl):S56-65.

MD06(125-138) 2/15/06 4:04 PM Page 137

Premenstrual Syndrome

137

18. Stevinson C, Ernst E. A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome. BJOG. 2000;107:870-6.
19. Huddleston M, Jackson EA. Is an extract of the fruit of Vitex agnus castus (chaste tree
or chasteberry) effective for prevention of symptoms of premenstrual syndrome (PMS)?
J Fam Pract. 2001;50:298.
20. Schellenberg R. Treatment for the premenstrual syndrome with Vitex agnus castus
fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322:134-7.
21. Born L, Steiner M. Current management of premenstrual syndrome and premenstrual
dysphoric disorder. Current Psychiatry Reports. 2001;3:463-9.
22. Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual
dysphoria [see Comment]. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative
Study Group. N Engl J Med. 1995;332:1529-34.
23. Yonkers KA, Halbreich U, Freeman E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment: a randomized controlled trial [see
Comment]. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA.
1997;278:983-8.
24. Yonkers KA, Gullion C, Williams A, et al. Paroxetine as a treatment for premenstrual
dysphoric disorder. J Clin Psychopharmacol. 1996;16:3-8.
25. Freeman EW, Jabara S, Sondheimer SJ, Auletto R. Citalopram in PMS patients with
prior SSRI treatment failure: a preliminary study. J Womens Health Gend Based Med.
2002;11:459-64.
26. Eriksson E, Hedberg MA, Andersch B, Sundblad C. The serotonin reuptake inhibitor
paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome. Neuropsychopharmacology. 1995;12:167-76.
27. Freeman EW, Rickels K, Sondheimer SJ, Wittmaack FM. Sertraline versus desipramine
in the treatment of premenstrual syndrome: an open-label trial. J Clin Psychiatry.
1996;57:7-11.
28. Pearlstein TB, Stone AB, Lund SA, et al. Comparison of fluoxetine, bupropion, and
placebo in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacology. 1997;17:261-6.
29. Halbreich U, Bergeron R, Yonkers KA, et al. Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder. Obstet Gynecol. 2002;100:1219-29.
30. Alpay FB, Turhan NO. Intermittent versus continuous sertraline therapy in the treatment of premenstrual dysphoric disorders. Int J Fertil Womens Med. 2001;46:228-31.
31. Jermain DM, Preece CK, Sykes RL, et al. Luteal phase sertraline treatment for premenstrual dysphoric disorder: results of a double-blind, placebo-controlled, crossover
study. Arch Fam Med. 1999;8:328-32.
32. Freeman EW, Rickels K, Arredondo F, et al. Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant. J Clin Psychopharmacol.
1999;19:3-8.
33. Young SA, Hurt PH, Benedek DM, Howard RS. Treatment of premenstrual dysphoric
disorder with sertraline during the luteal phase: a randomized, double-blind, placebocontrolled crossover trial. J Clin Psychiatry. 1998;59:76-80.
34. Halbreich U, Smoller JW. Intermittent luteal phase sertraline treatment of dysphoric
premenstrual syndrome. J Clin Psychiatry. 1997;58:399-402.
35. Steiner M, Korzekwa M, Lamont J, Wilkins A. Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria. Psychopharmacol Bull. 1997;33: 771-4.

MD06(125-138) 2/15/06 4:04 PM Page 138

138

Menstrual Disorders

36. Wikander I, Sundblad C, Andersch B, et al. Citalopram in premenstrual dysphoria: is

intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle? J Clin Psychopharmacol. 1998;18:390-8.
37. Miner C, Brown E, McCray S, et al. Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind,
placebo-controlled clinical trial. Clin Ther. 2002;24:417-33.
38. Rickels K, Freeman E, Sondheimer S. Buspirone in treatment of premenstrual syndrome. Lancet. 1989;1:777.
39. Graham CA, Sherwin BB. A prospective treatment study of premenstrual symptoms
using a triphasic oral contraceptive. J Psychosom Res. 1992;36:257-66.
40. Freeman EW, Kroll R, Rapkin A, et al. Evaluation of a unique oral contraceptive in the
treatment of premenstrual dysphoric disorder[see Comment]. J Womens Health Gend
Based Med. 2001;10:561-9.
41. Casson P, Hahn PM, Van Vugt DA, Reid RL. Lasting response to ovariectomy in severe
intractable premenstrual syndrome. Am J Obstet Gynecol. 1990;162:99-105.
42. Casper RF, Hearn MT. The effect of hysterectomy and bilateral oophorectomy in women
with severe premenstrual syndrome. Am J Obstet Gynecol. 1990;162:105-9.