New Treatment Approaches for Premenstrual Disorders Andrea J. Rapkin, MD Published Online: November 30, 2005 - 11:00:00 PM (CST) | |
Several approaches to alleviating the symptoms of
premenstrual disorders are available to women and
can be tailored according to individual needs and
preferences. This article discusses methods that entail
changes to lifestyle and diet and managing life stresses
without relying on drug therapy, as well as a variety
of medications that may be necessary in addition
to or in place of recommended lifestyle modifications.
New pharmacologic research is promising and
is discussed along with the need to provide empathetic
counseling for patients to determine the
approach that will work best for each individual.
(Am J Manag Care. 2005;11:S480-S491)
The term "premenstrual disorders"
covers a spectrum of premenstrual
symptom combinations, from mild
premenstrual syndrome (PMS) to premenstrual
dysphoric disorder (PMDD) that is
severe enough to interfere with work and
social functioning. Effective evaluation and
treatment of PMS were hampered until the
mid-1980s by the lack of established criteria
for diagnosing this common condition. The
American College of Obstetricians and
Gynecologists (ACOG) published a practice
bulletin in 2000 that included criteria for
PMS, based on an earlier article by Mortola
and colleagues, as well as a discussion of
different approaches for treating PMS,1,2
including lifestyle modifications such as regular
aerobic exercise and dietary changes.
Pharmacologic options studied for treating
severe PMS include selective serotonin reuptake
inhibitors (SSRIs), anxiolytic agents,
gonadotropin-releasing hormone (GnRH)
agonists, the diuretic spironolactone, and
combination oral contraceptives (OCs).
PMDD is defined as a psychiatric disorder
in Appendix B of the Diagnostic and
Statistical Manual of Mental Disorders,
Fourth Edition, Text Revision (DSM-IV-TR).3
Currently, selected SSRIs are the only pharmacologic
agents with a US Food and Drug
Administration (FDA) indication for PMDD.
Prior to the early 1990s when PMDD was
defined as "late luteal dysphoric disorder" in
DSM-III, various severities of PMS and
PMDD were often investigated and discussed
without differentiation. Therefore, many of
the early studies in which the term "PMS"
was used probably included patients with
PMDD as well. It is necessary to keep this
fact in mind when reviewing the literature
on premenstrual disorders.
In this article, a number of available nonpharmacologic
and pharmacologic treatments
are reviewed, as well as recent
advances in pharmacotherapy for premenstrual
disorders.
Lifestyle Modifications
Lifestyle modification rather than drug
therapy may be the most appropriate treatment
approach for women with mild PMS
symptoms. Physicians should always inform
their female patients about lifestyle changes
that may ameliorate their premenstrual
symptoms and advise them to evaluate the
effect of various approaches during the 2
months for which they keep a daily symptom
diary. (At least 2 months of prospective
daily symptom recording are required for a
diagnosis of PMS or PMDD.) Regular aerobic
exercise, for example, eases premenstrual
symptoms for many women.4 The decline in
endorphin levels that normally occurs in the
late luteal phase of the menstrual cycle has
been suggested to be an underlying mechanism
for premenstrual symptoms in some
women. Because regular aerobic exercise
leads to the release of endorphins in the central
nervous system, physicians should recommend
that women perform at least 20 to
30 minutes of aerobic exercise per day for at
least 3 days each week.5
Dietary and nutritional modifications
have also been used over the years to
treat premenstrual symptoms. One such
approach, calcium supplementation, was
studied by Thys-Jacobs and colleagues in
466 evaluable women with moderate-to-severe
premenstrual symptoms that had
been documented over 2 cycles.6 Participants
were randomized to receive 1200
mg/day of elemental calcium or a placebo for
3 cycles. Premenstrual symptoms were significantly
lower in the calcium-treated group
than in controls in the second (P = .007) and
third (P <.001) treatment cycles. Therefore,
calcium supplementation appeared to
reduce premenstrual symptoms in some
women.
Other studies have suggested that excess
alcohol, salt, and caffeine intakes may actually
worsen premenstrual symptoms by
decreasing magnesium levels.7 For example,
Walker et al conducted a double-blind,
placebo-controlled, crossover study in
which 41 evaluable women were randomized
to 200 mg/day of magnesium or placebo
for 2 cycles before being crossed over to the
alternate treatment for 2 additional cycles.8
Walker and colleagues observed that daily
magnesium supplementation significantly
lowered mild symptoms of fluid retention
(ie, weight gain, breast tenderness, swelling
of extremities, and abdominal bloating)
compared with placebo in the second cycle
of administration (P = .0009), but not in the
first cycle.7
Another study conducted by Freeman
and colleagues included 53 women with premenstrual
symptom rates that were 30%
higher during the late luteal phase than in
the follicular phase.9 Patients were randomized
to a commercial carbohydrate-rich
beverage or to an isocaloric placebo beverage
taken twice daily for 5 days before the
anticipated onset of menses. Mood symptoms
were decreased in approximately one
third of women consuming the carbohydrate-
rich beverage, compared with 5% of
the placebo group.
A study indicated that vitamin B6 had
some clinical benefit in reducing premenstrual
symptoms,10 but doses in excess of
100 mg/day can be harmful.1 Additionally,
the herbal product evening primrose oil has
not been shown to be effective in treating
premenstrual symptoms11; however, the
ACOG practice bulletin indicated that it
may decrease breast tenderness.1 Finally,
with regard to nutrition, reductions in salt,
sugar, alcohol, and caffeine intake are
often suggested for relieving premenstrual
symptoms, but these approaches have not
been investigated extensively in controlled
studies.12
Pharmacotherapeutic Options
Compared with the nonpharmacologic
approaches, pharmacotherapeutic options
for managing premenstrual disorders have
been investigated in greater detail. However,
the study techniques employed have varied
widely, including methods of diagnosis, outcomes
analyzed, and methods of outcome
measurement. Studies should include procedures
for recording improvements in
psychological symptoms and physical symptoms
as well as overall improvement. Daily
self-report diaries constitute the primary
measurement, but some clinician-rated
scales have also been validated. In addition,
symptom assessment should include several
months of tracking to confirm the diagnosis
before entry into the study and placebo runin
periods to exclude placebo responders.
Antidepressants. Of numerous options
available, antidepressants from the class of
the SSRIs may be considered the therapy
of choice for PMDD in many patients.
Currently, the only agents with an FDA
indication for PMDD are fluoxetine hydrochloride,
sertraline hydrochloride, and
paroxetine hydrochloride. Unlike tricyclic
antidepressants, which interact with several
receptors, the SSRIs interact minimally with
receptors other than the serotonin (5-HT)
reuptake receptor.13 Fluoxetine has a recommended dose of 20 mg/day (Figure 1); in
clinical studies, no added benefit was
observed with increasing the dosage to 60
mg/day. Sertraline is initiated at a dose of 50
mg/day and can be increased up to 150
mg/day for daily dosing or up to 100 mg/day
for dosing only during the luteal phase of the
cycle. Paroxetine is initiated at a dose of
12.5 mg/day and can be increased to 25
mg/day.14 Clinical trials that formed the
basis for approval of these 3 SSRIs for managing
PMDD symptoms and additional trials
with other SSRIs are listed in Table 1.
Several adverse effects are associated
with daily use of the SSRIs that have received
an FDA indication for PMDD (Table 2).
Individual response to these side effects may
lead to poor adherence or discontinuation of
these medications.
In a study to investigate compliance to
antidepressant agents prescribed for PMS,
Sundström-Poromaa and colleagues noted
reasons given by these patients for discontinuing
antidepressant use.15 A total of 170
(84.2%) of the 202 women who were prescribed
an SSRI or a tricyclic antidepressant
for PMS during a 4-year period completed a
written questionnaire. The 22 (12.9%)
women who never started treatment listed
their primary reasons as fear of negative side
effects (54.5%) and not wishing to take this
type of drug (54.5%). (A woman could give
more than 1 reason for not initiating antidepressant
therapy.) Of the 148 (87.1%)
women who did start therapy, 91 (61.5%)
had discontinued the antidepressant by the
end of 2 years. Table 3 lists the reasons for
discontinuation of therapy.
Women who experience severe side effects
can be advised to switch to a different SSRI.
Should they choose to switch to a different
drug class, the SSRI dose must be tapered
slowly to avoid discontinuation symptoms.
In addition, the FDA recently revised the
safety labeling for SSRIs to advise against
their use in patients younger than 18 years
and to warn patients with major depressive
disorder of the risk for worsening symptoms
and/or for suicidal ideations.
Studies with non-SSRI/selective norepinephrine
antidepressants have had less
favorable results compared with SSRIs. A
comparative study of treatment with sertraline
and desipramine (flexible dosage range
50-150 mg/day) vs placebo in 189 subjects
with PMS/PMDD showed that sertraline was
significantly more effective than placebo on
the Penn Daily Symptom Report (>50%
symptom decrease in 65% of subjects in the
sertraline groups), whereas desipramine
was not (symptom decrease in 36% of
subjects in the sertraline group and 29%
in the placebo group).16 Another comparative
study investigated fluoxetine 20
mg/day, bupropion 100 mg/day, and
placebo in 34 women with PMDD. Fluoxetine
was superior to both bupropion and
placebo in efficacy by Global Clinical
Impression ratings. Posttreatment Hamilton
Rating Scale for Depression and
Global Assessment Scale rating scores
were intermediate between but not significantly
different from fluoxetine or
placebo.17
On the whole, studies conducted with
antidepressants in women with PMS and
PMDD indicate that serotonergic activity is
required for efficacy. The SSRIs have been
investigated for both continuous and lutealphase
(intermittent) administration, and fluoxetine,
paroxetine CR (controlled release),
and sertraline are approved for use in PMDD
without specification of the regimen, so can
be employed continuously or intermittently.
Onset of efficacy is rapid: therapeutic benefit
is seen in the first menstrual cycle after
initiation of treatment with these agents.
Patients on systemic hormonal contraceptives
were excluded from many of the SSRI
trials, so the efficacy of SSRIs in combination
with systemic (including oral) hormonal
contraceptives for the continuous daily
treatment of PMDD is unknown.
Anxiolytics. The anxiolytic agent alprazolam
has not shown consistent results in
studies evaluating its effectiveness in alleviating
premenstrual symptoms, according to
the ACOG practice bulletin.1 In a study conducted
by Evans and colleagues, women
with premenstrual symptoms were given
either alprazolam (0.25, 0.50, or 0.75 mg) or
placebo during both the luteal and follicular
phases of the cycle under controlled laboratory
conditions.18 It was observed that acute
doses of alprazolam did not improve negative
premenstrual mood and actually were
associated with an increase in negative
mood in the follicular phase.18 Also, alprazolam
impaired task performance in both
phases of the cycle. As a result, acute administration
of alprazolam was not deemed a
clinically useful treatment for premenstrual
symptoms. In addition, continued use of
alprazolam can lead to dependency, and
some users develop a tolerance to this agent.
GnRH agonists. A third treatment option
is the class of GnRH agonists, which use a
hormonal approach to suppress ovarian
steroid hormone production and prevent
ovulation, in effect by inducing medical
oophorectomy.4 These agents have demonstrated
efficacy in alleviating several premenstrual
symptoms. For example, in a small
study conducted by Mortola and colleagues,19 GnRH monotherapy was associated
with at least a 75% improvement from
baseline in the Calendar of Premenstrual
Experiences (COPE) scores for behavioral
(P <.01), physical (P <.05), and total (P <.01)
symptoms. However, because GnRH agonists
induce medical menopause, estrogen
and progestin must be added back to prevent
bone loss and potentially for cardioprotection.4 According to an additional, small
study, 10 women with PMS symptoms given
leuprolide acetate at 3.75 mg/mo for 3
months had a significant decrease in symptoms
measured using a Daily Rating Form
and the observer form of the Rating Scale for
Premenstrual Tension Syndrome. Addition
of either progesterone vaginal suppositories
or a 17β-estradiol patch or the leuprolide
regimen resulted in significant return of
symptoms. No changes in mood occurred in
15 normal women who received the same
regimen. The authors conclude that in
women with PMS, the occurrence of symptoms
represents an abnormal response to
normal hormonal changes.20
Synthetic androgens. Danazol, a synthetic
androgen indicated in the United States
for the treatment of endometriosis, menorrhagia,
fibrocystic breast disease, and hereditary
angioedema, has also been investigated
for the management of PMS and premenstrual
mastalgia, with moderate results.
Luteal-phase-only danazol was not effective
for treating the general symptoms (daily
analogue scale scores) of premenstrual syndrome,
but appeared highly effective for
relieving premenstrual mastalgia in a study
conducted on 100 women.21 A smaller study,
conducted in 31 women meeting rigorous
criteria for a diagnosis of severe PMS, evaluated
effects of danazol treatment using the
Premenstrual Tension Self-Rating Scale, the
Beck Depression Inventory, and a visual
analogue scale. Danazol 200 mg bid provided
greater symptom relief than did placebo.22 Potential adverse effects of danazol are
a cause for concern with this agent.23
Diuretics. Another therapeutic consideration
is spironolactone, an aldosterone
receptor agonist derived from 17α-spirolactone. According to the ACOG
practice bulletin, thiazide diuretics have
not been demonstrated to be beneficial in
alleviating premenstrual fluid retention,
but spironolactone has, in fact, been
shown to have benefit in PMS.1 Spironolactone
also has been shown to relieve
other symptoms associated with the premenstrual
phase of the cycle,4 as noted in a
double-blind, parallel-group study over 3
cycles conducted by Vellacott and colleagues.
24 Sixty-three women, aged 16 to 45,
with a history of at least 6 months of cyclic
symptoms were randomized to spironolactone
100 mg/day or to placebo, given from
day 12 of the menstrual cycle to the onset of
menses. Spironolactone was significantly
superior to placebo in relieving the general
feeling of bloating (P = .001). By cycle 3,
more than half of the 26 women using
spironolactone also experienced improvement
of abdominal swelling, swelling of the
hands and feet, breast discomfort, irritability,
depression, anxiety, tension, and increase
in sexual interest.
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Spironolactone was also examined in a
double-blind, crossover study conducted by
Wang and colleagues in 35 women with
PMS.25 Two pretreatment cycles were used
to diagnose PMS, after which the treatment
phase began, consisting of two 3-month periods.
Women were randomized to 100 mg/day
of spironolactone or placebo administered
daily from day 14 of the menstrual cycle
until the onset of menses. The primary outcome
measure was the prospective daily
visual analogue scale. During the intervals
when women were taking spironolactone,
they experienced significant improvements
in negative symptoms (ie, anxiety and tension,
irritability, fatigue, and depression)
and in physical symptoms (ie, headache,
feelings of swelling, cravings for sweets, and
breast tenderness) compared with baseline
values and with placebo (P <.01 for all measures).
Spironolactone treatment was also
associated with an improvement in positive
symptoms (cheerfulness, well-being, friendliness,
feeling energetic) compared with
baseline values (P <.01).
Oral contraceptives. Another hormonal
option, combination OCs, is a popular
choice for helping to relieve several premenstrual
symptoms. In the United States, OCs
contain estrogen as ethinyl estradiol (EE) in
combination with a variety of progestins. EE
causes a rise in serum aldosterone levels,
which lead to sodium and water retention,
thereby contributing to bloating and breast
tenderness.26 All progestins have progestogenic
activity, but they can differ in terms of
other pharmacologic effects. The pharmacologic
profiles of progesterone and various
progestins used in OCs (as found in animal
models) are demonstrated in the work of
Krattenmacher.27
Until recently, very few controlled studies
had evaluated the efficacy of OCs in reducing
premenstrual symptoms, and those that
had been conducted yielded mixed results.
For example, in 1992 Graham and Sherwin
studied 82 women with moderate-to-severe
premenstrual symptoms in a double-blind,
placebo-controlled trial.28 The women charted
daily symptoms for 1 cycle, after which
they were randomly assigned to a triphasic
OC containing EE 35 μg and norethindrone
(0.5 mg, 1.0 mg, and 0.5 mg) or to placebo
for 3 cycles. A total of 23 women (28%)
dropped out of the study (18 in the OC
group and 5 in the placebo group). Com
pared with placebo, the OC significantly
reduced premenstrual breast pain and bloating
(P <.03) but did not have significantly
better effects on mood symptoms.
Similarly, in a double-blind crossover
study of 3 OCs, 36 women aged 20 to 40 who
either had PMS or experienced symptoms
throughout their entire menstrual cycle with
premenstrual aggravation were examined.29
The study consisted of 2 treatment cycles followed
by a crossover to the alternate preparation
for 2 additional treatment cycles.
Nineteen women were randomly assigned
to a monophasic OC containing EE combined
with either desogestrel (DSG) or levonorgestrel
(LNG), and 17 women were
randomized to treatment with either monophasic
EE/DSG or a triphasic OC containing
EE plus LNG. Mood scores improved from
baseline for all 3 OCs, but Bäckström and
colleagues concluded that the beneficial
effect observed in the study was no higher
than that reported for placebo in other
studies. The monophasic DSG pill resulted
in less change in mood parameters than did
the monophasic and triphasic LNG OCs.
However, physical complaints were less frequently
reported during the use of the
triphasic preparation as compared to the
monophasic DSG preparation.29
Finally, a nested case-control study conducted
by Joffe and colleagues examined a
cohort of 976 women, aged 36 to 45.30 Of the
658 women who had previously used a variety
of OCs, 107 (16.3%) reported pill-related
premenstrual mood deterioration, 81
(12.3%) reported premenstrual mood improvement,
and 470 (71.4%) reported no
effect of OCs on premenstrual mood. Therefore,
it was concluded that OCs do not affect
premenstrual mood in most women.30
All but one of the progestins being used in
OCs in the United States are derived from
19-nortestosterone. The exception is the
progestin drospirenone, which is derived
from 17α-spirolactone and is an analogue of
spironolactone. The pharmacologic profile
of drospirenone closely resembles that of
natural progesterone in that it has potent
progestogenic, antiandrogenic, and antimineralocorticoid
activities, and no androgenic
activity.26 The antimineralocorticoid
activity of 3 mg of drospirenone is comparable
with 25 mg of spironolactone.31
Drospirenone acts by binding to aldosterone
receptors, blocking aldosterone action in the
kidneys, resulting in a substantial rise in
sodium and water excretion and some retention
of potassium (Figure 2).27
In recent years, several studies have
examined the efficacy of the OC formulation
containing EE 30 μg plus drospirenone 3 mg
(30EE/drospirenone) on premenstrual symptoms.
For example, a double-blind trial
included 82 women with PMDD who were
randomized to 30EE/drospirenone (n = 42)
or placebo (n = 40).32 The drospirenone-containing
OC was observed to have a positive
effect on symptoms of PMDD, with the
between-group differences reaching statistical
significance in appetite, food cravings,
and acne (P = .03). In addition, Apter and
colleagues conducted an open, 6-cycle study
of 336 women to evaluate the actions of
30EE/drospirenone on fluid-related symptoms
during the luteal phase of the cycle and
the effects of these symptoms on overall well-being.33 Use of 30EE/drospirenone was associated
with a significant reduction in the
incidence and severity of the abdominal
bloating and breast tenderness (both P <.001)
associated with the menstrual cycle. Also, the
significant beneficial effect of 30EE/drospirenone
on psychologic well-being (P <.0001),
as measured by the Psychological General
Well-Being Index, observed at cycle 3 was
maintained at cycle 6.
Further, an open-label, 26-cycle study
was conducted by Foidart and colleagues of
627 evaluable women: 310 were randomized
to 30EE/drospirenone and 317 to EE 30 μg
plus DSG 150 μg.34 Compared with the
EE/DSG group, women who were given
30EE/drospirenone experienced a greater
incidence of premenstrual symptoms before
the study and a lesser incidence throughout
the study. The between-group differences
were not statistically significant. More
recently, Sangthawan and Taneepanichskul
conducted an open-label, 6-cycle study of 99
evaluable women who were randomized to
either 30EE/drospirenone or EE 30 μg plus
LNG 150 μg.35 The prevalence of premenstrual
symptoms was reduced from 58.0%
at baseline to 32.0% at cycle 6 in the
30EE/drospirenone group and rose from
59.2% at baseline to 61.2% at cycle 6 in the
EE/LNG group. The between-group difference
was statistically significant (P = .005).
Positive results with drospirenone were
also noted by Borenstein et al, who analyzed
responses of 858 women who completed a
survey when initiating 30EE/drospirenone
and again after 2 cycles of treatment.36
Compared with baseline values, 30EE/drospirenone
use was associated with significant
reductions in premenstrual symptoms
(P <.001) and improvement in the women's
sense of well-being (P <.05). Finally, Sillem
and colleagues conducted an observational
study of 1433 women using 30EE/drospirenone,
175 of whom continuously took this
OC between 42 and 126 days using an
extended regimen.37 Although it was not
designed specifically to evaluate premenstrual
symptoms, this study did monitor
some symptoms associated with PMS and
PMDD. A reduction in edema was experienced
by 31% of new users and 40% of the
switchers and by 34% of the women receiving
the standard regimen compared with
49% of the women receiving the extended
regimen (P <.001). A decrease in breast tenderness
was reported by 40% of new users
and 42% of the switchers and by 40% of the
women receiving the standard regimen compared
with 50% of the women receiving the
extended regimen (P = .046). A reduction in
bloating was experienced by 31% of new
users and 30% of the switchers and by 29% of
the women receiving the standard regimen
compared with 37% of the women receiving
the extended regimen. Table 4 summarizes
the results of the studies of OCs in women
with premenstrual symptoms.
The beneficial results observed in the
studies cited should be considered in light of
potential side effects associated with OC
use in some women, including nausea,
breakthrough bleeding, weight gain, breast
tenderness, and headache, as well as contraindications
with certain coexisting medical
conditions. However, as with SSRIs,
women can switch to a different OC if side
effects make this necessary. Given the
known noncontraceptive health benefits of
OCs, especially their favorable effects on
several premenstrual symptoms, they are
strong candidates for patient use.
Recent Research Findings for OC
Formulations and Regimens
Recently, several studies have assessed
the efficacy of a new OC formulation containing
EE 20 μg and drospirenone 3 mg
(20EE/drospirenone) administered for 24
days, followed by a 4-day hormone-free
interval (24/4), in the treatment of PMDD.
Yonkers and Foegh reported on a double-blind,
placebo-controlled, crossover study
of 20EE/drospirenone that consisted of two
3-cycle treatment periods separated by a
washout cycle.38 Of the 64 women, aged 18
to 40 years, with PMDD symptoms who
were randomized, 34 women initiated
active treatment with 20EE/drospirenone
followed by placebo, and 30 women initiated
placebo followed by the new OC formulation.
The change from baseline with
drospirenone/20EE was significantly superior
to that with placebo in the DRSP, which
was the primary outcome measure, and in
the secondary outcome measures (ie, the
CGI-Efficacy and CGI-Severity indexes), the
self-rated rating scale for premenstrual
tension syndrome (PMTS), and the Endicott
Quality of Life Enjoyment and Satisfaction
Questionnaire (Q-LES-Q) items 1 to 14 and
item 16 (Table 5).
More recently, Yonkers and colleagues
conducted another double-blind, placebo-controlled,
parallel-group study with
20EE/drospirenone used in a 24/4 regimen
in women with PMDD symptoms.39 The
study design consisted of 2 run-in menstrual
cycles (the qualification phase) followed by
3 treatment cycles. Of the 449 women who
were randomized, 231 were in the active-treatment
group and 218 received placebo.
The primary outcome measure was the 21
individual items in the DRSP. When these
individual items were grouped into physical,
mood, and behavioral symptoms, 20EE/drospirenone
was observed to be statistically
superior to placebo for all symptom groupings.
Improvement occurred as early as
cycle 1 and continued during all 3 cycles. In
addition, 20EE/drospirenone was significantly
more effective than placebo in the observer-
rated (P = .023) and self-rated (P = .004)
rating scale for PMTS, the observer-rated
(P = .004) and self-rated (P = .014) Clinical
Global Impression (CGI)-Improvement scales,
the 3 functional items of the DRSP (productivity
and enhanced enjoyment in social
activities, both P = .003; better quality of
relationships, P = .0003), and the Q-LES-Q,
items 1 to 14 (P = .05). (All P values have
normality correction.)
One means of assessing the effects of various
agents on premenstrual symptoms is
to compare response rates using the same
definition. For example, response rate was
defined as a score of "much" or "very
much" improved on the CGI-Improvement
scale in 2 studies of the SSRI sertraline
and in the crossover and parallel studies of
20EE/drospirenone 24/4. In a double-blind
study, women with PMDD were randomized
to a flexible daily dose (50-150
mg/day) of sertraline (n = 121) or to placebo
(n = 122).40 At end point, 62% of the
women in the active-treatment group and
34% of the women in the placebo group
were classified as responders (P <.001). In
a study of intermittent sertraline, the
response rate was 58% in the women
receiving active treatment and 45% in
the placebo group (P = .036).41 The
response rates in these 4 studies are compared
in Figure 3.
Counseling Women With
Premenstrual Disorders
To provide effective counseling for a
woman with bothersome or severe premenstrual
symptoms, physicians must be empathetic
and caring communicators as well as
knowledgeable about this complex area of
women's health. It is important to assure the
patient that her symptoms are real, with a
physiologic basis, and that she is not "crazy."42
The clinician or other counselor should
explain the details of the menstrual cycle to
the patient, especially how premenstrual
symptoms occur on a cyclic basis. Because
patients usually retain only part of the information
they receive during a visit, physicians
should provide them with interesting and
practical educational materials to reinforce
what is discussed. Patients should keep a daily
symptom diary for at least 2 months to
ensure that an accurate diagnosis of PMS or
PMDD is achieved. Clinicians or other counselors
should provide the diary for prospectively
recording the patient's symptoms,
making certain that she knows how to use it
properly.
Even before a diagnosis of PMS or PMDD
has been made, the physician or counselor
can help the patient identify ways to adjust
her lifestyle to manage stress that can contribute
to premenstrual symptoms. Patients
should be encouraged to seek nonthreatening
support from family and friends. In addition,
they should be instructed about how to
initiate lifestyle modifications, such as exercise,
dietary changes, appropriate use of
vitamin and mineral supplements, and stress
management, including relaxation and cognitive
behavioral approaches. Available
pharmacotherapeutic options should be discussed,
keeping in mind the patient's personal
preferences, side effects, the cost of
the treatments being considered, and her
needs. For example, use of an OC might be
the best first-line treatment choice for a
woman who also has contraceptive needs,
which can be reversed if so desired. OCs also
have noncontraceptive health benefits of
which the patient should be informed.
Finally, the patient should be assured that
she can try different therapeutic options
until she finds the one most suitable for her.
Conclusion
A variety of approaches have been used to
treat premenstrual symptoms. Lifestyle
modifications, such as regular physical
activity and dietary/nutritional changes, can
reduce premenstrual symptoms in some
women. Nonpharmacologic options are the
easiest forms of treatment to implement,
based on appropriate counseling, and can be
tried by any woman as she charts her symptoms
in a daily symptom record for at least
2 cycles to enable her physician to arrive at
a correct diagnosis.
Several pharmacologic options have been
shown to be effective and should be evaluated
in light of the patient's individual needs
and preferences. Some agents, such as particular
SSRIs, are effective in many patients
but also can be expensive and cause unwanted
side effects. Other options, such as GnRH
agonists, may be of limited use for similar
reasons. Combination OCs are often used to
treat premenstrual symptoms, even with a
lack of evidence-based support, although
new research is revealing more supportive
data. OC formulations containing progestin
drospirenone have been shown to be effective
in treating symptoms of PMDD in controlled
studies.
Counseling women about the nature of
their symptoms and the variety of treatment
possibilities provides much-needed reassurance
in many instances and makes it feasible
to individualize therapy based on the
patient's preferences, treatment cost, and
the most likely means of restoring patient
comfort, function, and overall health.
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Author InformationAddress correspondence to: Andrea J. Rapkin, MD, David Geffen School of Medicine at UCLA, Department of Obstetrics and Gynecology, 10833 Le Conte, Room 27-165 CHS, Los Angeles, CA 90095-1740; arapkin@mednet.ucla.edu.
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