Double-blind Studies of Treatments for Premenstrual Depression.

A MEDLINE Search by Ivan Goldberg, MD

1: Arch Women Ment Health. 2003 Feb; 6(1): 71-7.

Fluoxetine improves functional work capacity in women with premenstrual
dysphoric disorder.

Steiner M, Brown E, Trzepacz P, Dillon J, Berger C, Carter D, Reid R, Stewart D.

Women’s Health Concerns Clinic, St. Joseph’s Healthcare, Hamilton, ON, Canada.

Interference with social and occupational functioning is a key criterion for
premenstrual dysphoric disorder (PMDD) and distinguishes it from the less severe
premenstrual syndrome (PMS). We conducted a post hoc analysis of the results of
a previously reported study evaluating the efficacy of fluoxetine in the
management of PMDD, to determine the extent to which women with PMDD perceived
impairment in their functional work capacity during the luteal phase of their
menstrual cycle. The effects of two doses of fluoxetine vs placebo in
alleviating PMDD symptoms and restoring normal work capacity during this period
were assessed. We measured baseline follicular vs luteal phase presence of 8
patient-rated functional work capacity-related symptoms on the Premenstrual
Tension Scale-Self Rated in 320 women who met diagnostic criteria for late
luteal phase dysphoric disorder, now known as PMDD. Women were then randomized
to double-blind treatment with either fluoxetine 20 mg/d, fluoxetine 60 mg/d, or
placebo daily for 6 menstrual cycles. All 8 work capacity-related symptoms were
more likely to be present in the baseline luteal phase than in the baseline
follicular phase. A statistically significant improvement from baseline to the
average treatment score for the work capacity subscale was detected for both
fluoxetine groups compared to the placebo group. This beneficial response to
fluoxetine was evident by the first cycle of treatment. Our results demonstrate
that fluoxetine at a relatively low dose of 20 mg/d quickly reduced symptoms
that negatively affect work capacity and was well tolerated.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12715267 [PubMed – indexed for MEDLINE]


2: Eur J Contracept Reprod Health Care. 2002 Dec; 7 Suppl 3: 27-34; discussion

Evaluation of a unique oral contraceptive (Yasmin) in the management of
premenstrual dysphoric disorder.

Freeman EW.

Department of Obstetrics/Gynecology, University of Pennsylvania, Philadelphia,
Pennsylvania, USA.

Over three-quarters of women experience some physical and emotional changes
associated with the menstrual cycle. Irritability, tension, fatigue, depression,
breast tenderness and bloating are among the most common premenstrual symptoms.
Approximately 5-10% of women of childbearing age experience premenstrual
symptoms to a degree that disrupts their functioning in the home or workplace
and that meet criteria for premenstrual dysphoric disorder (PMDD). Serotonergic
antidepressants are clearly effective for PMDD, with about 60% of subjects
responding to this treatment in controlled studies. Oral contraceptives are
commonly used to treat premenstrual symptoms but are an understudied
intervention with no information on their efficacy for PMDD). The recent
introduction of an oral contraceptive (Yasmin, Schering AG, Berlin, Germany),
containing low-dose ethinylestradiol (EE) combined with a new progestogen,
drospirenone (DRSP), may offer clinical efficacy for PMDD as a result of the
unique pharmacological profile of this progestogen, which is a spirolactone
derivative with antimineralocorticoid and antiandrogenic activity. A randomized,
placebo-controlled study of DRSP/EE in women with PMDD found a consistently
greater reduction of symptoms-from baseline for all 22 premenstrual symptoms
assessed (using the Calendar of Premenstrual Experiences, COPE) and for the four
statistically derived symptom factors in the group taking DRSP/EE compared to
the placebo group. For appetite, acne and food craving (factor 3), the
difference between the DRSP/EE group and the placebo group was statistically
significant (p = 0.027). These preliminary results suggest the beneficial effect
of DRSP/EE on PMDD and offer an alternative class of medication that also
provides the range of benefits of oral contraception for women with PMDD.

Publication Types:
Clinical Trial
Evaluation Studies
Multicenter Study
Randomized Controlled Trial

PMID: 12659404 [PubMed – indexed for MEDLINE]


3: Cochrane Database Syst Rev. 2002; (4): CD001396.

Selective serotonin reuptake inhibitors for premenstrual syndrome.

Wyatt KM, Dimmock PW, O’Brien PM.

Exeter and North Devon RDSU, Royal Devon and Exeter Hospital, 1st Noy Scott
House, Haldon View Terrace, Wonford, Exeter, Devon, UK, EX2 5EQ.

BACKGROUND: Severe premenstrual syndrome affects between 3-5% of women of
reproductive age. Such severe PMS is classified under the Diagnostic and
Statistical Manual of Mental Disorders as premenstrual dysphoric disorder, PMDD.
Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used as a
front-line therapy for premenstrual syndrome (PMS). A systematic review was
undertaken on the efficacy of SSRIs in the management of severe PMS/PMDD, to
assess the evidence for this treatment option. OBJECTIVES: The objective of this
review was to evaluate the effectiveness of SSRIs in reducing premenstrual
syndrome symptoms in women diagnosed with severe premenstrual syndrome. SEARCH
STRATEGY: Electronic searches for relevant randomised controlled trials of the
Cochrane Menstrual Disorders and Subfertility Group specialised register of
controlled trials, Cochrane Controlled Trials Register, MEDLINE, EMBASE and
PsychLit were undertaken. References were searched interactively to identify
missed trials. Where insufficient data were presented original authors were
contacted for further details. SELECTION CRITERIA: All trials were considered in
which women with a prospective diagnosis of PMS/ PMDD were randomised to receive
SSRIs or placebo in a double blind trial for the treatment of premenstrual
syndrome. DATA COLLECTION AND ANALYSIS: 31 randomised controlled trials were
identified which reported the use of SSRIs in the management of PMS. 16 trials
were excluded, 15 trials were included in the systematic review, and ten trials
were included in the main analyses. The reviewers extracted the data
independently and standardised mean differences for continuous outcomes were
estimated from the data. MAIN RESULTS: The primary analysis of reduction in
overall symptomatology included data on 844 women with premenstrual syndrome.
SSRIs were found to be highly effective in treating premenstrual symptoms.
Secondary analysis showed that they were as effective in treating physical as
well as behavioural symptoms. There was no significant difference between trials
funded by pharmaceutical companies and those independently funded. Withdrawals
due to side effects were 2.5 times more likely to occur in the treatment group,
particularly at higher doses. REVIEWER’S CONCLUSIONS: There is now very good
evidence to support the use of selective serotonin reuptake inhibitors in the
management of severe premenstrual syndrome.

Publication Types:
Review, Academic

PMID: 12519554 [PubMed – indexed for MEDLINE]


4: World J Biol Psychiatry. 2002 Jul; 3(3): 147-9.

Myo-inositol has no beneficial effect on premenstrual dysphoric disorder.

Nemets B, Talesnick B, Belmaker RH, Levine J.

Department of Psychiatry, Faculty of Health Sciences, Ben Gurion University of
the Negev, Israel.

Inositol, a simple isomer of glucose, which serves as a precursor in the
phosphatidyl-inositol (PI) second messenger cycle, was shown to be effective in
double-blind, placebo-controlled studies of depression, panic and obsessive
compulsive disorders as well as in bulimia. The following study was designed to
investigate whether inositol has beneficial effects in another disorder shown to
be responsive to SSRIs: premenstrual dysphoric disorder (PMDD). Eleven female
patients with PMDD diagnosed according to DSM-IV participated in a cross-over,
double-blind, placebo-controlled trial. The active drug was myo-inositol, 12 g
daily, whereas placebo was d-glucose administered at the same dose. Each drug
was given during the luteal phase only (14 days prior to menses). For each
patient treatment alternated between these two drugs for six menstrual cycles.
No beneficial effect was demonstrated for inositol over placebo.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12478879 [PubMed – indexed for MEDLINE]


5: Obstet Gynecol. 2002 Dec; 100(6): 1219-29.

Efficacy of intermittent, luteal phase sertraline treatment of premenstrual
dysphoric disorder.

Halbreich U, Bergeron R, Yonkers KA, Freeman E, Stout AL, Cohen L.

State University of New York at Buffalo School of Medicine, 14215, USA.

OBJECTIVE: Premenstrual dysphoric disorder is a menstrually related disorder
that intermittently causes disabling emotional, behavioral, and physical
symptoms. The goal of the current study was to evaluate the efficacy and
tolerability of sertraline for premenstrual dysphoric disorder when treatment
was limited to the luteal phase. METHODS: Two hundred eighty-one women who met
Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria for
premenstrual dysphoric disorder and who completed two prospective screening
cycles and one single-blind placebo cycle were randomized to three cycles of
double-blind, luteal phase treatment with either a placebo or sertraline in a
flexible daily dose of 50-100 mg. Outcome measures included the Daily Record of
Severity of Problems and the Clinical Global Impression Severity and Improvement
scales. RESULTS: Luteal phase treatment with sertraline was significantly
superior to the placebo, as demonstrated by end- point analysis of Clinical
Global Impression Improvement scale scores (sertraline, 2.3 +/- 1.1, versus
placebo, 2.7 +/- 1.1; P <.001), and cycle 3 Daily Record of Severity of Problems
change scores (sertraline, 27.6 +/- 26.8, versus placebo, 17.6 +/- 23.3; P
<.002). A significant difference was also noted in responder rates in favor of
sertraline (50%) versus placebo (26%, P <.001) by cycle 1 (with responder
defined as a Clinical Global Impression Improvement scale score of 1 or 2).
Quality of life and functioning outcomes were also significantly improved.
Intermittent luteal administration of sertraline was well tolerated, with only
approximately 8% of patients on sertraline and less than 1% on placebo
discontinuing because of adverse events. CONCLUSION: Sertraline was
significantly more effective than a placebo and was well tolerated as a
treatment for premenstrual dysphoric disorder when administered intermittently
during the luteal phase of the menstrual cycle.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12468166 [PubMed – indexed for MEDLINE]


6: Obstet Gynecol. 2002 Sep; 100(3): 435-44.

Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a
placebo-controlled, clinical trial using computerized diaries.

Cohen LS, Miner C, Brown EW, Freeman E, Halbreich U, Sundell K, McCray S.

Perinatal Psychiatry Clinical Research Program, Massachusetts General Hospital,
Harvard Medical School, Boston 02114, USA.

OBJECTIVE: To evaluate premenstrual daily dosing with fluoxetine for treatment
of premenstrual dysphoric disorder. METHODS: After a two-cycle screening and
one-cycle single-blind placebo period, 260 women were randomized to fluoxetine
10 mg, fluoxetine 20 mg, or placebo (dosed daily from 14 days before next
expected menses through the first full day of bleeding) for three cycles. Women
recorded premenstrual dysphoric disorder symptoms daily using a computerized
version of the Daily Record of Severity of Problems. RESULTS: Premenstrual daily
fluoxetine 20 mg demonstrated significant improvement in mean Daily Record of
Severity of Problems luteal scores compared with placebo (P =.005); premenstrual
daily fluoxetine 10 mg did not (P =.100). Daily Record of Severity of Problems
total scores were statistically significantly improved by the first treatment
cycle for both active treatment groups. However, only fluoxetine 20 mg remained
statistically significantly superior to placebo throughout the active treatment
phase of the trial. Both fluoxetine groups showed significant treatment
advantage over placebo for mood-related symptoms (P <.05). Only premenstrual
daily fluoxetine 20 mg showed significant treatment advantage over placebo for
physical symptoms of breast tenderness (P <.001), bloating (P =.001), and
joint/muscle pain (P =.037). Treatment was well tolerated; discontinuations due
to adverse events did not differ among the three groups (P =.316). CONCLUSION:
Premenstrual daily dosing with fluoxetine effectively treats mood, physical, and
social functioning symptoms associated with premenstrual dysphoric disorder.
Fluoxetine 20 mg appears to have comparable tolerability with, and better
efficacy than, fluoxetine 10 mg.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 12220761 [PubMed – indexed for MEDLINE]


7: Obstet Gynecol. 2001 Nov; 98(5 Pt 1): 737-44.

Venlafaxine in the treatment of premenstrual dysphoric disorder.

Freeman EW, Rickels K, Yonkers KA, Kunz NR, McPherson M, Upton GV.

Department of Obstetrics/Gynecology, School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-generation
antidepressant that selectively inhibits serotonin and norepinephrine reuptake,
in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted
a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose
trial. After three screening cycles, including a single-blind placebo cycle, 164
women were randomly assigned to double-blind treatment with venlafaxine (50-200
mg/day) or placebo for four menstrual cycles. Primary outcome measures were the
total premenstrual symptom scores as assessed by a daily symptom report (DSR)
and the Hamilton Rating Scale for Depression. RESULTS: Venlafaxine was
significantly more effective than placebo in reducing PMDD symptoms as assessed
by DSR scores (P <.001 for last observation carried forward and observed
analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved
>50% (P =.003). Forty-three percent of venlafaxine subjects versus 25% of
placebo subjects experienced symptom remission, defined as reduction of DSR
scores to the postmenstrual level (P =.034). Venlafaxine treatment was
significantly better than placebo for all statistically derived DSR factors
(mood, function, pain, and physical symptoms). Improvement was relatively swift,
with approximately 80% symptom reduction in the first treatment cycle. Mean
venlafaxine doses ranged from 50 mg/day in the first treatment cycle to 130
mg/day in the fourth treatment cycle. Adverse events such as nausea, insomnia,
and dizziness were mild and transient. CONCLUSIONS: Venlafaxine is significantly
more efficacious than placebo for PMDD treatment. Response to treatment can
occur in the first treatment cycle, and venlafaxine is well tolerated. Further
studies are needed to evaluate the potential of intermittent (luteal phase)
dosing for this cyclic disorder and the efficacy of long-term maintenance
treatment with venlafaxine.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 11704162 [PubMed – indexed for MEDLINE]


8: J Clin Psychiatry. 2000; 61 Suppl 12: 22-7.

Non-antidepressant treatment of premenstrual syndrome.

Pearlstein T, Steiner M.

Butler Hospital, Department of Psychiatry and Human Behavior, Brown University
School of Medicine, Providence, RI 02906, USA.

Although selective serotonin reuptake inhibitors are considered the first-line
treatment option for premenstrual syndrome, several other such options are also
available. Multiple studies have indicated that medications that suppress
ovulation alleviate premenstrual emotional and physical symptoms. However. the
use of such medications, such as the gonadotropin-releasing hormone agonists,
leads to prolonged low estrogen levels and cardiac and osteoporotic health
risks. A recent double-blind, placebo-controlled study of 466 women with
premenstrual syndrome reported that calcium was effective in reducing emotional,
behavioral, and physical premenstrual symptoms. Recent preliminary trials have
suggested efficacy for cognitive therapy, light therapy, and tryptophan. Future
studies of diet recommendations, exercise, relaxation, magnesium, nonsteroidal
anti-inflammatory drugs, diuretics, opiate antagonists, and alternative
therapies are needed.

Publication Types:
Review, Tutorial

PMID: 11041381 [PubMed – indexed for MEDLINE]


9: J Womens Health Gend Based Med. 2000 Mar; 9(2): 131-9.

A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus
50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a
randomized, double-blind, crossover study.

De Souza MC, Walker AF, Robinson PA, Bolland K.

Department of Food Science and Technology, The University of Reading, United

To investigate single and combined effects of daily dietary supplementation with
50 mg of vitamin B6 and 200 mg magnesium (as MgO) for one cycle for the relief
of mild premenstrual symptoms, a randomized, double-blind, placebo-controlled,
crossover design was used. Forty-four women with an average age of 32 years took
part in the study. Each woman was randomly assigned, according to a Latin square
design, to take consecutively all four of the following treatments daily for one
menstrual cycle: (1) 200 mg Mg, (2) 50 mg vitamin B6, (3) 200 mg Mg + 50 mg
vitamin B6 and (4) placebo. Throughout the study, each volunteer kept a daily
record of symptoms using a 5-point ordinal scale in a menstrual diary of 30
symptoms. Symptoms were grouped into six categories: anxiety, craving,
depression, hydration, other, and total. Urinary magnesium output for 24 hours
was estimated using the Mg/creatinine concentration ratio. ANOVA showed no
overall difference between individual treatments, but predefined treatment
comparisons using factorial contrasts in ANOVA showed a significant effect of
200 mg/day Mg + 50 mg/day vitamin B6 on reducing anxiety-related premenstrual
symptoms (nervous tension, mood swings, irritability, or anxiety) (p = 0.040).
Urinary Mg output was not affected by treatment. A small synergistic effect of a
daily dietary supplementation with a combination of Mg + vitamin B6 in the
reduction of mild premenstrual anxiety-related symptoms was demonstrated during
treatment of 44 women for one menstrual cycle. In view of the modest effect
found, further studies are needed before making general recommendations for the
treatment of premenstrual symptoms. The study indicated that absorption from MgO
was poor and daily supplementation for longer than 1 month is necessary for
tissue repletion.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10746516 [PubMed – indexed for MEDLINE]


10: Adv Exp Med Biol. 1999; 467: 85-8.

A placebo-controlled study of the effects of L-tryptophan in patients with
premenstrual dysphoria.

Steinberg S, Annable L, Young SN, Liyanage N.

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

In a randomized controlled clinical trial, 37 patients with premenstrual
dysphoric disorder were treated with L-tryptophan 6 g per day and 34 were given
placebo. The treatments were given under double-blind conditions for 17 days,
from the time of ovulation to the third day of menstruation, during three
consecutive cycles. Visual Analog Mood Scales revealed a significant (p = 0.004)
therapeutic effect of L-tryptophan relative to placebo for the cluster of mood
symptoms comprising the items dysphoria, mood swings, tension and irritability.
These results suggest that increasing serotonin synthesis during the late luteal
phase of the menstrual cycle is therapeutic in patients with premenstrual
dysphoric disorder.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10721042 [PubMed – indexed for MEDLINE]


11: J Am Coll Nutr. 2000 Feb; 19(1): 3-12.

The potential for dietary supplements to reduce premenstrual syndrome (PMS)

Bendich A.

New Product Research, SmithKline Beecham Consumer Healthcare, Parsippany, New
Jersey 07054-3884, USA.

Many types of dietary supplements have been advocated for the reduction of
certain symptoms of premenstrual syndrome (PMS). However, only one
supplement-calcium-has been demonstrated to be of significant benefit in a
large, rigorous, double-blind, placebo-controlled trial. Limited evidence
suggests that magnesium, vitamin E and carbohydrate supplements might also be
useful, but additional research is needed to confirm these findings. Trials of
vitamin B6 supplementation have had conflicting results, and high doses of this
vitamin taken for prolonged periods of time can cause neurological symptoms.
Trials of evening primrose oil have also had conflicting results; the two most
rigorous studies showed no evidence of benefit. A variety of herbal products are
suggested to reduce symptoms of PMS. The efficacy of these products is uncertain
because of a lack of consistent data from scientific studies. Health
professionals should be aware of the possible use of these supplements and ask
those with PMS about their use of such products and counsel them based upon the
totality of evidence.

Publication Types:
Review, Tutorial

PMID: 10682869 [PubMed – indexed for MEDLINE]


12: Acta Obstet Gynecol Scand. 1999 Nov; 78(10): 891-9.

Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist
in a low dose regimen.

Sundstrom I, Nyberg S, Bixo M, Hammarback S, Backstrom T.

Department of Obstetrics and Gynecology, Umea University, Sweden.

BACKGROUND: GnRH agonists constitute a well-documented treatment for
premenstrual syndrome (PMS). However, the hypo-estrogenic state induced by the
treatment renders it less suitable for long-term clinical use. The aim of the
current study was to investigate the efficacy of a low dose GnRH agonist with
respect to its ability to relieve premenstrual symptoms and maintain regular
ovulatory cycles. METHODS: The effect of a low dose GnRH agonist (buserelin) on
luteal phase symptomatology was evaluated in 27 women with severe premenstrual
syndrome. The design was doubleblind, placebo-controlled and cross-over.
Patients were randomized to either GnRH-agonist intranasally in a dosage of 100
microg once daily for two months or placebo for two months before the cross-over
was made. The primary outcome measure consisted of daily symptom ratings for
mood and physical symptoms made by the patients throughout the study. Adverse
events and hormone concentrations were assessed at visits every second week.
RESULTS: Premenstrual irritability and depression were significantly relieved by
low dose GnRH agonist. Positive symptoms such as friendliness and cheerfulness
were also improved during the premenstrual week. Likewise physical symptoms of
swelling and headache displayed a significant improvement during buserelin
treatment, whereas breast tenderness scores were unaffected by the treatment.
The low dose GnRH agonist treatment regimen induced anovulation in as much as
56% of patients, but these subjects were significantly older than those women
who maintained ovulatory cycles throughout the study. CONCLUSION: GnRH treatment
significantly reduced premenstrual depression and irritability. However, low
dose GnRH therapy is prone to induce anovulation, particularly with increasing

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10577620 [PubMed – indexed for MEDLINE]


13: Psychiatry Res. 1999 Jun 30; 86(3): 185-92.

A controlled study of light therapy in women with late luteal phase dysphoric

Lam RW, Carter D, Misri S, Kuan AJ, Yatham LN, Zis AP.

Department of Psychiatry, University of British Columbia, Vancouver Hospital and
Health Sciences Centre, Canada.

Previous studies suggest that light therapy, as used to treat seasonal affective
disorder, may be beneficial for pre-menstrual depressive disorders. We conducted
a six-menstrual cycle randomized, double-blind, counter-balanced, crossover
study of dim vs. bright light therapy in women with late luteal phase dysphoric
disorder (LLPDD). Fourteen women who met DSM-III-R criteria for LLPDD completed
two menstrual cycles of prospective baseline monitoring of pre-menstrual
symptoms, followed by two cycles of each treatment. During the 2-week luteal
phase of each treatment cycle, patients were randomized to receive 30 min of
evening light therapy using: (1) 10000 lx cool-white fluorescent light (active
condition); or (2) 500 lx red fluorescent light (placebo condition),
administered by a light box at their homes. After two menstrual cycles of
treatment, patients were immediately crossed over to the other condition for
another two cycles. Outcome measures were assessed at the mid-follicular and
luteal phases of each cycle. Results showed that the active bright white light
condition significantly reduced depression and pre-menstrual tension scores
during the symptomatic luteal phase, compared to baseline, while the placebo dim
red light condition did not. These results suggest that bright light therapy is
an effective treatment for LLPDD.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10482337 [PubMed – indexed for MEDLINE]


14: Arch Fam Med. 1999 Jul-Aug; 8(4): 328-32.

Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results
of a double-blind, placebo-controlled, crossover study.

Jermain DM, Preece CK, Sykes RL, Kuehl TJ, Sulak PJ.

Department of Pharmacy, Scott & White Memorial Hospital, Temple, Tex., USA.

OBJECTIVE: To test the efficacy of late-luteal phase dosing of sertraline
hydrochloride in women with moderate-to-severe premenstrual dysphoric disorder.
This highly prevalent disorder often causes significant psychosocial impairment.
DESIGN: Double-blind, crossover trial of each 2-menstrual cycle of baseline,
sertraline treatment, and placebo. Randomization to sertraline treatment vs
placebo occurred after a 2-cycle, drug-free period. SETTING: A large outpatient
multispecialty clinic in central Texas. PATIENTS: Fifty-seven women aged 19 to
49 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, diagnosis of premenstrual dysphoric disorder. INTERVENTIONS:
Late-luteal phase treatment with sertraline hydrochloride in daily doses of 50
mg (cycle 1) followed by 100 mg (cycle 2) vs placebo. MAIN OUTCOME MEASURES: The
22-item calendar of premenstrual experiences was completed daily and constituted
the primary outcome measure, consisting of a total score and behavioral and
physical factor scores. RESULTS: A repeated-measures analysis of variance for
crossover designs found a significant beneficial effect from sertraline
treatment in improving the calendar of premenstrual experiences total (P < .01),
behavioral factor (P < .01), and physical factor (P < .04) scores. Most women
improved when taking sertraline, 50 mg, although a dose increase to 100 mg
yielded further improvement in approximately 25% of women. Use of sertraline was
extremely well tolerated; the only adverse event reported by 10% or more of
women was insomnia in 8 (14%) of them. CONCLUSIONS: Luteal phase treatment with
sertraline was a safe and effective treatment for moderate-to-severe
premenstrual dysphoric disorder. Further controlled studies are needed to
confirm the results of this preliminary study.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10418540 [PubMed – indexed for MEDLINE]


15: Am J Obstet Gynecol. 1999 Jan; 180(1 Pt 1): 18-23.

Randomized controlled trial of the management of premenstrual syndrome and
premenstrual mastalgia using luteal phase-only danazol.

O’Brien PM, Abukhalil IE.

Academic Department of Obstetrics and Gynaecology, North Staffordshire Hospital
Trust/Keele University, Stoke-on-Trent, United Kingdom.

OBJECTIVE: Our goal was to evaluate the efficacy and side effects of danazol 200
mg daily given only in the luteal phase of the menstrual cycle to treat
premenstrual syndrome and premenstrual mastalgia. STUDY DESIGN: We conducted a
randomized, double-blind, placebo-controlled study of 3 menstrual cycles in a
postgraduate medical school and National Health Service hospital. The subjects
of the study were 100 women who had been referred to the premenstrual syndrome
clinic at the North Staffordshire Hospital for the management of premenstrual
syndrome and premenstrual breast pain. Outcome measures for the study included
assessment of improvement in symptoms measured by specific daily visual analogue
scales for 4 principal symptoms of premenstrual syndrome and for premenstrual
mastalgia and assessment of side effects and adverse events. RESULTS:
Significant improvement in symptoms was seen in visual analog scores for
mastalgia in months 1 (P =.03), 2 (P =.004), and 3 (P =.01) of the study during
active therapy compared with placebo. No improvement was seen for any other
symptom or for the global premenstrual syndrome score. Side effects on danazol
and on placebo were equal and minimal. CONCLUSIONS: Luteal phase-only danazol is
not effective for the treatment of the general symptoms of premenstrual syndrome
but appears highly effective for the relief of premenstrual mastalgia. This
approach to therapy is associated with few side effects. Studies of cyclic
mastalgia using strict diagnostic criteria are required to see whether the
freedom from symptomatic side effects is found in longer-term studies and to
determine whether such a regimen avoids potentially detrimental effects on the
lipid status.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9914571 [PubMed – indexed for MEDLINE]


16: Am J Obstet Gynecol. 1998 Aug; 179(2): 444-52.

Summary for patients in:
Can Fam Physician. 2002 Apr;48:705-7.

Calcium carbonate and the premenstrual syndrome: effects on premenstrual and
menstrual symptoms. Premenstrual Syndrome Study Group.

Thys-Jacobs S, Starkey P, Bernstein D, Tian J.

St. Luke’s-Roosevelt Hospital Center, College of Physicians and Surgeons,
Columbia University, New York, New York 10019, USA.

OBJECTIVE: Previous reports have suggested that disturbances in calcium
regulation may underlie the pathophysiologic characteristics of premenstrual
syndrome and that calcium supplementation may be an effective therapeutic
approach. To evaluate the effect of calcium carbonate on the luteal and
menstrual phases of the menstrual cycle in premenstrual syndrome, a prospective,
randomized, double-blind, placebo-controlled, parallel-group, multicenter
clinical trial was conducted. STUDY DESIGN: Healthy, premenopausal women between
the ages of 18 and 45 years were recruited nationally across the United States
at 12 outpatient centers and screened for moderate-to-severe, cyclically
recurring premenstrual symptoms. Symptoms were prospectively documented over 2
menstrual cycles with a daily rating scale that had 17 core symptoms and 4
symptom factors (negative affect, water retention, food cravings, and pain).
Participants were randomly assigned to receive 1200 mg of elemental calcium per
day in the form of calcium carbonate or placebo for 3 menstrual cycles. Routine
chemistry, complete blood cell count, and urinalysis were obtained on all
participants. Daily documentation of symptoms, adverse effects, and compliance
with medications were monitored. The primary outcome measure was the
17-parameter symptom complex score. RESULTS: Seven hundred twenty women were
screened for this trial; 497 women were enrolled; 466 were valid for the
efficacy analysis. There was no difference in age, weight, height, use of oral
contraceptives, or menstrual cycle length between treatment groups. There were
no differences between groups in the mean screening symptom complex score of the
luteal (P = .659), menstrual (P = .818), or intermenstrual phase (P = .726) of
the menstrual cycle. During the luteal phase of the treatment cycle, a
significantly lower mean symptom complex score was observed in the
calcium-treated group for both the second (P = .007) and third (P < .001)
treatment cycles. By the third treatment cycle calcium effectively resulted in
an overall 48% reduction in total symptom scores from baseline compared with a
30% reduction in placebo. All 4 symptom factors were significantly reduced by
the third treatment cycle. CONCLUSIONS: Calcium supplementation is a simple and
effective treatment in premenstrual syndrome, resulting in a major reduction in
overall luteal phase symptoms.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9731851 [PubMed – indexed for MEDLINE]


17: Int J Gynaecol Obstet. 1998 Jul; 62(1): 63-7.

A double-blind trial of four medications to treat severe premenstrual syndrome.

Diegoli MS, da Fonseca AM, Diegoli CA, Pinotti JA.

Department of Gynecology and Obstetrics, University of Sao Paulo, Brazil.

OBJECTIVE: To determine the efficacy of fluoxetine (10 mg), alprazolam,
propanolol and pyridoxine in the treatment of severe premenstrual syndrome
(PMS). METHOD: One-hundred and twenty women were divided into four groups of 30
patients. Patients were submitted to a randomized, double-blind,
placebo-controlled treatment and were given 3 months of placebo and 3 months of
active drug. The active drug was pyridoxine (300 mg/day) in group 1; alprazolam
(0.75 mg/day) in group 2; fluoxetine (10 mg/day) in group 3; and propanolol (20
mg/day and 40 mg during the menstrual period) in group 4. RESULTS: Fluoxetine in
10-mg doses obtained a mean reduction of 65.4% in symptoms, followed by
propanolol (58.7%), alprazolam (55.6%), pyridoxine (45.3%) and placebo
(39.4-46.1%). CONCLUSION: Fluoxetine in 10-mg doses presented the best results
for treating premenstrual syndrome.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9722128 [PubMed – indexed for MEDLINE]


18: Harv Rev Psychiatry. 1995 Jan-Feb; 2(5): 233-45.

Pharmacological management of premenstrual disorder.

Altshuler LL, Hendrick V, Parry B.

Department of Psychiatry, UCLA Neuropsychiatric Hospital, USA.

Over the last decade there has been increasing recognition of premenstrual
disorders, and numerous treatments have been tried for symptom relief. A
literature search using Medline was conducted to locate all articles written in
English and including the terms “premenstrual treatment,” “premenstrual
syndrome,” “late luteal phase dysphoric disorder,” or “menstruation and mood”
over the last 30 years. Although more than 300 articles were retrieved, only
one-third of them described double-blind studies and just 41 of the double-blind
studies involved prospective diagnosed patients. The definition of the disorder
varied across studies, as did research design and outcome measures. Many studies
did not assess for Axis I comorbidity, which may have a significant impact on
drug response. We attempted to do a metaanalysis of the existing double-blind,
prospectively diagnosed studies, broken down by drug class and symptom
reduction. However, we could not make statistical comparisons within or across
drug groups to assess efficacy of treatment for specific symptoms due to
differences in outcome-assessment measures across studies. Several promising
pharmacological strategies exist to treat the patient with premenstrual
dysphoric disorder. We review double-blind studies for each class of drugs,
highlight some open studies, and present guidelines. Additional double-blind
studies with prospectively diagnosed patients are needed. Standardization of
definition, design, and outcome measures used in this field is important to
enable direct comparison across studies of different treatment strategies.

Publication Types:

PMID: 9384908 [PubMed – indexed for MEDLINE]


19: Acta Obstet Gynecol Scand. 1995 Nov; 74(10): 803-8.

Treatment of premenstrual syndrome by spironolactone: a double-blind,
placebo-controlled study.

Wang M, Hammarback S, Lindhe BA, Backstrom T.

Department of Obstetrics and Gynecology, Umea University Hospital, Sweden.

BACKGROUND. To reevaluate whether spironolactone, a steroid receptor antagonist,
is effective in improving premenstrual syndrome (PMS) in a double-blind,
placebo-controlled cross over study. METHODS. Thirty-five women with PMS were
given one tablet of 100 mg spironolactone or placebo daily from day 14 of the
menstrual cycle until the first day of the following menstruation. Two
pretreatment cycles were observed for diagnosis in each woman, followed by 6
treatment cycles with spironolactone and placebo applied in either the first or
second 3 months. The assessment of symptoms and diagnosis of PMS were based on
prospective daily self-ratings made by the women using a validated visual
analogue scale. RESULTS. The treatment with spironolactone was associated with
an improvement in PMS symptoms compared to placebo as judged by significant
decrease in negative mood symptom scores (p < 0.001) and somatic symptom scores
(p < 0.001). Of the individual symptoms, spironolactone significantly improved
irritability, depression, feeling of swelling, breast tenderness and food
craving in comparison to placebo. A lasting effect of spironolactone was
observed in women started with spironolactone after cross over to placebo.
CONCLUSIONS. Spironolactone appears to be an effective therapy for the negative
mood changes and somatic symptoms in PMS.

Publication Types:
Clinical Trial
Clinical Trial, Phase II
Randomized Controlled Trial

PMID: 8533564 [PubMed – indexed for MEDLINE]


20: Psychoneuroendocrinology. 1995; 20(2): 193-209.

A randomized, placebo-controlled, crossover trial of danazol for the treatment
of premenstrual syndrome.

Hahn PM, Van Vugt DA, Reid RL.

Department of Obstetrics and Gynaecology, Queen’s University, Kingston, Ontario,

To investigate whether danazol is more effective than placebo for the treatment
of premenstrual syndrome (PMS), we conducted a randomized, double-blind,
crossover study comparing three successive cycles of danazol (200 mg bid) to
three cycles of placebo. Thirty-one women meeting rigorous criteria for a
diagnosis of severe PMS over two pretreatment cycles were enrolled; 28 of these
subjects completed at least one cycle of treatment with symptom recordings,
which were entered into the analysis. A significant period effect confounded the
planned within-subject analysis and therefore, the main treatment comparisons
were confined to the first period only. Symptom scores on the Premenstrual
Tension Self-Rating Scale (PMTS), Beck Depression Inventory (BDI), and a Visual
Analogue Scale (VAS) were compared for the premenstrual week in the last cycle
of treatment. For the 16 patients on danazol, scores on the PMTS decreased by an
average of 14.0 (10.7) (standard deviation) points from a baseline of 25.4 (5.6)
points. For the 12 patients on placebo, PMTS scores decreased by an average of
3.6 (9.5) points from a baseline of 23.5 (5.8) points (14.0 vs. 3.6; p = .0133,
unpaired t-test). Seven (43.8%) of the subjects on danazol achieved a clinically
relevant reduction of symptoms into the asymptomatic range (PMTS scores < or =
5) as compared to one (8.3%) of the subjects on placebo. Thus, danazol (200 mg
bid) provided greater relief from severe PMS during the premenstrual week than
did placebo.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 7899538 [PubMed – indexed for MEDLINE]


21: Obstet Gynecol. 1994 Sep; 84(3): 379-85.

Alprazolam in the treatment of two subsamples of patients with late luteal phase
dysphoric disorder: a double-blind, placebo-controlled crossover study.

Berger CP, Presser B.

Department of Obstetrics and Gynaecology, Montreal General Hospital, Quebec,

OBJECTIVE: To assess the efficacy of alprazolam in the treatment of two groups
of patients diagnosed with late luteal phase dysphoric disorder (LLPDD). The
first group met only the diagnostic criteria for LLPDD. The second group
experienced LLPDD and mild symptoms of anxiety and depression during the
follicular phase. METHODS: A double-blind, placebo-controlled crossover design
was used. Patients were treated with alprazolam and placebo for 3 months each
and completed daily measures of anxiety, tension, depression, irritability, and
feelings of being out of control. RESULTS: The response to alprazolam differed
significantly by group. For the first group, alprazolam (0.25 mg three times a
day) relieved the severity of tension (P = .001), irritability (P = .005),
anxiety (P = .008), and feelings of being out of control (P = .012) more than
placebo. Few side effects were reported; the incidence (P = .001) and severity
(P = .001) of side effects were dose-related. Alprazolam and placebo did not
differ for the second group, and the incidence and severity of side effects were
unrelated to dose. CONCLUSIONS: Alprazolam benefits women diagnosed solely with
LLPDD. It is not recommended for patients who experience LLPDD as well as
symptoms of mild anxiety or depression during the follicular phase.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8058235 [PubMed – indexed for MEDLINE]


22: Obstet Gynecol. 1993 Jan; 81(1): 93-8.

Essential fatty acids in the treatment of premenstrual syndrome.

Collins A, Cerin A, Coleman G, Landgren BM.

Department of Psychiatry, Karolinska Institute, Stockholm, Sweden.

OBJECTIVE: To determine whether essential fatty acids are effective in the
treatment of premenstrual syndrome (PMS). METHODS: In a randomized,
double-blind, crossover trial, we studied 27 women diagnosed with PMS over ten
menstrual cycles and 22 symptom-free controls over one cycle. The first cycle
was used for diagnostic assessment. For the women with PMS, placebos were
administered during the second cycle. This was followed by randomization to four
cycles of active treatment with essential fatty acids and four cycles of
placebo, with a crossover after completion of the fourth cycle. Assessment of
symptoms and diagnosis of PMS were based on daily self-ratings made by the women
throughout the study. RESULTS: Treatment with essential fatty acids did not
reduce premenstrual symptoms or symptom cyclicity. However, time had a
significant effect on a number of symptoms, indicating either a placebo effect
or an effect from participation in the study. Women with PMS had a significantly
higher frequency of dysmenorrhea and familial PMS than did the symptom-free
controls. CONCLUSION: Treatment with essential fatty acids is ineffective
therapy for PMS. The improvement we observed over time can be ascribed to either
a placebo effect or participation in the study.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8416468 [PubMed – indexed for MEDLINE]


23: Aust N Z J Obstet Gynaecol. 1991 Nov; 31(4): 366-8.

Premenstrual syndrome and spironolactone.

Burnet RB, Radden HS, Easterbrook EG, McKinnon RA.

Endocrine and Metabolic Unit, Royal Adelaide Hospital, South Australia.

A double blind placebo controlled randomized cross over study was conducted to
assess the response to spironolactone by patients suffering from ‘Premenstrual
Syndrome’. Somatic and neuropsychiatric symptoms were self-assessed daily and a
total score was calculated for each symptom for the 14 days prior to
menstruation. No significant difference was noted for the symptoms assessed on
or off spironolactone. The levels of oestradiol, progesterone and prolactin
showed no changes from the first to the second half of the cycle. In those
patients who did respond to spironolactone, a significant difference in androgen
levels from the follicular to the luteal phase of the cycle prior to treatment
was demonstrated. Significant differences in androgen levels from the follicular
to the luteal phase of the menstrual cycle may therefore be an important
determinant in predicting those patients with premenstrual syndrome likely to
respond to spironolactone therapy.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 1799355 [PubMed – indexed for MEDLINE]


24: Obstet Gynecol. 1991 Aug; 78(2): 177-81.

Oral magnesium successfully relieves premenstrual mood changes.

Facchinetti F, Borella P, Sances G, Fioroni L, Nappi RE, Genazzani AR.

University Centre for Adaptive Disorders and Headache, Department of Obstetrics
and Gynecology, University of Pavia, Italy.

Reduced magnesium (Mg) levels have been reported in women affected by
premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation
on premenstrual symptoms, we studied, by a double-blind, randomized design, 32
women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress
Questionnaire. After 2 months of baseline recording, the subjects were randomly
assigned to placebo or Mg for two cycles. In the next two cycles, both groups
received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was
administered three times a day, from the 15th day of the menstrual cycle to the
onset of menstrual flow. Blood samples for Mg measurement were drawn
premenstrually, during the baseline period, and in the second and fourth months
of treatment. The Menstrual Distress Questionnaire score of the cluster “pain”
was significantly reduced during the second month in both groups, whereas Mg
treatment significantly affected both the total Menstrual Distress Questionnaire
score and the cluster “negative affect.” In the second month, the women assigned
to treatment showed a significant increase in Mg in lymphocytes and
polymorphonuclear cells, whereas no changes were observed in plasma and
erythrocytes. These data indicate that Mg supplementation could represent an
effective treatment of premenstrual symptoms related to mood changes.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 2067759 [PubMed – indexed for MEDLINE]


25: JAMA. 1990 Jul 18; 264(3): 349-53.

Comment in:
JAMA. 1990 Jul 18;264(3):387.
JAMA. 1991 Jan 2;265(1):26.

Ineffectiveness of progesterone suppository treatment for premenstrual syndrome.

Freeman E, Rickels K, Sondheimer SJ, Polansky M.

Department of Obstetrics/Gynecology, School of Medicine, University of
Pennsylvania, Philadelphia 19104.

Progesterone is the most widely used treatment for premenstrual syndrome. To
answer definitely the question of whether progesterone suppositories are
effective for the treatment of premenstrual syndrome, a randomized,
placebo-controlled, double-blind crossover study of 168 women, receiving
progesterone in doses of 400 and 800 mg or placebo, was carried out.
Premenstrual symptoms were not significantly improved by progesterone compared
with placebo in any measure used in the study, including daily symptom reports
maintained throughout treatment, clinician evaluation of improvement, and
patient global reports of symptoms severity, relief, and disruption of daily
activity. No symptom cluster or individual symptom differed significantly
between progesterone and placebo treatment. These treatment results were not
significantly affected by fluctuations in response during the placebo washout
period, pretreatment levels of depression or anxiety at either postmenstrual or
premenstrual times, or any of 19 other background, medical history, or symptom
variables examined individually as covariates with treatment.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 2194047 [PubMed – indexed for MEDLINE]


26: J R Coll Gen Pract. 1989 Sep; 39(326): 364-8.

Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover

Doll H, Brown S, Thurston A, Vessey M.

Department of Community Medicine and General Practice, Oxford.

A randomized double-blind crossover trial was conducted to study the effects of
pyridoxine (vitamin B6) at a dose of 50 mg per day on symptoms characteristic of
the premenstrual syndrome. Sixty three women aged 18-49 years, identified by
means of a general practice based survey of menstrual patterns in the community,
entered the trial. All of the women had noticed moderate to severe premenstrual
symptoms during the previous year. The women kept a daily menstrual diary which
graded the severity of nine individual symptoms from zero to three. After
completing a diary for an initial month the women were randomized to receive
either drug or placebo for three months, after which the treatments were crossed
over for a further three months. Thirty two women completed the full seven
months of the study. In these women a significant beneficial effect (P less than
0.05) of pyridoxine was observed on emotional type symptoms (depression,
irritability and tiredness). No significant effect was observed on premenstrual
symptoms of any other type.

PIP: Researchers initiated a randomized double blind crossover trial as part of
a community based postal survey of menstrual patterns of 68 women in England.
Each woman jotted down daily the severity of symptoms (e.g., depression,
headache, etc.). After this 1st study cycle and being randomly assigned to the
pyridoxine or placebo group, they either took 50 mg/day of pyridoxine or placebo
tablets for 3 months. At the end of 3 months, they followed the other
treatment. 37 women completed 6 months and only 32 completed the full 7 months.
The results of the study show pyridoxine to significantly affect emotional type
symptoms (depression, irritability, and tiredness [p.05]), but not somatic
(headache, breast discomfort, swollen abdomen, swollen hands or feet) or
menstrual (stomach cramps, backache, other) symptoms. Women who took oral
contraceptives (OCs) had nonsignificant higher adjusted premenstrual symptom
scores, particularly for emotional type symptoms, during both pyridoxine and
placebo months that did those who did not take OCs. This study was complicated
by a placebo effect. It revealed a significant decrease in the level of all
symptom scores from the 1st month to the 4th month by a mean of 57% (p=.001)
when the women took the placebo initially. Emotional type symptoms decreased by
69% (p.05), somatic type by 52% (p.05), and menstrual type nonsignificantly by
15%. On the other hand, when women took the placebo after taking pyridoxine for
a month, the combined level of all symptom scores only increased 37% on average
(nonsignificant). Based on the results of this study, pyridoxine appears to
alleviate premenstrual depression. Further research is needed to confirm the
results of this and other similar studies.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 2558186 [PubMed – indexed for MEDLINE]


27: J Gen Intern Med. 1989 May-Jun; 4(3): 183-9.

Calcium supplementation in premenstrual syndrome: a randomized crossover trial.

Thys-Jacobs S, Ceccarelli S, Bierman A, Weisman H, Cohen MA, Alvir J.

Department of Medicine, Metropolitan Hospital, New York Medical College, New

OBJECTIVE: To determine the efficacy of calcium supplementation in women with
premenstrual syndrome (PMS). DESIGN: Randomized, double-blind crossover trial.
SETTING: Outpatient medical clinic of a large city hospital. PARTICIPANTS:
Seventy-eight women were initially screened. Trial selection was based on a
history of recurrent PMS symptoms and on the results of a prospective assessment
of daily symptom scores. Only women with symptom scores during the late luteal
phase that were at least 50% greater than those during the intermenstrual phase
were selected. Thirty-three women completed the trial. INTERVENTION: A
preliminary evaluation included physical examination, routine laboratory tests,
dietary assessment, and psychiatric evaluation. Each participant received six
months of treatment involving three months of daily calcium supplementation
(1,000 mg of calcium carbonate) and three months of placebo. MEASUREMENTS:
Efficacy was assessed prospectively by changes in daily symptom scores over a
six-month period and retrospectively by an overall global assessment.
Multivariate repeated measures analysis of variance on symptom ratings derived
from daily PMS symptom scores demonstrated a reduction in symptoms on calcium
treatment during both the luteal (p = 0.011) and the menstrual phases (p =
0.032) of the reproductive cycle. Calcium supplementation had no effect during
the intermenstrual phase. Retrospective assessment of overall symptoms confirmed
this reduction: 73% of the women reported fewer symptoms during the treatment
phase on calcium, 15% preferred placebo, and 12% had no clear preference. Three
premenstrual factors (negative affect [p = 0.045]; water retention [p = 0.003];
pain [p = 0.036]) and one menstrual factor (pain [p = 0.02]) were significantly
alleviated by calcium. CONCLUSION: Calcium supplementation is a simple and
effective treatment for premenstrual syndrome, but further studies will be
needed to determine its precise role in PMS.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 2656936 [PubMed – indexed for MEDLINE]


28: Obstet Gynecol. 1987 Aug; 70(2): 145-9.

The effects of vitamin B6 supplementation on premenstrual symptoms.

Kendall KE, Schnurr PP.

A double-blind controlled study of the effects of vitamin B6 supplementation on
premenstrual symptoms was conducted. Fifty-five women who reported moderate to
severe premenstrual mood changes participated in the study. Symptoms were
monitored prospectively through daily home record-keeping over a one-month
baseline period followed by two months of treatment. Subjects were randomly
assigned to receive daily supplements of 150 mg of vitamin B6 or placebo over
the entire two-month treatment period. Analysis of covariance suggested that
even though vitamin B6 may improve premenstrual symptoms related to autonomic
reactions (eg, dizziness and vomiting) and behavioral changes (eg, poor
performance and decreased social activities), a significant amount of physical
and affective symptomatology remained during the premenstrual phase. In light of
recently reported, potentially toxic effects of low doses of vitamin B6, our
results call for caution in using this therapy for premenstrual symptoms.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 3299182 [PubMed – indexed for MEDLINE]


29: Curr Med Res Opin. 1987; 10(7): 450-6.

A double-blind, placebo-controlled evaluation of spironolactone in the
premenstrual syndrome.

Vellacott ID, Shroff NE, Pearce MY, Stratford ME, Akbar FA.

The effect of spironolactone in the alleviation of the symptoms of the
premenstrual syndrome was compared with placebo in a double-blind, parallel
group controlled study. One tablet daily of 100 mg spironolactone or placebo was
given to 63 women from Day 12 of the menstrual cycle until the first day of the
next menstrual bleed. This regimen was repeated for two consecutive cycles.
Spironolactone was statistically significantly superior in providing relief from
bloatedness (p less than 0.001). No statistically significant changes were
observed in blood biochemistry of plasma hormone levels of oestradiol,
progesterone or prolactin, though an increase in serum aldosterone levels was
seen in the spironolactone-treated group. No differences were detected in
weight, blood pressure or the incidence and severity of complaints following

Publication Types:
Clinical Trial
Controlled Clinical Trial
Randomized Controlled Trial

PMID: 3621990 [PubMed – indexed for MEDLINE]