Evidence-Based Management of Premenstrual Disorders (PMDs)

 
 
EVIDENCE-BASED MANAGEMENT OF PREMENSTRUAL DISORDERS (PMDS )
 
 Note: This guide is intended primarily as a resource for healthcare providers. If you are a patient, we recommend you also check out our treatment options
page designed for patients: iapmd.org/treatment-options.  
 
Premenstrual Disorders such as Premenstrual Dysphoric Disorder (PMDD) and Premenstrual Exacerbation (PME) of psychiatric disorders are complex to
diagnose and treat. Below, we provide guidelines to help healthcare providers educate and treat their patients effectively. 
 
 
ASSESSMENT AND DIAGNOSIS OF PMDS :
 
Ultimately, each patient with premenstrual symptoms is unique and deserves a compassionate healthcare provider who will work with them to find an
effective treatment--or set of treatments-- for their unique needs. To confirm the diagnosis, two months of daily symptom ratings are recommended to
differentiate between PMDD (symptoms present only premenstrually), PME (symptoms always present but worsened premenstrually), and non-cyclical
symptoms. Daily ratings can also be continued in the context of treatment to evaluate effectiveness over time. A daily symptom rating form can be
downloaded at iapmd.org/provider-resources. If desired, standardized scoring of these daily ratings to determine diagnosis can be accomplished using the
C-PASS scoring system available at iapmd.org/c-pass-- this is especially encouraged in research contexts.

Please note that it is possible to have both PMDD (five symptoms that are present only in the luteal phase) and also PME of other underlying disorders.  
 
 

TREATMENT OF PMDS :
 
Since this is a relatively new area of medical science, the number of randomized controlled trials for PMDs remains relatively small. However, several
treatments have been found to be effective, and more are currently under investigation. Below, we outline what the scientific evidence indicates about
how the average person with a premenstrual disorder (typically PMDD - PME is less well-studied) will respond to various treatments. Many patients utilizing
IAPMD services have already tried many of the treatments below with no relief, whereas others have tried none. 

The purpose of this document is not to provide a “one-size-fits-all” recommendation for the treatment of premenstrual disorders; rather, it is to help those
seeking information about effective treatments by reviewing the best evidence about general efficacy and safety of each treatment in those with
premenstrual disorders.  
 
 

 
Please visit iapmd.org for more information and resources. Join the IAPMD Professional Community to increase your skills
and knowledge in treating PMDs: iapmd.org/pro.
 
  This guide was prepared by the IAPMD Clinical Advisory Board under the direction of Dr. Tory Eisenlohr-Moul.

© 2023 International Association for Premenstrual Disorders

 
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)

TREATMENTS WITH STRONG SCIENTIFIC EVIDENCE FOR EFFICACY AND SAFETY IN PMDD 
Important Note: Because nearly all clinical trials in this area have focused on PMDD, the tables below are organized according to effectiveness and  safety
of treatments for PMDD; however, please note accompanying information about possible efficacy in PME of psychiatric disorders. 
   
 
 
TREATMENT EFFICACY IN
PMDD EFFICACY
IN PME SIDE EFFECTS

AND MECHANISM

OF
SAFETY ACTION

SELECTIVE SEROTONIN REUPTAKE

Strong evidence of efficacy for Untested for PME of psychiatric  Well tolerated in general, but Normalizes altered 
INHIBITORS (SSRIS)
PMDD in many trials. Response disorders, but is a rational  side effects are common. Most premenstrual serotonin 
rates in randomized controlled treatment choice for PME of  frequent side effects are function in PMDD, and
- fluoxetine 20mg (“Prozac”)
trials are around 60%. SSRIs disorders for which SSRIs are nausea, low energy, sleepiness, alters metabolism of
- sertraline 50-150mg (“Zoloft”)
tend to have a rapid effect, the first-line treatment (i.e.,  and decreased libido. progesterone to its
- paroxetine 20-30mg (“Paxil”)
often performing better than depression and anxiety).  neuroactive metabolites.
- citalopram 20-30mg (“Celexa”)

placebo after just one day.

- escitalopram 10-20mg (“Lexapro”)

Dosing Schedule:
Symptom-Onset, Luteal, or
Continuous

DROSPIRENONE-CONTAINING ORAL
CONTRACEPTIVE PILL WITH
SHORTENED HORMONE-FREE
INTERVAL
- drospirenone 3mg/
ethinylestradiol .02mg daily (e.g.,
“Yaz”)
Evidence of efficacy for PMDD  One study shows no benefit for  Well tolerated, generally few Prevention of ovulation
from two randomized PME of depressive disorders  side  effects. Risk of blood and  related hormone
controlled  trials. Usually when given as an adjunctive  clot and  estrogen- flux in PMDD.  
effective in first  month of treatment to SSRI.  dependent cancers  should
treatment. Response  rates be considered based on 
were 48% and 61%. Effects  may individual risk profiles.  
be smaller than SSRIs.   
  Some individuals do not
tolerate  progestins and

develop chronic  symptoms

Dosing: 24-4 or continuous similar to PMDD;  progestin
dosing (i.e., shortened or treatment should be 
  eliminated hormone-free discontinued in these
  interval)   patients. 

© 2023 International Association for Premenstrual Disorders page 1 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH STRONG SCIENTIFIC EVIDENCE FOR EFFICACY AND SAFETY IN PMDD 
 
TREATMENT EFFICACY IN
PMDD EFFICACY
IN PME SIDE EFFECTS

AND MECHANISM

OF
SAFETY ACTION

GNRH ANALOGUES Many trials demonstrate  Two studies (1, 2) show no Menopausal symptoms. Suppression of ovulation
effectiveness for severe PMDD.   benefit for subsamples with PME Requires Suppression of and  related hormone
Dosing: Monthly outpatient   of depressive disorders. ovulation and hormone flux. 
injections Typically reserved for those who   
replacement to prevent related
have failed to respond to both However, no evidence is hormone flux bone loss.
- leuprolide 3.75mg monthly SSRI and OCs.  available regarding
injection (“Lupron”)   effectiveness
- goserelin 3.6mg monthly Not effective when ovulation is not  when long-term hormone
injection
suppressed. addback is provided

(see below).

(“Zoladex”)  
Note: If PME (e.g., of depression)
is comorbid with other symptoms
(e.g., anxiety, irritability) that DO
show a PMDD-like confinement
to the luteal phase, treatment
may still be indicated for PMDD.

GNRH ANALOGUES + STABLE Many trials demonstrate  Untested for PME of depressive In two studies, the first month Suppression of ovulation
HORMONE ADDBACK effectiveness for severe PMDD.   disorders, but represents a of  stable oral estrogen + and  related hormone flux. 
  rational option to trial for vaginal  progesterone  
- transdermal estradiol addback Typically reserved for those who  treatment-resistant patients. addback caused a 
(“Climara”) have failed to respond to both SSRI  resurgence of PMDD
- progestogen addback for and OCs.  Note: If PME (e.g., of symptoms,  but symptoms
endometrial protection
depression) is comorbid

with remitted after 1 
month.

(“Prometrium”) other symptoms (e.g., anxiety, Patients should be  informed

irritability) that DO show a of possible short-term 
  PMDD-like confinement to the symptom flare and
    luteal phase, treatment may be appropriate  supports should
indicated for PMDD. be provided. 

© 2023 International Association for Premenstrual Disorders page 2 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH STRONG SCIENTIFIC EVIDENCE FOR EFFICACY AND SAFETY IN PMDD 
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF



ACTION

SAFETY

TOTAL HYSTERECTOMY WITH  Studies indicate that THBSO is Untested, but a rational A very routine and safe  Complete cessation of
BILATERAL SALPINGO- Untested, but a rational treatment choice for a patient gynecologic procedure, but ovarian activity and related
OOPHORECTOMY  effective for those patients who who has improved during hormone flux.
still major abdominal surgery
treatment choice for a patient GnRH agonist trial.
(THBSO)  improve during GnRH agonist who with risks (including bleeding, 
If patient does not tolerate
  has improved during GnRH infection, and death). Risk 
- removal of both ovaries is  GnRH analogues (and
trial. agonist trial. increases with other medical 
required  therefore cannot get a “fair
- removal of uterus is indicated to  GnRH trial”), THBSO may still conditions (heart, lung, liver,
If patient does not tolerate GnRH

eliminate need for progestin 

be indicated given evidence

analogues (and therefore cannot or kidney disease, obesity,

addback post-surgery  of severe cyclicity.
get a “fair GnRH trial”), THBSO diabetes, history of prior
may still be indicated given may still
surgery). 
be indicated given evidence of
severe cyclicity. Permanent. Requires hormone 
replacement to prevent bone 
loss. 

COGNITIVE-BEHAVIORAL CBT is a useful tool for  reducing Untested for PME of Well tolerated, generally few Reduction in
THERAPIES  functional  impairment related to psychiatric  disorders but is a side  effects when provided neurobiological  stress
Dosing: Weekly sessions with a  emotional symptoms across rational  treatment choice by a  qualified professional.  responses, improved 
qualified therapist with  appropriate disorders, and some evidence given the  widespread   coping and relationships. 
training in CBT and  DBT.  suggests it may be supportive for effectiveness of CBT  for  
  patients with PMDD specifically. psychiatric disorders.  
- Cognitive Behavioral Therapy  (CBT)   
- Dialectical Behavior Therapy  DBT is effective for preventing 
  (DBT)  suicidal behaviors, a common 
  outcome in severe cases of 
    should be paid to  the

Close attention PMDD.  

quality of the therapy being  provided;
providers not engaging  in skills
training or providing  behavioral
homework  assignments to patients
should  be replaced with providers
more  adherent to CBT principles.  

© 2023 International Association for Premenstrual Disorders page 3 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH LIMITED BUT PROMISING SCIENTIFIC EVIDENCE FOR EFFICACY AND SAFETY IN PMDD
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF


SAFETY
ACTION

5-ALPHA REDUCTASE INHIBITORS
- dutasteride 2.5mg/day (“Avodart”)
Note: finasteride is untested in
clinical trials but is sometimes used in
clinical practice due
to its shorter
is
be monitored 
One study shows improvement
in PMDD symptoms with
dutasteride; dosage must be
high enough to inhibit
formation of
allopregnanolone.
disorders, this medication
Untested for PME of psychiatric
disorders. Given evidence of
reduced biosynthesis of
GABAergic neurosteroids (e.g.,
allopregnanolone) in chronic
depressive and anxiety
Causes birth defects if  Prevents formation of (and
conception occurs while on flux in) neurosteroid
the drug; a period of washout metabolites of progesterone.
is needed prior to pregnancy
to avoid birth defects. 
 
Patients should

half-life, which may reduce the risk of

not recommended for PME of
closely for side effects since
birth defects in the event of psychiatric disorders as it may
no long-term trials exist in
pregnancy. further exacerbate
PMDD. In other populations,
neurosteroid deficits.
Available primarily in USA these medications can cause 

depression.  

OVULATION SUPPRESSION USING
TRANSDERMAL ESTRADIOL +
CYCLICAL PROGESTOGEN
.1mg Transdermal E2 Patch (twice
weekly; “Vivelle”) + norethisterone
1mg/day, 10 days per cycle18
There have been two positive  Increased risk of blood clots,  Suppression of ovulation
Not tested.  increased breast cancer risk,
trials (1,2).   and  related hormone flux.
  and  increased endometrial   
May represent alternative to OCs  thickening/cancer risk can
for those who cannot tolerate  occur  in at-risk women,
synthetic progestins if  particularly  with inadequate
progestogen  opposition. 
anovulation can be achieved at 
safe doses. 

Alternative Progestogen for
Endometrial Protection:
  - levonorgestrel-containing IUD
  (“Mirena”)  
More work is needed to 
determine the safety and
efficacy  of various doses.  
 

Available primarily in the UK

QUETIAPINE (LUTEAL PHASE;

Generally safe and well Unknown. 
One small trial demonstrated  Not tested. 
ADJUNCT TO SSRI) benefit as an adjunctive  tolerated,  but potential for
treatment to SSRI.   serious and  life-threatening


side effects. 

- 25mg quetiapine/day during the

luteal phase (“Seroquel”)

© 2023 International Association for Premenstrual Disorders page 4 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH LIMITED BUT PROMISING SCIENTIFIC EVIDENCE FOR EFFICACY AND SAFETY IN PMDD
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF


SAFETY
ACTION

ISOALLOPREGNANOLONE Two clinical trials have tested  One study demonstrated no  Initial studies show few side  Blocks or reverses
Sepranolone against placebo in  benefit for PME of psychiatric  effects.  paradoxical effects of
INJECTIONS  PMDD. In the first randomized  disorders. progesterone-derived
(“Sepranolone”)  neurosteroids (e.g.,
controlled trial, Sepranolone 
  allopregnanolone) at
Varying; dosages in development  showed effectiveness for 
  PMDD. However, Sepranolone  GABA-A

NOT YET AVAILABLE  receptor in PMDD.

failed to beat placebo in the 
 
second trial, which may have 
been due to a very large and 
persistent placebo response.  
 

OVULATION SUPPRESSION USING
TRANSDERMAL ESTRADIOL +
CYCLICAL PROGESTOGEN
.1mg Transdermal E2 Patch (twice
weekly; “Vivelle”) + norethisterone
1mg/day, 10 days per cycle18
There have been two positive  Increased risk of blood clots,  Suppression of ovulation
Not tested.  increased breast cancer risk,
trials (1,2).   and  related hormone flux.
  and  increased endometrial   
May represent alternative to OCs  thickening/cancer risk can
for those who cannot tolerate  occur  in at-risk women,
synthetic progestins if  particularly  with inadequate
progestogen  opposition. 
anovulation can be achieved at 
safe doses. 

Alternative Progestogen for
Endometrial Protection:
  - levonorgestrel-containing IUD
  (“Mirena”)  
More work is needed to 
determine the safety and
efficacy  of various doses.  
 

Available primarily in the UK

QUETIAPINE (LUTEAL PHASE;

Generally safe and well Unknown. 
One small trial demonstrated  Not tested. 
ADJUNCT TO SSRI) benefit as an adjunctive  tolerated,  but potential for
treatment to SSRI.   serious and  life-threatening


side effects. 

- 25mg quetiapine/day during the

luteal phase (“Seroquel”)

© 2023 International Association for Premenstrual Disorders page 5 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH NO EVIDENCE, MIXED EVIDENCE, OR NEGATIVE EVIDENCE FOR EFFICACY IN PMDD
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF


SAFETY
ACTION

LIFESTYLE CHANGES   A healthy lifestyle improves Not studied.  N/A  N/A 

  general mental and physical
- Improved diet  health. However, only low-quality
- Increased exercise  evidence is available linking these
- Reduced caffeine
outcomes to premenstrual
intake 

symptoms, and findings are

- Reduced alcohol intake 
mixed. May be more appropriate
for mild
premenstrual symptoms than for
PMDD.

 
VITAMIN AND MINERAL  Mixed evidence. May be more Not tested.  Supplements are readily  N/A 
SUPPLEMENTS  appropriate for mild available, but also poorly 
regulated in the United
premenstrual symptoms than for
States.  Risk of overdose or
PMDD. toxicity. Very  safe if taken


in consultation
with  a

Some evidence that calcium, provider. 

magnesium, Vit D, and Vit B6
supplements may improve
premenstrual symptoms.

LEVONORGESTREL-  Four studies show inconsistent  Risk of blood clot and 

Not tested.  Prevention of ovulation. 
CONTAINING  CONTINUOUS effects in PMDD, with some  estrogen-dependent
ORAL CONTRACEPTIVE  PILL  cancers  should be
  demonstrating benefit and 
  considered based on 
- levonorgestrel others not. 
    .09mg + .02mg  individual risk profiles.  
ethinylestradiol daily with no  pill-  
free interval (“Lybrel”)  Some individuals do not

tolerate  oral contraceptives

and develop  chronic or

cyclical symptoms  similar to
PMDD;  progestin-
containing medications
should be  discontinued for
these patients. 

© 2023 International Association for Premenstrual Disorders page 6

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH NO EVIDENCE, MIXED EVIDENCE, OR NEGATIVE EVIDENCE FOR EFFICACY IN PMDD
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF


SAFETY
ACTION

COMBINED EE + PROGESTIN  Not yet tested, but is known Not tested.   Risk of blood clot and  Efficacy not yet
VAGINAL RING CONTRACEPTIVE to consistently suppress   established.
estrogen-dependent cancers 
RING  ovulation and may be a rational Given the lack of efficacy of should be considered based on 
(“Nuvaring”)  treatment  other ovulation-inhibiting agents individual risk profiles.  
  given efficacy of other  in PME of depression, a  

Can be easily removed by 

ovulation-suppression agents in  beneficial effect is not

patient. 
PMDD; however, patient should  necessarily  expected. 
be monitored for 
progestin-induced mood 
symptoms. 

LEVONORGESTREL-CONTAINING  No evidence available, but not a  No evidence, but not a rational  May have adverse effects N/A; not expected to be
INTRAUTERINE DEVICE (IUD) rational treatment given that  treatment given that they do on  physiological stress effective.
  they do NOT consistently  NOT consistently suppress  responses;  many women
(“Mirena”, “Skyla”) 

suppress ovulation.  ovulation 

discontinue due
to 

  depressive symptoms. 
 

 
No evidence available, but not a  No evidence, but not a rational  Heavy periods. N/A; not expected to be
COPPER IUD rational treatment given its  treatment given its inability to  effective.
inability to suppress ovulation.  suppress ovulation.
(“Paragard”) 

    Not effective for emotional  Not tested. Not recommended 

DANAZOL Common side effects include Efficacy not yet
PMDD symptoms when  given side effect profile.  acne, weight gain, hirsutism, established. 
(“Danocrine”)  considering the whole cycle.   deepening of the voice; some


changes may be
irreversible.

May cause birth defects.

© 2023 International Association for Premenstrual Disorders page 7 

   
  
 
Evidence-Based Management of Premenstrual Disorders (PMDs)
  TREATMENTS WITH NO EVIDENCE, MIXED EVIDENCE, OR NEGATIVE EVIDENCE FOR EFFICACY IN PMDD
 
TREATMENT EFFICACY IN PMDD EFFICACY IN PME SIDE EFFECTS AND MECHANISM OF


SAFETY
ACTION

BENZODIAZEPINES  Mixed evidence, with  well-
  controlled studies showing  either
- alprazolam (“Xanax”)  no benefit or some  benefit.
  Tolerance and reduced  efficacy
expected with long-term  use. Not
indicated for those with  marked
Not tested for PME. High risk of addiction and Sedation.
abuse; indicated for those  
 
with marked tolerance
often develops. Withdrawal
can be life-threatening.  

impulsivity or  family/personal

history of drug  abuse. Not  
indicated for daily or  long-term
use. 
 
   

ORAL MICRONIZED PROGESTERONE  Several studies show that this  Not tested in PME.  Progestins can trigger mood  N/A, not effective. 
OR PROGESTINS ONLY.  is ineffective, and is likely to  symptoms, particularly acutely.
  worsen symptoms in the first 
- usually given in the luteal phase  month.  

only 

 
RECOMMENDED READING:  
 
- Up-to-Date Guidelines for Management of Premenstrual Syndrome and PMDD
  - Royal College of Obstetrics and Gynecology Guidelines for the Management of Premenstrual Syndrome
  -  
International Society for Premenstrual Disorders Consensus Guidelines 
 

© 2023 International Association for Premenstrual Disorders page 8