Cyclical physical and mood symptoms in the luteal phase; PMDD is the severe form.
Also known as: PMS, PMDD, premenstrual dysphoric disorder, premenstrual syndrome
Overview
PMS is the cyclical occurrence of one or more bothersome physical, behavioral, or mood symptoms in the luteal phase, resolving within a few days of menses onset, with a symptom-free interval in the follicular phase. PMDD (DSM-5-TR diagnosis) requires >=5 symptoms with at least one being a mood symptom and causing significant impairment.
Epidemiology
Up to 80% of menstruating women report some premenstrual symptoms. PMS affects 20-30% with bothersome symptoms; PMDD affects 3-8%.
Try two board-style Premenstrual Syndrome (PMS) and PMDD questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1PsychiatryMedium
A 28-year-old woman presents with five months of mood swings, irritability, tearfulness, and difficulty concentrating that occur in the week before menses and resolve within a few days of menstrual onset. She charts her symptoms prospectively for two consecutive cycles and reports symptom-free intervals during the follicular phase. The symptoms cause significant impairment at work and strain her marriage. Her medical history and physical exam are unremarkable. Which of the following is the most appropriate first-line pharmacologic therapy?
ALithium
BBupropion
CSertraline
DAlprazolam
EProgesterone
Reveal answer & full explanation
Correct answer: C — Sertraline
ALithium
BBupropion
CSertraline✓
DAlprazolam
EProgesterone
Why Sertraline is correct
This patient meets DSM-5 criteria for premenstrual dysphoric disorder (PMDD): affective and somatic symptoms confined to the luteal phase, prospectively confirmed across at least two cycles, with full remission shortly after menses and clinically significant impairment
SSRIs are first-line pharmacotherapy for PMDD; sertraline, fluoxetine, paroxetine, and citalopram have the strongest evidence
SSRIs for PMDD can be dosed either continuously or only during the luteal phase, with onset of benefit within days rather than the weeks required for major depressive disorder
Why the others are wrong
Alprazolam — can blunt premenstrual anxiety but carries dependence and sedation risks and is not first-line for PMDD
Bupropion — lacks efficacy data for PMDD and is generally avoided because it does not address the serotonergic mechanism implicated in luteal-phase mood symptoms
Lithium — a mood stabilizer used for bipolar disorder; has no role in PMDD, which is a depressive-spectrum disorder confined to the luteal phase
Progesterone — the luteal-phase timing invites the idea of a progesterone deficiency, but PMDD reflects an abnormal response to normal cyclic hormone changes rather than low progesterone, and trials have not shown progesterone supplementation to outperform placebo
Question 2ReproductiveMedium
A 29-year-old woman reports that for the past year she develops severe irritability, depressed mood, breast tenderness, and bloating beginning about 8 days before each period and resolving within 2 days of menses onset. A prospective symptom diary kept over three consecutive cycles confirms that she is symptom-free during the follicular phase. Serum estradiol, progesterone, and TSH levels checked in the luteal phase are all within normal limits. She is diagnosed with premenstrual dysphoric disorder. Which of the following best explains the findings?
ACNS sensitivity to normal cyclical ovarian hormone shifts
BElevated prolactin producing breast tenderness and mood symptoms
CSubclinical major depression unmasked in the luteal phase
DMineralocorticoid excess driving luteal sodium and water retention
EProstaglandin excess in the endometrium driving systemic symptoms
Reveal answer & full explanation
Correct answer: A — CNS sensitivity to normal cyclical ovarian hormone shifts
ACNS sensitivity to normal cyclical ovarian hormone shifts✓
BElevated prolactin producing breast tenderness and mood symptoms
CSubclinical major depression unmasked in the luteal phase
DMineralocorticoid excess driving luteal sodium and water retention
EProstaglandin excess in the endometrium driving systemic symptoms
Why CNS sensitivity to normal cyclical ovarian hormone shifts is correct
In PMS/PMDD, ovarian hormone levels are NORMAL; symptoms arise because genetically susceptible individuals have altered serotonergic and GABAergic responses to the ordinary luteal-phase rise and fall of estradiol and progesterone.
Allopregnanolone, a progesterone metabolite that modulates GABA-A receptors, is implicated, which is why symptoms track the luteal phase and remit with menses.
This explains the normal estradiol, progesterone, and TSH in this patient: the abnormality is the CNS response, not the hormone concentrations themselves.
Why the others are wrong
Prostaglandin excess in the endometrium driving systemic symptoms — endometrial prostaglandins mediate primary dysmenorrhea, producing cramping pelvic pain that begins with bleeding, not affective symptoms that start 8 days before menses and remit once flow starts.
Subclinical major depression unmasked in the luteal phase — that pattern is premenstrual exacerbation of an underlying mood disorder, which her prospective three-cycle diary excludes by documenting complete freedom from symptoms during the follicular phase.
Elevated prolactin producing breast tenderness and mood symptoms — hyperprolactinemia causes noncyclical mastalgia with galactorrhea and oligomenorrhea or amenorrhea; her symptoms are strictly luteal with regular menses, and prolactin excess is not the mechanism of PMDD.
Mineralocorticoid excess driving luteal sodium and water retention — luteal fluid retention is the intuitive explanation for her bloating and breast tenderness, but aldosterone-driven sodium retention is not a consistent finding in PMDD and could not produce the irritability and depressed mood that dominate her symptoms; the abnormality is the CNS response to normal hormone shifts.
ACOG and DSM-5-TR frame PMDD as an abnormal neurobiologic response to normal cyclical hormone changes, confirmed by prospective symptom diaries across at least 2 cycles.
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Premenstrual Syndrome (PMS) and PMDD outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Symptoms are triggered by normal cyclical changes in ovarian hormones (estradiol and progesterone) in genetically susceptible individuals with altered serotonergic and GABAergic responses. Allopregnanolone, a progesterone metabolite acting on GABA-A receptors, is implicated.
Clinical presentation
Symptoms
Mood: irritability, depression, anxiety, mood lability, anger, sense of being overwhelmed, decreased interest, difficulty concentrating
Physical: bloating, breast tenderness, headache, fatigue, joint/muscle aches, appetite/sleep changes
Symptoms appear in late luteal phase (~1-2 weeks before menses) and resolve within a few days of menses onset
Signs / physical exam
Physical exam is typically normal
Mental status exam may demonstrate dysphoria during luteal phase
Differential diagnosis
Major depressive disorder or anxiety disorder — Persistent symptoms NOT confined to luteal phase; prospective symptom diary distinguishes
Bipolar disorder — Mood symptoms not strictly cyclical; manic/hypomanic episodes
Thyroid disease — TSH and free T4 abnormal
Premenstrual exacerbation (PME) of an underlying disorder — Symptoms present throughout cycle but worsen premenstrually; treat the primary disorder
Perimenopause — Irregular cycles, vasomotor symptoms, age usually >40
Prospective symptom diary across at least 2 cycles documenting symptom timing and resolution. ACOG PMS criteria: >=1 affective or somatic symptom, in the 5 days before menses, in 3 consecutive cycles, with relief within 4 days of menses, no symptoms days 5-12 of cycle, and impairment. DSM-5-TR PMDD: >=5 symptoms with at least 1 from mood category, prospective documentation across 2 cycles, significant impairment.
Labs
Targeted to rule out medical mimics: TSH, CBC if fatigue, prolactin if galactorrhea/amenorrhea
For PMDD or severe PMS: SSRI (fluoxetine, sertraline, paroxetine, citalopram, escitalopram) — either continuous OR luteal-phase dosing (cycle days 14-28); rapid onset (often within days)
Combined oral contraceptive containing drospirenone with a 24/4 regimen (e.g., Yaz) — FDA-approved for PMDD
Second-line / adjunct
Spironolactone 50-100 mg in luteal phase for bloating, mastalgia
Targeted symptom therapy: NSAIDs for dysmenorrhea/headache, diuretics for edema
Surgical: bilateral oophorectomy (with hysterectomy) — last resort for severe, refractory PMDD
GnRH agonists (leuprolide) with add-back estrogen/progestin for severe refractory cases after SSRI and COC failure
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.