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
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Question 1ReproductiveMedium
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?
AProstaglandin excess in the endometrium driving systemic symptoms
BSubclinical major depression unmasked in the luteal phase
CElevated prolactin producing breast tenderness and mood symptoms
DCNS sensitivity to normal cyclical ovarian hormone shifts
Reveal answer & full explanation
Correct answer: D — CNS sensitivity to normal cyclical ovarian hormone shifts
AProstaglandin excess in the endometrium driving systemic symptoms
BSubclinical major depression unmasked in the luteal phase
CElevated prolactin producing breast tenderness and mood symptoms
DCNS sensitivity to normal cyclical ovarian hormone shifts✓
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.
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.
Question 2ReproductiveMedium
A 29-year-old woman reports irritability, depressed mood, breast tenderness, and a sense of being overwhelmed that begin about a week before her period each month and resolve within a few days of menses onset. A prospective symptom diary kept over two consecutive cycles confirms that her mood symptoms are confined to the luteal phase, with a symptom-free follicular phase, and that they significantly impair her work and relationships. TSH and a CBC are normal. She does not currently desire contraception. Which of the following is the most appropriate initial pharmacologic management?
ASpironolactone
BLeuprolide
CSertraline
DAlprazolam
Reveal answer & full explanation
Correct answer: C — Sertraline
ASpironolactone
BLeuprolide
CSertraline✓
DAlprazolam
Why Sertraline is correct
This vignette meets DSM-5-TR criteria for PMDD: >=5 symptoms including mood symptoms, confined to the luteal phase with a symptom-free follicular phase, prospectively documented over 2 cycles, with significant impairment.
SSRIs (sertraline, fluoxetine, paroxetine, citalopram, escitalopram) are the guideline first-line pharmacotherapy for PMDD and severe PMS. They work rapidly here, often within days, unlike in major depression, so they can be dosed continuously or only during the luteal phase (cycle days 14-28).
A drospirenone-containing 24/4 combined oral contraceptive is the other FDA-approved first-line option, but this patient does not desire contraception, making an SSRI the preferred initial choice.
Why the others are wrong
Spironolactone is a second-line, targeted therapy for premenstrual bloating and breast tenderness; it does not address the predominant mood and impairment burden that defines PMDD.
Leuprolide is a GnRH agonist that induces medical menopause; it is reserved (with add-back estrogen and progestin) for severe, refractory cases after first-line therapy fails.
Alprazolam is occasionally used for premenstrual anxiety but carries dependence and sedation risk and is not a guideline-recommended first-line agent for PMDD.
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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
GnRH agonists (leuprolide) with add-back estrogen/progestin for severe refractory cases
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
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