Eduovisual
Female Reproductive & Breast
Premenstrual syndrome and PMDD: diagnosis and treatment
— Premenstrual syndrome (PMS): physical and/or affective symptoms occurring in the luteal phase (5–7 days before menses), resolving within 4 days of menses onset, causing functional impairment
— Premenstrual dysphoric disorder (PMDD): severe affective variant in DSM-5-TR; ≥5 symptoms with at least one being mood-related (marked depression, anxiety, affective lability, or irritability/anger), causing significant distress or interference
— Premenstrual exacerbation (PME): worsening of a preexisting disorder (MDD, GAD, bipolar, migraine, IBS) in the luteal phase — not PMDD
— Up to 80% of cycling persons report mild premenstrual symptoms; 20–30% meet PMS criteria; 3–8% meet PMDD criteria
— Onset typically late teens to 20s; symptoms often worsen in late 30s–40s and remit at menopause
— Pregnancy and anovulation suppress symptoms (confirming ovulatory etiology)
— Normal ovarian steroid fluctuations trigger aberrant CNS response, particularly in serotonergic and GABAergic (allopregnanolone) systems — not an absolute hormone excess or deficiency
— Implication: SSRIs and ovulation suppression both work; checking estradiol/progesterone is not diagnostic
— Cyclical irritability, mood lability, bloating, breast tenderness, food cravings, fatigue in a reproductive-age woman
— Symptom-free week after menses is the diagnostic anchor
— Functional impairment differentiates disorder from normal premenstrual molimina
Board pearl: The single most distinguishing feature of PMDD vs MDD is the symptom-free follicular phase (roughly cycle days 6–13). If a patient is symptomatic throughout the cycle with luteal worsening, think PME of MDD, not PMDD — treatment strategy differs (continuous SSRI rather than luteal-phase dosing as an option).
Step 3 management anchor: Diagnosis is clinical and prospective via 2 cycles of daily symptom charting — not by labs, imaging, or single-visit history.
— Affective core (≥1 required): marked affective lability; marked irritability/anger or interpersonal conflict; marked depressed mood/hopelessness/self-deprecation; marked anxiety/tension/"on edge"
— Additional symptoms: decreased interest, concentration difficulty, lethargy/fatigue, appetite change/food cravings, hypersomnia or insomnia, feeling overwhelmed/out of control
— Physical: breast tenderness/swelling, joint/muscle pain, bloating, weight gain sensation, headache
— Symptoms present in most cycles over the prior year
— Begin in the week before menses (luteal phase)
— Improve within a few days after onset of menses
— Minimal or absent in the week post-menses (follicular phase)
— "Are there any days each month when you feel completely back to your baseline?" — a clear yes points to PMDD/PMS
— Cycle regularity, contraception use, prior pregnancies (postpartum depression history increases PMDD risk)
— Screen for suicidality — PMDD carries elevated suicidal ideation risk concentrated in the luteal phase
— Substance use, sleep, exercise, caffeine, alcohol (alcohol sensitivity often worsens luteally)
— Family history of PMS/PMDD, mood disorders, postpartum depression
— Daily Record of Severity of Problems (DSRP) or similar tool over 2 consecutive ovulatory cycles
— Without prospective data, the diagnosis is provisional — retrospective recall is unreliable and overdiagnoses PMDD
Key distinction: A patient who says symptoms are "always there but worse before my period" should not be diagnosed with PMDD on history alone — chart first, because PME of an underlying disorder is more likely and changes treatment (treat the primary disorder continuously).
Step 3 management: When a patient describes classic cyclical symptoms, the next best step is prospective symptom diary for 2 cycles, not empiric SSRI, not serum hormones, not pelvic ultrasound.
— PMS/PMDD has no diagnostic physical findings — exam is performed to exclude mimics and assess comorbidities, not to confirm the diagnosis
— A normal exam in a patient with classic cyclical symptoms supports the diagnosis
— Vital signs: BP (baseline before SSRI; rule out hypertension that might mimic headaches/anxiety), BMI (obesity worsens symptoms and influences treatment selection), thyroid-relevant HR
— Thyroid: palpate for goiter or nodules — hypothyroidism mimics fatigue, weight gain, low mood; hyperthyroidism mimics anxiety, irritability
— Breast exam: evaluate cyclic mastalgia; rule out dominant mass or skin changes
— Abdominal exam: assess for tenderness, masses, hepatomegaly (relevant if considering hepatically metabolized agents)
— Pelvic exam: indicated if dysmenorrhea, dyspareunia, abnormal bleeding, or pelvic pain accompany the picture — rule out endometriosis, fibroids, adenomyosis, ovarian cyst
— Neurologic and mental status: affect, mood, suicidality assessment, cognition
— Quantify impairment: missed work/school days per cycle, relationship conflict, parenting difficulties
— Validated instruments: PHQ-9 (screen for underlying MDD), GAD-7, MDQ (rule out bipolarity before starting SSRI), AUDIT-C
— Document baseline functional metrics — useful for tracking response
— Orthostatics if reporting marked fatigue or syncope (consider anemia from heavy menses)
— Suicide risk stratification: ideation, plan, intent, access to means, prior attempts; PMDD-specific peri-menstrual suicide spikes are recognized
Board pearl: A reproductive-age woman with cyclical mood symptoms and a positive MDQ for hypomania should not be started on an SSRI before psychiatric clarification — risk of inducing mania. Step 3 management: screen for bipolarity in every patient before initiating an SSRI for presumed PMDD.
— There is no blood test, imaging study, or hormone level that confirms PMS or PMDD
— Ordering serum estradiol, progesterone, FSH, or LH for PMDD workup is a wrong answer on Step 3
— Tool: Daily Record of Severity of Problems (DRSP) — patient rates 21 items daily on a 1–6 scale
— Duration: minimum 2 consecutive cycles
— Diagnostic criteria require:
— ≥30% increase in symptom severity in the luteal phase vs follicular phase (PMS)
— DSM-5-TR criteria fulfilled in ≥2 prospectively charted cycles (PMDD)
— TSH — fatigue, weight changes, mood symptoms overlap with thyroid disease
— CBC — anemia from menorrhagia worsens fatigue/irritability
— Comprehensive metabolic panel if considering pharmacotherapy or symptoms suggest electrolyte disturbance
— Beta-hCG before initiating SSRIs, hormonal therapy, or spironolactone in a person who could become pregnant
— Vitamin D, B12 if fatigue prominent or dietary concerns
— Ferritin if heavy menstrual bleeding
— PHQ-9 and GAD-7 at baseline and to monitor response
— MDQ or CIDI-3 to screen for bipolar spectrum before SSRI initiation
— Columbia Suicide Severity Rating Scale (C-SSRS) if suicidality endorsed
— Pelvic ultrasound only if abnormal bleeding, palpable mass, or pelvic pain — not for PMDD diagnosis
— No role for brain imaging unless focal neurologic findings or atypical headaches
Key distinction: A patient whose "diary" shows symptoms every day of the cycle has not confirmed PMDD — they have confirmed a chronic mood or anxiety disorder requiring continuous treatment.
Step 3 management: First-step workup = 2-cycle prospective symptom diary + TSH + pregnancy test before any pharmacotherapy decision.
— When prospective charting is equivocal or the patient has failed first-line therapy, a 3-month trial of leuprolide (with or without add-back hormone therapy) can confirm ovarian-cycle dependence
— Symptom resolution during medical ovarian suppression strongly supports PMDD/PMS
— Persistence of symptoms despite suppression suggests an underlying mood disorder (PME) rather than PMDD
— Not first-line due to cost, bone density loss, and vasomotor side effects — reserved for diagnostic confirmation prior to considering oophorectomy
— Charting that shows no symptom-free week post-menses → PME
— Charting that shows clear luteal worsening with symptom-free follicular phase → PMDD
— This distinction drives treatment: PME needs continuous treatment of the primary disorder; PMDD can be treated continuously OR luteal-phase only
— Suspect hyperthyroidism, Cushing syndrome, PCOS, or perimenopause if irregular cycles or systemic features
— FSH/estradiol useful for perimenopausal transition diagnosis (not PMDD per se)
— 24-hour urine free cortisol or dexamethasone suppression only if Cushing features present
— Consider polysomnography if hypersomnia, snoring, or daytime sleepiness disproportionate to mood — OSA can mimic the fatigue/irritability cluster
— Iron deficiency (even without anemia, ferritin <30) contributes to fatigue and cognitive symptoms; supplementation may meaningfully improve PMS-like fatigue
— Suicidality, bipolar features, treatment-resistant PMDD, substance use comorbidity, history of trauma/PTSD
Board pearl: A leuprolide trial that abolishes symptoms in a patient with chronic mood complaints is diagnostic of PMDD and predicts response to definitive ovarian suppression strategies.
Step 3 management: Reserve advanced testing for refractory or diagnostically unclear cases; do not order GnRH trials before SSRIs.
— Step 1 — Lifestyle and conservative measures (mild PMS): aerobic exercise 30 min ≥3×/week, sleep hygiene, stress reduction (CBT, mindfulness), reduced caffeine/alcohol/sodium in luteal phase, complex carbohydrates
— Step 2 — Supplements with reasonable evidence: calcium carbonate 1000–1200 mg/day (best evidence), vitamin B6 ≤100 mg/day (avoid higher doses — neuropathy risk), magnesium 200–360 mg/day, chasteberry (Vitex agnus-castus) — variable evidence
— Step 3 — Pharmacotherapy (moderate-severe PMS or PMDD): SSRIs (first-line for PMDD) or combined oral contraceptives (drospirenone/EE 20 mcg 24/4 regimen is FDA-approved)
— Step 4 — Second-line pharmacotherapy: SNRIs, alternative COCs, continuous COC dosing
— Step 5 — GnRH agonists with add-back hormone therapy
— Step 6 — Surgical (bilateral salpingo-oophorectomy ± hysterectomy) — last resort, only after confirmed response to medical ovarian suppression
— PMDD with prominent mood symptoms → SSRI (sertraline, fluoxetine, escitalopram, paroxetine)
— PMS with prominent physical symptoms or contraception desired → drospirenone-containing COC
— Mixed picture → either, often SSRI first given rapid response in PMDD
— Continuous daily dosing — preferred if PME suspected or partial luteal response
— Luteal-phase dosing (14 days before menses through day 1) — equally effective for pure PMDD; reduces side-effect burden and cost
— Symptom-onset dosing — emerging evidence; start at first symptoms each cycle
Key distinction: SSRIs in PMDD work within days (not weeks like in MDD) because they act via rapid neurosteroid modulation, not chronic receptor downregulation — this enables luteal-phase dosing.
Step 3 management: For moderate-severe PMDD with no contraindications, initiate sertraline 50 mg daily or luteal-phase as first-line.
— FDA-approved for PMDD: fluoxetine, sertraline, paroxetine CR
— Typical dosing:
— Sertraline 50–150 mg/day (start 25–50 mg)
— Fluoxetine 20 mg/day (10–20 mg)
— Escitalopram 10–20 mg/day
— Paroxetine 12.5–25 mg CR/day
— Dosing schedules: continuous daily, luteal-phase (14 days pre-menses), or symptom-onset
— Onset: mood and irritability often improve within 1–2 days of dosing — distinct from MDD
— Common side effects: nausea, headache, insomnia/somnolence, sexual dysfunction (often dose-limiting in PMDD population), GI upset
— Discontinuation: luteal-phase dosing avoids withdrawal; for continuous use, taper gradually (especially paroxetine)
— Caution: screen for bipolar disorder before initiation; pregnancy considerations (avoid paroxetine — category D); QT prolongation with high-dose citalopram
— First-line COC: drospirenone 3 mg / ethinyl estradiol 20 mcg, 24 active/4 placebo — FDA-approved for PMDD
— Drospirenone has antimineralocorticoid and antiandrogenic activity — mitigates bloating and acne
— Shortened hormone-free interval (4 days) reduces hormone withdrawal symptoms
— Alternative strategies: continuous (no placebo week) or extended-cycle COCs
— Drospirenone caution: hyperkalemia risk — avoid with renal/hepatic/adrenal insufficiency or concurrent potassium-sparing agents (ACEi/ARB/spironolactone/NSAIDs chronic use)
— VTE risk: drospirenone COCs carry slightly elevated VTE risk vs levonorgestrel; screen for thrombophilia history, smoking >35, migraine with aura (absolute contraindication)
— Progestin-only methods (DMPA, levonorgestrel IUD) — not first-line; can worsen mood symptoms in susceptible patients
— Venlafaxine XR 75–112.5 mg/day — effective in PMDD; consider if SSRIs fail or anxiety predominant
Board pearl: Combined SSRI + COC is reasonable if monotherapy fails — they act on different mechanisms (CNS serotonin vs ovarian suppression).
Step 3 management: Smoker >35 with PMDD → SSRI, not COC (COC contraindicated).
— Indication: severe PMDD refractory to SSRIs and COCs
— Mechanism: pituitary downregulation → anovulation → eliminates hormonal trigger
— Add-back therapy required if used >6 months: low-dose estrogen + progestin (continuous combined HRT) to prevent bone loss and vasomotor symptoms
— Monitor: bone density (DEXA) at baseline and annually, lipids, vasomotor symptoms
— Serves as a diagnostic and therapeutic trial before considering surgery
— Dose: 50–100 mg/day in luteal phase or continuous
— Best for physical symptoms: bloating, breast tenderness, fluid retention, mastalgia
— Monitor potassium and creatinine; avoid combining with drospirenone COCs
— Mefenamic acid or naproxen for mastalgia, headache, dysmenorrhea, myalgias
— Start 1–2 days before expected symptoms, continue through menses
— Alprazolam — limited luteal-phase role for severe anxiety/insomnia; risk of dependence limits utility; not first-line
— Buspirone — modest benefit, can be used continuously
— CBT — effective, durable, recommended alongside pharmacotherapy
— Light therapy — modest benefit if seasonal pattern
— Acupuncture, yoga, mindfulness — supportive, low harm
— Allopregnanolone modulators (sepranolone, ulipristal in trials) — investigational
— Reserved for severe, refractory, life-disrupting PMDD
— Prerequisites: confirmed response to medical ovarian suppression (GnRH trial), completed childbearing, age-appropriate, comprehensive informed consent
— Requires lifelong HRT until age of natural menopause (~51) to prevent osteoporosis, cardiovascular disease, cognitive decline
— Hysterectomy permits estrogen-only HRT (avoids progestin-induced mood symptoms)
CCS pearl: Order DEXA at baseline before GnRH initiation, repeat at 12 months; advance clock through 2 cycles for treatment-response assessment.
Step 3 management: Surgery is never the first or second answer — confirm medical ovarian suppression response first.
— Drospirenone-containing COCs contraindicated in renal insufficiency (CrCl <50 mL/min reduced; renal failure absolute contraindication) due to hyperkalemia risk
— SSRIs: generally safe; reduce dose modestly in severe CKD; sertraline preferred (hepatic metabolism, low active metabolite burden)
— Spironolactone: avoid in CKD stage 3b–5; monitor K+ closely if used
— NSAIDs: avoid in CKD ≥ stage 3
— COCs contraindicated in active liver disease, cirrhosis with portal hypertension, hepatic adenoma, acute hepatitis
— SSRIs: reduce dose; sertraline and escitalopram preferred over fluoxetine (long half-life accumulates)
— Avoid paroxetine in hepatic impairment
— COC contraindications: prior VTE/PE, known thrombophilia, ischemic heart disease, stroke, uncontrolled hypertension, migraine with aura, smoker >35
— SSRIs: monitor QTc with citalopram (max 20 mg in age >60 or CYP2C19 poor metabolizers); sertraline safer
— Hypertension: COCs may raise BP; check at 3 months after initiation
— COCs generally safe in uncomplicated DM without vascular disease; avoid with neuropathy, nephropathy, retinopathy, or DM >20 years
— Weight neutrality favors SSRIs over mirtazapine/TCAs for comorbid mood symptoms
— Migraine with aura = absolute contraindication to estrogen-containing COCs (stroke risk)
— Use SSRI ± progestin-only contraception or SSRI alone
— Triptans + SSRIs/SNRIs: monitor for serotonin syndrome (clinically rare but board-favorite)
— Fluoxetine and paroxetine are strong CYP2D6 inhibitors — affect tamoxifen, opioids (reduce tramadol/codeine efficacy), antipsychotics
— SSRIs + NSAIDs/anticoagulants → bleeding risk
— COCs reduce lamotrigine levels (relevant in epilepsy/bipolar)
Key distinction: Smoker >35, migraine with aura, prior VTE, or uncontrolled HTN → SSRI pathway, not COC pathway, regardless of patient preference.
Step 3 management: Always reconcile potassium status before drospirenone or spironolactone.
— PMS/PMDD symptoms resolve during pregnancy (anovulation) — diagnostic confirmation
— Postpartum recurrence is common and may overlap with postpartum depression — screen with EPDS at 6-week visit and beyond
— History of PMDD predicts postpartum depression — high-yield association
— If pharmacotherapy needed in pregnancy: sertraline preferred; avoid paroxetine (cardiac malformations, category D)
— COCs contraindicated in pregnancy; spironolactone contraindicated (antiandrogenic, feminization of male fetus)
— Sertraline is first-line SSRI in lactation (lowest infant serum levels)
— Fluoxetine: longer half-life, more accumulation in infant — caution especially in preterm/neonates
— COCs containing estrogen may reduce milk supply early postpartum — progestin-only methods preferred <6 weeks postpartum
— Drospirenone/EE acceptable after 6 weeks if breastfeeding well established and no VTE risk
— PMS/PMDD often worsens in late reproductive years and perimenopause due to erratic ovarian function
— Hormone variability increases — symptoms may become less predictable
— Treatment shifts toward continuous SSRI and menopausal hormone therapy rather than COCs as fertility declines
— Symptoms resolve at menopause — natural endpoint
— PMS/PMDD can begin shortly after menarche; diagnosis still requires prospective charting
— Consider developmental context: academic stress, eating disorders, depression frequently overlap
— First-line: lifestyle, CBT, calcium; SSRIs reserved for moderate-severe PMDD (fluoxetine and escitalopram have adolescent depression data)
— Black-box warning: SSRIs increase suicidal ideation in patients <25 — close monitoring weekly for first month
— COCs acceptable if contraception also desired and no contraindications; bone density implications minor in healthy teens
— Premenopausal oophorectomy for PMDD requires HRT until age ~51 to mitigate osteoporosis, cardiovascular, and cognitive risks
Board pearl: A patient with prior PMDD presents 3 weeks postpartum with severe mood symptoms → screen aggressively for postpartum depression; the conditions share neurosteroid sensitivity.
Step 3 management: Pregnancy test before every prescription of teratogenic or pregnancy-incompatible agents.
— Suicidality — PMDD is associated with a roughly 2–4× increased lifetime suicide attempt risk; ideation concentrated in late luteal phase
— Occupational impairment: absenteeism, presenteeism, missed promotions
— Relationship and family dysfunction: increased divorce risk, interpersonal violence (both victim and perpetrator), impaired parenting
— Academic underperformance in students
— Comorbid mood and anxiety disorder development (PMDD predicts MDD)
— Substance use disorders (self-medication with alcohol, cannabis)
— SSRI: sexual dysfunction (very common, often dose-limiting), GI upset, insomnia or somnolence, weight changes, hyponatremia (especially elderly — uncommon in PMDD-typical age), bleeding risk with NSAIDs/anticoagulants, discontinuation syndrome (paroxetine, venlafaxine), rare serotonin syndrome
— COC: VTE (3–9 per 10,000 woman-years; drospirenone slightly higher than levonorgestrel), arterial events (MI, stroke — especially smokers >35 and migraine with aura), hypertension, breast tenderness, breakthrough bleeding, mood worsening in some
— Drospirenone-specific: hyperkalemia — especially with ACEi/ARB/spironolactone/NSAIDs
— GnRH agonists: bone mineral density loss, vasomotor symptoms, vaginal atrophy, lipid changes, mood effects
— Spironolactone: hyperkalemia, menstrual irregularity, breast tenderness, dehydration
— Surgery: surgical menopause sequelae — osteoporosis, CV disease, cognitive decline, sexual dysfunction; surgical complications
— Misdiagnosis as MDD or bipolar leading to inappropriate continuous antipsychotic/mood stabilizer use
— Under-recognition — patients normalize symptoms and don't seek care for years
— Diagnostic delay averages 5–10 years from symptom onset
— Children of mothers with severe PMDD show increased behavioral difficulties during maternal luteal phases — argues for active treatment
Board pearl: A PMDD patient newly started on COC who develops unilateral leg swelling and pleuritic chest pain → CT-PA, anticoagulation, and discontinue the COC.
Step 3 management: Counsel every PMDD patient explicitly about suicidality, especially in the late luteal phase, and document a safety plan.
— Active suicidal ideation with plan/intent or recent attempt → emergency department, psychiatric evaluation, possible inpatient admission
— Acute psychosis (rare but reported in severe PMDD)
— Severe interpersonal violence concern (perpetration or victimization)
— Catastrophic functional collapse (unable to perform ADLs)
— Failure of two adequate SSRI trials at therapeutic doses
— Suspected bipolar spectrum disorder (positive MDQ, family history, prior antidepressant-induced hypomania)
— Comorbid PTSD, eating disorder, substance use disorder
— Treatment-resistant PMDD requiring GnRH consideration
— Postpartum recurrence with severe symptoms
— Need for GnRH agonist therapy and add-back management
— Consideration of surgical management (BSO ± hysterectomy)
— Coexisting conditions: endometriosis, fibroids, abnormal uterine bleeding interfering with COC selection
— Contraceptive complexity (history of VTE, thrombophilia)
— Cardiovascular risk stratification before COC
— Thrombophilia workup if VTE history or strong family history
— Bone density monitoring during GnRH use
— Metabolic monitoring (lipids, glucose, BP, weight) on long-term hormonal therapy
— Worsening despite 8 weeks of optimized first-line therapy → switch agent or add COC
— Patient develops VTE on COC → discontinue, start anticoagulation, switch to non-estrogen strategy, hematology consult for thrombophilia evaluation
— New-onset migraine with aura on COC → discontinue COC immediately, switch to SSRI/progestin-only contraception
— Suicidality requiring stabilization
— Severe COC complications (VTE, stroke)
— Adrenal crisis-like presentations on spironolactone/drospirenone with hyperkalemia and AKI
CCS pearl: A PMDD patient on drospirenone COC + lisinopril presents with weakness and K+ 6.4 — discontinue both, give calcium gluconate, insulin/dextrose, kayexalate as needed, telemetry, recheck K+ q2h, recheck creatinine.
Step 3 management: Always document suicide risk assessment and safety plan in the chart at every PMDD visit.
— Most important mimic — symptoms present throughout cycle, worse luteally
— Underlying: MDD, GAD, panic disorder, bipolar II, PTSD, ADHD, migraine, IBS, asthma, seizure disorders, eating disorders
— Treatment: continuous treatment of the primary disorder (not luteal-phase SSRI)
— Pain-predominant, occurs during menses (not before)
— Treat with NSAIDs, COCs; not characterized by mood symptoms
— Chronic pelvic pain, dysmenorrhea, dyspareunia, infertility
— May overlap with PMS but pain is the dominant feature and often persists beyond menses
— Workup: pelvic exam, US, laparoscopy if needed
— Heavy menstrual bleeding, bulk symptoms, dysmenorrhea
— Imaging-confirmed; treatment differs
— Oligomenorrhea/amenorrhea, hyperandrogenism, metabolic features
— Absence of regular ovulatory cycles makes typical PMS/PMDD pattern less common
— Irregular cycles, vasomotor symptoms, sleep disruption, mood lability
— FSH variability; age 40+ context
— May overlap with worsening PMDD
— Galactorrhea, menstrual irregularity, headache, visual changes
— Check prolactin if atypical
— Isolated breast tenderness without other PMS symptoms — typically responds to evening primrose oil, NSAIDs, supportive bra; minor entity
— Mid-cycle pain (mittelschmerz) — different timing
— Ovarian cyst rupture can mimic acute abdomen, unrelated to PMS
Key distinction: PMS/PMDD requires a symptom-free follicular phase; if symptoms persist throughout the cycle, the diagnosis is not PMDD — chart, identify underlying disorder, treat continuously.
Board pearl: A patient with "PMDD" who fails 3 SSRIs and 2 COCs has likely been misdiagnosed — re-chart and look for bipolar II or PME of MDD.
Step 3 management: Re-examine the prospective diary before escalating therapy — most "treatment-resistant PMDD" is misdiagnosis.
— Persistent low mood ≥2 weeks, no cyclic pattern
— May have premenstrual exacerbation but baseline is depressed
— Treatment: continuous antidepressant therapy; consider augmentation, psychotherapy
— Chronic worry/anxiety without clear cyclic remission
— PME common; treat the primary disorder
— Cyclic mood changes can be confused with cyclic premenstrual mood
— Key features: episodes lasting days–weeks not tied to menstrual cycle, hypomania, family history
— Critical to identify before SSRI start — risk of inducing mania or rapid cycling
— Screen with MDQ, CIDI-3
— Trauma history, hyperarousal, avoidance, re-experiencing
— Symptoms triggered by reminders, not cycle phase
— May coexist with PMDD; trauma-informed care essential
— Pervasive affective instability, identity disturbance, impulsivity, interpersonal chaos across all contexts
— Not cyclic; requires DBT/structured psychotherapy
— Hypothyroidism: fatigue, weight gain, depression, cold intolerance
— Hyperthyroidism: anxiety, irritability, palpitations, weight loss
— Check TSH; treat primary disease
— Fatigue, irritability, poor concentration
— Common with heavy menstrual bleeding
— CBC, ferritin; iron supplementation
— Alcohol, cannabis, stimulants — can mimic or worsen mood symptoms
— Pattern of use may correlate with cycle (self-medication) confounding the picture
— OSA, insomnia → fatigue, irritability, mood disturbance
— Menstrual migraine occurs perimenstrually; mood symptoms may co-occur but headache is the primary complaint
— Treat with triptans, NSAIDs, preventive therapy
Key distinction: Cyclical pattern with complete follicular-phase remission is the discriminator — every other psychiatric and medical mimic lacks this feature.
Step 3 management: Always check TSH and CBC as part of initial PMS/PMDD workup before pharmacotherapy; rule out bipolarity with MDQ.
— PMS/PMDD is a chronic, cyclic disorder that persists until menopause unless interrupted by pregnancy or ovarian suppression
— Plan for multi-year therapy with periodic reassessment
— Consider annual trials off therapy in stable patients to reassess need
— Continuous dosing: reassess annually; maintain therapeutic dose if effective
— Luteal-phase dosing: continue as long as cycle-tied benefit; reduces side-effect burden and cost
— Watch for SSRI tachyphylaxis (waning response) — consider dose adjustment, agent switch, or holiday
— Monitor for sexual dysfunction, weight changes, bone density (long-term SSRI mildly increases osteoporosis/fracture risk in older adults)
— Annual BP check, periodic lipid screening, weight monitoring
— Reassess VTE/migraine status annually
— At age 35 reassess smoking status — must discontinue COC if smoking persists
— Transition to progestin-only or non-hormonal contraception if new contraindication develops
— Add-back HRT mandatory if therapy >6 months
— DEXA at baseline and yearly; calcium 1200 mg/day + vitamin D 800–1000 IU/day; weight-bearing exercise
— Aerobic exercise ≥150 min/week — sustained benefit on mood symptoms
— Mediterranean-style diet, reduced caffeine/alcohol/sodium luteally
— Sleep regularity, especially during luteal phase
— Stress management: CBT, mindfulness-based stress reduction — durable benefit
— Screen annually for depression (PHQ-9), anxiety (GAD-7), substance use (AUDIT-C)
— Cardiovascular risk assessment on COC users
— Cervical cancer screening per USPSTF
— Mammography per USPSTF (every 2 years age 50–74; shared decision making 40–49)
— Bone density at appropriate age intervals; earlier if GnRH or chronic steroid exposure
— Annual influenza, age-appropriate HPV, Tdap, COVID-19 boosters
— Reinforce that hormonal therapy does not alter vaccine schedule
Board pearl: Patients on chronic SSRIs and COCs should still meet all standard USPSTF preventive benchmarks — Step 3 loves layering preventive care onto chronic disease vignettes.
Step 3 management: Reassess PMS/PMDD therapy at least annually; consider an off-therapy trial in patients stable >2 years.
— 2–4 weeks after starting SSRI or COC: assess tolerability, side effects, suicidality (especially <25), early efficacy signals
— 8–12 weeks: assess full treatment response using continued symptom diary (DRSP)
— 6 months: comprehensive reassessment, dose optimization
— Annually: preventive care, screening, ongoing-need reassessment
— ≥50% reduction in DRSP severity scores luteally
— Restoration of premorbid functioning at work, school, relationships
— Patient-reported satisfaction and shared decision making
— SSRI: mood, suicidality, sexual function, GI symptoms, weight, sleep, bleeding (especially with concurrent NSAIDs/anticoagulants); periodic BMP if elderly (hyponatremia)
— COC (drospirenone): BP at baseline and 3 months, weight, breakthrough bleeding, mood, VTE symptoms, potassium at baseline and 1 month if any interacting agent or comorbidity
— Spironolactone: potassium, creatinine, BP at 1–2 weeks and periodically
— GnRH agonist: DEXA at baseline and annually, vasomotor symptoms, lipid panel, mood, bone-protective measures
— Surgical menopause: HRT adherence, bone density, lipid panel, cardiovascular risk factors
— Set expectations: PMS/PMDD is chronic and treatable, not curable until menopause/oophorectomy
— Continue prospective symptom diary during treatment to objectively track response
— Reinforce lifestyle measures as adjuncts, not replacements
— Suicide safety plan — crisis line numbers, removal of lethal means, identified support contacts
— Family/partner education — engage support network in understanding cyclic nature
— Discuss contraception status independent of PMDD treatment (SSRIs don't provide contraception)
— Pregnancy planning — preconception counseling 1–3 months in advance, transition off teratogenic agents
— DRSP for ongoing tracking
— PHQ-9, GAD-7 every 3–6 months
— Quality of life metrics
CCS pearl: Schedule a 2-week post-SSRI-start check focused on suicidality and tolerability — high-yield Step 3 follow-up cadence.
Step 3 management: Document objective outcome measures (DRSP, PHQ-9) at each visit; subjective "feeling better" is insufficient.
— Discuss risks/benefits of SSRIs including black-box suicidality warning in patients <25, sexual side effects (often understated), discontinuation syndrome, pregnancy considerations
— COCs: explicit VTE risk discussion (3–9/10,000 woman-years), arterial event risk in smokers >35 and migraine with aura, hypertension risk
— Drospirenone-specific consent: hyperkalemia risk, especially with concurrent ACEi/ARB/spironolactone
— Failure to screen with MDQ before SSRI initiation can precipitate manic episode → liability concern
— Document screening result in chart
— All PMDD patients should be screened for suicidality at every visit
— Document risk level, safety plan, means restriction, crisis resources
— Black-box monitoring for patients <25 — weekly contact first month; document each
— Premenopausal BSO for PMDD is irreversible — requires:
— Confirmed GnRH agonist response as a "trial"
— Completed childbearing or documented decision-making capacity around fertility loss
— Discussion of lifelong HRT need until natural menopause age
— Multidisciplinary input (gynecology, psychiatry)
— Consideration of second opinion
— Particular caution with younger patients — risk of regret, fertility loss, long-term hormone replacement burden
— Document pregnancy intention before each prescription
— Avoid paroxetine and spironolactone in patients trying to conceive
— Respect patient autonomy in contraceptive decisions
— Intimate partner violence: screen routinely; report per state requirements (variable — most US states do not mandate IPV reporting in competent adults but encourage referral to resources)
— Suicide risk requiring involuntary hold: per state laws (5150 in California, etc.)
— Child welfare concerns if parental PMDD severity impairs child safety — mandated reporter obligations
— Handoff at SSRI taper or switch — risk of discontinuation syndrome, return of symptoms, suicidality
— Coordinate with psychiatry, gynecology, primary care; share medication list, allergies, pregnancy status
— Validate cyclical mood symptoms — patients are often dismissed as "hormonal"; this dismissal contributes to diagnostic delay
Step 3 management: Before any irreversible step (BSO), document confirmed GnRH response, multidisciplinary input, and patient understanding of HRT through age ~51.
— PMS/PMDD requires prospective charting over 2 cycles — DRSP is the standard tool
— DSM-5-TR PMDD: ≥5 symptoms, ≥1 affective, with luteal onset and follicular remission
— Symptom-free follicular phase distinguishes PMDD from PME
— Aberrant CNS response to normal ovarian hormone fluctuations (not abnormal hormone levels)
— Allopregnanolone (progesterone metabolite) modulation of GABA-A receptors implicated
— Serotonergic system dysregulation — basis for SSRI efficacy
— SSRIs work within days in PMDD (vs weeks in MDD) — enables luteal-phase dosing
— FDA-approved SSRIs for PMDD: fluoxetine, sertraline, paroxetine CR
— FDA-approved COC for PMDD: drospirenone 3 mg / EE 20 mcg 24/4 (Yaz)
— Calcium 1200 mg/day has the best supplement evidence
— Vitamin B6 max 100 mg/day — higher doses cause peripheral neuropathy
— GnRH agonists >6 months require add-back HRT for bone protection
— Bilateral oophorectomy is curative but last resort
— Smokers >35 + COC = NO
— Migraine with aura + estrogen COC = NO (stroke risk)
— Prior VTE + estrogen COC = NO
— Drospirenone + ACEi/ARB/spironolactone = hyperkalemia risk
— Paroxetine in pregnancy = avoid (cardiac malformations)
— PMDD history → increased postpartum depression risk
— PMDD → increased suicidal ideation/attempt risk (luteal-peak)
— PMDD often coexists with migraine, IBS, anxiety
— Symptoms remit at menopause
— No symptom-free week → think PME of MDD/GAD/bipolar
— Treatment-resistant PMDD → re-chart, screen for bipolar
— Cyclical breast mass that disappears post-menses → fibrocystic, not malignancy
— DRSP available in public domain — patients can download and self-track
— SSRI <25 → black-box monitoring weekly for first month
Board pearl: If a Step 3 stem describes a woman with cyclic mood symptoms relieved by menses, asks "next best step," and lists hormone labs vs symptom diary — choose symptom diary.
Step 3 management: First-line for moderate-severe PMDD = SSRI; for PMS with contraception need = drospirenone/EE 24/4 COC.
— 28-year-old reports 7–10 days of irritability, mood swings, bloating, breast tenderness before each period, resolving with menses, causing missed work
— Next step: prospective symptom diary for 2 cycles (NOT hormone labs, NOT pelvic ultrasound, NOT empiric SSRI on first visit unless severe)
— Confirmed PMDD on diary, no contraception need, no comorbid medical issues
— Answer: SSRI (sertraline 50 mg daily or luteal-phase)
— Variant — also desires contraception, nonsmoker, no contraindications
— Answer: drospirenone/EE 20 mcg 24/4
— 36-year-old smoker with PMDD requests COC
— Answer: SSRI (COC contraindicated due to smoking >35)
— Variant — migraine with aura
— Answer: SSRI; estrogen contraindicated
— Patient reports daily depression "but worse before period"
— Diagnosis: PME of MDD
— Management: continuous SSRI for primary disorder, not luteal-phase dosing
— PMDD-appearing presentation with prior antidepressant-induced "energy bursts" or family history of bipolar
— Next step: screen with MDQ, refer to psychiatry before starting SSRI
— Patient on drospirenone COC and lisinopril presents with weakness, K+ 6.0
— Management: discontinue drospirenone, treat hyperkalemia, switch to non-drospirenone strategy
— Failed two SSRIs and a COC, severe symptoms persist
— Next step: GnRH agonist trial with add-back HRT — confirms ovarian dependence and provides therapy
— Patient with PMDD history, 4 weeks postpartum with severe mood symptoms
— Diagnosis: postpartum depression (PMDD predicts PPD)
— Management: sertraline (lactation-friendly), psychotherapy
— 17-year-old with confirmed PMDD; SSRI considered
— Counseling: black-box suicidality warning, weekly follow-up first month
— Patient requests BSO for PMDD
— Answer: confirm response to GnRH trial first; multidisciplinary discussion; HRT planning
Board pearl: When in doubt between "order labs" and "begin charting" — chart first.
Step 3 management: Match the patient profile (smoking, migraine, VTE history) to the appropriate pathway (SSRI vs COC).
PMS/PMDD is a prospectively charted cyclical disorder of the luteal phase with a symptom-free follicular week, treated first-line with SSRIs (FDA-approved: fluoxetine, sertraline, paroxetine CR) — daily or luteal-phase — or with drospirenone/EE 20 mcg 24/4 COC when contraception is desired and no estrogen contraindications exist.
— Prospective DRSP charting over 2 cycles is mandatory; no hormone test confirms PMDD
— DSM-5-TR PMDD: ≥5 symptoms with ≥1 affective, luteal onset, follicular remission, functional impairment
— Always screen for bipolar disorder (MDQ) and suicidality before initiating treatment
— Symptom-free follicular phase distinguishes PMDD from premenstrual exacerbation (PME) of an underlying disorder
— First-line PMDD: SSRI continuous or luteal-phase dosing — works within days
— First-line PMS with contraception need: drospirenone 3 mg/EE 20 mcg 24/4
— Adjuncts: calcium 1200 mg/day, aerobic exercise, CBT, NSAIDs for physical symptoms, spironolactone for fluid retention
— Refractory: GnRH agonist + add-back HRT; surgical BSO only after confirmed GnRH response
— Smoker >35, migraine with aura, prior VTE, uncontrolled HTN → no estrogen, use SSRI
— Renal impairment, hyperkalemia risk, ACEi/ARB use → avoid drospirenone and spironolactone
— Pregnancy planning → avoid paroxetine and spironolactone; sertraline preferred in pregnancy/lactation
— Chart before treating; screen for bipolarity before SSRI; assess suicide risk every visit
— Document objective response with DRSP/PHQ-9, reassess annually, plan natural endpoint at menopause
— Coordinate care across primary care, gynecology, and psychiatry; engage shared decision-making for irreversible interventions
Board pearl: The Step 3 PMDD question is rarely about pathophysiology — it is about the right next step: chart, screen, match treatment to patient profile, monitor objectively.