405.3 🩺 內科專科考前版

405.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Letrozole > clomiphene for PCOS ovulation (PPCOS II trial)
    • GLP-1 RA + tirzepatide off-label for PCOS weight + insulin resistance
    • Inositol (myo-inositol + d-chiro-inositol) dietary supplement; some evidence for PCOS metabolic
    • Anti-MÃŒllerian Hormone (AMH) for ovarian reserve assessment
    • Endometrial protection in PCOS: cyclic progestin q3 mo if not on COC
    • Functional hypothalamic amenorrhea (FHA) treatment paradigm: address underlying first
  • Taiwan: 健保 COC, metformin, spironolactone, clomiphene, letrozole; 健保 cabergoline; 健保 HRT for POI; CTAOH/TES + DAROC + ASRM/Endocrine Society 指匕

405.3.0.2 🌟 Pearls (15)

405.3.0.2.1 PCOS
  1. Rotterdam, NIH, AE-PCOS criteria: Rotterdam most inclusive
  2. Anti-MÃŒllerian Hormone (AMH) > 4-5 ng/mL suggests PCOS (alternative to follicle count)
  3. Letrozole ovulation rate ~ 88% per cycle (vs clomiphene ~ 67%) per PPCOS II
  4. Metformin: modest benefit for ovulation; primary for IR + weight
  5. Inositol (4 g myo + 1 g D-chiro daily): improves ovulation + cycle regularity (RCTs)
  6. GLP-1 RA + tirzepatide off-label: substantial weight loss + IR improvement; 22E expansion
  7. Endometrial protection: COC OR cyclic progestin ≥ 4x/yr if not COC
  8. Hidradenitis suppurativa: associated with PCOS + IR
  9. NAFLD in PCOS: 30-70%; resmetirom (THRβ agonist) approved for NASH (22E)
  10. Acanthosis nigricans + skin tags: severe IR markers
405.3.0.2.2 POI + FHA
  1. Fragile X premutation (FMR1): 14% of POI; autosomal dominant pre-mutation; family history of intellectual disability
  2. Autoimmune POI + APS-2: 21-hydroxylase Ab+ (Addison’s risk)
  3. POI HRT regimen: full-dose estrogen + cyclic progestin; transdermal preferred (less DVT risk than oral)
  4. FHA bone health critical: dual concern of low estrogen + low energy availability + low IGF-1 → pre-mature osteoporosis
  5. FHA before HRT: address underlying first; HRT can mask underlying issue

405.3.0.3 📍 Taiwan + 健保

405.3.0.3.1 PCOS
  • 健保 COC (drospirenone-containing for hirsutism)
  • 健保 metformin (off-label for PCOS, 條件)
  • 健保 spironolactone (off-label for hirsutism)
  • 健保 clomiphene + letrozole 條件 (fertility)
  • 健保 GLP-1 RA + tirzepatide for diabetes/obesity (PCOS use 倚 自費)
  • 健保 ovarian US + endometrial US
405.3.0.3.2 POI + FHA
  • 健保 HRT (estrogen + progestin)
  • 健保 CGM, DXA
  • 健保 FMR1, karyotype, autoimmune panel (條件)
  • 健保 IVF + donor egg 限制
405.3.0.3.3 孞會 + 指匕
  • TES 內分泌孞會 + DAROC
  • ASRM (American Society for Reproductive Medicine)
  • ESHRE PCOS Guideline 2018
  • Endocrine Society POI 2017
  • ESHRE FHA Guideline

405.3.0.4 🎓 內專必懂 (15)

  1. HPG axis female + cycle phases + endometrial changes
  2. PCOS Rotterdam + comprehensive workup (rule out 5 imitators)
  3. PCOS metabolic surveillance (T2DM, MetS, NAFLD, OSA)
  4. PCOS endometrial protection (CA risk)
  5. PCOS fertility (letrozole 1st)
  6. PCOS weight management (GLP-1, tirzepatide 22E)
  7. POI etiology + workup (Turner, fragile X, autoimmune APS-2)
  8. POI HRT until natural menopause age
  9. POI infertility (donor egg ART)
  10. FHA recognition + multidisciplinary
  11. FHA bone health + HRT decision
  12. Hyperprolactinemia + amenorrhea + cabergoline
  13. Sudden virilization → tumor workup
  14. Premature menarche + delayed puberty workup
  15. 22E new: AMH for reserve, GLP-1/tirzepatide PCOS, inositol

405.3.0.5 ⚙ PCOS Comprehensive Workflow (內專)

Step 1 — Confirm Rotterdam (≥ 2 of 3) + exclude imitators:
- Oligo/anovulation (cycle > 35 d or < 8 cycle/yr)
- Hyperandrogenism (clinical hirsutism/acne or biochemical T ↑)
- PCO US (≥ 12 follicles 2-9 mm or ovary > 10 mL)
- Exclude: CAH (17-OH-prog), Cushing's (24-h urine cortisol or 1mg dex), prolactinoma (PRL), hypothyroid (TSH), tumor (T very high or DHEA-S high)

Step 2 — Phenotyping (4 phenotypes per Rotterdam):
- A: hyperandrogenism + oligo/anov + PCO
- B: hyperandrogenism + oligo/anov (no PCO US)
- C: hyperandrogenism + PCO (regular cycles)
- D: oligo/anov + PCO (no hyperandrogen) — most controversial

Step 3 — Comorbidity workup:
- Glucose + HbA1c + lipid + BP
- LFT (NAFLD)
- TSH (already excluded)
- Cardiac risk assessment
- OSA screen if BMI > 30 or symptoms
- Mental health screen

Step 4 — Tailored management:
- Lifestyle (always; weight loss 5-10%)
- Cycle regulation: COC (drospirenone for hirsutism)
- Hirsutism: spironolactone 50-200 mg/d + COC
- Insulin resistance: metformin
- Weight + IR: GLP-1 RA, tirzepatide (22E)
- Inositol: myo + D-chiro
- Fertility: letrozole > clomiphene > metformin

Step 5 — Endometrial protection:
- COC indefinitely OR
- Cyclic progestin q3 mo if not on COC
- TVS or biopsy if abnormal bleeding

Step 6 — Long-term surveillance:
- Annual: glucose/HbA1c, lipid, BP, LFT
- 3-5 yr: OGTT
- Annual: mental health, OSA reassessment
- Endometrial assessment if symptoms

405.3.0.6 ⚙ POI Detailed Management

Diagnosis:
- Amenorrhea/oligomenorrhea < 40 yr
- FSH > 25-40 IU/L on 2 separate days
- Estradiol low

Workup:
- Karyotype (Turner + variants)
- FMR1 (fragile X premutation)
- Autoimmune panel: 21-hydroxylase Ab (Addison's), TPO/Tg (Hashimoto), GAD (T1DM), IF (PA)
- TSH, prolactin
- Pelvic US

Etiology:
- Idiopathic ~ 90% (often no identifiable cause)
- Genetic 10-15% (Turner, fragile X, autosomal genes)
- Autoimmune 5-15%
- Iatrogenic (chemo, RT, surgery)
- Galactosemia (rare)

Management:
1. Hormone Replacement Therapy until natural menopause age (~ 51):
   - Estrogen (oral or transdermal; transdermal preferred for DVT reduction)
   - Progestin (cyclic or continuous if uterus present)
   - Doses adequate: full estrogen replacement (estradiol 1-2 mg PO or 50-100 ÎŒg patch)
2. Bone health:
   - DXA baseline
   - Calcium 1200 mg/d + Vit D 1000-2000 IU/d
3. Cardiovascular surveillance:
   - Lipid + BP + lifestyle
4. Mental health support:
   - Depression, anxiety, body image, fertility loss
5. Fertility options:
   - ART with donor egg (most successful)
   - Spontaneous pregnancy possible (~ 5%)
   - Pregnancy preconception care
   - Adoption
6. Comorbid surveillance:
   - Annual TSH, anti-21-hydroxylase if APS-2 risk
   - Family education + screening (fragile X carrier)

405.3.0.7 ⚙ FHA Detailed Management

Diagnosis:
- Amenorrhea > 6 mo (or oligomenorrhea)
- Functional cause (eating, exercise, stress)
- Low LH/FSH + low estradiol
- Exclude: pregnancy, structural, endocrine other

Workup:
- TSH, prolactin, hCG
- Pelvic US (rule out structural)
- DXA (bone health)
- Energy assessment (caloric intake, exercise hours)

Multidisciplinary:
- Endocrinology
- Reproductive endocrinology
- Psychiatry / psychology (eating disorder, depression)
- Dietitian / nutrition (weight restoration, energy availability)
- Sports medicine (athletes)

Treatment:
1. Address underlying:
   - Weight restoration (BMI > 18.5 ideal)
   - Reduce excessive exercise
   - Stress management, therapy
2. Energy availability > 30 kcal/kg lean body mass/d
3. Bone health:
   - DXA baseline + repeat
   - Calcium + Vit D
   - Bisphosphonate generally NOT preferred (young + reproductive plans; reserve for severe)
4. HRT decision:
   - Address underlying first (weight gain often restores cycles)
   - HRT only if persistent + significant bone density loss
   - Transdermal preferred
   - Doesn't replace addressing underlying
5. Fertility:
   - Restoration with weight gain typically
   - If desired sooner: gonadotropin therapy (hCG + FSH)
6. Long-term:
   - Mental health + nutrition + bone surveillance

⚠ AI 草皿。