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    children: [new TextRun({ text: "Applied Physiology - FRS", bold: true, size: 40, color: "1F3864", font: "Calibri" })],
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  titlePara("Comprehensive Exam-Oriented Short Notes"),
  new Paragraph({
    children: [new TextRun({ text: "Reference: DC Dutta's Textbook of Gynecology | Berek & Novak's Gynecology | Guyton & Hall | Ganong's Physiology", size: 18, italics: true, color: "595959", font: "Calibri" })],
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  // ===== 1. ENDOCRINOLOGY IN PUBERTY =====
  heading1("1. Endocrinology in Puberty"),
  bold("Definition", "The hormonal cascade that triggers and sustains the physical and sexual changes of puberty."),
  heading3("Key Hormonal Events:"),
  bullet("Childhood (pre-puberty): Hypothalamus secretes minimal GnRH; pituitary is suppressed due to high CNS sensitivity to low levels of gonadal steroids."),
  bullet("Onset trigger: Maturation of KNDy (Kisspeptin-Neurokinin B-Dynorphin) neurons in the hypothalamus → increased pulsatile GnRH secretion."),
  bullet("Kisspeptin (encoded by KISS1 gene) acts on GPR54 receptors → releases GnRH."),
  bullet("Activating mutation of kisspeptin receptor → Central precocious puberty; inactivating mutations → Delayed/absent puberty."),
  bullet("Adrenarche (age 6-8 yrs): Adrenal androgens (DHEA, DHEAS) rise → axillary and pubic hair (pubarche)."),
  bullet("Gonadarche: Rising GnRH → FSH & LH secretion. FSH > LH in early puberty."),
  bullet("FSH → follicular development → Estradiol (E2) production."),
  bullet("LH surge → ovulation (occurs after ~1-2 yrs of anovulatory cycles post-menarche)."),
  bullet("Estradiol → breast development (thelarche), uterine growth, vaginal cornification, fat redistribution."),
  bullet("Growth hormone + IGF-1 → pubertal growth spurt; estrogen causes epiphyseal fusion."),
  heading3("Normal Sequence in Girls (Thelarche → Pubarche → Growth Spurt → Menarche):"),
  bullet("Breast budding (thelarche) – first sign of puberty in girls (Tanner Stage 2), average age 9-10 yrs."),
  bullet("Pubic hair (pubarche) follows."),
  bullet("Peak height velocity (growth spurt) during Tanner Stage 3."),
  bullet("Menarche – last major event, average age 12-13 yrs (range 10-16 yrs)."),
  heading3("Exam Tip:"),
  bullet("First sign of puberty in girls = Thelarche (breast budding)."),
  bullet("Last event = Menarche."),
  bullet("FSH rises before LH in puberty; LH surge triggers ovulation."),
  divider(),

  // ===== 2. PHYSIOLOGY OF MENSTRUATION =====
  heading1("2. Physiology of Menstruation – Hormonal Changes"),
  bold("Normal Cycle", "28 days (range 21-35 days). Day 1 = first day of bleeding."),
  bold("Duration", "3-7 days. Blood loss: 30-80 mL (>80 mL = abnormal)."),
  bold("Blood", "Predominantly arterial (75%); contains fibrinolysin (prevents clotting), prostaglandins, tissue debris."),
  divider(),
  heading3("Phase 1 – Menstrual Phase (Days 1-5):"),
  bullet("Corpus luteum degenerates → fall in E2 and progesterone."),
  bullet("Vasospasm of spiral arterioles → ischemia → endometrial sloughing."),
  bullet("Prostaglandins (PGF2α > PGE2) cause myometrial contractions."),
  bullet("Fibrinolysin prevents clot formation in menstrual blood."),
  divider(),
  heading3("Phase 2 – Follicular/Proliferative Phase (Days 1/5-14):"),
  bullet("FSH rises (released from negative feedback) → recruits 5-15 follicles."),
  bullet("Dominant follicle selected by Day 6-8; secretes rising Estradiol."),
  bullet("Estradiol → endometrial proliferation (glands elongate, stroma thickens)."),
  bullet("Estradiol exerts negative feedback on FSH/LH (mid-follicular)."),
  bullet("Late follicular: Estradiol peaks (>200 pg/mL for 36-48 hrs) → POSITIVE feedback → LH surge."),
  bullet("Cervical mucus becomes thin, watery, clear, 'spinnbarkeit' (can stretch 8-12 cm), ferning pattern."),
  bullet("Phase length variable (determines cycle length variation)."),
  divider(),
  heading3("Phase 3 – Ovulation (Day 14 in 28-day cycle):"),
  bullet("Midcycle LH surge (peak at 24-36 hrs before ovulation)."),
  bullet("FSH also surges (smaller)."),
  bullet("Ovulation occurs 36-40 hrs after LH surge onset, or 10-12 hrs after LH peak."),
  bullet("Basal body temperature rises 0.2-0.5°C after ovulation (progesterone effect)."),
  divider(),
  heading3("Phase 4 – Luteal/Secretory Phase (Days 15-28):"),
  bullet("Constant duration: 14 days (± 2 days)."),
  bullet("LH stimulates corpus luteum → produces Progesterone + Estradiol."),
  bullet("Progesterone peaks at Day 21 (mid-luteal) – marker of ovulation."),
  bullet("Endometrium: becomes tortuous, secretory glands, stromal edema (preparation for implantation)."),
  bullet("Inhibin B rises → further suppresses FSH."),
  bullet("If no fertilization: Corpus luteum degenerates at Day 26-27 (luteolysis) → progesterone falls → menstruation."),
  bullet("Cervical mucus: thick, tenacious, cellular (sperm hostile)."),
  heading3("Hormonal Summary Table:"),
  bullet("Early Follicular: FSH↑, LH↓, E2↑ (slowly), Prog↓"),
  bullet("Pre-ovulatory: FSH↑↑ (small), LH↑↑ (surge), E2↑↑ (peak), Prog↑ (small)"),
  bullet("Mid-Luteal: FSH↓, LH↓, E2↑ (moderate), Prog↑↑ (peak)"),
  bullet("Late Luteal: FSH↑ (starts rising), LH↓, E2↓, Prog↓↓"),
  divider(),

  // ===== 3. UTERINE CHANGES =====
  heading1("3. Uterine Changes During Menstrual Cycle"),
  heading3("Proliferative Phase (Estrogenic):"),
  bullet("Endometrium: 1-2 mm → 8-10 mm thick."),
  bullet("Glands: straight, narrow, tubular with tall columnar cells."),
  bullet("Stroma: compact, mitotic figures common."),
  bullet("Blood vessels: straight, thin-walled."),
  heading3("Secretory Phase (Progestogenic):"),
  bullet("Glands: tortuous, 'saw-tooth' appearance; glycogen vacuoles (sub-nuclear Day 17, supra-nuclear Day 19)."),
  bullet("Stroma: edematous → decidualization."),
  bullet("Spiral arteries: become coiled."),
  bullet("Late secretory: stromal cells become large, pale (pre-decidua)."),
  heading3("Menstrual Phase:"),
  bullet("Vasospasm of spiral arterioles (prostaglandin-mediated) → ischemic necrosis."),
  bullet("Shedding of functionalis layer (stratum functionale)."),
  bullet("Basalis layer is retained → regeneration source."),
  heading3("Cervical Changes:"),
  bullet("Follicular phase: E2 → thin, watery, alkaline mucus; ferning pattern; high spinnbarkeit."),
  bullet("Luteal phase: Progesterone → thick, tenacious, cellular mucus; no ferning."),
  heading3("Vaginal Changes:"),
  bullet("E2 → cornification of epithelium (karyopyknotic index rises)."),
  bullet("Progesterone → abundant superficial cells, folded edges."),
  divider(),

  // ===== 4. PUBERTY =====
  heading1("4. Puberty"),
  bold("Definition", "Period when a child acquires secondary sexual characteristics and becomes capable of reproduction. Caused by gradual increase in gonadotropins from ~8 years onward."),
  heading3("Normal Age Range (Girls):"),
  bullet("Onset: 8-13 years."),
  bullet("Menarche: 10-16 years (mean 12-13 years)."),
  bullet("Total duration of puberty: 2-5 years."),
  heading3("Tanner Stages of Breast Development (Girls):"),
  bullet("Stage 1: Pre-pubertal, flat nipple."),
  bullet("Stage 2: Breast bud; slight elevation of nipple (first sign, ~9-10 yrs)."),
  bullet("Stage 3: Enlargement of breast and areola."),
  bullet("Stage 4: Secondary mound of areola above breast."),
  bullet("Stage 5: Adult contour, only nipple projects."),
  heading3("Tanner Stages of Pubic Hair:"),
  bullet("Stage 1: None."),
  bullet("Stage 2: Sparse, slightly pigmented along labia."),
  bullet("Stage 3: Darker, coarser, curly, extending over pubis."),
  bullet("Stage 4: Adult type but smaller area."),
  bullet("Stage 5: Adult type, spread to medial thighs."),
  heading3("Events in Order:"),
  bullet("1. Thelarche (breast budding) – first sign"),
  bullet("2. Adrenarche (pubic/axillary hair)"),
  bullet("3. Growth spurt (peak height velocity)"),
  bullet("4. Menarche (last major event)"),
  heading3("Exam Tips:"),
  bullet("GH + IGF-1 → pubertal growth spurt; Estrogen → epiphyseal fusion (ends growth)."),
  bullet("Early cycles post-menarche are usually anovulatory."),
  divider(),

  // ===== 5. PRECOCIOUS PUBERTY =====
  heading1("5. Precocious Puberty"),
  bold("Definition", "Development of secondary sexual characteristics before age 8 in girls (or age 9 in boys)."),
  bold("Incidence", "20x more common in girls than boys. 90% idiopathic in girls, only 10% idiopathic in boys."),
  heading3("Classification:"),
  heading3("A. GnRH-Dependent (Central/True Precocious Puberty):"),
  bullet("Premature activation of hypothalamic-pituitary-gonadal (HPG) axis."),
  bullet("LH and FSH respond to GnRH stimulation (pubertal pattern)."),
  bullet("In girls: 90% idiopathic; in boys: always look for CNS pathology."),
  bullet("Causes: Idiopathic (most common in girls), CNS tumors (hamartoma, craniopharyngioma), hydrocephalus, head trauma, post-meningitis, McCune-Albright syndrome (some cases)."),
  bullet("Activating mutation of kisspeptin receptor (KISS1R) = first identified genetic cause."),
  heading3("B. GnRH-Independent (Peripheral/Pseudo-Precocious Puberty):"),
  bullet("Gonadotropin-independent sex steroid production."),
  bullet("LH/FSH do NOT respond to GnRH stimulation."),
  bullet("Causes: Ovarian/testicular tumors, adrenal tumors/CAH (congenital adrenal hyperplasia), exogenous estrogen/androgens, McCune-Albright syndrome."),
  heading3("Incomplete Precocious Puberty:"),
  bullet("Isolated thelarche (premature breast development) – benign, no treatment."),
  bullet("Isolated adrenarche (premature pubic hair) – benign."),
  bullet("Isolated menarche – rare, look for vaginal foreign body or tumor."),
  heading3("Evaluation:"),
  bullet("Tanner staging, bone age (advanced)."),
  bullet("Basal LH/FSH, GnRH stimulation test."),
  bullet("Pelvic and CNS imaging."),
  bullet("Estradiol, DHEAS, 17-OHP, testosterone, thyroid function."),
  heading3("Treatment:"),
  bullet("Central: GnRH agonists (leuprolide) – paradoxical suppression via receptor downregulation."),
  bullet("Goal: halt secondary sexual development, normalize growth velocity, preserve adult height."),
  heading3("Exam Tips:"),
  bullet("Central PP: LH/FSH respond to GnRH. Peripheral PP: LH/FSH do NOT respond."),
  bullet("McCune-Albright: triad of precocious puberty + café-au-lait spots + polyostotic fibrous dysplasia."),
  divider(),

  // ===== 6. DELAYED PUBERTY =====
  heading1("6. Delayed Puberty"),
  bold("Definition", "Absence of any pubertal development by age 13 in girls (no breast development) or absence of menarche by age 16 (also = primary amenorrhea)."),
  bold("Note", "Normal variation so wide that puberty is not considered pathologically delayed until menarche absent by age 17 (Ganong)."),
  heading3("Classification:"),
  heading3("A. Hypogonadotropic Hypogonadism (Low FSH/LH):"),
  bullet("Constitutional delay of growth and puberty (CDGP) – most common cause overall (especially boys)."),
  bullet("Functional: Anorexia nervosa, excessive exercise, chronic illness, hypothyroidism."),
  bullet("Structural: Craniopharyngioma, pituitary tumors, hyperprolactinemia."),
  bullet("Kallmann syndrome: GnRH deficiency + anosmia (due to KAL1 gene mutation)."),
  bullet("Panhypopituitarism."),
  heading3("B. Hypergonadotropic Hypogonadism (High FSH/LH = Gonadal Failure):"),
  bullet("Turner syndrome (45,X) – most common cause of delayed puberty in girls."),
  bullet("Gonadal dysgenesis, XX gonadal dysgenesis."),
  bullet("Premature ovarian insufficiency."),
  heading3("C. Eugonadotropic (Normal FSH/LH):"),
  bullet("Anatomic causes: Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), imperforate hymen, transverse vaginal septum."),
  bullet("Androgen insensitivity syndrome (46,XY)."),
  heading3("Evaluation:"),
  bullet("FSH, LH, estradiol, prolactin, TSH, karyotype."),
  bullet("Bone age (delayed in constitutional delay)."),
  bullet("MRI brain, pelvic ultrasound."),
  heading3("Treatment:"),
  bullet("Constitutional delay: Reassurance ± low-dose estrogen."),
  bullet("Hypogonadism: Estrogen replacement → breast development, uterine growth, prevent osteoporosis."),
  bullet("Kallmann: Pulsatile GnRH or gonadotropins (if fertility desired)."),
  divider(),

  // ===== 7. PUBERTY MENORRHAGIA =====
  heading1("7. Puberty Menorrhagia"),
  bold("Definition", "Heavy or prolonged menstrual bleeding occurring around the time of puberty (within 1-2 years of menarche)."),
  bold("Cause", "Primarily anovulatory cycles due to immature HPO axis. Without ovulation, no corpus luteum forms → no progesterone. Unopposed estrogen causes continued endometrial proliferation → irregular, heavy breakdown bleeding."),
  heading3("Features:"),
  bullet("Irregular, heavy, prolonged bleeding in young adolescent."),
  bullet("Cycles usually anovulatory."),
  bullet("Can cause anemia if severe."),
  heading3("Other Contributing Causes:"),
  bullet("Coagulopathy (von Willebrand disease – must exclude in adolescents)."),
  bullet("Thyroid dysfunction."),
  bullet("PCOS (if anovulation persists)."),
  heading3("Management:"),
  bullet("Mild: Reassurance, iron supplementation, NSAIDs."),
  bullet("Moderate: Combined oral contraceptive pill (OCP) – provides progestogen opposition, regulates cycle."),
  bullet("Severe/acute hemorrhage: High-dose conjugated estrogen IV (25 mg IV q4-6h), then taper. Alternatively, high-dose OCP."),
  bullet("Rule out: coagulopathy (platelet function, PT, APTT), thyroid disorder, PCOS."),
  heading3("Exam Tips:"),
  bullet("Puberty menorrhagia = anovulatory DUB (dysfunctional uterine bleeding) of adolescence."),
  bullet("Always screen for coagulopathy (vWD) in adolescent menorrhagia."),
  divider(),

  // ===== 8. AMENORRHEA =====
  heading1("8. Amenorrhea"),
  bold("Definition", "Absence of menstruation."),
  bold("Physiological", "Pre-puberty, pregnancy, lactation, post-menopause."),
  bold("Pathological", "Primary or Secondary amenorrhea."),
  para("A complex hormonal interaction must occur for normal menstruation: Hypothalamus (GnRH, pulsatile) → Pituitary (FSH, LH) → Ovary (estrogen, progesterone) → Uterus (endometrium) → Outflow tract. Failure at any level → amenorrhea."),
  heading3("Basic Workup for Amenorrhea:"),
  bullet("Rule out pregnancy (hCG) first."),
  bullet("Prolactin, TSH."),
  bullet("FSH, LH, estradiol."),
  bullet("Physical exam: secondary sexual characteristics, pelvic anatomy."),
  bullet("AMH (anti-Mullerian hormone) may be helpful."),
  divider(),

  // ===== 9. PRIMARY AMENORRHEA =====
  heading1("9. Primary Amenorrhea"),
  bold("Definition (Updated)", "Absence of menarche by age 13 with no secondary sexual characteristics, OR by age 15 with normal secondary sexual characteristics (2 SD above mean). The former cut-off was 14/16 yrs."),
  bold("Key Rule", "Failure of breast development by age 13 always warrants investigation."),
  heading3("Classification by Secondary Sexual Characteristics:"),
  heading3("A. No Secondary Sexual Characteristics (No Breast Development):"),
  bullet("Hypergonadotropic (FSH/LH elevated): Gonadal dysgenesis (Turner 45,X – most common), pure gonadal dysgenesis (46,XX or 46,XY – Swyer syndrome)."),
  bullet("Hypogonadotropic (FSH/LH low): Hypothalamic failure (Kallmann syndrome, constitutional delay), pituitary failure, chronic illness, anorexia."),
  heading3("B. Secondary Sexual Characteristics Present, Abnormal Pelvic Anatomy:"),
  bullet("Imperforate hymen (cyclic pain, hematocolpos) – most common outflow obstruction."),
  bullet("Transverse vaginal septum."),
  bullet("Cervical stenosis."),
  bullet("Mullerian agenesis/MRKH syndrome (absent uterus/upper vagina, normal ovaries, 46,XX)."),
  bullet("Androgen Insensitivity Syndrome (46,XY, testes, blind vaginal pouch, absent uterus, female phenotype)."),
  heading3("C. Secondary Sexual Characteristics Present, Normal Pelvic Anatomy:"),
  bullet("PCOS, hyperprolactinemia, hypothyroidism, functional hypothalamic amenorrhea."),
  bullet("Asherman syndrome (if prior uterine instrumentation)."),
  heading3("Exam Tips:"),
  bullet("Turner syndrome (45,X): Short stature, webbed neck, shield chest, coarctation of aorta, streak gonads → Primary amenorrhea."),
  bullet("MRKH: Normal female appearance, blind vaginal pouch, absent uterus, 46,XX, normal ovaries."),
  bullet("AIS: 46,XY, inguinal testes, blind vagina, absent uterus, female phenotype – testosterone in male range."),
  bullet("Imperforate hymen: Cyclic pelvic pain, bulging bluish membrane, hematocolpos."),
  divider(),

  // ===== 10. SECONDARY AMENORRHEA =====
  heading1("10. Secondary Amenorrhea"),
  bold("Definition", "Absence of menstruation for 3 consecutive cycles or 6 months in a previously menstruating woman. A woman with >35-day cycles or <9 cycles/year should also be evaluated."),
  bold("Most Important Rule", "Always exclude pregnancy first."),
  heading3("Common Causes (by level):"),
  heading3("Hypothalamic (Low FSH/LH, Low E2):"),
  bullet("Functional hypothalamic amenorrhea: Stress, weight loss, excessive exercise, eating disorders."),
  bullet("Most common cause of secondary amenorrhea after pregnancy."),
  heading3("Pituitary:"),
  bullet("Hyperprolactinemia (prolactinoma, drugs): Prolactin suppresses GnRH → amenorrhea. 15-20% of secondary amenorrhea."),
  bullet("Sheehan syndrome: Post-partum pituitary necrosis (after massive PPH)."),
  bullet("Empty sella, other pituitary tumors."),
  heading3("Ovarian:"),
  bullet("Premature ovarian insufficiency/POI (FSH >25-40 IU/L before age 40): Idiopathic, autoimmune, iatrogenic (chemo/radiation)."),
  bullet("PCOS: Most common endocrine disorder; anovulation, elevated androgens, insulin resistance."),
  heading3("Uterine:"),
  bullet("Asherman syndrome: Intrauterine adhesions after D&C, myomectomy, TB endometritis."),
  heading3("Other:"),
  bullet("Thyroid disease (hypo/hyperthyroidism), Cushing disease, Addison's disease."),
  heading3("Workup:"),
  bullet("βhCG → FSH, LH, E2 → Prolactin, TSH → Progestogen challenge test."),
  bullet("Progestogen challenge: Withdrawal bleed = estrogen present, anovulation."),
  bullet("No bleed → Estrogen-progestogen challenge → if bleed: hypoestrinism; if no bleed: outflow obstruction."),
  heading3("Exam Tips:"),
  bullet("Commonest cause: Pregnancy. Commonest pathological cause: Hypothalamic (functional)."),
  bullet("Secondary amenorrhea + galactorrhea = Hyperprolactinemia."),
  bullet("POI: FSH >40 IU/L (×2, 4-6 weeks apart) before age 40."),
  divider(),

  // ===== 11. CRYPTOMENORRHEA =====
  heading1("11. Cryptomenorrhea"),
  bold("Definition", "Menstruation occurs but blood is retained due to obstruction of the outflow tract. Monthly cyclical abdominal pain WITHOUT external bleeding."),
  heading3("Causes:"),
  bullet("Imperforate hymen (most common)."),
  bullet("Transverse vaginal septum."),
  bullet("Cervical stenosis (rare)."),
  heading3("Consequences of Retention:"),
  bullet("Hematocolpos: Blood in vagina."),
  bullet("Hematometra: Blood in uterus."),
  bullet("Hematosalpinx: Blood in fallopian tubes."),
  bullet("Hemoperitoneum: Blood in peritoneal cavity (if severe)."),
  heading3("Clinical Features:"),
  bullet("Cyclical pelvic pain at time of expected menses (primary amenorrhea or apparent amenorrhea)."),
  bullet("Imperforate hymen: Bluish, bulging membrane at introitus."),
  bullet("Urinary retention in severe cases."),
  heading3("Treatment:"),
  bullet("Imperforate hymen: Cruciate incision (hymenectomy)."),
  bullet("Vaginal septum: Surgical excision."),
  heading3("Exam Tips:"),
  bullet("Cryptomenorrhea = hidden menstruation. Cyclic pain + no visible bleeding = hallmark."),
  bullet("X-ray pelvis may show fluid-filled mass (hematocolpos)."),
  divider(),

  // ===== 12. HYPOMENORRHEA =====
  heading1("12. Hypomenorrhea"),
  bold("Definition", "Scanty menstrual flow – less than normal amount (< 20 mL), with regular or shortened duration. Cycle length is normal."),
  heading3("Causes:"),
  bullet("Intrauterine adhesions (Asherman syndrome) – most common serious cause."),
  bullet("Endometrial damage (post-curettage, TB endometritis)."),
  bullet("Hormonal: Hypoestrogenism (approaching menopause, POI)."),
  bullet("Thyroid disease."),
  bullet("Use of oral contraceptives (reduces endometrial thickness)."),
  bullet("Normal variant in some women."),
  heading3("Management:"),
  bullet("Investigate for Asherman syndrome (hysteroscopy)."),
  bullet("Treat underlying cause."),
  bullet("OCP-related: Reassurance."),
  heading3("Exam Tips:"),
  bullet("Hypomenorrhea after D&C = Asherman syndrome until proven otherwise."),
  bullet("Scanty flow + infertility = endometrial adhesions."),
  divider(),

  // ===== 13. OLIGOMENORRHEA =====
  heading1("13. Oligomenorrhea"),
  bold("Definition", "Infrequent menstruation – cycle length > 35 days (menstruation occurs at intervals of more than 5 weeks but less than 6 months). (FIGO: irregular cycles > 20 days variation)."),
  heading3("Causes:"),
  bullet("PCOS – most common cause in reproductive age."),
  bullet("Hypothalamic dysfunction (stress, weight loss, exercise)."),
  bullet("Hyperprolactinemia."),
  bullet("Thyroid dysfunction."),
  bullet("Approaching menopause (perimenopause)."),
  bullet("Post-menarche (immature HPO axis) – physiological."),
  heading3("Management:"),
  bullet("Identify and treat underlying cause."),
  bullet("OCP for cycle regularization if contraception also needed."),
  bullet("Fertility: Ovulation induction (clomiphene, letrozole) if pregnancy desired."),
  heading3("Exam Tips:"),
  bullet("Oligomenorrhea + hyperandrogenism + polycystic ovaries = PCOS."),
  bullet(">6 months of absence = secondary amenorrhea."),
  divider(),

  // ===== 14. POLYMENORRHEA =====
  heading1("14. Polymenorrhea"),
  bold("Definition", "Frequent menstruation – cycle interval < 21 days (menstruation occurring too frequently)."),
  heading3("Causes:"),
  bullet("Short follicular phase (most common): Rapid folliculogenesis."),
  bullet("Short luteal phase (luteal phase defect): Inadequate progesterone production."),
  bullet("Approaching menopause (anovulatory cycles, shortened cycles)."),
  bullet("Post-menarche (immature HPO axis)."),
  heading3("Consequences:"),
  bullet("Iron deficiency anemia."),
  bullet("Reduced fertility (luteal phase defect → implantation failure)."),
  heading3("Management:"),
  bullet("Identify phase defect (LH monitoring, Day 21 progesterone)."),
  bullet("Luteal phase defect: Progesterone supplementation; clomiphene."),
  bullet("Cycle regulation: OCP."),
  heading3("Exam Tips:"),
  bullet("Polymenorrhea ≠ menorrhagia (amount not increased, only frequency)."),
  bullet("Short luteal phase: Day 21 progesterone < 5 ng/mL suggests anovulation."),
  divider(),

  // ===== 15. METRORRHAGIA =====
  heading1("15. Metrorrhagia"),
  bold("Definition (Classic)", "Irregular uterine bleeding occurring between menstrual periods. Bleeding at irregular intervals, often light."),
  bold("FIGO Current Term", "Intermenstrual Bleeding (IMB) – replaces metrorrhagia."),
  heading3("Causes:"),
  bullet("Cervical causes: Cervicitis, cervical polyp, cervical ectropion, cervical carcinoma."),
  bullet("Uterine causes: Endometrial polyp, submucous fibroid, endometrial hyperplasia, endometrial carcinoma."),
  bullet("Hormonal: Breakthrough bleeding on OCP, anovulatory cycles."),
  bullet("Post-coital bleeding: Cervical pathology (must exclude cancer)."),
  bullet("IUCD-related bleeding."),
  heading3("Management:"),
  bullet("History, speculum exam, cervical swab."),
  bullet("Transvaginal ultrasound, endometrial biopsy (>45 yrs or risk factors)."),
  bullet("Hysteroscopy and biopsy if indicated."),
  heading3("Exam Tips:"),
  bullet("Post-coital bleeding = investigate cervix (cancer until proven otherwise)."),
  bullet("New onset metrorrhagia after menopause = postmenopausal bleeding (high risk of malignancy)."),
  divider(),

  // ===== 16. MENORRHAGIA =====
  heading1("16. Menorrhagia"),
  bold("Definition (Classic)", "Excessive menstrual bleeding (>80 mL per cycle) or prolonged bleeding (>7 days) occurring at regular intervals."),
  bold("FIGO Current Term", "Heavy Menstrual Bleeding (HMB) – defined as menstrual blood loss that interferes with physical, emotional, social, or material quality of life (subjective, patient-defined)."),
  heading3("Causes (FIGO PALM-COEIN):"),
  heading3("Structural (PALM):"),
  bullet("P – Polyp (endometrial or cervical)."),
  bullet("A – Adenomyosis."),
  bullet("L – Leiomyoma (particularly submucosal)."),
  bullet("M – Malignancy and Hyperplasia."),
  heading3("Non-Structural (COEIN):"),
  bullet("C – Coagulopathy (von Willebrand disease, platelet disorders, anticoagulants)."),
  bullet("O – Ovulatory dysfunction (anovulation, PCOS, thyroid disease)."),
  bullet("E – Endometrial causes (primary endometrial disorder, increased fibrinolysis)."),
  bullet("I – Iatrogenic (IUCD, hormones, anticoagulants)."),
  bullet("N – Not yet classified."),
  heading3("Investigations:"),
  bullet("FBC (hemoglobin, platelets), coagulation screen."),
  bullet("TFT, prolactin."),
  bullet("Pelvic ultrasound (fibroid, polyp, adenomyosis)."),
  bullet("Endometrial biopsy (>45 yrs or risk factors for cancer)."),
  bullet("Hysteroscopy (direct visualization)."),
  heading3("Management:"),
  bullet("Medical: NSAIDs (tranexamic acid reduces blood loss 40-50%), combined OCP, progestogens (norethisterone), levonorgestrel IUS (Mirena) – most effective medical Rx."),
  bullet("Surgical: Endometrial ablation (destroys endometrium), hysterectomy (definitive)."),
  heading3("Exam Tips:"),
  bullet("Commonest organic cause: Fibroid (submucous)."),
  bullet("Best medical treatment: LNG-IUS (Mirena)."),
  bullet("Menorrhagia + adolescent: Rule out coagulopathy (vWD)."),
  divider(),

  // ===== 17. AUB =====
  heading1("17. Abnormal Uterine Bleeding (AUB)"),
  bold("Definition", "Bleeding that is abnormal in regularity, volume, frequency, or duration. Bleeding may be acute or chronic and present for at least 6 months."),
  bold("FIGO Classification (PALM-COEIN 2011/2018)", "International standard replacing older terms."),
  heading3("FIGO Terminology (replaces older terms):"),
  bullet("Heavy Menstrual Bleeding (HMB) – replaces 'menorrhagia'"),
  bullet("Intermenstrual Bleeding (IMB) – replaces 'metrorrhagia'"),
  bullet("Irregular Menstrual Bleeding (variations >20 days) – replaces 'oligomenorrhea/polymenorrhea'"),
  bullet("Prolonged Menstrual Bleeding – >8 days"),
  bullet("Absent for >6 months – 'amenorrhea'"),
  bullet("Postmenopausal Bleeding – any bleeding >12 months after last menses"),
  heading3("Discarded/Obsolete Terms (by FIGO):"),
  bullet("Dysfunctional uterine bleeding (DUB), menorrhagia, metrorrhagia, hypermenorrhea, hypomenorrhea, menometrorrhagia, oligomenorrhea, polymenorrhea."),
  heading3("Acute AUB:"),
  bullet("Episode of bleeding sufficient to require immediate intervention."),
  bullet("Can be from structural cause (fibroid, polyp) or coagulopathy."),
  heading3("Causes by Age Group:"),
  bullet("Adolescence: Anovulatory cycles, coagulopathy (vWD)."),
  bullet("Reproductive age: Pregnancy complications, fibroids, polyps, adenomyosis, PCOS, endometrial hyperplasia/cancer."),
  bullet("Perimenopause: Anovulatory cycles, fibroids, hyperplasia/cancer."),
  bullet("Post-menopause: Endometrial atrophy (most common), endometrial cancer, polyps, cervical cancer."),
  heading3("Exam Tips:"),
  bullet("PALM = structural; COEIN = non-structural."),
  bullet("AUB-M (malignancy) must be excluded in all peri/postmenopausal women with AUB."),
  divider(),

  // ===== 18. METROPATHIA HEMORRHAGICA =====
  heading1("18. Metropathia Hemorrhagica"),
  bold("Definition", "A specific type of dysfunctional uterine bleeding due to prolonged unopposed estrogen stimulation causing cystic glandular hyperplasia of the endometrium (Swiss cheese endometrium). Also called cystic glandular hyperplasia or Schroeder's disease."),
  heading3("Pathophysiology:"),
  bullet("Persistent follicle → prolonged estrogen secretion without progesterone (anovulation)."),
  bullet("Endometrium undergoes cystic glandular hyperplasia (endometrial glands become dilated, cystic – 'Swiss cheese' appearance)."),
  bullet("Endometrium eventually outgrows its blood supply → irregular breakdown → prolonged, irregular, sometimes heavy bleeding."),
  heading3("Clinical Features:"),
  bullet("Irregular, prolonged (sometimes very heavy) uterine bleeding after a period of amenorrhea (6-12 weeks of amenorrhea followed by sudden heavy bleeding)."),
  bullet("Typically seen in perimenopausal women (approaching menopause with anovulatory cycles)."),
  bullet("Also seen post-menarche."),
  bullet("No pelvic pain (unless complicated)."),
  heading3("Investigations:"),
  bullet("Pelvic ultrasound: Thickened endometrium."),
  bullet("Endometrial biopsy/D&C: Cystic glandular hyperplasia – hallmark."),
  bullet("No atypia (benign hyperplasia)."),
  heading3("Treatment:"),
  bullet("Progestogen therapy (norethisterone 5mg TDS ×21 days/month) – induces secretory transformation and withdrawal bleed."),
  bullet("OCP for cycle regulation."),
  bullet("D&C is both diagnostic and therapeutic (stops acute bleeding)."),
  bullet("Hysterectomy if medical treatment fails or malignancy risk."),
  heading3("Exam Tips:"),
  bullet("Metropathia = anovulatory DUB of perimenopausal/postmenarchal age."),
  bullet("Swiss cheese endometrium on histology = diagnostic."),
  bullet("Amenorrhea followed by heavy irregular bleeding = classic presentation."),
  divider(),

  // ===== 19. DYSMENORRHEA =====
  heading1("19. Dysmenorrhea"),
  bold("Definition", "Painful menstruation (literally 'difficult monthly flow')."),
  bold("Prevalence", "One of the most common gynecological complaints; affects up to 50-90% of women of reproductive age."),
  heading3("Classification:"),
  bullet("Primary (Spasmodic): No identifiable pelvic pathology."),
  bullet("Secondary (Congestive): Associated with underlying pelvic pathology."),
  divider(),

  // ===== 20. PRIMARY DYSMENORRHEA =====
  heading1("20. Primary Dysmenorrhea"),
  bold("Definition", "Cyclic menstrual pain in the absence of identifiable pelvic pathology."),
  heading3("Pathophysiology:"),
  bullet("Prostaglandins (mainly PGF2α, also PGE2) produced by secretory endometrium during menstruation."),
  bullet("PGF2α → intense, rhythmic uterine contractions → uterine ischemia → pain."),
  bullet("Associated systemic effects of prostaglandins: nausea, vomiting, diarrhea, headache, backache."),
  bullet("Elevated PGF2α levels in menstrual fluid of women with primary dysmenorrhea."),
  bullet("Omega-6 fatty acids (dietary) → increased PGF2α; Omega-3 fatty acids → compete, reduce PGF2α."),
  heading3("Clinical Features:"),
  bullet("Onset: Within 6-12 months of menarche (coincides with onset of ovulatory cycles)."),
  bullet("Pain: Begins few hours before or at onset of menses, spasmodic (cramp-like), lower abdominal/suprapubic, may radiate to back and thighs."),
  bullet("Duration: 48-72 hours (peak in first 1-2 days of flow)."),
  bullet("Heaviest flow coincides with worst pain."),
  bullet("Normal pelvic examination."),
  bullet("Tends to improve with age and after childbirth."),
  heading3("Treatment:"),
  bullet("First line: NSAIDs (ibuprofen 400mg TDS, mefenamic acid 500mg TDS) – inhibit prostaglandin synthesis (cyclo-oxygenase inhibitors). Start 1-2 days before menses."),
  bullet("Second line: Combined oral contraceptive pill (OCP) – suppresses ovulation, reduces endometrial prostaglandin."),
  bullet("Progestogen-only: Norethisterone, LNG-IUS."),
  bullet("Adjuncts: Heat pad, exercise, dietary omega-3."),
  bullet("Vitamin B1 (100mg/day) – evidence-based alternative."),
  bullet("Surgical (rare): Laparoscopic uterosacral nerve ablation (LUNA), presacral neurectomy – for intractable cases."),
  heading3("Exam Tips:"),
  bullet("Primary dysmenorrhea = prostaglandin-mediated. NSAIDs = first-line treatment."),
  bullet("Pain starts at onset of flow (not before). Normal pelvic exam."),
  bullet("Ovulatory cycles required for PGF2α production → primary dysmenorrhea rare in first year post-menarche."),
  divider(),

  // ===== 21. SECONDARY DYSMENORRHEA =====
  heading1("21. Secondary Dysmenorrhea"),
  bold("Definition", "Cyclic menstrual pain associated with underlying pelvic pathology."),
  heading3("Key Distinguishing Feature:"),
  bullet("Pain begins 1-2 weeks BEFORE menses and may persist until a few days AFTER menstruation (unlike primary which starts at onset)."),
  heading3("Causes (Mnemonic: APES CIC):"),
  bullet("A – Adenomyosis (diffuse endometrial glands in myometrium)"),
  bullet("E – Endometriosis (most common cause of secondary dysmenorrhea)"),
  bullet("P – Pelvic Inflammatory Disease (PID)"),
  bullet("S – Submucosal fibroids / Subserosal fibroids"),
  bullet("C – Cervical stenosis"),
  bullet("I – Intrauterine device (copper IUD)"),
  bullet("C – Congenital pelvic malformations, Ovarian cysts"),
  heading3("Endometriosis (Most Common Cause):"),
  bullet("Endometrial glands and stroma outside uterine cavity (ovaries, POD, uterosacral ligaments)."),
  bullet("Classic triad: Dysmenorrhea + Dyspareunia + Infertility."),
  bullet("Chocolate cysts (endometriomas) in ovaries."),
  bullet("Uterosacral nodularity on rectovaginal exam."),
  bullet("Gold standard diagnosis: Laparoscopy with biopsy."),
  heading3("Adenomyosis:"),
  bullet("Endometrial glands within myometrium."),
  bullet("Classic: Enlarged, tender, 'boggy' uterus; dysmenorrhea + menorrhagia in parous women 40-50 yrs."),
  bullet("Diagnosis: MRI (gold standard), TVUS."),
  heading3("Management:"),
  bullet("Treat underlying cause."),
  bullet("NSAIDs and OCP are less effective than in primary dysmenorrhea."),
  bullet("Endometriosis: Laparoscopic ablation/excision, hormonal suppression (GnRH agonist, danazol, dienogest, OCP)."),
  bullet("Adenomyosis: LNG-IUS, GnRH agonist, hysterectomy (definitive)."),
  bullet("PID: Antibiotics."),
  heading3("Exam Tips:"),
  bullet("Secondary dysmenorrhea: Pain PRE-DATES menses; underlying pathology."),
  bullet("Endometriosis: Deep dyspareunia, subfertility, laparoscopy required for diagnosis."),
  bullet("10% general population, 20% infertile women, >30% chronic pelvic pain."),
  divider(),

  // ===== 22. PMS =====
  heading1("22. Premenstrual Syndrome (PMS)"),
  bold("Definition", "A complex of physical and emotional symptoms that occur repetitively in the luteal phase of the menstrual cycle and diminish or disappear with menstruation (or a few days after)."),
  bold("Also known as", "Premenstrual tension (PMT), premenstrual molimina."),
  bold("Prevalence", "50% of menstruating women have some symptoms. Severe (qualifying for PMDD) in 3-5%."),
  heading3("Diagnostic Criteria:"),
  bullet("Symptoms occur ONLY in luteal phase (Days 14-28)."),
  bullet("Symptoms absent in follicular phase (confirms cyclic pattern)."),
  bullet("Must be confirmed by 2-3 months of prospective daily symptom diary."),
  bullet("Symptoms significantly interfere with daily life."),
  heading3("Physical Symptoms:"),
  bullet("Bloating/abdominal distension, breast engorgement and tenderness (mastalgia), peripheral edema, weight gain, headache, acne, constipation/diarrhea."),
  heading3("Emotional/Behavioral Symptoms:"),
  bullet("Irritability (most common), mood swings, anxiety, depression, fatigue, food cravings (sweet/salty), insomnia, difficulty concentrating, withdrawal from social activities."),
  heading3("Etiology (Unknown – Theories):"),
  bullet("Progesterone or its metabolites (allopregnanolone) → CNS effects."),
  bullet("Serotonin deficiency in luteal phase (explains SSRI efficacy)."),
  bullet("Not specific hormone level but sensitivity to normal hormonal changes."),
  bullet("No specific serum hormone level is diagnostic."),
  heading3("PMDD (Premenstrual Dysphoric Disorder):"),
  bullet("Severe form of PMS; DSM-5 diagnosis."),
  bullet("Must have ≥5 symptoms (≥1 mood symptom: irritability, depressed mood, anxiety, affective lability)."),
  bullet("Symptoms markedly interfere with work/relationships."),
  bullet("Confirmed by 2 months of daily prospective ratings."),
  heading3("Treatment:"),
  bullet("Lifestyle: Regular exercise, reduced caffeine/salt/sugar, stress reduction, adequate sleep."),
  bullet("Vitamin B6 (pyridoxine) – mild evidence."),
  bullet("First-line pharmacological for PMDD: SSRIs (fluoxetine, sertraline, paroxetine) – FDA approved; can be used continuously or luteal-phase only."),
  bullet("OCP: Drospirenone/EE (Yaz) – FDA approved for PMDD; anti-mineralocorticoid effect reduces bloating."),
  bullet("GnRH agonists + add-back: For severe, refractory cases (suppresses ovulation)."),
  bullet("For mastalgia: Bromocriptine, danazol."),
  heading3("Exam Tips:"),
  bullet("PMS symptoms ONLY in luteal phase; absent post-menstruation."),
  bullet("Diagnosis requires 2-3 months prospective diary (not retrospective)."),
  bullet("PMDD = severe PMS with predominant mood symptoms; treat with SSRIs."),
  bullet("PMS ≠ underlying psychiatric disorder (though may worsen it)."),
  divider(),

  // ===== 23. MENOPAUSE =====
  heading1("23. Menopause"),
  bold("Definition", "Permanent cessation of menstruation due to loss of ovarian follicular activity. Diagnosed retrospectively after 12 consecutive months of amenorrhea."),
  bold("Average Age", "51-52 years (range 45-55). Natural process."),
  bold("Perimenopause/Climacteric", "Transition period beginning up to 10 years before menopause; FSH rises, cycles become irregular."),
  heading3("Pathophysiology:"),
  bullet("Progressive depletion of ovarian primordial follicles throughout reproductive life (~400 ovulate; hundreds of thousands undergo atresia)."),
  bullet("By ~45-50 yrs, few follicles remain → ovaries unresponsive to gonadotropins."),
  bullet("Estradiol production falls → loss of negative feedback on pituitary."),
  bullet("FSH rises markedly (FSH >40 IU/L – diagnostic). LH also elevated (less dramatically)."),
  bullet("Post-menopause: Estrone (from peripheral conversion of androstenedione in adipose) replaces estradiol as main estrogen."),
  heading3("Symptoms (due to Estrogen Deficiency):"),
  heading3("Vasomotor (most troublesome):"),
  bullet("Hot flushes/flashes: 75% of women; due to estrogen-sensitive event in hypothalamus triggering LH burst + cutaneous vasodilation; may persist up to 40 years."),
  bullet("Night sweats."),
  heading3("Urogenital Atrophy (GSM – Genitourinary Syndrome of Menopause):"),
  bullet("Vaginal dryness, dyspareunia, pruritus vulvae."),
  bullet("Urinary urgency, frequency, recurrent UTIs, stress incontinence."),
  heading3("Psychological:"),
  bullet("Irritability, anxiety, mood changes, depression, poor concentration, fatigue."),
  heading3("Long-term Consequences:"),
  bullet("Osteoporosis: Accelerated bone loss (first 5-10 years post-menopause). ↑ fracture risk (hip, vertebrae, Colles')."),
  bullet("Cardiovascular disease: Loss of estrogen's cardioprotective effect → ↑ LDL, ↓ HDL → atherosclerosis."),
  bullet("Cognitive: Possible ↑ dementia risk (controversial)."),
  heading3("Diagnosis:"),
  bullet("Clinical (12 months amenorrhea in women >45 yrs)."),
  bullet("FSH >30-40 IU/L (measured if <45 yrs or uncertain)."),
  heading3("Treatment:"),
  bullet("Hormone Replacement Therapy (HRT/MHT): Most effective for vasomotor symptoms and GSM."),
  bullet("Benefits: ↓ hot flushes, ↓ vaginal atrophy, ↓ osteoporosis, possible ↓ CVD (if started <60 yrs or <10 yrs post-menopause – 'timing hypothesis')."),
  bullet("Risks: ↑ Breast cancer (combined E+P), ↑ VTE, ↑ stroke (oral route)."),
  bullet("Non-hormonal: SSRIs/SNRIs (venlafaxine, paroxetine) for hot flushes; gabapentin."),
  bullet("Vaginal estrogen: For GSM, minimal systemic absorption."),
  heading3("Exam Tips:"),
  bullet("Hot flushes = most common menopausal symptom (75%)."),
  bullet("FSH >40 IU/L + 12 months amenorrhea = menopause."),
  bullet("Post-menopausal: Estrone (not estradiol) is main estrogen (from adipose conversion of androstenedione)."),
  divider(),

  // ===== 24. PERIMENOPAUSE =====
  heading1("24. Perimenopause"),
  bold("Definition", "The transitional period immediately before and one year after the final menstrual period (FMP). Can last 2-10 years. Also called the climacteric or menopausal transition."),
  heading3("Hormonal Changes:"),
  bullet("FSH begins rising (falls in inhibin B → loss of FSH suppression) – earliest hormonal change."),
  bullet("LH rises later."),
  bullet("Estradiol fluctuates (can be very high or very low) → irregular cycles."),
  bullet("Progesterone: Reduced (fewer ovulatory cycles → less corpus luteum)."),
  bullet("Inhibin A and B decrease."),
  heading3("Clinical Features:"),
  bullet("Menstrual irregularity: Cycles become longer (oligomenorrhea) or shorter; anovulatory cycles increase."),
  bullet("Heavy or irregular bleeding (AUB is common)."),
  bullet("Vasomotor symptoms (hot flushes, night sweats)."),
  bullet("Sleep disturbance, mood changes."),
  bullet("Fertility reduced but NOT zero – contraception still needed."),
  heading3("Duration:"),
  bullet("Variable: Average 4-5 years; can range from months to >10 years."),
  heading3("Exam Tips:"),
  bullet("First hormonal change = FSH rise (due to ↓ inhibin B)."),
  bullet("Estradiol levels can be paradoxically elevated in perimenopause."),
  bullet("Pregnancy possible in perimenopause → contraception required."),
  divider(),

  // ===== 25. ARTIFICIAL MENOPAUSE =====
  heading1("25. Artificial Menopause"),
  bold("Definition", "Cessation of menstruation induced by medical/surgical intervention rather than natural follicular depletion."),
  heading3("Causes:"),
  bullet("Surgical: Bilateral oophorectomy (castration) – most common; can be combined with hysterectomy."),
  bullet("Radiation: Pelvic irradiation to ovaries (castration dose ~6 Gy for ovarian ablation)."),
  bullet("Medical/Chemical: GnRH agonists (leuprolide, goserelin) – reversible 'medical menopause'; used for endometriosis, fibroids, precocious puberty."),
  heading3("Features:"),
  bullet("Symptoms appear ABRUPTLY (unlike gradual natural menopause) → often more severe vasomotor symptoms."),
  bullet("Surgical menopause post-bilateral oophorectomy → immediate, severe hot flushes."),
  bullet("Also: ↑ cardiovascular risk, rapid bone loss, genital atrophy."),
  heading3("Treatment:"),
  bullet("HRT strongly indicated (especially if <45 yrs) to prevent long-term sequelae until age of natural menopause."),
  heading3("Exam Tips:"),
  bullet("Bilateral oophorectomy before natural menopause = premature surgical menopause (if <40 yrs = premature menopause)."),
  bullet("Medical menopause (GnRH agonist) is reversible; surgical/radiation is permanent."),
  divider(),

  // ===== 26. PREMATURE MENOPAUSE =====
  heading1("26. Premature Menopause / Premature Ovarian Insufficiency (POI)"),
  bold("Definition", "Loss of normal ovarian function before age 40. Previously called 'premature ovarian failure (POF)'. Now termed POI (insufficiency) as ovarian function can be intermittent."),
  bold("Incidence", "1% of women <40 yrs; 0.1% <30 yrs."),
  heading3("Diagnostic Criteria (POI):"),
  bullet("Age <40 years."),
  bullet("Oligomenorrhea or amenorrhea for ≥4 months."),
  bullet("FSH >25-40 IU/L on two occasions 4-6 weeks apart."),
  heading3("Causes:"),
  bullet("Idiopathic (most common, ~50%)."),
  bullet("Genetic: Turner syndrome (45,X), fragile X premutation (FMR1), other X-chromosome abnormalities."),
  bullet("Autoimmune: Autoimmune oophoritis (anti-ovarian antibodies); associated with Addison's disease, Type 1 DM, hypothyroidism (APS type 2)."),
  bullet("Iatrogenic: Bilateral oophorectomy, chemotherapy (alkylating agents), pelvic radiation."),
  bullet("Infections: Mumps oophoritis (rare)."),
  heading3("Clinical Features:"),
  bullet("Oligomenorrhea/amenorrhea."),
  bullet("Menopausal symptoms (hot flushes, night sweats, vaginal dryness)."),
  bullet("Infertility (but ~5-10% chance of spontaneous pregnancy)."),
  bullet("High risk: Osteoporosis, cardiovascular disease, cognitive decline."),
  heading3("Investigations:"),
  bullet("FSH, LH, estradiol (×2, 4-6 wks apart)."),
  bullet("AMH (very low/undetectable)."),
  bullet("Karyotype (Turner syndrome, X-chromosome anomaly)."),
  bullet("Autoimmune screen: Anti-thyroid antibodies, adrenal antibodies, fasting glucose."),
  bullet("FMR1 premutation testing."),
  bullet("DEXA scan (bone mineral density)."),
  heading3("Treatment:"),
  bullet("HRT (estrogen ± progestogen) – mandatory until age of natural menopause (50-51 yrs) to prevent osteoporosis and cardiovascular disease."),
  bullet("Psychological support, fertility counseling."),
  bullet("Fertility: Egg donation (most successful), or spontaneous (if intermittent function)."),
  bullet("Treat associated conditions (autoimmune)."),
  heading3("Exam Tips:"),
  bullet("POI ≠ menopause (intermittent function possible; HRT does not suppress potential ovulation)."),
  bullet("FMR1 premutation = most common genetic cause of non-chromosomal POI."),
  bullet("HRT is required (unlike natural menopause where it is optional)."),
  divider(),

  // ===== 27. DELAYED MENOPAUSE =====
  heading1("27. Delayed Menopause"),
  bold("Definition", "Menopause occurring after age 55 (some use >52-53 years as threshold). Normal range extends to 55-58 years."),
  heading3("Causes/Associations:"),
  bullet("Familial tendency (genetic predisposition)."),
  bullet("Higher body weight/obesity (peripheral estrogen production from adipose tissue)."),
  bullet("Nulliparity."),
  bullet("Use of OCP (does not affect actual ovarian reserve but may mask symptoms)."),
  heading3("Clinical Significance:"),
  bullet("↑ Prolonged estrogen exposure → ↑ risk of: Endometrial cancer, breast cancer, ovarian cancer."),
  bullet("Relative protection from osteoporosis and cardiovascular disease for longer."),
  heading3("Management:"),
  bullet("Regular screening for endometrial pathology if AUB occurs."),
  bullet("Breast screening per age-based guidelines."),
  heading3("Exam Tips:"),
  bullet("Delayed menopause = risk factor for estrogen-dependent cancers (endometrial, breast)."),
  bullet("Protective against osteoporosis."),
  divider(),

  // ===== 28. POSTMENOPAUSAL BLEEDING =====
  heading1("28. Post-Menopausal Bleeding (PMB)"),
  bold("Definition", "Any vaginal bleeding occurring more than 12 months after the last natural menstrual period (last menstrual period = FMP). Even a single episode must be investigated."),
  bold("Golden Rule", "Post-menopausal bleeding = endometrial carcinoma until proven otherwise."),
  heading3("Causes (in approximate order of frequency):"),
  bullet("1. Endometrial atrophy – most common benign cause (~30-40%)."),
  bullet("2. Endometrial carcinoma – most important cause to exclude (~10-15% of all PMB)."),
  bullet("3. Endometrial hyperplasia."),
  bullet("4. Endometrial polyp."),
  bullet("5. Cervical pathology: Cervicitis, cervical polyp, cervical carcinoma."),
  bullet("6. Vaginal atrophic vaginitis."),
  bullet("7. Ovarian tumor (estrogen-secreting, e.g., granulosa cell tumor)."),
  bullet("8. Exogenous estrogens/HRT withdrawal/breakthrough."),
  bullet("9. Vulval/vaginal carcinoma."),
  bullet("10. Blood dyscrasias, anticoagulants."),
  heading3("Risk Factors for Endometrial Cancer in PMB:"),
  bullet("Obesity, nulliparity, late menopause, diabetes, hypertension, unopposed estrogen use, tamoxifen, HNPCC."),
  heading3("Investigation:"),
  bullet("Step 1: Transvaginal ultrasound (TVUS) – measure endometrial thickness (ET)."),
  bullet("ET ≤4 mm: Low risk of malignancy (~1%). Further biopsy not mandatory unless bleeding recurs."),
  bullet("ET >4 mm: Endometrial sampling mandatory."),
  bullet("Step 2: Endometrial biopsy (Pipelle sampler – 90% accuracy)."),
  bullet("Step 3: Hysteroscopy + directed biopsy – gold standard if biopsy inconclusive or ET >4mm."),
  bullet("Cervical smear, speculum exam."),
  heading3("Management:"),
  bullet("Atrophic endometritis: Topical/systemic estrogen."),
  bullet("Polyp/fibroid: Hysteroscopic polypectomy/myomectomy."),
  bullet("Endometrial hyperplasia without atypia: Progestogen."),
  bullet("Endometrial hyperplasia with atypia / Carcinoma: Surgical staging (TAH + BSO + lymph node dissection)."),
  heading3("Exam Tips:"),
  bullet("ET ≤4 mm on TVUS = low risk; ET >4 mm = biopsy."),
  bullet("Endometrial carcinoma present in ~10% of PMB cases → cannot miss."),
  bullet("Pipelle biopsy = first-line investigation for endometrial sampling."),
  bullet("Hysteroscopy = gold standard for endometrial visualization."),
  bullet("Any PMB in a woman on tamoxifen → high suspicion (increases endometrial cancer risk 2-3x)."),
  divider(),

  // Final note
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        text: "References: Berek & Novak's Gynecology 16th Ed | Guyton & Hall Medical Physiology 14th Ed | Ganong's Review of Medical Physiology 26th Ed | Costanzo Physiology 7th Ed | DC Dutta's Textbook of Gynecology 8th Ed | Goldman-Cecil Medicine | FIGO Guidelines 2018",
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