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pres.author = "Medical Education";
pres.title = "Postmenopausal Syndrome – Comprehensive Review";

// ── COLOUR PALETTE ──────────────────────────────────────────────────
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// ── HELPERS ──────────────────────────────────────────────────────────
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// ─────────────────────────────────────────────────────────────────────
// SLIDE 1 – TITLE
// ─────────────────────────────────────────────────────────────────────
{
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// ─────────────────────────────────────────────────────────────────────
// SLIDE 2 – TABLE OF CONTENTS
// ─────────────────────────────────────────────────────────────────────
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    ["06", "Genitourinary Syndrome of Menopause (GSM)", "80CBC4"],
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// ─────────────────────────────────────────────────────────────────────
// SECTION 1 – DEFINITION & TERMINOLOGY
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("01 | Definition & Terminology", "Understanding the menopausal transition and its nomenclature", C.deepPurple);

addContentSlide("What is Menopause?", [
  { text: "Definition (WHO / NAMS)", bold: true },
  { text: "Permanent cessation of menstruation due to loss of ovarian follicular activity", sub: true },
  { text: "Diagnosed RETROSPECTIVELY after 12 consecutive months of amenorrhea", sub: true },
  { text: "Natural menopause: median age 51 years (range 40–58) in developed nations", sub: true },
  { text: "Premature ovarian insufficiency (POI): menopause before age 40", sub: true },
  "",
  { text: "Perimenopause / Menopausal Transition", bold: true },
  { text: "Period of irregular cycles with fluctuating hormones preceding final menstrual period (FMP)", sub: true },
  { text: "Typically begins 2–8 years before FMP; FSH starts rising", sub: true },
  "",
  { text: "Postmenopause", bold: true },
  { text: "All time following the FMP; divided into early (<5 yrs) and late (>5 yrs)", sub: true },
  { text: "Postmenopausal syndrome = constellation of symptoms and long-term health consequences arising from estrogen deficiency", sub: true },
]);

addContentSlide("Types of Menopause", [
  { text: "Natural Menopause", bold: true },
  { text: "Physiological cessation of menses from gradual ovarian follicular depletion", sub: true },
  "",
  { text: "Surgical (Iatrogenic) Menopause", bold: true },
  { text: "Bilateral oophorectomy → abrupt, severe estrogen withdrawal; more intense symptoms", sub: true },
  { text: "More rapid onset of osteoporosis & CVD risk compared to natural menopause", sub: true },
  "",
  { text: "Premature Ovarian Insufficiency (POI)", bold: true },
  { text: "Primary ovarian insufficiency before age 40; affects ~1% of women", sub: true },
  { text: "Causes: autoimmune, genetic (Turner syndrome, FMR1 premutation), iatrogenic, idiopathic", sub: true },
  "",
  { text: "Chemotherapy / Radiation-Induced Menopause", bold: true },
  { text: "Ovarian toxicity from alkylating agents, pelvic radiation; may be reversible", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 2 – EPIDEMIOLOGY
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("02 | Epidemiology & Global Burden", "Who is affected and how many?", C.midPurple);

addContentSlide("Epidemiology of Postmenopausal Syndrome", [
  { text: "Global Burden", bold: true },
  { text: "~1.1 billion women worldwide will be postmenopausal by 2025 (UN estimate)", sub: true },
  { text: "Average life expectancy: women spend ~30–35 years in postmenopause", sub: true },
  "",
  { text: "Vasomotor Symptoms", bold: true },
  { text: "Up to 75% of perimenopausal/postmenopausal women experience hot flashes", sub: true },
  { text: "Symptoms last 1–2 years in most; persist >10 years in ~10% of women", sub: true },
  { text: "Higher prevalence in Black women; lower in Asian and Hispanic women", sub: true },
  "",
  { text: "Genitourinary Syndrome of Menopause (GSM)", bold: true },
  { text: "Affects 27–84% of postmenopausal women; under-reported and under-treated", sub: true },
  "",
  { text: "Osteoporosis & Fractures", bold: true },
  { text: "~35 million US women; ~66% of women >50 years have low bone mass or osteoporosis", sub: true },
  { text: "1 in 2 postmenopausal women will have an osteoporotic fracture in their lifetime", sub: true },
  "",
  { text: "Cardiovascular Disease", bold: true },
  { text: "Leading cause of death in postmenopausal women; 90% have ≥1 CVD risk factor", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 3 – STRAW STAGING
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("03 | Reproductive Aging – STRAW+10 Staging", "A standardised framework for the menopausal transition", "3949AB");

addContentSlide("STRAW+10 Staging System (2011)", [
  { text: "Stages of Reproductive Aging Workshop (STRAW) – Gold Standard Framework", bold: true },
  { text: "7 stages spanning reproductive life to late postmenopause", sub: true },
  "",
  { text: "REPRODUCTIVE STAGES (–5 to –3)", bold: true },
  { text: "Stage –5 to –3: Regular cycles, peak fertility → subtle FSH rise, AMH decline", sub: true },
  "",
  { text: "MENOPAUSAL TRANSITION (–2 to –1)", bold: true },
  { text: "Stage –2 (Early): Variable cycle length ≥7 days different from normal; elevated FSH", sub: true },
  { text: "Stage –1 (Late): Amenorrhea ≥60 days; FSH >25 IU/L; increased anovulatory cycles", sub: true },
  { text: "Duration of late transition: ~1–3 years before FMP", sub: true },
  "",
  { text: "POSTMENOPAUSE (+1 to +2)", bold: true },
  { text: "Stage +1a: First 1 year after FMP – still high symptom burden (vasomotor, sleep)", sub: true },
  { text: "Stage +1b: Years 1–5 – FSH stabilises; vasomotor symptoms may persist", sub: true },
  { text: "Stage +1c: Years 5–8 – FSH plateau; primary concern shifts to bone and CVD", sub: true },
  { text: "Stage +2 (Late): >8 years post-FMP; aging-related issues predominate", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 4 – PATHOPHYSIOLOGY
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("04 | Pathophysiology – Hormonal Changes", "Ovarian failure, HPO axis disruption, and downstream effects", C.deepPurple);

addContentSlide("Hormonal Changes in Menopause", [
  { text: "Ovarian Changes", bold: true },
  { text: "Progressive loss of ovarian follicles → depletion of oocytes and granulosa cells", sub: true },
  { text: "Peak follicle count: ~6–7 million at 20 weeks gestation → ~1 million at birth → ~400,000 at menarche → near-zero at menopause", sub: true },
  "",
  { text: "Estrogen", bold: true },
  { text: "Estradiol (E2): primary ovarian estrogen; drops from 100–400 pg/mL to <20 pg/mL", sub: true },
  { text: "Estrone (E1): becomes the dominant circulating estrogen post-menopause; derived from peripheral aromatisation of androstenedione (adipose, skin, muscle)", sub: true },
  "",
  { text: "Progesterone", bold: true },
  { text: "Essentially absent post-menopause (no corpus luteum formation)", sub: true },
  { text: "Loss of progesterone → unopposed estrogen effect on endometrium if exogenous estrogen given", sub: true },
  "",
  { text: "Gonadotrophins (Pituitary)", bold: true },
  { text: "Loss of ovarian negative feedback → FSH rises markedly (>25 IU/L, typically 40–200 IU/L)", sub: true },
  { text: "LH rises but less dramatically than FSH (lost inhibin-B suppression of FSH is key)", sub: true },
  "",
  { text: "Androgens", bold: true },
  { text: "Gradual decline with aging; ovarian stroma continues DHEA/androstenedione production; adrenal contribution persists", sub: true },
]);

addTwoColumnSlide(
  "Hormonal Milieu: Reproductive vs. Postmenopausal",
  {
    header: "Reproductive Years",
    bullets: [
      "Estradiol: 100–400 pg/mL (follicular/luteal)",
      "Progesterone: 1–20 ng/mL (luteal phase)",
      "FSH: 3–10 IU/L",
      "LH: 2–15 IU/L",
      "Inhibin-B: measurable",
      "AMH: age-dependent, reflects follicle pool",
      "Androstenedione: ~1.5 ng/mL",
      "DHEAS: 1,500–3,000 ng/mL",
    ],
  },
  {
    header: "Postmenopause",
    bullets: [
      "Estradiol: <20 pg/mL (often <10)",
      "Estrone (E1) becomes dominant",
      "Progesterone: <1 ng/mL (near undetectable)",
      "FSH: 25–150 IU/L (greatly elevated)",
      "LH: elevated but less than FSH",
      "Inhibin-B: undetectable",
      "AMH: undetectable",
      "Androstenedione: reduced ~50%",
    ],
  },
  { headerColor: C.midPurple }
);

addContentSlide("KNDy Neurons & Vasomotor Symptoms – The Central Mechanism", [
  { text: "Hypothalamic Thermoregulation", bold: true },
  { text: "Hot flashes originate from a central hypothalamic event → narrow thermoneutral zone", sub: true },
  { text: "Small rise in core temperature triggers sweating and peripheral vasodilation", sub: true },
  "",
  { text: "KNDy Neurons (Arcuate Nucleus of Hypothalamus)", bold: true },
  { text: "Neurons co-expressing Kisspeptin, Neurokinin B (NKB), and Dynorphin", sub: true },
  { text: "Estrogen normally suppresses KNDy neuron activity; withdrawal → hyper-activation", sub: true },
  { text: "NKB acts on the median preoptic nucleus → thermoregulatory dysregulation", sub: true },
  { text: "IV NKB infusion in premenopausal women reproduces hot flash physiology", sub: true },
  "",
  { text: "Monoaminergic Pathways", bold: true },
  { text: "Noradrenergic: lowered threshold for heat dissipation response (sweating)", sub: true },
  { text: "Serotonergic: estrogen modulates 5-HT receptor density; accounts for SSRI/SNRI efficacy", sub: true },
  { text: "Dopaminergic: mesolimbic pathway changes → mood symptoms, brain fog", sub: true },
  "",
  { text: "NEW DRUG TARGET: NK3R Antagonists", bold: true },
  { text: "Fezolinetant (Veozah, FDA-approved 2023) blocks NK3 receptor → reduces hot flashes 60–70%", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 5 – VASOMOTOR SYMPTOMS
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("05 | Vasomotor Symptoms", "Hot flashes, night sweats, and sleep disruption", "C62828");

addContentSlide("Vasomotor Symptoms (VMS) – Clinical Features", [
  { text: "Prevalence & Duration", bold: true },
  { text: "Up to 75% of perimenopausal women; most common reason women seek care at menopause", sub: true },
  { text: "Last 1–2 years in most women; persist >7 years in ~50% (SWAN study); >10 years in 10%", sub: true },
  { text: "Black women have the longest duration and highest frequency; Japanese women shortest", sub: true },
  "",
  { text: "Hot Flash Characteristics", bold: true },
  { text: "Sudden intense warmth starting centrally (chest, neck, face)", sub: true },
  { text: "Lasts 2–4 minutes; may be followed by chills and shivering", sub: true },
  { text: "Often accompanied by profuse sweating and heart palpitations", sub: true },
  { text: "Nocturnal: night sweats → sleep fragmentation → daytime fatigue, cognitive impairment", sub: true },
  "",
  { text: "Frequency Classification", bold: true },
  { text: "Mild: <7 per week", sub: true },
  { text: "Moderate: 7–49 per week (1–6/day)", sub: true },
  { text: "Severe: ≥50 per week (≥7/day) – significant quality of life impact", sub: true },
  "",
  { text: "Impact", bold: true },
  { text: "Disrupts work productivity, social function, sexual activity, and psychological wellbeing", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 6 – GSM
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("06 | Genitourinary Syndrome of Menopause", "GSM: The underdiagnosed estrogen-responsive condition", "00695C");

addContentSlide("Genitourinary Syndrome of Menopause (GSM)", [
  { text: "Definition (NAMS/ISSWSH 2014)", bold: true },
  { text: "Collection of vulvovaginal, sexual, and urinary symptoms from estrogen deficiency", sub: true },
  { text: "Replaces older terms 'vulvovaginal atrophy' (VVA) and 'atrophic vaginitis'", sub: true },
  "",
  { text: "Pathophysiology", bold: true },
  { text: "Estrogen receptors in vaginal epithelium, urethra, bladder trigone, pelvic floor", sub: true },
  { text: "Estrogen loss → thin, pale, dry vaginal epithelium; loss of rugae; raised pH (>4.5)", sub: true },
  { text: "Reduced glycogen → decreased Lactobacillus → dysbiosis, recurrent UTIs", sub: true },
  "",
  { text: "Vulvovaginal Symptoms (most common)", bold: true },
  { text: "Vaginal dryness, burning, itching, discharge", sub: true },
  { text: "Dyspareunia (superficial and deep) – unlike hot flashes, does NOT improve spontaneously", sub: true },
  "",
  { text: "Urinary Symptoms", bold: true },
  { text: "Urgency, frequency, nocturia, dysuria; stress urinary incontinence (SUI)", sub: true },
  { text: "Recurrent urinary tract infections (UTIs) due to loss of protective colonisation", sub: true },
  "",
  { text: "Key Clinical Point", bold: true },
  { text: "GSM symptoms worsen over time without treatment; require long-term management", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 7 – SEXUAL DYSFUNCTION
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("07 | Sexual Dysfunction", "Female sexual dysfunction in the postmenopausal woman", "6A1B9A");

addContentSlide("Sexual Dysfunction – Overview", [
  { text: "Prevalence", bold: true },
  { text: "~40% of US women report sexual problems; distressing in 12% (PRESIDE study)", sub: true },
  { text: "Distressing sexual dysfunction peaks in midlife women (45–64 years)", sub: true },
  "",
  { text: "Contributing Factors (Multifactorial)", bold: true },
  { text: "Menopause-related: VMS, sleep disruption, fatigue; dyspareunia from GSM", sub: true },
  { text: "Psychological: depression, anxiety, body image, prior abuse, stress", sub: true },
  { text: "Relationship: partner factors, relationship conflict, communication", sub: true },
  { text: "Medications: SSRIs (↓ libido), antihypertensives", sub: true },
  { text: "Androgen decline: testosterone levels fall gradually with aging", sub: true },
  "",
  { text: "Domains of Female Sexual Dysfunction (DSM-5)", bold: true },
  { text: "Female Sexual Interest/Arousal Disorder (FSIAD)", sub: true },
  { text: "Genito-Pelvic Pain/Penetration Disorder (GPPPD) – includes dyspareunia", sub: true },
  { text: "Female Orgasmic Disorder", sub: true },
  "",
  { text: "Management Approach", bold: true },
  { text: "Treat GSM (local/systemic ET, ospemifene, vaginal DHEA)", sub: true },
  { text: "Psychosexual therapy, couples counselling, bupropion as adjunct", sub: true },
  { text: "Testosterone (off-label): benefit for FSIAD in some studies; no approved product in women", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 8 – OSTEOPOROSIS
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("08 | Osteoporosis & Bone Health", "The silent epidemic of postmenopausal bone loss", "E65100");

addContentSlide("Osteoporosis – Pathophysiology & Risk Factors", [
  { text: "Bone Remodelling in Menopause", bold: true },
  { text: "Estrogen inhibits osteoclast activity; its loss → uncoupling of bone resorption > formation", sub: true },
  { text: "Bone loss accelerates 3–5% per year in the first 5 years post-menopause", sub: true },
  { text: "~15% of trabecular bone and 10% of cortical bone lost within 10 years of FMP", sub: true },
  "",
  { text: "WHO Diagnostic Criteria (DXA T-score)", bold: true },
  { text: "Normal: T-score ≥ −1.0", sub: true },
  { text: "Osteopenia (low bone density): T-score −1.0 to −2.5", sub: true },
  { text: "Osteoporosis: T-score ≤ −2.5", sub: true },
  { text: "Severe (established) osteoporosis: T-score ≤ −2.5 + fragility fracture", sub: true },
  "",
  { text: "Risk Factors", bold: true },
  { text: "Non-modifiable: age, Asian/Caucasian race, small frame, early menopause, family Hx, prior fracture", sub: true },
  { text: "Modifiable: low Ca/Vit D, smoking, excess alcohol, physical inactivity, low BMI", sub: true },
  { text: "Secondary causes: hyperparathyroidism, hyperthyroidism, RA, chronic steroid use, CKD", sub: true },
]);

addTableSlide(
  "Osteoporosis Pharmacotherapy",
  ["Agent", "Class", "Route", "Key Feature"],
  [
    ["Alendronate / Risedronate", "Bisphosphonate", "Oral weekly/daily", "First-line; reduces vertebral + hip Fx 50%"],
    ["Zoledronic acid", "Bisphosphonate", "IV yearly", "Best adherence; given once-yearly infusion"],
    ["Denosumab (Prolia)", "Anti-RANKL mAb", "SC 6-monthly", "Reduces hip + vertebral Fx; reversible with drug holiday"],
    ["Raloxifene (Evista)", "SERM", "Oral daily", "Reduces vertebral Fx; reduces breast Ca risk; ↑VTE"],
    ["Teriparatide (Forteo)", "PTH analogue (anabolic)", "SC daily", "Stimulates bone formation; max 18–24 months"],
    ["Abaloparatide (Tymlos)", "PTHrP analogue", "SC daily", "Anabolic; reduces vertebral + non-vertebral Fx"],
    ["Romosozumab (Evenity)", "Anti-sclerostin mAb", "SC monthly", "Dual anabolic + anti-resorptive; max 12 months"],
    ["Conjugated estrogens", "HT", "Oral/transdermal", "Prevents bone loss; reduces hip Fx 33%"],
  ],
  { colW: [2.8, 2.3, 1.8, 2.5] }
);

// ─────────────────────────────────────────────────────────────────────
// SECTION 9 – CARDIOVASCULAR DISEASE
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("09 | Cardiovascular Disease", "Leading cause of death in postmenopausal women", "B71C1C");

addContentSlide("Cardiovascular Risk After Menopause", [
  { text: "Premenopausal Protection Lost", bold: true },
  { text: "Estrogen maintains endothelial function, vasodilation (↑NO), favorable lipid profile", sub: true },
  { text: "Post-menopause: LDL-C ↑, HDL-C ↓, triglycerides ↑, BP ↑, insulin resistance ↑", sub: true },
  { text: "CVD incidence equalises with men within 10 years of menopause", sub: true },
  "",
  { text: "Metabolic Changes Driving CVD Risk", bold: true },
  { text: "Visceral adiposity increases even without weight gain (estrogen-regulated adipogenesis)", sub: true },
  { text: "Accelerated atherosclerosis: endothelial dysfunction, ↑CRP, ↑fibrinogen", sub: true },
  { text: "Hypertension: loss of vasodilatory estrogen effect; SNS activation", sub: true },
  "",
  { text: "WHI Trial Findings (Cardiovascular)", bold: true },
  { text: "EPT (CEE + MPA): HR for CHD 1.3; stroke HR 1.4; PE HR 2.1 — in women avg age 63", sub: true },
  { text: "ET alone (hysterectomised): no increased CHD or breast cancer risk", sub: true },
  { text: "KEY: 'Timing Hypothesis' — benefits in women <60 or <10 yrs from menopause; risks in older women", sub: true },
  "",
  { text: "Premature Menopause & CVD", bold: true },
  { text: "Women with natural menopause before 40: 1.5× higher CVD risk; HT indicated until average age of menopause", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 10 – NEUROPSYCHIATRIC
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("10 | Neuropsychiatric & Cognitive Changes", "Brain estrogen, mood, memory and dementia risk", "1A237E");

addContentSlide("Neuropsychiatric Manifestations", [
  { text: "Mood Disturbances", bold: true },
  { text: "Increased risk of depression during menopausal transition (2–5× vs. premenopausal)", sub: true },
  { text: "Irritability, anxiety, mood lability common; often secondary to sleep disruption from VMS", sub: true },
  { text: "Prior history of PMS/PMDD or postpartum depression is a risk factor", sub: true },
  "",
  { text: "Cognitive Symptoms ('Brain Fog')", bold: true },
  { text: "Forgetfulness, poor concentration, word-finding difficulties", sub: true },
  { text: "Largely transient and recovers in late postmenopause (SWAN cognitive study)", sub: true },
  { text: "Estrogen supports cholinergic neurotransmission and hippocampal neuroplasticity", sub: true },
  "",
  { text: "Sleep Disturbances", bold: true },
  { text: "Insomnia in 39–47% of perimenopausal women; exacerbated by night sweats", sub: true },
  { text: "Reduced REM and slow-wave sleep; increased sleep fragmentation", sub: true },
  "",
  { text: "Dementia Risk", bold: true },
  { text: "Premature surgical menopause: increased Alzheimer's risk; mitigated by HT until natural age", sub: true },
  { text: "HT timing hypothesis applies to neuroprotection — early use may reduce dementia risk", sub: true },
  { text: "No evidence that late HT initiation (>65 years) improves cognitive outcomes", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 11 – METABOLIC
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("11 | Metabolic & Other Systemic Effects", "Weight, skin, musculoskeletal, oral health and more", "2E7D32");

addContentSlide("Metabolic & Systemic Changes", [
  { text: "Body Composition & Metabolism", bold: true },
  { text: "Central adiposity ↑ (visceral > subcutaneous) without total weight change in some women", sub: true },
  { text: "Insulin sensitivity ↓ → type 2 DM risk increases by ~40% post-menopause", sub: true },
  { text: "Metabolic syndrome prevalence rises significantly post-menopause", sub: true },
  "",
  { text: "Skin & Collagen", bold: true },
  { text: "Estrogen regulates dermal collagen; skin loses 30% collagen in first 5 years post-menopause", sub: true },
  { text: "Dryness, thinning, ↓ elasticity, slower wound healing", sub: true },
  "",
  { text: "Musculoskeletal", bold: true },
  { text: "Sarcopenia accelerates with estrogen loss (estrogen has anabolic effect on muscle)", sub: true },
  { text: "Joint pain (arthralgia) affects ~60% of menopausal women; estrogen has anti-inflammatory role", sub: true },
  "",
  { text: "Oral Health", bold: true },
  { text: "Burning mouth syndrome: associated with low estrogen; responds to HT in some cases", sub: true },
  { text: "Increased alveolar bone resorption → tooth loss risk increases", sub: true },
  "",
  { text: "Thyroid", bold: true },
  { text: "Thyroid disease prevalence increases with age; thyroid function should be tested if VMS atypical or HT-resistant", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 12 – DIAGNOSIS
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("12 | Diagnosis & Investigations", "Clinical assessment and laboratory workup", "004D40");

addTwoColumnSlide(
  "Clinical Diagnosis & Key Investigations",
  {
    header: "Clinical Diagnosis",
    bullets: [
      "Menopause is primarily CLINICAL",
      "History: menstrual pattern, VMS, GSM, mood, sleep, sexual function",
      "Age context: >45 yrs → clinical dx without testing",
      "STRAW staging using cycle pattern",
      "Rule out secondary causes: thyroid, pregnancy, medications",
      "Validated tools: Menopause Rating Scale (MRS), MENQOL questionnaire",
      "Physical exam: BP, weight/BMI, pelvic exam (signs of GSM), breast exam",
    ],
  },
  {
    header: "Key Investigations",
    bullets: [
      "FSH: >25 IU/L (x2, 4–6 wks apart if <45) supports dx",
      "Estradiol: low; not routinely needed for dx",
      "LH: elevated (less useful alone)",
      "AMH: undetectable in menopause",
      "TSH: exclude thyroid disease",
      "FBC, fasting glucose, lipids",
      "DXA bone densitometry (BMD): ≥65 yrs, or earlier if risk factors",
      "FRAX score: 10-yr fracture risk assessment",
      "Endometrial biopsy / USS: if PMB (postmenopausal bleeding)",
      "Mammogram: screening per guidelines",
    ],
  },
  { headerColor: C.deepPurple }
);

addContentSlide("Differential Diagnosis of Postmenopausal Symptoms", [
  { text: "Hot Flash Mimics", bold: true },
  { text: "Carcinoid syndrome: flushing + diarrhoea + wheeze (urinary 5-HIAA, serum serotonin)", sub: true },
  { text: "Pheochromocytoma: episodic hypertension + sweating + headache (plasma metanephrines)", sub: true },
  { text: "Mastocytosis: urticaria + GI symptoms + flushing (serum tryptase, urine histamine)", sub: true },
  { text: "Hyperthyroidism: heat intolerance + weight loss + tachycardia (TSH, free T4)", sub: true },
  { text: "Medications: niacin, tamoxifen, opioid withdrawal, alcohol", sub: true },
  "",
  { text: "Postmenopausal Bleeding (PMB) – Always Investigate", bold: true },
  { text: "Defined as any vaginal bleeding ≥12 months after FMP", sub: true },
  { text: "Endometrial cancer in ~5–10% of cases (most likely cause)", sub: true },
  { text: "Other causes: atrophic endometritis, polyps, submucosal fibroids, HT effects, cervical cancer", sub: true },
  { text: "Workup: Pelvic USS (endometrial thickness >4 mm on HT or >3 mm off HT → biopsy)", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 13 – HORMONE THERAPY TYPES
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("13 | Hormone Therapy – Types & Regimens", "Estrogens, progestogens, SERMs, and routes of administration", C.midPurple);

addContentSlide("Hormone Therapy (HT) – Principles & Indications", [
  { text: "Indications", bold: true },
  { text: "Bothersome VMS (first-line pharmacological treatment)", sub: true },
  { text: "Genitourinary syndrome of menopause (local ET preferred for isolated GSM)", sub: true },
  { text: "Prevention of osteoporosis (where other agents inappropriate or declined)", sub: true },
  { text: "Surgical/premature menopause: HT indicated until natural menopausal age (~51)", sub: true },
  "",
  { text: "Key Principle: Individualize", bold: true },
  { text: "Benefits vs risks depend on patient age, time since menopause, route, dose, formulation", sub: true },
  { text: "'Window of opportunity': initiate HT close to FMP for maximal CVD/neuro benefit", sub: true },
  "",
  { text: "Rule for Progestogen Addition", bold: true },
  { text: "Women WITH intact uterus: must add progestogen to protect endometrium from estrogen-driven hyperplasia/cancer", sub: true },
  { text: "Women WITHOUT uterus (hysterectomy): estrogen alone (ET) is appropriate", sub: true },
  "",
  { text: "'Bioidentical' Hormones", bold: true },
  { text: "Compounded BHT: not FDA-approved; unregulated potency; no safety superiority over approved formulations", sub: true },
]);

addTableSlide(
  "Estrogen Preparations & Routes",
  ["Preparation", "Type", "Route", "Advantages / Notes"],
  [
    ["Conjugated equine estrogens (CEE, Premarin)", "Estrogens", "Oral", "Most studied; WHI used CEE 0.625 mg"],
    ["17β-Estradiol (E2)", "Bioidentical", "Oral, transdermal patch/gel/spray", "Transdermal bypasses hepatic first-pass → ↓VTE, ↓TG risk"],
    ["Estradiol valerate", "Oral estrogen", "Oral", "Converted to E2; used in Europe"],
    ["Estradiol vaginal ring (Estring)", "Low-dose local", "Intravaginal ring 90-day", "Minimal systemic absorption; GSM only"],
    ["Estradiol vaginal cream / tablet / suppository", "Local", "Intravaginal", "Preferred for isolated GSM; no systemic effect at low dose"],
    ["Prasterone / DHEA (Intrarosa)", "Vaginal DHEA", "Intravaginal daily", "Local conversion to E + T; dyspareunia treatment"],
  ],
  { colW: [3.0, 1.8, 2.0, 3.1] }
);

addTableSlide(
  "Progestogens & Combined Preparations",
  ["Agent", "Type", "Key Properties"],
  [
    ["Micronized progesterone (Prometrium, Utrogestan)", "Natural bioidentical", "Favorable metabolic profile; may improve sleep; preferred in HT"],
    ["Medroxyprogesterone acetate (MPA, Provera)", "Synthetic progestin", "Used in WHI EPT arm; may negate some CVD benefit of E"],
    ["Norethindrone/norethisterone acetate", "19-nortestosterone derivative", "Androgenic; used in lower doses in patches"],
    ["Dydrogesterone", "Retroprogesterone", "Neutral metabolic profile; used with oral E2 in Europe"],
    ["Levonorgestrel IUD (Mirena)", "Local progestogen", "Endometrial protection with systemic estrogen; no systemic progestogen effects"],
    ["CEE + bazedoxifene (Duavee/Duavive)", "TSEC", "Tissue-selective; no progestogen needed; reduces hot flashes + bone loss"],
  ],
  { colW: [3.2, 2.2, 4.0] }
);

addContentSlide("HT Regimens", [
  { text: "1. Continuous Combined (Continuous Sequential)", bold: true },
  { text: "Daily estrogen + daily progestogen → amenorrhoea in most after 6 months", sub: true },
  { text: "Preferred in women >1 year post-FMP", sub: true },
  "",
  { text: "2. Sequential (Cyclic) Regimens", bold: true },
  { text: "Daily estrogen + progestogen added for 12–14 days/month → predictable withdrawal bleed", sub: true },
  { text: "Preferred in perimenopausal women or those <1 year post-FMP", sub: true },
  "",
  { text: "3. Local/Topical Estrogen", bold: true },
  { text: "Vaginal: cream, tablet (Vagifem), ring, suppository → minimal systemic absorption", sub: true },
  { text: "No progestogen needed even with intact uterus for ultra-low-dose vaginal preparations", sub: true },
  "",
  { text: "4. Transdermal Estrogen", bold: true },
  { text: "Patch, gel, spray: bypasses hepatic first-pass; preferred in women with VTE risk, hypertriglyceridemia, liver disease, migraine", sub: true },
  "",
  { text: "Monitoring on HT", bold: true },
  { text: "Annual review: BP, breast examination, symptom response, desire to continue", sub: true },
  { text: "Mammogram per screening schedule; no need to routinely check serum hormone levels", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 14 – HT BENEFITS/RISKS
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("14 | HT – Benefits, Risks & The WHI Trial", "Interpreting 20 years of evidence", "7B1FA2");

addCalloutSlide(
  "WHI Trial – The Pivotal Evidence (2002–2010)",
  "Women's Health Initiative: ~27,000 women aged 50–79; RCT of CEE+MPA vs CEE alone vs placebo",
  [
    {
      label: "EPT Arm\n(CEE+MPA)",
      items: ["CHD: HR 1.29*", "Breast cancer: HR 1.26*", "Stroke: HR 1.41*", "DVT/PE: HR 2.06*", "Hip fracture: HR 0.66 ✓", "Colorectal Ca: HR 0.63 ✓", "*Absolute risk small"],
    },
    {
      label: "ET Arm\n(CEE alone)",
      items: ["CHD: HR 0.91 (neutral)", "Breast cancer: HR 0.77 ✓", "Stroke: HR 1.37*", "DVT/PE: HR 1.33*", "Hip fracture: HR 0.61 ✓", "No colorectal effect"],
    },
    {
      label: "Key Caveat:\nTiming Hypothesis",
      items: ["WHI avg age 63 yrs", "Many were >10 yrs post-FMP", "When re-analysed:", "Ages 50-59: CVD benefit", "Ages 60-69: neutral", "Ages 70-79: harm", "Early HT = best outcome"],
    },
  ],
  { bg: C.deepPurple }
);

addTwoColumnSlide(
  "HT: Benefits vs. Risks Summary",
  {
    header: "Benefits",
    bullets: [
      { text: "Eliminates VMS (80–90% reduction in hot flashes)", bold: false },
      "Treats and prevents GSM",
      "Prevents osteoporosis and fractures",
      "Improves sleep quality",
      "Reduces risk of type 2 diabetes",
      "ET alone may reduce breast cancer (WHI)",
      "Cardioprotective when started <60 or <10 yrs post-FMP",
      "May reduce colorectal cancer risk (EPT)",
      "Reduces depression / mood symptoms",
      "May delay dementia if started early",
    ],
  },
  {
    header: "Risks",
    bullets: [
      { text: "Breast cancer ↑ with EPT (HR 1.26 after 5 yrs); less with ET alone", bold: false },
      "Stroke: ↑ with oral ET and EPT; minimal with transdermal",
      "VTE/PE: ↑ with oral HT; not significantly with transdermal",
      "Gallbladder disease: ↑ with oral estrogen",
      "Endometrial cancer: ↑ with unopposed estrogen (prevented by progestogen)",
      "Uterine bleeding / spotting",
      "Side effects: breast tenderness, bloating, mood changes",
      "Risk greatest in older, obese, hypertensive women",
    ],
  },
  { headerColor: C.midPurple }
);

addContentSlide("HT Contraindications & Precautions", [
  { text: "Absolute Contraindications to Systemic HT", bold: true },
  { text: "Undiagnosed vaginal / uterine bleeding", sub: true },
  { text: "Known or suspected hormone-sensitive malignancy (breast cancer, endometrial cancer)", sub: true },
  { text: "Active or recent (<12 months) VTE (DVT/PE)", sub: true },
  { text: "Active or recent arterial thromboembolic event (stroke, MI)", sub: true },
  { text: "Severe active liver disease", sub: true },
  { text: "Known thrombophilia (relative — transdermal preferred if considered)", sub: true },
  "",
  { text: "Relative Contraindications / Cautions", bold: true },
  { text: "Personal or strong family Hx breast cancer: individualise shared decision-making", sub: true },
  { text: "Hypertriglyceridaemia: use transdermal (avoids hepatic triglyceride synthesis ↑)", sub: true },
  { text: "Active gallbladder disease: HT may exacerbate", sub: true },
  { text: "Migraine with aura: ↑stroke risk; transdermal preferred over oral", sub: true },
  { text: "Endometriosis: progestogen-dominant regimen preferred", sub: true },
  "",
  { text: "Duration", bold: true },
  { text: "No mandatory time limit for HT in women <60 initiating for bothersome VMS", sub: true },
  { text: "Annual review with lowest effective dose; taper on discontinuation to reduce rebound", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 15 – NON-HORMONAL MANAGEMENT
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("15 | Non-Hormonal Management", "Pharmacological alternatives to HT", "00796B");

addCalloutSlide(
  "Non-Hormonal Pharmacological Options for VMS",
  "When HT is contraindicated, declined, or insufficient — evidence-based alternatives",
  [
    {
      label: "NK3R Antagonists\n(NEWEST – FDA 2023)",
      items: ["Fezolinetant (Veozah)", "NK3 receptor blocker", "↓ hot flash frequency 60–70%", "Non-hormonal mechanism", "Meta-analysis 2025: superior to placebo", "Liver monitoring required"],
    },
    {
      label: "SNRI / SSRI\nAntidepressants",
      items: ["Venlafaxine 37.5–75 mg", "Desvenlafaxine 50–100 mg", "Paroxetine 7.5 mg (Brisdelle – only FDA-approved for VMS)", "Citalopram, Escitalopram", "↓ hot flash frequency 40–60%"],
    },
    {
      label: "Gabapentinoids",
      items: ["Gabapentin 300 mg TID", "Pregabalin 75–150 mg BD", "↓ VMS 40–50%", "Useful for comorbid neuropathic pain or insomnia", "Side effects: dizziness, somnolence"],
    },
    {
      label: "Other Agents",
      items: ["Clonidine: modest benefit; side effects limit use", "Oxybutynin: ↓ hot flashes 70%", "Ospemifene: SERM for GSM dyspareunia", "Prasterone (DHEA): local for GSM"],
    },
  ],
  { bg: C.deepPurple }
);

addContentSlide("Management of GSM – Non-Hormonal & Hormonal", [
  { text: "First-Line (Non-Hormonal)", bold: true },
  { text: "Vaginal moisturisers (regular use): hyaluronic acid, polycarbophil gels (e.g., Replens) – reduce dryness, itching", sub: true },
  { text: "Lubricants (during intercourse): water-based or silicone-based; avoid oil-based with latex", sub: true },
  { text: "Continued sexual activity: maintains vaginal blood flow and epithelial health", sub: true },
  "",
  { text: "First-Line Pharmacological (Local Hormonal)", bold: true },
  { text: "Low-dose vaginal estrogen: cream (Premarin, Estrace), tablet (Vagifem 10 µg), ring (Estring 7.5 µg/day)", sub: true },
  { text: "Prasterone / Vaginal DHEA (Intrarosa): locally converts to E + T; treats dyspareunia", sub: true },
  { text: "Low systemic absorption → generally safe even in breast cancer survivors (discuss with oncologist)", sub: true },
  "",
  { text: "Oral Option", bold: true },
  { text: "Ospemifene (Osphena) 60 mg daily: SERM; FDA-approved for VVA-related dyspareunia; no vaginal application", sub: true },
  { text: "Avoid in women with breast cancer (theoretical agonist activity)", sub: true },
  "",
  { text: "Physical / Energy-Based Therapies (emerging evidence)", bold: true },
  { text: "Fractional CO₂ / Er:YAG laser, radiofrequency: stimulate collagen; 2024 network meta-analysis shows benefit for GSM", sub: true },
  { text: "Pelvic floor physiotherapy: effective for SUI and pelvic floor dysfunction", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 16 – LIFESTYLE & CAM
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("16 | Lifestyle & CAM Interventions", "Diet, exercise, phytoestrogens and mind-body approaches", "33691E");

addContentSlide("Lifestyle Modifications", [
  { text: "Vasomotor Symptom Triggers – Avoidance", bold: true },
  { text: "Avoid: spicy foods, alcohol (especially wine), caffeine, hot beverages, hot environments, stress", sub: true },
  { text: "Dress in layers; cooling fans/low room temperature; wicking fabrics at night", sub: true },
  "",
  { text: "Exercise", bold: true },
  { text: "Aerobic exercise reduces VMS frequency and severity; improves sleep, mood, CVD risk", sub: true },
  { text: "Resistance training: essential for sarcopenia prevention, bone density maintenance", sub: true },
  { text: "Weight-bearing exercise: reduces fracture risk by increasing bone mineral density", sub: true },
  { text: "Pelvic floor exercises (Kegel): reduce SUI and improve sexual function", sub: true },
  "",
  { text: "Diet", bold: true },
  { text: "Mediterranean diet: ↓ CVD risk, inflammation; anti-obesity effects", sub: true },
  { text: "Calcium: 1,200 mg/day total (diet + supplement); prevents bone loss", sub: true },
  { text: "Vitamin D: 800–1,000 IU/day; supports bone and muscle; many postmenopausal women deficient", sub: true },
  { text: "Soy isoflavones: modest ↓ in hot flash frequency; 2025 meta-analysis confirms benefit in perimenopausal women", sub: true },
  "",
  { text: "Weight Management", bold: true },
  { text: "Obesity amplifies VMS, CVD risk, and breast cancer risk; weight loss reduces hot flash burden", sub: true },
]);

addContentSlide("CAM & Phytoestrogen Therapies", [
  { text: "Phytoestrogens (plant estrogens)", bold: true },
  { text: "Isoflavones (soy, red clover): genistein, daidzein; weak ER agonist/antagonist activity", sub: true },
  { text: "Meta-analysis 2025: significant reduction in VMS frequency and severity", sub: true },
  { text: "Effect size smaller than HT; requires 6–12 weeks for benefit", sub: true },
  { text: "Safe for most women; caution in hormone-sensitive cancers (theoretical concern)", sub: true },
  "",
  { text: "Black Cohosh (Actaea racemosa)", bold: true },
  { text: "Evidence mixed; some RCTs show modest ↓ in VMS; likely non-estrogenic mechanism", sub: true },
  { text: "Duration limited to 6 months; rare hepatotoxicity reported", sub: true },
  "",
  { text: "Mind-Body Therapies", bold: true },
  { text: "Cognitive Behavioural Therapy (CBT): effectively reduces hot flash bother and impact (strong evidence)", sub: true },
  { text: "Mindfulness-based stress reduction (MBSR): improves sleep, mood, and menopausal quality of life", sub: true },
  { text: "Hypnotherapy: RCT evidence for 70% reduction in VMS (Elkins, 2013)", sub: true },
  "",
  { text: "Other CAM", bold: true },
  { text: "Acupuncture: some benefit for VMS; evidence inconclusive", sub: true },
  { text: "Evening primrose oil, vitamin E: minimal evidence; low risk", sub: true },
  { text: "Avoid: kava (hepatotoxic), dong quai (drug interactions)", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SECTION 17 – SPECIAL POPULATIONS
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("17 | Special Populations & Contraindications", "Individualising management in complex cases", C.deepPurple);

addTwoColumnSlide(
  "HT in Special Populations",
  {
    header: "Breast Cancer Survivors",
    bullets: [
      "Systemic HT: generally avoid (especially ER+)",
      "Tamoxifen / Aromatase inhibitors worsen VMS",
      "Non-hormonal VMS treatment: SSRIs/SNRIs, gabapentin, clonidine, fezolinetant",
      "Avoid paroxetine if on tamoxifen (CYP2D6 inhibition → ↓ tamoxifen efficacy)",
      "Vaginal estrogen: debate; recent data suggest vaginal E2 at low dose may be safe; discuss with oncologist",
      "Vaginal DHEA/ospemifene: alternatives for GSM",
    ],
  },
  {
    header: "Premature Ovarian Insufficiency (POI)",
    bullets: [
      "HT strongly indicated until natural age of menopause (~51)",
      "Long-term health consequences of premature E deficiency are serious",
      "Higher doses of HT often needed vs natural menopause",
      "Fertility: spontaneous pregnancy possible (5–10%); refer to specialist",
      "Bone density monitoring (DXA every 2 years)",
      "Psychological support: loss of fertility, premature aging concerns",
    ],
  },
  { headerColor: C.midPurple }
);

addTwoColumnSlide(
  "HT in Other Special Situations",
  {
    header: "Cardiovascular Disease / VTE",
    bullets: [
      "Active CVD or stroke: avoid oral HT",
      "Transdermal E with micronised progesterone: lowest thrombotic risk",
      "CHARGE-AF / prior VTE: transdermal preferred; risk-benefit discussion",
      "Statin use does not modify HT VTE risk",
      "Hypertension not a contraindication; monitor BP on HT",
    ],
  },
  {
    header: "Migraines, Diabetes, Liver Disease",
    bullets: [
      "Migraine with aura: transdermal route; avoid oral estrogen",
      "Diabetes: HT improves insulin sensitivity; transdermal preferred",
      "Non-alcoholic fatty liver disease: transdermal avoids hepatic first pass",
      "Gallbladder disease: HT (esp. oral) ↑ risk; consider non-HT options",
      "Endometriosis: progestogen-dominant continuous regimen; hysterectomy + ET post-menopause generally safe",
    ],
  },
  { headerColor: C.deepPurple }
);

// ─────────────────────────────────────────────────────────────────────
// SECTION 18 – MANAGEMENT ALGORITHM
// ─────────────────────────────────────────────────────────────────────
addSectionDivider("Summary: Practical Management Algorithm", "A step-by-step clinical approach", "1B5E20");

addContentSlide("Practical Approach to the Postmenopausal Patient", [
  { text: "Step 1: Confirm Diagnosis", bold: true },
  { text: "History (12 months amenorrhoea), age context, FSH if needed; rule out secondary causes", sub: true },
  "",
  { text: "Step 2: Assess Symptom Burden (MRS / MENQOL) & Impact", bold: true },
  { text: "VMS (mild/moderate/severe), GSM, mood, sleep, sexual function, bone/CVD risk", sub: true },
  "",
  { text: "Step 3: Identify Contraindications & Risk Factors", bold: true },
  { text: "Cancer Hx, VTE Hx, CVD, liver disease, BMI, family Hx", sub: true },
  "",
  { text: "Step 4: Baseline Investigations", bold: true },
  { text: "TSH, lipids, fasting glucose, BP; DXA if indicated; mammogram current", sub: true },
  "",
  { text: "Step 5: Treat", bold: true },
  { text: "Lifestyle modifications for ALL patients", sub: true },
  { text: "No contraindication + bothersome VMS → offer HT (individualized regimen)", sub: true },
  { text: "Contraindication to HT or patient preference → non-hormonal: fezolinetant, SSNIs, gabapentin, CBT", sub: true },
  { text: "Isolated GSM → local estrogen ± moisturizers (no systemic HT required)", sub: true },
  { text: "Osteoporosis → bisphosphonates ± denosumab; anabolics for severe disease", sub: true },
  { text: "Annual review of HT with shared decision-making", sub: true },
]);

// ─────────────────────────────────────────────────────────────────────
// SLIDE – KEY TAKE-AWAYS
// ─────────────────────────────────────────────────────────────────────
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    ["1", "Menopause is a clinical diagnosis (12 months amenorrhoea); FSH confirms only if age <45 or in doubt.", C.accentPink],
    ["2", "Postmenopausal syndrome encompasses VMS, GSM, sexual dysfunction, osteoporosis, CVD, and neuropsychiatric changes.", C.accentTeal],
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    ["4", "The WHI trial results apply mainly to older women (avg 63); HT started <60 or <10 yrs from FMP has a favourable benefit:risk profile.", "64B5F6"],
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// ─────────────────────────────────────────────────────────────────────
// SLIDE – REFERENCES
// ─────────────────────────────────────────────────────────────────────
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    "Berek JS & Novak E. Berek & Novak's Gynecology, 16th ed. Philadelphia: Wolters Kluwer, 2020. (Chapter 18: Menopause)",
    "Goldman L & Schafer AI. Goldman-Cecil Medicine, 27th ed. Elsevier, 2024.",
    "Katzung BG. Basic & Clinical Pharmacology, 16th ed. McGraw-Hill, 2022. (Chapter 40)",
    "Goodman & Gilman's Pharmacological Basis of Therapeutics, 14th ed. McGraw-Hill, 2023.",
    "NAMS. 2022 Hormone Therapy Position Statement. Menopause 2022;29(7):767-794.",
    "Gu Y, et al. Benefits and risks of menopause hormone therapy for CVS in postmenopausal women. BMC Womens Health 2024;24:60. [PMID 38263123]",
    "Morga A, et al. Efficacy of fezolinetant vs hormone and nonhormone therapies for VMS. Menopause 2024;31:1. [PMID 38016166]",
    "Sarmento ACA, et al. Physical energies for genitourinary syndrome of menopause. IJGO 2024. [PMID 38102987]",
    "Danan ER, et al. Hormonal treatments and vaginal moisturizers for GSM. Ann Intern Med 2024. [PMID 39250810]",
    "Hemachandra C, et al. Systematic review and critical appraisal of menopause guidelines. BMJ Sex Reprod Health 2024. [PMID 38336466]",
    "Luan H, et al. Soy isoflavones and menopausal symptoms. PeerJ 2025. [PMID 40718787]",
    "Menegaz de Almeida A, et al. Fezolinetant and Elinzanetant for VMS. Obstet Gynecol 2025. [PMID 39746208]",
  ];

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// ─────────────────────────────────────────────────────────────────────
// FINAL SLIDE
// ─────────────────────────────────────────────────────────────────────
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  s.addText("Postmenopausal Syndrome | Comprehensive Review | June 2026", { x: 0.65, y: 3.6, w: 8.5, h: 0.5, fontSize: 13, color: C.midGray, fontFace: "Calibri", align: "center" });
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// ─────────────────────────────────────────────────────────────────────
// WRITE FILE
// ─────────────────────────────────────────────────────────────────────
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