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Make a notes on Applied physiology of FRS - under the following topics for short notes with exam oriented answers of each question 1.Endocrinology in Puberty 2.Physiology of menstruation Hormonal changes during each phase of menstruation 3.Uterine changes 4. Puberty 5.Precocious Puberty 6.Delayed Puberty 7.Puberty menorrhagia 8.Amenorrhea 9.Primary Amenorrhea 10.Secondary Amenorrhea 11. Cryptomenorrhea 12.Hypomenorrhea 13.Oligomenorrhea 13.Polymenorrhea 14.Metrorrhagia 15.Menorrhagia 16.AUB 17. Metropathia Hemorrhagia 18.Dysmenorrhea 19.Primary Dysmenorrhoea 20.Secondary Dysmenorrhoea 21.Pms 22.Menopause 23.Peri menopause 24.Artificial menopause 25.Premature menopause 26.Delayed menopause 27.Post menopausal Bleeding

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Applied Physiology FRS Notes

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Applied Physiology – FRS: Comprehensive Exam-Oriented Notes

Sources: DC Dutta's Textbook of Gynecology | Berek & Novak's Gynecology | Guyton & Hall | Ganong's Physiology | FIGO Guidelines

1. Endocrinology in Puberty

Key Hormonal Events:
  • Childhood: Hypothalamus secretes minimal GnRH; CNS is hypersensitive to low gonadal steroid levels → suppression.
  • Onset trigger: Maturation of KNDy neurons (Kisspeptin-Neurokinin B-Dynorphin) → increased pulsatile GnRH secretion.
  • Kisspeptin (KISS1 gene) acts on GPR54 receptors → GnRH release. Activating mutations = central precocious puberty; inactivating mutations = delayed puberty.
  • Adrenarche (age 6-8): DHEA/DHEAS rise → axillary and pubic hair.
  • Gonadarche: Rising GnRH → FSH and LH secretion (FSH > LH in early puberty).
  • FSH → follicular development → estradiol; LH surge → ovulation (after 1-2 years of anovulatory cycles).
  • Estradiol → thelarche, uterine growth, vaginal cornification, fat redistribution.
  • GH + IGF-1 → growth spurt; estrogen → epiphyseal fusion (ends growth).
Sequence in Girls: Thelarche → Pubarche → Growth Spurt → Menarche
Exam Tips: First sign = Thelarche. Last event = Menarche. FSH rises before LH.

2. Physiology of Menstruation – Hormonal Changes

Normal cycle: 28 days (range 21-35). Blood loss 30-80 mL. Duration 3-7 days. Mostly arterial blood; fibrinolysin prevents clotting.
PhaseDaysKey HormonesEvents
Menstrual1-5E2↓, Prog↓Corpus luteum degenerates, vasospasm of spiral arteries, PGF2α mediated sloughing
Follicular/Proliferative1-14FSH↑, E2↑Follicle growth, endometrial proliferation, thin watery cervical mucus (ferning, spinnbarkeit)
OvulationDay 14LH surge (peak), FSH surgeE2 peak → positive feedback → LH surge → ovulation 36-40 hrs later
Luteal/Secretory15-28Prog↑↑ (peak Day 21), E2↑ (moderate)Corpus luteum, secretory endometrium, thick mucus
  • Luteal phase is constant at 14 days - all cycle variation is in the follicular phase.
  • Day 21 progesterone >5 ng/mL confirms ovulation.

3. Uterine Changes During the Cycle

PhaseGlandsStromaVessels
ProliferativeStraight, narrow, tall columnar cellsCompact, mitotic figuresStraight, thin-walled
SecretoryTortuous, 'saw-tooth'; glycogen vacuoles (sub-nuclear Day 17 → supra-nuclear Day 19)Edematous → decidualizationCoiled spiral arteries
MenstrualShedding of functionalisNecrosisVasospasm
  • Cervix: E2 → thin watery alkaline mucus, ferning, spinnbarkeit up to 8-12 cm. Progesterone → thick, tenacious, no ferning.
  • Basalis layer retained → regeneration source.

4. Puberty

  • Onset: Girls 8-13 yrs. Menarche: 10-16 yrs (mean 12-13 yrs).
  • Tanner Stages (Breast): Stage 2 (breast bud) = first sign ~9-10 yrs → Stage 5 (adult).
  • Early post-menarchal cycles are usually anovulatory (immature HPO axis).

5. Precocious Puberty

Definition: Secondary sexual characteristics before age 8 in girls (age 9 in boys). 20x more common in girls.
TypeFSH/LH Response to GnRHCause
Central (GnRH-dependent)Pubertal response (LH rises)90% idiopathic in girls; CNS tumors, hamartoma, KISS1R mutation
Peripheral (GnRH-independent)No responseOvarian/adrenal tumor, CAH, McCune-Albright, exogenous hormones
McCune-Albright Triad: Precocious puberty + café-au-lait spots + polyostotic fibrous dysplasia. Incomplete forms: Isolated thelarche, adrenarche - benign. Treatment (central): GnRH agonists (leuprolide) - receptor downregulation.
Exam Tips: Central PP: LH responds to GnRH. Peripheral PP: LH does NOT respond.

6. Delayed Puberty

Definition: No breast development by age 13 in girls; no menarche by 16.
CategoryFSH/LHExamples
HypogonadotropicLowConstitutional delay (CDGP), Kallmann syndrome (anosmia), anorexia, chronic illness, pituitary tumors
HypergonadotropicHighTurner syndrome (45,X) - most common in girls; POI, gonadal dysgenesis
EugonadotropicNormalMRKH syndrome, androgen insensitivity, imperforate hymen

7. Puberty Menorrhagia

  • Heavy/prolonged bleeding around menarche due to anovulatory cycles (immature HPO axis → no progesterone → unopposed estrogen → irregular breakdown).
  • Always exclude: von Willebrand disease (most important coagulopathy in adolescents), thyroid disease.
  • Treatment: Mild - NSAIDs + iron; Moderate - OCP; Severe acute - IV conjugated estrogen (25 mg q4-6h).

8. Amenorrhea

Physiological: Pregnancy, lactation, pre-puberty, post-menopause.
Basic workup: βhCG (first!) → Prolactin, TSH → FSH, LH, E2 → physical exam (2° sexual chars + pelvic anatomy).

9. Primary Amenorrhea

Definition (Updated): Absence of menarche by age 13 (no 2° sexual characteristics) OR age 15 (with normal 2° sexual characteristics).
PresentationDiagnosis
No breasts + High FSHTurner syndrome (45,X), Pure gonadal dysgenesis
No breasts + Low FSHKallmann syndrome, constitutional delay, anorexia
Breasts present + Blind vagina + No uterus + 46,XXMRKH syndrome
Breasts present + Blind vagina + No uterus + 46,XYAndrogen Insensitivity Syndrome
Cyclic pain + Bulging membraneImperforate hymen (hematocolpos)
Exam Tips: Turner = short stature, webbed neck, coarctation; MRKH = normal ovaries, absent uterus, 46,XX; AIS = testosterone in male range, inguinal testes.

10. Secondary Amenorrhea

Definition: Absence of menses for 3 consecutive cycles or 6 months. Always exclude pregnancy first.
LevelCause
HypothalamicStress, weight loss, exercise, anorexia (most common pathological cause)
PituitaryHyperprolactinemia (prolactinoma, drugs), Sheehan syndrome
OvarianPCOS (most common endocrine disorder), POI (FSH >40, age <40)
UterineAsherman syndrome (post-D&C adhesions)
Progesterone challenge test: Bleed = estrogen present, anovulation; No bleed → E+P challenge → no bleed = outflow obstruction.
Exam Tips: Secondary amenorrhea + galactorrhea = hyperprolactinemia. POI: FSH >40 IU/L ×2, 4-6 wks apart, age <40.

11. Cryptomenorrhea

  • Definition: Menstruation occurring but blood retained due to outflow obstruction. Cyclic pain WITHOUT external bleeding.
  • Causes: Imperforate hymen (most common), transverse vaginal septum.
  • Consequences: Hematocolpos (vagina) → Hematometra (uterus) → Hematosalpinx (tubes) → Hemoperitoneum.
  • Treatment: Cruciate incision (hymenectomy); septum excision.

12. Hypomenorrhea

  • Definition: Scanty flow (<20 mL), regular interval.
  • Causes: Asherman syndrome (post-D&C) - most important; hypoestrogenism; OCP use.
  • Exam Tip: Hypomenorrhea after D&C = Asherman syndrome until proven otherwise.

13. Oligomenorrhea

  • Definition: Cycles >35 days (infrequent menstruation).
  • Causes: PCOS (most common in reproductive age), hypothalamic dysfunction, hyperprolactinemia, thyroid disease, perimenopause.
  • 6 months absence = secondary amenorrhea.

14. Polymenorrhea

  • Definition: Cycles <21 days (too frequent).
  • Causes: Short follicular phase, luteal phase defect (inadequate progesterone), approaching menopause.
  • Exam Tip: Day 21 progesterone <5 ng/mL → anovulation/luteal phase defect.

15. Metrorrhagia

  • Definition (classic): Irregular bleeding between normal periods. FIGO term: Intermenstrual Bleeding (IMB).
  • Causes: Cervical polyp/carcinoma/ectropion; endometrial polyp; submucosal fibroid; OCP breakthrough.
  • Post-coital bleeding = investigate cervix (cancer until proven otherwise).

16. Menorrhagia

  • Definition (classic): >80 mL blood loss per cycle or >7 days duration. FIGO term: Heavy Menstrual Bleeding (HMB).
FIGO PALM-COEIN Classification:
  • PALM (Structural): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia
  • COEIN (Non-structural): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not classified
Exam Tips: Commonest organic cause = submucosal fibroid. Best medical treatment = LNG-IUS (Mirena). Adolescent menorrhagia → always screen for vWD.

17. Abnormal Uterine Bleeding (AUB)

FIGO 2011/2018: Standard classification replacing all old terms.
Old Term (Discarded)New FIGO Term
MenorrhagiaHeavy Menstrual Bleeding (HMB)
MetrorrhagiaIntermenstrual Bleeding (IMB)
DUBAUB-O (ovulatory dysfunction)
Oligomenorrhea/PolymenorrheaIrregular Menstrual Bleeding
Postmenopausal bleedingBleeding >12 months after FMP
AUB by Age:
  • Adolescence: Anovulation, coagulopathy
  • Reproductive: Fibroids, polyps, PCOS, pregnancy
  • Perimenopause: Anovulation, hyperplasia/cancer
  • Postmenopause: Atrophy (most common), cancer

18. Metropathia Hemorrhagica

  • Definition: Anovulatory DUB due to prolonged unopposed estrogen → cystic glandular hyperplasia (Swiss cheese endometrium). Also called Schroeder's disease.
  • Pathophysiology: Persistent follicle → continuous E2 → no progesterone → endometrium proliferates excessively → irregular breakdown.
  • Classic presentation: Period of amenorrhea (6-12 weeks) followed by sudden prolonged, heavy, irregular bleeding.
  • Histology: Cystic dilated glands in hyperplastic endometrium ("Swiss cheese pattern").
  • Seen in: Perimenopausal and post-menarchal women.
  • Treatment: Progestogens (norethisterone 5mg TDS ×21 days), OCP; D&C (diagnostic + therapeutic).
Exam Tip: Swiss cheese endometrium = diagnostic. Amenorrhea → heavy irregular bleed = classic.

19. Dysmenorrhea

Definition: Painful menstruation. Classified as Primary (no pathology) or Secondary (underlying pathology).

20. Primary Dysmenorrhea

  • Mechanism: Secretory endometrium → PGF2α (& PGE2) → intense uterine contractions → ischemia → pain. Also systemic: nausea, vomiting, diarrhea, headache.
  • Onset: Within 6-12 months of menarche (requires ovulatory cycles).
  • Pain: Spasmodic, lower abdominal, begins at onset of flow, peaks Days 1-2, duration 48-72 hrs. Normal pelvic exam.
  • Tends to improve after childbirth and with age.
Treatment:
  1. First line: NSAIDs (ibuprofen, mefenamic acid) – start 1-2 days before menses
  2. Second line: Combined OCP (suppresses ovulation)
  3. LNG-IUS, progestogens, heat
  4. Surgical (rare): LUNA, presacral neurectomy

21. Secondary Dysmenorrhea

  • Pain begins 1-2 weeks BEFORE menses (unlike primary - starts at onset).
  • Most common cause: Endometriosis (10% general population; 30%+ in CPP).
  • Causes (APES CIC): Adenomyosis, Endometriosis, PID, Submucosal fibroid, Cervical stenosis, IUD (copper), Congenital anomalies.
Endometriosis: Glands/stroma outside uterus. Triad: Dysmenorrhea + Deep dyspareunia + Infertility. Gold standard diagnosis: Laparoscopy.
Adenomyosis: Glands within myometrium. Boggy, tender, enlarged uterus. Parous women 40-50 yrs. Diagnosis: MRI.
Management: Treat underlying cause. NSAIDs/OCP less effective than in primary.

22. Premenstrual Syndrome (PMS)

  • Definition: Physical and emotional symptoms recurring in the luteal phase, resolving with/after menstruation.
  • Prevalence: 50% have some symptoms; 3-5% severe (PMDD).
Symptoms (Luteal Phase Only):
  • Physical: Bloating, breast tenderness, edema, headache, acne, weight gain.
  • Emotional: Irritability (most common), mood swings, anxiety, depression, food cravings, fatigue.
Diagnosis: Requires 2-3 months prospective daily symptom diary (retrospective recall is unreliable; <50% who report PMS confirmed).
Etiology: Unknown. Serotonin deficiency in luteal phase (explains SSRI efficacy). Not absolute hormone levels but sensitivity to hormonal changes.
PMDD: Severe PMS; DSM-5 diagnosis; ≥5 symptoms including ≥1 mood symptom.
Treatment:
  • Lifestyle: Exercise, ↓ caffeine/salt/sugar, stress reduction.
  • First-line for PMDD: SSRIs (fluoxetine, sertraline, paroxetine) - FDA approved; continuous or luteal-phase dosing.
  • OCP (drospirenone/EE - Yaz) - FDA approved for PMDD.
  • GnRH agonists for severe refractory cases.

23. Menopause

  • Definition: Permanent cessation of menstruation. Diagnosed retrospectively after 12 consecutive months of amenorrhea. Average age 51-52 yrs.
  • Pathophysiology: Progressive follicular depletion → ↓ E2 → loss of negative feedback → FSH markedly elevated (>40 IU/L). Post-menopause: Estrone (from adipose conversion of androstenedione) = main estrogen.
Symptoms:
  • Vasomotor (75%): Hot flushes (coincide with LH surges), night sweats.
  • GSM: Vaginal dryness, dyspareunia, UTIs, urinary urgency.
  • Psychological: Irritability, anxiety, mood changes.
Long-term: Osteoporosis, cardiovascular disease.
Treatment:
  • HRT: Most effective for vasomotor symptoms. Benefit > risk if started <60 yrs or <10 yrs post-menopause.
  • Non-hormonal: SSRIs/SNRIs (venlafaxine) for hot flushes.

24. Perimenopause

  • Definition: Transitional period before (up to 10 yrs) and 1 year after FMP.
  • First hormonal change: FSH rises (↓ inhibin B). LH rises later. Estradiol fluctuates (can be paradoxically HIGH).
  • Features: Irregular cycles, heavy or scanty periods, vasomotor symptoms, reduced fertility (but NOT zero - contraception still needed).

25. Artificial Menopause

  • Definition: Menopause induced by intervention.
  • Causes: Bilateral oophorectomy (surgical), pelvic radiation (ovarian ablation dose ~6 Gy), GnRH agonists (medical - reversible).
  • Features: Abrupt onset → more severe vasomotor symptoms than natural menopause.
  • Treatment: HRT strongly indicated, especially if <45 yrs.

26. Premature Menopause / POI

  • Definition: Loss of ovarian function before age 40 (POI = Premature Ovarian Insufficiency). Incidence 1% of women <40 yrs.
Diagnosis: Age <40 + oligomenorrhea/amenorrhea ≥4 months + FSH >25-40 IU/L on two occasions 4-6 weeks apart.
Causes:
  • Idiopathic (50%), Turner syndrome, FMR1 premutation (most common genetic cause), Autoimmune (APS type 2), Iatrogenic (chemo, radiation, surgery).
Management:
  • HRT mandatory until age of natural menopause (prevents osteoporosis, CVD).
  • DEXA scan, fertility counseling (egg donation most successful).
Exam Tips: FMR1 premutation = most common non-chromosomal genetic cause. HRT is mandatory (unlike natural menopause).

27. Delayed Menopause

  • Definition: Menopause after age 55.
  • Associations: Obesity, nulliparity, familial, OCP use.
  • Significance: ↑ risk of endometrial cancer, breast cancer, ovarian cancer (prolonged estrogen exposure). ↓ osteoporosis risk.

28. Post-Menopausal Bleeding (PMB)

Definition: Any vaginal bleeding >12 months after FMP. Even ONE episode must be investigated.
Golden Rule: PMB = endometrial carcinoma until proven otherwise.
Causes (frequency):
  1. Endometrial atrophy (most common benign cause, ~30-40%)
  2. Endometrial carcinoma (~10-15%) - must not miss
  3. Endometrial hyperplasia, polyp
  4. Cervical pathology (polyp, carcinoma)
  5. Atrophic vaginitis, ovarian tumor (granulosa cell)
Investigation Algorithm:
  1. TVUS (first step): Endometrial thickness (ET)
    • ET ≤4 mm: Low risk (~1% cancer), can monitor
    • ET >4 mm: Endometrial biopsy mandatory
  2. Pipelle biopsy (90% accuracy, outpatient)
  3. Hysteroscopy + directed biopsy = gold standard
Exam Tips: ET ≤4 mm on TVUS = low risk. Tamoxifen use → 2-3x ↑ endometrial cancer risk. Granulosa cell tumor of ovary = estrogen-secreting → PMB.
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Applied Physiology FRS Notes

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Quick Reference - High-Yield Exam Points:
TopicKey Exam Fact
Puberty - first signThelarche (breast budding)
Puberty - last eventMenarche
Luteal phase durationConstant 14 days
Day 21 progesterone>5 ng/mL = ovulation occurred
Primary amenorrheaNo menarche by age 13 (no 2° chars) or 15 (with 2° chars)
Secondary amenorrheaAbsent >3 cycles or 6 months
PMBAny bleed >12 months post FMP
PMB - TVUS threshold>4 mm ET = biopsy
Primary dysmenorrheaPGF2α; NSAIDs first line
Secondary dysmenorrheaMost common cause = endometriosis
MetropathiaSwiss cheese endometrium; anovulatory
POIFSH >40, age <40, ×2 samples 4-6 wks apart
PMS diagnosis2-3 months prospective diary
PMDD treatmentSSRIs (FDA approved)
AUB classificationFIGO PALM-COEIN

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