LO 3 · Positive Feedback Switch FA 3.03 · BnB 2.01 · Physeo 7.03
At what estradiol threshold and for how long must E2 be sustained to flip the HPG axis from negative to positive feedback?
Answer
Threshold ≈ 200 pg/mL E2, sustained > 48 hours.
When met, E2 switches from inhibiting to stimulating GnRH neurons in the anterior hypothalamus (AVPV region) and sensitizes gonadotropes → LH surge (~10-fold rise, smaller FSH rise).
LH surge → ovulation ~36 hours later. Only estradiol positive-feedbacks; progesterone is always inhibitory. This is why continuous-progestin contraception prevents ovulation.
LO 3 · Pulsatile vs Continuous GnRH FA 3.03 · Bootcamp 2.03 · In House
Why does continuous leuprolide cause chemical castration but pulsatile leuprolide induce ovulation?
Answer
Physiologic GnRH is pulsatile (every ~60–90 min). Gonadotropes need the "off" between pulses to re-sensitize.
Continuous GnRH-agonist → sustained receptor occupancy → receptor internalization + desensitization → ↓LH/FSH → ↓E2/T. Used for prostate cancer, endometriosis, central precocious puberty, fibroid shrinkage.
Pulsatile leuprolide (SC pump) mimics physiology → normal LH/FSH → used in hypothalamic amenorrhea to induce ovulation.
GnRH antagonists (cetrorelix, degarelix) → immediate LH/FSH block without the initial flare.
LO 4 · Meiosis Arrest Points FA 3.01 · BnB 2.01 · Physeo 7.03
At what stages are oocytes arrested during life, what resumes each arrest, and why is this relevant to trisomy risk?
Answer
Arrest 1 — Prophase I (diplotene): begins fetal life (week 20) through puberty. Resumed by LH surge → secondary oocyte + first polar body.
Arrest 2 — Metaphase II: post-ovulation until fertilization. Resumed only by sperm penetration → second polar body; unfertilized eggs degenerate.
Clinical relevance: the longer a primary oocyte sits in prophase I, the higher the risk of non-disjunction — this is the mechanism behind the ↑ risk of trisomy 21, 18, 13 and 47,XXY with maternal age.
LO 4 · hCG & Corpus Luteum Rescue FA 3.01 · BnB 2.02 · Bootcamp 2.05
What structural property lets hCG rescue the corpus luteum, and when does the placenta take over progesterone production?
Answer
hCG shares the α-subunit with LH/FSH/TSH and has a β-subunit very similar to LH. hCG binds the LH receptor on corpus luteum lutein cells → sustained progesterone output.
Trophoblast secretes hCG from ~day 8 post-fertilization (detectable in serum by pregnancy test).
Luteal–placental shift: ~8–10 weeks gestation, the placenta takes over progesterone production (luteoplacental handoff). If CL removed before 10 weeks → miscarriage.
LO 5 · Cycle Hormone Peaks FA 3.03 · BnB 2.03 · Physeo 7.03
In a textbook 28-day cycle, which day does FSH, E2, LH, and progesterone each peak? Which hormones rise during menses?
Answer
FSH peak 1 (early follicular, ~day 3): recruits antral follicles. E2 peak (late follicular, ~day 13): from dominant follicle granulosa. LH peak (~day 14): the surge, 36 h before ovulation — small FSH mid-cycle rise too. Progesterone peak (~day 21): mid-luteal, from corpus luteum.
Menses (days 1–5): progesterone and E2 are low; FSH begins to rise as negative feedback lifts. Luteal phase is fixed at ~14 days; follicular phase length varies.
LO 5 · Endometrial Layers FA 3.03 · Pathoma 13.04 · BnB 3.03
Which layer of the endometrium sheds monthly, and what vascular supply causes menses?
Ovaries: "streak gonads" — accelerated follicular atresia during fetal life; all oocytes gone by age ~2.
Clinical: short stature (SHOX haploinsufficiency), webbed neck & lymphedema (cystic hygroma), shield chest with wide-set nipples, bicuspid aortic valve, coarctation of the aorta, horseshoe kidney, primary amenorrhea, infertility (but pregnancy possible with donor oocyte).
Tx: GH during childhood + cyclic estrogen at puberty.
LO 6 · Kallmann Syndrome FA 3.04 · BnB 7.02 · In House
What is the developmental defect in Kallmann, how does it distinguish from constitutional pubertal delay, and what's the classic extra-gonadal finding?
Answer
Defect: failed migration of GnRH neurons + olfactory neurons from the olfactory placode to the hypothalamus (KAL1/ANOS1 mutation, X-linked; also FGFR1).
Presentation: delayed puberty + anosmia/hyposmia — the Step 1 buzz.
Labs: low LH, low FSH, low E2 (or T) — hypogonadotropic hypogonadism. No response to GnRH stim? → pituitary problem. Responds with LH/FSH rise? → hypothalamic (classic for Kallmann).
Tx: exogenous estrogen/progesterone for secondary sex characteristics; pulsatile GnRH or gonadotropins for fertility.
LO 6 · Complete Androgen Insensitivity FA 3.04 · Pathoma 13.07 · BnB 7.01
Why does a 46,XY CAIS patient develop breasts but have absent pubic/axillary hair?
Answer
X-linked androgen-receptor loss-of-function → no androgen signaling in any tissue.
Testes still make AMH → Müllerian regression → no uterus/fallopian tubes/upper vagina (blind-ended vagina). Testes make testosterone but target cells can't respond → Wolffian ducts regress, external genitalia default to female.
Breast development: peripheral aromatization of testosterone → estradiol acts normally on breast (ER is intact) → normal Tanner V breasts at puberty.
Absent pubic/axillary hair: hair follicles need AR signaling. Classic triad: 46,XY · primary amenorrhea · breasts but no sexual hair.
Gonadectomy after puberty (malignancy risk).
LO 6 · 5α-Reductase Deficiency FA 3.04 · BnB 7.01 · In House
Why do 46,XY patients with 5α-reductase deficiency look female at birth but virilize at puberty?
Answer
Testosterone is normal, but DHT (required for external genital virilization) is deficient. Internal male ducts (T-dependent) are intact, but external genitalia default to female-appearing at birth.
Labs: ↑ T : DHT ratio (diagnostic). Tx: finasteride is the opposite (5α-RD inhibitor → treats BPH, male-pattern baldness, by inhibiting this same enzyme).
LO 6 · PCOS Pathophysiology FA 3.04 · Pathoma 13.05 · BnB 4.04 · Bootcamp 2.04
Walk through the vicious cycle that links insulin resistance, ↑LH, and endometrial hyperplasia in PCOS.
Answer
Insulin resistance → hyperinsulinemia → (1) stimulates theca androgen synthesis AND (2) suppresses hepatic SHBG → more free androgen.
Consequences: anovulation (no LH surge), hyperandrogenism (hirsutism, acne), unopposed estrogen (no progesterone from CL) → endometrial hyperplasia / carcinoma risk, metabolic syndrome, ↑ T2DM, OSA, NAFLD.
Tx: OCPs (cycle control + protect endometrium); metformin; letrozole for fertility; spironolactone for hirsutism; weight loss.
LO 6 · Premature Ovarian Insufficiency FA 3.04 · BnB 7.02 · In House
A 32 y/o has missed periods for 6 months with hot flashes. FSH is 45 mIU/mL. Differential and most common genetic cause?
Answer
POI = premature ovarian insufficiency (menopause < age 40). Hypergonadotropic hypogonadism pattern (↑FSH > 40 x2 separated by ≥1 month, ↓E2).
Etiologies: • Genetic:Fragile X pre-mutation (FMR1) — most common identifiable cause; also Turner mosaics • Autoimmune (AIRE/APS-1 with adrenal) • Iatrogenic: chemo (alkylators), pelvic radiation, surgery • Infectious: mumps oophoritis (rare) • Idiopathic (>50%)
Tx: HRT (systemic E2 + progestin) until ~age 51 to prevent osteoporosis, CV disease, GU atrophy. Fertility via donor oocyte.
Quick recall MCQs · single best answer6 questions
Question 1 of 6 · LO 3 — HPG Axis FA 3.03 · Physeo 7.03
Which of the following best describes the dominant ovarian cell–gonadotropin pairing during the late follicular phase?
ATheca cells respond to FSH to synthesize estradiol directly
BGranulosa cells respond to LH in the early follicular phase to aromatize androgens
CTheca cells respond to LH to synthesize androgens; granulosa cells respond to FSH and aromatize them to estradiol
DCorpus luteum theca cells respond to prolactin to synthesize progesterone
EGranulosa cells express aromatase only after ovulation
C is correct. The two-cell, two-gonadotropin model: theca interna (LH-R) makes androgens; granulosa (FSH-R) aromatizes them to estradiol. After the LH surge, granulosa acquire LH-R and luteinize → progesterone production.
Question 2 of 6 · LO 2 — Sexual Differentiation FA 3.01 · BnB 2.01
A newborn 46,XX infant with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency has ambiguous external genitalia. The internal female ducts (uterus, fallopian tubes, upper vagina) are normal. What best explains this pattern?
AAMH from fetal ovary regressed the Müllerian ducts partially
BAdrenal-derived androgens virilized external genitalia; ovaries do not make AMH so Müllerian ducts persist normally
CDHT signaling is absent in the female fetus so internal ducts default to female even in CAH
D21-hydroxylase deficiency uniquely spares the Müllerian ducts because they lack androgen receptors
EWolffian ducts are retained and become the uterus under androgen stimulation
B is correct. Internal female ducts develop from Müllerian ducts, which require AMH for regression. Ovaries (including CAH 46,XX) do not make AMH → Müllerian ducts persist normally. External genitalia, in contrast, are virilized by adrenal androgens (T/androstenedione → DHT peripherally).
Question 3 of 6 · LO 3 — Feedback Sign FA 3.03 · Bootcamp 2.03
At which point in the menstrual cycle does estradiol exert positive feedback on the HPG axis?
AThroughout the follicular phase
BThroughout the luteal phase
COnly when estradiol >200 pg/mL is sustained for >48 hours
DWhen progesterone is also elevated (> 10 ng/mL)
EImmediately after menses as FSH rises
C is correct. Positive feedback requires both a threshold (~200 pg/mL) AND sustained duration (>48 h). Only then does E2 stimulate GnRH → LH surge. Progesterone always suppresses the surge, which is why the luteal phase shuts down the axis.
Question 4 of 6 · LO 4 — CL Rescue FA 3.01 · BnB 2.02
Which hormone is responsible for maintaining the corpus luteum if implantation occurs, and on which receptor does it act?
AFSH binding the FSH receptor on granulosa-lutein cells
BhCG binding the LH receptor on corpus-luteum lutein cells
CEstradiol binding a membrane ERα on theca-lutein cells
DInhibin A binding activin receptors on granulosa cells
EProlactin binding its receptor on granulosa-lutein cells
B is correct. hCG shares its α-subunit with LH and binds the LH receptor on CL. This signal keeps progesterone output up until the luteal–placental shift at ~8–10 weeks.
Question 5 of 6 · LO 6 — Hypogonadism Pattern FA 3.04 · In House
A 16-year-old with primary amenorrhea has a karyotype 46,XY, palpable inguinal gonads, well-developed breasts, and absent axillary/pubic hair. Which lab pattern is most consistent?
A↓ Testosterone, ↑ FSH/LH, ↓ E2
B↑ Testosterone, ↓ FSH/LH, ↓ E2
C↑ Testosterone, ↑ LH, normal or ↑ E2
DNormal testosterone, ↓ FSH/LH, ↑ prolactin
E↓ Testosterone, ↓ DHT, ↑ FSH/LH
C is correct. Complete Androgen Insensitivity Syndrome (CAIS): AR doesn't work → no testosterone negative feedback → ↑ LH → ↑ T (unused). Peripheral aromatization of T → ↑ E2 (breast dev). No AR → no axillary/pubic hair. Müllerian regression from AMH → blind vagina.
Question 6 of 6 · LO 6 — PCOS Mechanism FA 3.04 · Bootcamp 2.04 · Pathoma 13.05
In PCOS, which mechanism most directly explains the increased risk of endometrial hyperplasia and endometrial adenocarcinoma?
CChronic anovulation → no corpus luteum → no progesterone → unopposed estrogen (from adipose aromatization)
DElevated FSH chronically proliferates the endometrium
ETestosterone directly binds endometrial androgen receptors to drive hyperplasia
C is correct. Anovulation means no CL, no progesterone — yet estrogen continues from ongoing aromatization of androgens in adipose. Unopposed estrogen on endometrium → proliferation without secretory maturation → hyperplasia → Type I endometrial carcinoma. Protective Tx: cyclic progestin or OCPs.
Drag to order each sequence correctly4 drills
Drill 1 · LO 1 — Fetal Sexual Differentiation Timeline In House · FA 3.01
From fertilization to complete external genital differentiation.
Vignette 1 of 4 · LO 2/6 — DSD Work-up FA 3.04 · BnB 7.01
A 16-year-old phenotypic female is evaluated for primary amenorrhea. Breast development is Tanner V, pubic and axillary hair are absent, and on pelvic exam a blind-ended vaginal pouch is noted without cervix or uterus. Bilateral inguinal masses are palpable. Serum testosterone is elevated. Karyotype is 46,XY. What is the diagnosis and the most appropriate management of the gonads?
A5α-reductase deficiency — leave gonads in place
BMüllerian agenesis (MRKH) — no intervention
CComplete androgen insensitivity — gonadectomy after puberty
DTurner syndrome mosaic — estrogen replacement only
C — Complete androgen insensitivity syndrome (CAIS). The triad of 46,XY + female external phenotype + absent uterus + absent pubic/axillary hair is classic. AMH regresses Müllerian ducts → no uterus. Absent AR signaling → absent sexual hair but preserved breast development (aromatization of testosterone → estradiol). Testes often reside in inguinal canals. Gonadectomy after puberty (malignancy risk ~2–5% lifetime) and estrogen replacement. MRKH would have normal AR signaling (→ normal pubic hair) and 46,XX karyotype.
Vignette 2 of 4 · LO 3/6 — HPG Axis Failure FA 3.04 · In House
A 15-year-old male has failed to enter puberty. He has anosmia, cryptorchidism, and micropenis. Morning testosterone is <50 ng/dL, LH 0.3 mIU/mL (low), FSH 0.5 mIU/mL (low). Pulsatile GnRH stimulation produces a brisk LH/FSH response. What is the most likely diagnosis and what is the defect?
AKlinefelter syndrome — 47,XXY with seminiferous tubule dysgenesis
BKallmann syndrome — failed GnRH neuron migration from olfactory placode
CConstitutional delay — normal variant, reassurance
DProlactinoma — mass effect on gonadotropes
EPrimary testicular failure — bilateral torsion in utero
B — Kallmann syndrome. Hypogonadotropic hypogonadism (low T, low LH/FSH) + anosmia + micropenis/cryptorchidism = classic Kallmann. Olfactory-placode-derived GnRH neurons and olfactory neurons fail to migrate. Brisk response to GnRH stimulation localizes the defect to the hypothalamus (pituitary is intact). Klinefelter would have elevated LH/FSH (primary hypogonadism) and small firm testes.
Vignette 3 of 4 · LO 6 — PCOS with Endometrial Concern FA 3.04 · Pathoma 13.05 · Bootcamp 2.04
A 28-year-old woman with BMI 34 and oligomenorrhea (2–3 periods/year) presents with hirsutism and one episode of heavy vaginal bleeding after 7 months of amenorrhea. Transvaginal ultrasound shows an endometrial stripe of 14 mm and multiple small follicles arranged in a "string of pearls" pattern bilaterally. Which step will reduce her endometrial cancer risk while preserving future fertility?
DHysterectomy with bilateral salpingo-oophorectomy
EAromatase inhibitor (letrozole) continuously
B — Cyclic progestin. PCOS patients have unopposed estrogen from chronic anovulation (no CL → no progesterone). Endometrial hyperplasia/cancer is the main worry. A cyclic progestin induces withdrawal bleeding and prevents hyperplasia without suppressing ovulation attempts. OCPs (A) also protect the endometrium but suppress ovulation (fertility). GnRH depot induces menopause-like state. Letrozole (E) is used cyclically to induce ovulation, not continuously.
Vignette 4 of 4 · LO 4/5 — Early Pregnancy Hormones FA 3.01 · BnB 2.02
A 29-year-old at 7 weeks gestation by LMP presents with hyperemesis and a quantitative β-hCG of 145,000 mIU/mL. TSH is 0.1 μIU/mL (low). Free T4 is mildly elevated. She denies Graves-like symptoms; there is no goiter or proptosis. Which mechanism best explains her lab pattern?
ADestructive thyroiditis from β-hCG inflammation
BPituitary TSH-secreting adenoma stimulated by pregnancy
CCross-reactivity of β-hCG at the TSH receptor (structural α-subunit homology)
DElevated TBG from estrogen directly raising free T4
EHashimoto thyroiditis exacerbation
C — β-hCG cross-reactivity. hCG and TSH share an α-subunit (as do LH and FSH). Very high hCG (e.g., molar pregnancies, multiple gestations, hyperemesis gravidarum) can weakly activate the TSH-R → transient subclinical hyperthyroidism (suppressed TSH, mildly ↑fT4). Usually self-limited as hCG plateaus at 10–12 wks. This is gestational thyrotoxicosis, distinct from Graves (no TSH-R-Ab, no ophthalmopathy).
TRUE or FALSE — each trap reverses a common misconception7 traps
Trap 01 · LO 1 — Female Default In House · FA 3.01
"Normal female internal genital development requires active estrogen signaling from the fetal ovary."
FALSE. Female internal ducts develop in the absence of AMH, not because of estrogen. Müllerian ducts persist by default when AMH is absent. Even AMH-knockout 46,XY mice develop uteri. The fetal ovary is quiescent.
Trap 02 · LO 2 — Androgens and External Genitalia FA 3.01 · In House
"Testosterone, not DHT, is the primary hormone responsible for virilization of fetal external genitalia."
FALSE.DHT virilizes external genitalia (via 5α-reductase). Testosterone maintains the Wolffian ducts (internal). Hence 5α-RD deficiency → normal male internal ducts but female-looking external genitalia at birth.
Trap 03 · LO 3 — GnRH Administration FA 3.03 · Bootcamp 2.03
"Continuous administration of a GnRH agonist increases LH and FSH release chronically."
FALSE. Continuous GnRH causes desensitization after a transient flare → chronically suppresses LH/FSH. Used as chemical castration. Pulsatile GnRH is what drives physiologic LH/FSH release.
Trap 04 · LO 3 — Progesterone Feedback FA 3.03
"High progesterone in the luteal phase exerts positive feedback, priming the next LH surge."
FALSE. Progesterone is always inhibitory on the HPG axis. Luteal progesterone suppresses GnRH pulse frequency, preventing another follicle from maturing. Only estradiol (above threshold, sustained) does positive feedback.
Trap 05 · LO 4 — Meiosis Completion at Ovulation FA 3.01 · BnB 2.01
"The oocyte released at ovulation has completed both meiosis I and meiosis II."
FALSE. At ovulation, meiosis I has just completed (first polar body extruded) and the oocyte is arrested in metaphase II. Only sperm penetration completes meiosis II (second polar body).
Trap 06 · LO 5 — Luteal Phase Length FA 3.03
"In irregular cycles, variation in cycle length is typically due to varying luteal-phase duration."
FALSE. Luteal phase is fixed at ~14 days (CL lifespan). Cycle variation comes from the follicular phase. For a 35-day cycle, ovulation ~day 21 not day 14 — critical for fertility timing.
Trap 07 · LO 6 — CAIS Physical Exam FA 3.04 · BnB 7.01
"A 16-year-old with complete androgen insensitivity syndrome typically has normal adult-pattern pubic and axillary hair."
FALSE. CAIS = absent AR signaling → absent or scant pubic and axillary hair. Breast development is normal via peripheral T → E2 aromatization. The triad is 46,XY · breast dev · absent sexual hair. MRKH (46,XX, normal AR) retains pubic hair.
High-yield comparison tables3 tables
Table 1 · Hypogonadism — Primary vs Secondary vs DSD
Pattern banks, memory hooks, and common errors4 cards
Pattern Bank Buzzword → Diagnosis
"Webbed neck + short stature + no menses" → Turner syndrome (45,XO). "Anosmia + delayed puberty" → Kallmann syndrome. "46,XY + breast dev + blind vagina + absent pubic hair" → CAIS. "Guevedoces / penis at 12" → 5α-reductase deficiency. "String of pearls on TVUS + hirsutism + oligomenorrhea" → PCOS. "FMR1 pre-mutation + FSH > 40" → POI. "Hot flashes + vaginal dryness + FSH ↑ after age 50" → menopause. "Female athlete + amenorrhea + low bone density" → female athlete triad (hypothalamic amenorrhea). "hCG > 100,000 + hyperemesis + low TSH" → gestational thyrotoxicosis (hCG/TSH-R cross-reactivity).
High-Yield Rules of the HPG Axis
1.Problem is wherever the hormone isn't — ↑FSH/LH + ↓E2 = primary (ovary); ↓FSH/LH + ↓E2 = secondary (HPG). 2.Pulsatile = on; continuous = off. Applies to GnRH for pituitary, and to hCG/LH for CL — although hCG from placenta is "continuous" but overwhelming. 3.Estradiol is the only hormone that positive-feedbacks — and only at >200 pg/mL sustained >48 h. 4.Luteal phase = 14 days, fixed; follicular phase varies. 5.Two-cell model: Theca = LH → androgens; Granulosa = FSH → aromatase → estradiol. 6.Internal ducts vs external genitalia: T maintains Wolffian; DHT virilizes external; AMH regresses Müllerian.
Memory Hooks Mnemonics
"T-I-D-E" — what each hormone does: Testosterone = Internal (Wolffian); DHT = External (penis, prostate). "FSH Feeds Follicles (Granulosa); LH Lights up Leydig/Theca" — gonadotropin targets. "MPR" (Meiosis: Menarche, Pregnancy, Really?) — Meiosis I resumes at menarche's surge (actually LH surge each month); Meiosis II resumes with fertilization. "A-R-O-M-A" — Aromatase Releases Oestrogen from Male Androgens (also in granulosa and adipose). "PCOS = Probably Can't Ovulate Sometimes": anovulation, obesity, insulin resistance; tx OCPs + metformin + letrozole.
Common Errors Traps Corner
Trap: Saying "estrogen is required for female external genitalia development." Reality: female external genitalia develop in the absence of DHT; no fetal estrogen required. Trap: "Leuprolide stimulates ovulation." Reality: depends on schedule — continuous depot suppresses; pulsatile pump stimulates. Trap: "PCOS is caused by androgens alone." Reality: insulin resistance drives hyperandrogenism via ↓SHBG and theca stimulation — metformin helps. Trap: "CAIS patients have elevated FSH." Reality: CAIS typically has ↑LH (from lost T negative feedback), not ↑FSH. FSH is governed by inhibin (gonadal function mostly preserved). Trap: "All 46,XY infants who look female at birth have CAIS." Reality: differential includes 5α-RD, Swyer (46,XY gonadal dysgenesis), complete gonadal dysgenesis — labs distinguish.
Bedside/clinical connections expanding on the lecture6 correlates
LO 3/6 · Hyperprolactinemia and Amenorrhea FA 3.04 · BnB 5.04
Prolactin directly inhibits hypothalamic GnRH pulsatility → suppresses LH/FSH → hypogonadotropic hypogonadism. Causes: prolactinoma (most common pituitary adenoma); dopamine-blocking drugs (antipsychotics, metoclopramide); hypothyroidism (TRH cross-stimulates lactotropes). Presentation: amenorrhea-galactorrhea in women; ↓ libido and ED in men. Treatment: cabergoline (D2 agonist) first-line — shrinks most prolactinomas AND normalizes PRL; surgery rarely needed.
LO 5/6 · Female Athlete Triad / RED-S FA 3.04 · In House
Chronic low-energy availability (over-exercise + under-eating) suppresses hypothalamic GnRH pulsatility → low LH/FSH/E2 → functional hypothalamic amenorrhea. Estrogen deficiency → accelerated bone loss, stress fractures, early osteoporosis. Often comorbid with disordered eating. Screen all amenorrheic athletes. Management: increase caloric intake and decrease training load FIRST; consider transdermal estradiol + cyclic progestin if no improvement.
LO 3/5 · OCP Mechanism FA 3.06 · Bootcamp 2.03
Combined oral contraceptives (estrogen + progestin): primary mechanism is negative feedback on GnRH/LH/FSH → no follicular selection, no LH surge, no ovulation. Progestin thickens cervical mucus and atrophies endometrium (secondary mechanisms). Ethinyl estradiol stabilizes the endometrium (prevents breakthrough bleeding). Progestin-only pills (POP) work mostly via mucus thickening + endometrial thinning — less reliable at blocking ovulation; require strict timing.
LO 4 · Clomiphene vs Letrozole for Ovulation Induction FA 3.06 · In House
Clomiphene: SERM (antagonist in hypothalamus) → blocks E2 negative feedback → ↑ GnRH pulses → ↑ FSH → follicular recruitment. Side effect: multi-follicular development (twin pregnancy risk); thins endometrium (antagonist at uterus). Letrozole: aromatase inhibitor → ↓E2 → loss of E2 feedback → ↑ FSH. Newer first-line for PCOS ovulation induction (higher live-birth rate than clomiphene in the PPCOS II trial). Doesn't thin endometrium.
LO 6 · Menopause Transition & HRT Principles FA 3.04 · In House
Menopause = 12 months of amenorrhea from ovarian follicle depletion (average age 51). ↓E2 → hot flashes, vaginal atrophy, osteoporosis, ↑ LDL, ↑ CV risk. Labs: FSH >40 mIU/mL on 2 occasions. HRT: most effective for vasomotor symptoms and bone protection. Give estrogen alone only if no uterus (prevents endometrial cancer); add progestin if uterus present. Short-duration systemic HRT for symptomatic women <10 yrs post-menopause under age 60 is favored; avoid in breast cancer history, active clots, unexplained vaginal bleeding, liver disease.
LO 6 · Androgen-Secreting Tumors FA 3.04 · Pathoma 13.06 · In House
Rapid-onset virilization in a woman (clitoromegaly, deepening voice, severe hirsutism within months) — think androgen-secreting tumor, NOT PCOS (which is gradual). Differential: • Sertoli–Leydig cell tumor of ovary — ↑T, normal DHEA-S • Granulosa-theca cell tumor — ↑E2 (not virilization) • Adrenal adenoma/carcinoma — ↑↑DHEA-S • Late-onset CAH (21-OH) — ↑17-OH-progesterone Workup: serum T, DHEA-S, 17-OHP; imaging (TVUS → adrenal CT). Pelvic exam for palpable mass.