Click a card to flip · 16 cards totalOvary Endocrinology
LO 1 · 6 Levels of Sexual Differentiation
Name the six hierarchical levels of sexual differentiation in order. Which one determines all the others?
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Answer
1. Genetic (chromosomal) sex — XX vs XY; the master switch that drives all downstream sex. 2. Gonadal sex — ovary vs testis; controlled by SRY on Yp (makes TDF). 3. Phenotypic sex — internal ducts + external genitalia. 4. Germ-cell sex — oocyte vs spermatocyte fate. 5. Hormonal sex — estrogen/progesterone vs testosterone/DHT profile. 6. Behavioral/psychological sex — brain sexual dimorphism.
Genetic sex sits at the top and determines gonadal sex, which then drives phenotypic and hormonal sex.
LO 1 · Default vs Induced Pathway
Female development is often called the "default" pathway. What exactly is defaulted, and which signaling events actively drive male development?
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Answer
Without SRY / TDF, bipotential gonads → ovaries by default. Without AMH, paramesonephric (Müllerian) ducts persist → uterus, fallopian tubes, upper vagina. Without testosterone, mesonephric (Wolffian) ducts regress.
Which hormone is required for each: Wolffian duct maintenance, external genital virilization, feminization of external genitalia, and bone epiphyseal fusion in both sexes?
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Answer
Wolffian ducts (epididymis, vas deferens, seminal vesicles) → testosterone. External male genitalia (penis, scrotum, prostate) → DHT (via 5α-reductase). External female genitalia → develop in absence of DHT (not actively "feminized" by estrogen). Epiphyseal closure in both sexes → estrogen (even in males, T is aromatized to E2).
Mnemonic — "Testosterone = internal, DHT = external (DICK)": DHT drives Differentiation of external genitalia, the prostate, and post-pubertal hair/acne/balding.
LO 3 · HPG Pipeline Order
Trace the HPG axis from hypothalamus to target tissue in a female. Which hormone is pulsatile and which is tonic?
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Answer
Hypothalamus → pulsatileGnRH (every 60–90 min) → median eminence → portal system → Anterior pituitary gonadotropes → LH & FSH (tonic levels with cycle-dependent surges) → Ovary → estradiol (granulosa, from thecal androgens) & progesterone (corpus luteum) → target tissues.
KEY: Pulsatile GnRH = physiologic. Continuous GnRH (e.g., leuprolide given continuously) → gonadotrope desensitization → ↓LH/FSH → chemical castration.
LO 3 · Two-Cell, Two-Gonadotropin Model
Which ovarian cell has which gonadotropin receptor, and which enzyme does each cell provide in estrogen synthesis?
Androgens must cross from theca → granulosa to be aromatized. At the LH surge, granulosa cells also express LH receptors → shift to progesterone production (luteinization).
LO 3 · Feedback Switch
Estradiol normally gives negative feedback, but once a month it gives positive feedback. What are the two conditions for the switch?
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Answer
The switch to positive feedback requires: 1. E2 concentration > ~200 pg/mL (high threshold) 2. Sustained for > ~48 hours (duration)
When both are met, estradiol stimulates GnRH/LH release → the LH surge → ovulation. At all other times (low or transiently high E2), E2 inhibits GnRH, LH, FSH.
Progesterone always gives negative feedback — there is no positive feedback phase for progesterone. This is why the luteal phase shuts down gonadotropins.
LO 4 · Follicle Pool Across Life
How many oocytes does a female have at 20 weeks gestation, at birth, at puberty, and at menopause? When does meiosis I arrest occur and when does it resume?
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Answer
Peak: 20 wk gestation ≈ 6–7 million oogonia. Birth ≈ 1–2 million primary oocytes (all arrested in prophase I). Puberty ≈ 300–400,000. Menopause ≈ <1000 (functionally 0).
Meiosis I arrest occurs in fetal life at prophase I (diplotene). It resumes at the LH surge just before ovulation (polar body extruded). Meiosis II arrest occurs at metaphase II after ovulation. Only fertilization completes meiosis II.
LO 4 · Follicle Stages in Order
Starting from primordial follicle, name the 5 stages of follicular development. Which one is FSH-independent and which is FSH-dependent?
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Answer
1. Primordial follicle — single layer flat squamous granulosa, arrested since fetal life. FSH-independent. 2. Primary follicle — cuboidal granulosa; zona pellucida appears. FSH-independent. 3. Secondary (preantral) follicle — multi-layer granulosa + theca layers form. Starts to become FSH-responsive. 4. Antral (Graafian) follicle — fluid-filled antrum; estradiol-secreting. FSH-dependent. 5. Preovulatory / dominant follicle — one follicle wins; LH surge → ovulation.
Post-ovulation → corpus luteum → corpus albicans if no pregnancy.
LO 4 · Corpus Luteum
What cells form the corpus luteum, what hormones does it secrete, and what rescues it if pregnancy occurs?
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Answer
After ovulation, granulosa-lutein cells (from granulosa) and theca-lutein cells (from theca interna) luteinize under continued LH stimulation.
CL secretes progesterone (dominant), estradiol, and inhibin A.
Lifespan without pregnancy = ~14 days → regresses → corpus albicans.
Rescue: if fertilization → implantation day ~7 → trophoblast hCG (LH-like) binds CL LH-receptors → CL maintained. By ~8–10 weeks, placenta takes over progesterone production (luteal-placental shift).
LO 5 · 3 Phases of the Cycle
Name the three ovarian phases and the two endometrial phases of the 28-day cycle. Which day is ovulation and which hormone drives each phase?
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Answer
Ovarian: • Follicular (days 1–13) — FSH selects dominant follicle; granulosa-driven estradiol rises. • Ovulation (day 14) — LH surge ~36 h before ovulation. • Luteal (days 15–28) — CL dominates; progesterone peaks day 21–22.
Secondary (hypogonadotropic hypogonadism): hypothalamus/pituitary fails → ↓GnRH or ↓FSH/LH → ↓E2 with low or normal FSH/LH. Examples: Kallmann syndrome (anosmia + ↓GnRH), hypothalamic amenorrhea (stress/athletes/eating disorders), hyperprolactinemia, pituitary adenoma.
Rule: Problem is wherever the hormone isn't.
LO 6 · Turner Syndrome
A 14 y/o with short stature, webbed neck, and no breast development has never menstruated. What is the karyotype, the ovarian histology, and the hormone profile?
Treatment: estrogen replacement at puberty; pregnancy possible only with donor oocyte.
LO 6 · Androgen Insensitivity Syndrome
A 46,XY patient is raised female, presents at puberty with primary amenorrhea, breast development, but absent pubic/axillary hair. Testosterone is elevated. Diagnosis and hormonal explanation?
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Answer
Complete Androgen Insensitivity Syndrome (CAIS) — X-linked mutation in the androgen receptor (AR).
Mechanism: 46,XY with functional testes → make testosterone + AMH. AMH regresses Müllerian ducts → no uterus/upper vagina. Testosterone cannot signal → Wolffian ducts regress → external genitalia default to female. Peripheral aromatization of T → E2 → breast development at puberty.
Labs: ↑↑T, ↑LH, normal/↑E2. Testes often in inguinal canal — remove after puberty (malignancy risk). Absent pubic/axillary hair = classic clue (needs androgen signaling).
LO 6 · PCOS Hormone Pattern
A 22 y/o with oligomenorrhea, hirsutism, and acne has BMI 32. List the Rotterdam criteria and the classic hormonal/metabolic abnormalities.
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Answer
Rotterdam criteria — need 2 of 3: 1. Oligo/anovulation 2. Clinical or biochemical hyperandrogenism 3. Polycystic ovaries on ultrasound (≥12 follicles 2–9 mm, "string of pearls")
Hormonal: ↑LH, normal/↓FSH → LH:FSH ratio > 2–3:1; ↑testosterone, ↑androstenedione, ↓SHBG, ↑ estrone (aromatization in adipose).
The SRY gene on encodes testis-determining factor, which directs the bipotential gonad toward becoming a . In its absence, the gonad defaults to an .
Question 2 · LO 2 — Hormone Requirements
Müllerian (paramesonephric) duct regression in males requires from Sertoli cells. Wolffian (mesonephric) duct retention requires from Leydig cells. Virilization of external genitalia requires produced by the enzyme .
Question 3 · LO 3 — GnRH Pulsatility
GnRH is released in pulses every minutes. Continuous GnRH administration paradoxically causes of the GnRH receptor, producing a functional chemical . This is the mechanism of leuprolide in prostate cancer.
Question 4 · LO 3 — Two-Cell Model
In the ovarian two-cell model, cells respond to and synthesize androstenedione, while cells respond to and aromatize androgens into .
Question 5 · LO 3 — Feedback Switch
Estradiol normally exerts feedback on the HPG axis. However, when estradiol exceeds ~ pg/mL for more than ~48 hours, it switches to feedback, triggering the .
Question 6 · LO 4 — Oocyte Numbers
The peak number of oogonia occurs at weeks of gestation with approximately cells. At birth there are ~, and oocytes remain arrested in until the LH surge.
Question 7 · LO 4 — Corpus Luteum Rescue
Without pregnancy, the corpus luteum involutes after ~ days to form the corpus . If pregnancy occurs, from trophoblasts binds CL LH receptors and maintains progesterone production until the takes over at ~8–10 weeks.
Question 8 · LO 5 — Cycle Hormone Peaks
In a standard 28-day cycle, estradiol peaks just before ovulation on day driving the LH surge. Progesterone peaks at day , mirrored by from the corpus luteum. The luteal phase has a fixed length of days.
Question 9 · LO 6 — Kallmann Syndrome
Kallmann syndrome is defective migration of neurons from the olfactory placode to the hypothalamus. Patients present with delayed puberty and . Labs show low FSH/LH and low estradiol — a pattern called hypogonadism.
Question 10 · LO 6 — 5α-Reductase Deficiency
A 46,XY neonate with 5α-reductase deficiency has normal testosterone but deficient . Internal ducts are (T-driven) but external genitalia appear . At puberty, rising testosterone causes virilization — classically described as "."
Drag the tiles to arrange each sequence in the correct physiologic order, then click Check.
Drill 1 · LO 4 — Follicle Maturation Sequence
Arrange from earliest (fetal life) to post-ovulatory.
Step 1 traps. Read each statement carefully — each one reverses or distorts a common misconception. Choose TRUE or FALSE.
Trap 01 · LO 1 — SRY Source
"The SRY gene is located on the long arm of the Y chromosome (Yq)."
FALSE. SRY is on the short arm of Y (Yp11.3). Translocation of SRY to an X chromosome during aberrant meiosis causes 46,XX sex-reversed males (de la Chapelle syndrome). Remember: Short arm → SRY.
Trap 02 · LO 2 — "Female is Active Estrogen-Driven"
"Normal female external genitalia development requires estradiol signaling from the fetal ovary."
FALSE. Female external genitalia develop in the absence of androgens, not because of estrogens. This is why 46,XY CAIS (AR mutation) patients still have normal female-appearing external genitalia despite XY karyotype. Fetal estrogen is not required; the default pathway is female.
Trap 03 · LO 3 — Continuous vs Pulsatile GnRH
"Continuous GnRH administration would be expected to stimulate LH/FSH release and induce ovulation."
FALSE. GnRH must be pulsatile (every ~60–90 min). Continuous GnRH (e.g., leuprolide depot) desensitizes gonadotropes and suppresses LH/FSH — used as chemical castration in prostate cancer, endometriosis, and central precocious puberty. Pulsatile leuprolide, by contrast, induces ovulation.
Trap 04 · LO 3 — Aromatase Location
"Theca cells express aromatase and directly synthesize estradiol from cholesterol."
FALSE.Granulosa cells have aromatase (FSH-driven). Theca cells have desmolase + 17α-hydroxylase + 17,20-lyase (LH-driven) and supply androstenedione to granulosa. This is the two-cell, two-gonadotropin model. At the LH surge, granulosa acquire LH receptors and luteinize.
Trap 05 · LO 3 — Progesterone Feedback
"Sustained high progesterone during the luteal phase exerts positive feedback that primes the next LH surge."
FALSE. Progesterone exerts only negative feedback on the HPG axis. High luteal progesterone suppresses GnRH pulse frequency, which is exactly why another dominant follicle can't mature during the luteal phase — and why continuous-progestin contraception prevents ovulation. Only estradiol switches to positive feedback.
Trap 06 · LO 4 — Oocyte Meiosis Completion
"The secondary oocyte released at ovulation has already completed meiosis II."
FALSE. At ovulation, the oocyte has completed meiosis I (first polar body extruded) and is arrested in metaphase II. Meiosis II only completes when sperm penetrates (fertilization) — this is when the second polar body forms. An unfertilized oocyte degenerates in metaphase II.
Trap 07 · LO 5 — Luteal Phase Length
"In irregular cycles, variation in cycle length is due to variation in the luteal phase."
FALSE. The luteal phase is fixed at ~14 days (corpus luteum lifespan). Variability in cycle length comes from the follicular phase. That's why you count backwards from the next expected menses to estimate ovulation (e.g., a 35-day cycle → ovulation day 21, not day 14).
Trap 08 · LO 6 — CAIS and Pubic Hair
"A 17-year-old with complete androgen insensitivity syndrome presents with well-developed pubic and axillary hair despite primary amenorrhea."
FALSE. In CAIS, androgen receptors don't work, so pubic and axillary hair are absent or scant. Breast development is present (from peripheral T → E2 aromatization). Classic triad: 46,XY · primary amenorrhea · breast dev but absent sexual hair · blind-ended vagina, no uterus.
Wolffian ducts retained → epididymis, vas, seminal vesicles
Phenotypic — external
DHT (5α-reductase)
Clitoris, labia, lower vagina (default)
Penis, scrotum, prostate (DHT-driven)
Germ cell
Gonadal environment
Oocyte (meiosis I arrest fetal)
Spermatocyte (meiosis starts at puberty)
Hormonal
HPG axis at puberty
E2, P, inhibin B
T, DHT, inhibin B
Table 2 · The Two-Cell, Two-Gonadotropin Model
Cell
Receptor
Key Enzymes
Product
Theca interna
LH-R
Desmolase (CYP11A1), 17α-hydroxylase, 17,20-lyase — no aromatase
Androstenedione → testosterone (diffuses to granulosa)
Granulosa
FSH-R (+ LH-R late follicular)
Aromatase (CYP19) — no 17α-hydroxylase
Estradiol; inhibin B (follicular), inhibin A (luteal)
Corpus luteum (lutein cells)
LH-R / hCG-R
Steroidogenic cascade → progesterone
Progesterone >> estradiol > inhibin A
Clinical anchor: Aromatase inhibitors (letrozole, anastrozole) block granulosa estrogen synthesis — used in estrogen-receptor+ breast cancer and for ovulation induction in PCOS.
Table 3 · HPG Feedback Rules — Female
State
Estradiol
Progesterone
Inhibin
Net Effect
Early follicular
Low → negative feedback
Low
Inhibin B suppresses FSH
↓LH/FSH; FSH slowly rises
Late follicular (>200 pg/mL ×48 h)
Positive feedback
Low
Low
LH surge → ovulation
Luteal
Mod/negative
High → negative
Inhibin A high
↓LH/FSH — no new follicles
Late luteal (CL regress)
Low
Low
Low
FSH rises → new cycle
Table 4 · Folliculogenesis Stages
Stage
Granulosa
Theca
FSH/LH
Timing
Primordial
Flat squamous, 1 layer
—
FSH-independent
Present since fetal life
Primary
Cuboidal + zona pellucida
None yet
FSH-independent
~months
Secondary (preantral)
Multiple layers
Theca interna + externa
Early FSH response
~2–3 months prior
Antral (tertiary)
Fluid-filled antrum; aromatase active
LH-driven androgen supply
FSH-dependent
Final 2 weeks of cycle
Preovulatory (Graafian)
Granulosa now also LH-R
Active
LH surge → ovulation
Day 13–14
Corpus luteum
Lutein granulosa
Lutein theca
LH/hCG maintains
Days 15–28
Table 5 · Differential of Amenorrhea by FSH/LH Pattern