Reproductive

Primary Amenorrhea Workup

No period at 15. Breast tissue or not, uterus or not. Two questions🔑Question 1: Secondary sex characteristics present? Question 2: Uterus on imaging? Those two forks collapse the entire differential. narrow every cause.

Clinical Images

Turner syndrome 45,X karyotype
📷 Turner syndrome: 45,X karyotype · tap to expand
Imperforate hymen anatomical diagram
📷 Imperforate hymen: anatomical diagram · tap to expand

REPRO · GYN

Primary Amenorrhea Workup

She has cyclic pain but no period. Walk the algorithm🔑The entire differential splits on two binary questions. Master those two forks and every vignette writes itself., flip the cards, and learn to tell imperforate hymen from androgen insensitivity at a glance.

THE CASE

Something Is Blocked

Read the vignette. Commit to an answer before revealing.

Clinical Vignette
A 15-year-old girl is brought by her mother for evaluation of 9 months of cyclic lower abdominal pain. She has never had a menstrual period. She developed breast buds at age 11 and has Tanner stage 4 breast and pubic hair development. Vitals are normal. On abdominal exam, there is suprapubic tenderness without rebound or guarding. Pelvic exam reveals a bulging, bluish membrane at the vaginal introitus. No vaginal canal is visible behind it.

What is the most likely diagnosis?
This is an imperforate hymen🔑Imperforate hymen: the most satisfying diagnosis in gynecology. Dramatic presentation, simple cure. One incision and normal periods start. causing cryptomenorrhea (hidden menstruation) and hematocolpos (blood collecting in the vagina). She is menstruating on schedule internally, but the blood has nowhere to go. The cyclic pain tracks her monthly cycles. The bulging blue membrane is trapped menstrual blood pushing against the hymen from behind. Treatment: hymenectomy (a simple surgical incision to open the hymen and let the blood drain). Once opened, normal menses follow.
💡
Cyclic pain + no menses + blue bulge at introitus = imperforate hymen. The cyclic part tells you ovulation and menstruation are happening internally🔑Cyclic pain proves: (1) ovaries are working, (2) uterus is present and contracting. The only thing missing is an exit.. The bulge tells you there is a physical barrier. Three clues, one diagnosis.
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The Distractor Trap
Boards love to put androgen insensitivity syndrome (AIS) as a distractor here. The giveaway that rules it out: this patient has pubic hair (Tanner 4). AIS patients have NO pubic or axillary hair because their tissues cannot respond to androgens🔑AIS hair rule: pubic hair needs androgen receptors. Broken receptors = no hair. If she has pubic hair, she can respond to androgens. AIS is out.. She also has cyclic pain, meaning she has a uterus that contracts monthly. AIS patients have no uterus. Pubic hair + cyclic pain = cannot be AIS.
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KNOW YOUR VILLAINS

The Six Causes

Each card front shows the single diagnostic clue🔑Board questions test ONE distinguishing feature per condition. Lock in that one clue before you flip.. Tap to reveal the full profile.

📋
Turner Syndrome (45,X)
Short stature + webbed neck + NO secondary characteristics🔑Turner = short, webbed, shield chest. Streak ovaries make no estrogen = no puberty. High FSH because the pituitary is screaming at dead ovaries.
Tap to flip
Turner Syndrome (45,X)
Karyotype45,X (missing one X)
BreastsABSENT (streak ovaries, no estrogen)
Pubic hairMinimal/absent
UterusPresent but infantile
FSHHIGH (pituitary screaming at dead ovaries)
ClassicShort, webbed neck, shield chest, coarctation, bicuspid AoV
TreatGrowth hormone for height; estrogen to induce puberty + protect bones
⚧
Complete AIS (46,XY)
Breasts YES, pubic hair NO, inguinal masses🔑AIS: broken androgen receptors. Body hears estrogen (breasts), is deaf to androgens (no hair). Testes are in the groin making the testosterone that gets aromatized to estradiol for breast growth.
Tap to flip
Complete Androgen Insensitivity (AIS)
Karyotype46,XY
BreastsPresent (testosterone aromatized to estradiol)
Pubic hairABSENT (androgen receptors nonfunctional)
UterusABSENT (MIS from testes caused Mullerian regression)
GonadsUndescended testes (inguinal or labial masses)
VaginaBlind vaginal pouch (urogenital sinus-derived)
TreatGonadectomy after puberty (malignancy risk); vaginal dilators
🔌
Mullerian Agenesis (MRKH)
46,XX. Normal secondary characteristics. Absent uterus + vaginal dimple.🔑MRKH vs AIS: both have no uterus and breasts. One feature separates them: pubic hair. MRKH has it (46,XX, working androgen receptors). AIS does not.
Tap to flip
Mullerian Agenesis (MRKH)
Karyotype46,XX
BreastsNormal (ovaries work fine)
Pubic hairPRESENT (normal androgen receptors)
UterusABSENT (Mullerian ducts never formed)
OvariesNormal and functional
Cyclic painNO (no uterus to contract)
TreatVaginal dilators (progressive dilation) or neovagina surgery
🔴
Imperforate Hymen
Bulging blue membrane + cyclic pain + normal puberty.🔑Blue bulge = menstrual blood pressing against the membrane. The uterus, ovaries, everything works. Just a membrane in the way. One incision fixes it all.
Tap to flip
Imperforate Hymen
Karyotype46,XX
BreastsNormal (Tanner 4-5)
Pubic hairPresent
UterusPresent
Key examBulging blue membrane at introitus (hematocolpos)
Cyclic painYES (trapped blood, monthly)
TreatHymenectomy (cruciate incision); normal periods follow
⌛
Constitutional Delay
All normal. Bone age delayed. Diagnosis of exclusion.🔑Constitutional delay = late bloomer. Everything is intact, just running on a slower clock. Bone age lags chronological age. Everything eventually catches up on its own.
Tap to flip
Constitutional Delay of Puberty
Karyotype46,XX (normal)
HormonesNormal; FSH/LH low-normal for stage
Bone ageDelayed (lags chronological age by 2+ years)
Family hxOften positive (parent was also a "late bloomer")
DiagnosisExclusion: rule out all pathology first
TreatReassurance; short-course low-dose estrogen to initiate puberty if needed
🧠
Hypothalamic Amenorrhea
Low FSH. Anorexia or extreme exercise.🔑Hypothalamic suppression = the brain says "too dangerous to get pregnant now." GnRH shuts off, LH/FSH drop, no estrogen, no puberty. Reversible with weight restoration. Brain turned off the signal.
Tap to flip
Hypothalamic (Functional) Amenorrhea
Karyotype46,XX
BreastsAbsent or underdeveloped
FSHLOW (pituitary not signaling)
CausesAnorexia, extreme exercise, caloric restriction, stress
Also thinkProlactinoma (headaches + visual change + galactorrhea); Kallmann (low FSH + anosmia)
UterusPresent, normal
TreatRestore body weight and reduce exercise; HRT if needed
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THE ALGORITHM

Primary Amenorrhea Workup

Walk each branch of the decision tree🔑The tree has two main forks: secondary sex characteristics (estrogen) and uterus present (Mullerian). Everything else follows from those two questions.. Pick your answer at each fork before seeing the next step.

Definition: No menses by age 15 with secondary sex characteristics present, OR by age 13 without them🔑Age 15 vs 13 rule: the 2-year difference accounts for the time puberty normally takes. Without puberty starting, you have fewer years to wait before investigating.. Those two numbers are the entry point.

TWO-FORK DECIDER

Answer Two Questions. Land the Diagnosis.

Breasts or no breasts. Uterus or no uterus. Every primary amenorrhea diagnosis lives at the end of those two forks.

Two-Fork Decider
Pick your answer at each branch. The algorithm animates to the diagnosis bucket.
Fork 1: Breasts?
Fork 2: Uterus?
Fork 3: FSH?
Diagnosis
Does she have breast development (secondary sex characteristics)?
She has breasts. Estrogen works. Is a uterus present on pelvic ultrasound?
No breasts = no estrogen. Check FSH: is it elevated or low?
Breasts + uterus both present. Is there cyclic pelvic pain?
📆
The tree splits on one question: does she have secondary sex characteristics? That single observation separates the entire differential into two halves. Secondary characteristics present means estrogen is flowing, so the ovaries work. No secondary characteristics means estrogen is absent, so check FSHFollicle-stimulating hormone. High FSH = pituitary screaming at ovaries that are not responding (gonadal failure). Low FSH = pituitary itself is not sending the signal (central cause).🔑High FSH = ovary problem. Low FSH = brain problem. The gonadotropin level points the arrow at the correct level of the axis. to figure out whether the problem is central or gonadal.
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SIDE BY SIDE

At-a-Glance Comparison

The four details🔑The four power columns: Karyotype, Breasts, Pubic Hair, Uterus. Lock in those four for each diagnosis and the table does the heavy lifting on boards. that separate every cause.

Condition Karyotype Breasts Pubic Hair Uterus Key Exam Treatment
Imperforate Hymen 46,XX Yes Yes Yes Blue bulge, cyclic pain Hymenectomy
Transverse Septum 46,XX Yes Yes Yes Cyclic pain, no visible bulge Surgical excision
MRKH (Mullerian Agenesis) 46,XX Yes Yes Absent Vaginal dimple, no cyclic pain Dilators / neovagina
Androgen Insensitivity 46,XY Yes NO Absent Blind pouch, no pubic hair Gonadectomy post-puberty
Turner Syndrome 45,X No Sparse Infantile Short, webbed neck, high FSH GH + estrogen
Constitutional Delay 46,XX Delayed Delayed Yes Bone age delayed, family history Reassurance
Hypothalamic 46,XX No/underdeveloped Sparse Yes Low FSH, weight loss/exercise hx Treat cause, HRT
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AIS vs MRKH: The Two "No Uterus" Diagnoses
Both present with amenorrhea, breast development, and no uterus. The single distinguishing feature: pubic hair🔑Pubic hair is the one-feature discriminator between AIS and MRKH. Both have breasts. Both lack a uterus. Hair is the fork.. MRKH patients are 46,XX with normal pubic hair (their androgen receptors work fine). AIS patients are 46,XY with no pubic hair (androgen receptors are nonfunctional). If you see "absent uterus" on a stem, immediately check for pubic hair. That is the fork.
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KNOW YOUR VILLAINS

Six Key Causes

One distinguishing feature per card. Tap to flip and see the full profile.

Turner Syndrome
45,X / Gonadal dysgenesis

Short stature, webbed neck, no secondary sex characteristics. Streak gonads make no estrogen.

tap to flip

Karyotype: 45,X (missing one X chromosome)

Breasts: Absent. Streak ovaries produce no estrogen.

FSH: High. Pituitary screams at silent gonads.

Classic features: Webbed neck, shield chest, coarctation of aorta, bicuspid aortic valve.

Board pearl: High FSH + no puberty + short stature = Turner until proven otherwise.

Androgen Insensitivity
CAIS / 46,XY female phenotype

Breasts present, pubic hair absent, blind vaginal pouch, no uterus. 46,XY karyotype.

tap to flip

Karyotype: 46,XY with nonfunctional androgen receptors.

Breasts: Present. Testes aromatize testosterone to estradiol.

Pubic hair: Absent. Receptors deaf to androgens.

Uterus: Absent. MIS from testes caused Mullerian regression.

Board pearl: Breasts + no pubic hair + no uterus = CAIS. Gonadectomy after puberty.

Mullerian Agenesis
MRKH / 46,XX structural absence

Normal puberty, normal ovaries, absent uterus and upper vagina. 46,XX.

tap to flip

Karyotype: 46,XX with fully functional ovaries.

Pubic hair: Present. Androgen receptors intact.

Uterus: Absent. Mullerian ducts failed to form.

Cyclic pain: None. No uterus to contract.

Board pearl: Normal puberty + pubic hair present + no uterus = MRKH, not AIS.

Hypothalamic Amenorrhea
Functional GnRH suppression

Low GnRH pulses from anorexia or excessive exercise. Low FSH and LH, normal anatomy.

tap to flip

Karyotype: 46,XX, normal anatomy throughout.

FSH/LH: Low. Brain suppressed GnRH signaling.

Cause: Anorexia, extreme exercise, severe stress, caloric restriction.

Reversible: Yes, with weight restoration and reduced exercise load.

Board pearl: Low FSH + underweight athlete + no puberty = hypothalamic suppression.

Hyperprolactinemia
Prolactinoma / galactorrhea

Pituitary adenoma overproduces prolactin. Blocks GnRH. Galactorrhea, headache, visual field cut.

tap to flip

Mechanism: Excess prolactin inhibits hypothalamic GnRH pulsatility.

Signs: Galactorrhea, bitemporal hemianopia from optic chiasm compression.

Labs: Elevated prolactin, low FSH and LH.

Imaging: MRI pituitary shows macroadenoma or microadenoma.

Board pearl: Galactorrhea + amenorrhea + visual changes = get prolactin level and MRI.

Constitutional Delay
Late bloomer / diagnosis of exclusion

All anatomy and hormones normal. Bone age lags. Often family history of late puberty.

tap to flip

Karyotype: 46,XX, everything normal.

Bone age: Delayed by 2 or more years relative to chronological age.

Hormones: Normal for pubertal stage, just delayed onset.

Family history: Parent was often also a late bloomer.

Board pearl: Diagnosis of exclusion. Rule out all pathology first. Reassurance is the treatment.

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TEST YOURSELF

Board-Style Questions

5 of 10 questions🔑Read the last sentence of every stem first. That is the actual question. Then hunt the stem for the one clue that answers it.. Walk the tree, read the clues, pick your answer.

Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last reviewed June 2026
Bone Wizardry · REPRO
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